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PMID:28162 | [Use of acetylcholinesterase reactivators and central cholinolytics in the treatment of experimental tetanus poisoning]. | Experiments were conducted on rabbits with tetanus intoxication induced by the intravenous injection of a lethal dose of the toxin; a study was made of the therapeutic efficacy of the acetylcholinesterase reactivators--dipyroxim and isonitrosine, and also of the central cholinolytics--amizyl and diphacyl. In dose of 25 mg/kg dipyroxim produced no therapeutic effect, and in doses of 30--40 mg/kg caused the animal death. Amizyl and diphacil in a dose of 3--4 mg/kg caused elimination of tonic convulsions for 1 1/2--2 hours. As to isonitrosin--it produced the same effect for 4--5 hours. In case of combined administration of reactivators and cholinolytics convulsions were eliminated for 4--5 hours. | [Use of acetylcholinesterase reactivators and central cholinolytics in the treatment of experimental tetanus poisoning]. Experiments were conducted on rabbits with tetanus intoxication induced by the intravenous injection of a lethal dose of the toxin; a study was made of the therapeutic efficacy of the acetylcholinesterase reactivators--dipyroxim and isonitrosine, and also of the central cholinolytics--amizyl and diphacyl. In dose of 25 mg/kg dipyroxim produced no therapeutic effect, and in doses of 30--40 mg/kg caused the animal death. Amizyl and diphacil in a dose of 3--4 mg/kg caused elimination of tonic convulsions for 1 1/2--2 hours. As to isonitrosin--it produced the same effect for 4--5 hours. In case of combined administration of reactivators and cholinolytics convulsions were eliminated for 4--5 hours. | [
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PMID:28166 | Prediction of wound sepsis following gastric operations. | Gastric aspirates were obtained from 12 healthy volunteers, 49 patients with duodenal ulcer, 14 with gastric ulcer and 35 with gastric carcinoma. The mean total viable bacterial counts in these groups were as follows: volunteers 0, duodenal ulcer 3.8 X 10(1), gastric ulcer 6.95 X 10(4), carcinoma 1.9 X 10(7) organisms/ml. The incidence of wound sepsis in patients without antibiotic cover was; duodenal ulcer 17 per cent, gastric ulcer 38 per cent, carcinoma 56 per cent. Regardless of the underlying pathology, patients with counts greater than 5 X 10(6) organisms/ml in the gastric aspirate had a 93 per cent incidence of wound sepsis, compared with 16 per cent in patients with counts of less than 5 X 10(6) organisms/ml (P less than 0.001). In the group with high counts all except one of the wound infections were caused by organisms present in the stomach at the time of operation. There was a good correlation in the bacteriology of apirates obtained during preoperative endoscopy compared with operative nasogastric samples (n = 31) both for viable counts (r = 0.93) and for the counts of individual organisms. Therefore, preoperative endoscopy can be used to identify patients who are at risk of developing wound sepsis after gastric surgery. | Prediction of wound sepsis following gastric operations. Gastric aspirates were obtained from 12 healthy volunteers, 49 patients with duodenal ulcer, 14 with gastric ulcer and 35 with gastric carcinoma. The mean total viable bacterial counts in these groups were as follows: volunteers 0, duodenal ulcer 3.8 X 10(1), gastric ulcer 6.95 X 10(4), carcinoma 1.9 X 10(7) organisms/ml. The incidence of wound sepsis in patients without antibiotic cover was; duodenal ulcer 17 per cent, gastric ulcer 38 per cent, carcinoma 56 per cent. Regardless of the underlying pathology, patients with counts greater than 5 X 10(6) organisms/ml in the gastric aspirate had a 93 per cent incidence of wound sepsis, compared with 16 per cent in patients with counts of less than 5 X 10(6) organisms/ml (P less than 0.001). In the group with high counts all except one of the wound infections were caused by organisms present in the stomach at the time of operation. There was a good correlation in the bacteriology of apirates obtained during preoperative endoscopy compared with operative nasogastric samples (n = 31) both for viable counts (r = 0.93) and for the counts of individual organisms. Therefore, preoperative endoscopy can be used to identify patients who are at risk of developing wound sepsis after gastric surgery. | [
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PMID:28174 | Characteristics of Thiobacillus thioparus and its thiocyanate assimilation. | Thiocyanate-assimilatig bacterium, TK 21, was isolated from activated sludge used for the treatment of thiocyanate contained in coke-oven liquor. This organism oxidized thiosulfate and elemental sulfur, causing a decrease of pH of the medium. These facts indicated that it belongs to the genus Thiobacillus. Potassium thiocyanate (0.5 g/l) was completely assimilated during 60 h. Thiosulfate inhibited the assimilation of thiocyanate but elemental sulfur did not. This bacterium did not evolve cyanide as its oxidation product after the decomposition of thiocyanate. The isoalted bacterium was identified as Thiobacillus thioparus. Examination of the composition of cellular fatty acid of three strains of T. thioparus showed that they prossessed 3-hydroxy fatty acid of C10 and C12; saturated straight chains of C10, C12, C15, C16, C17, and C18; monounsaturated straight chains of C16 and C18; and cyclopropane acid of C17. | Characteristics of Thiobacillus thioparus and its thiocyanate assimilation. Thiocyanate-assimilatig bacterium, TK 21, was isolated from activated sludge used for the treatment of thiocyanate contained in coke-oven liquor. This organism oxidized thiosulfate and elemental sulfur, causing a decrease of pH of the medium. These facts indicated that it belongs to the genus Thiobacillus. Potassium thiocyanate (0.5 g/l) was completely assimilated during 60 h. Thiosulfate inhibited the assimilation of thiocyanate but elemental sulfur did not. This bacterium did not evolve cyanide as its oxidation product after the decomposition of thiocyanate. The isoalted bacterium was identified as Thiobacillus thioparus. Examination of the composition of cellular fatty acid of three strains of T. thioparus showed that they prossessed 3-hydroxy fatty acid of C10 and C12; saturated straight chains of C10, C12, C15, C16, C17, and C18; monounsaturated straight chains of C16 and C18; and cyclopropane acid of C17. | [
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PMID:28175 | Oxidation of gallium sulfides by Thiobacillus ferrooxidans. | The bacterial oxidation of naturally occurring gallium-bearing chalcopyrite concentrate and a pure synthetic gallium (III) sulfide has been investigated at pH 1.8 and 35 degree C, using an active culture of Thiobacillus ferrooxidans. This oxidation process may proceed by direct or by indirect bacterial action. The highest dissolved gallium and copper concentrations were about 2.2 and 40.2 g/l, respectively. The order of the specific rate of oxygen uptake by T. ferrooxidans in approximately CuFES2 greater than or equal to gallium-bearing CuFeS2 greater than FeS2 greater than Cu2S greater than Cu2S greater than Ga2S3. | Oxidation of gallium sulfides by Thiobacillus ferrooxidans. The bacterial oxidation of naturally occurring gallium-bearing chalcopyrite concentrate and a pure synthetic gallium (III) sulfide has been investigated at pH 1.8 and 35 degree C, using an active culture of Thiobacillus ferrooxidans. This oxidation process may proceed by direct or by indirect bacterial action. The highest dissolved gallium and copper concentrations were about 2.2 and 40.2 g/l, respectively. The order of the specific rate of oxygen uptake by T. ferrooxidans in approximately CuFES2 greater than or equal to gallium-bearing CuFeS2 greater than FeS2 greater than Cu2S greater than Cu2S greater than Ga2S3. | [
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PMID:28178 | Cyclophosphamide-induced oncogenic transformation, chromosomal breakage, and sister chromatid exchange following microsomal activation. | Cyclophosphamide, an extensively used cancer chemotherapeutic agent, requires metabolic activation through a mixed-function oxygenase system. The capacity of this agent to produce oncogenic transformation and chromosomal damage, including increases in sister chromatid exchanges, was investigated in cell culture with or without an exogenous liver metabolic activation system. No oncogenic transformation or chromosomal aberrations were produced by cyclophosphamide in the absence of metabolic activation, whereas significant transformation, chromosomal breaks, and increases in sister chromatid exchanges were observed when the activation system was incorporated into the assays. The oncogenic transformation and chromosomal changes were completely eliminated by removing glucose 6-phosphate and nicotinamide adenine dinucleotide phosphate from the metabolic generating system. These studies emphasize the necessity to incorporate some activation procedure into short-term assays used for evaluating the mutagenic and/or oncogenic potential of various chemicals. | Cyclophosphamide-induced oncogenic transformation, chromosomal breakage, and sister chromatid exchange following microsomal activation. Cyclophosphamide, an extensively used cancer chemotherapeutic agent, requires metabolic activation through a mixed-function oxygenase system. The capacity of this agent to produce oncogenic transformation and chromosomal damage, including increases in sister chromatid exchanges, was investigated in cell culture with or without an exogenous liver metabolic activation system. No oncogenic transformation or chromosomal aberrations were produced by cyclophosphamide in the absence of metabolic activation, whereas significant transformation, chromosomal breaks, and increases in sister chromatid exchanges were observed when the activation system was incorporated into the assays. The oncogenic transformation and chromosomal changes were completely eliminated by removing glucose 6-phosphate and nicotinamide adenine dinucleotide phosphate from the metabolic generating system. These studies emphasize the necessity to incorporate some activation procedure into short-term assays used for evaluating the mutagenic and/or oncogenic potential of various chemicals. | [
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PMID:28181 | Complexes of trivalent oxygenated phosphorus compounds with cytochrome P-450 and cytochrome P-420: the origin of double Soret spectra. | Trivalent oxygenated phosphorus ligands include alkyl and aryl phosphites, (RO)3P, phosphonites, (RO)2PR, and phosphinites, ROPR2. All such compounds tested, with the exception of triphenyl phosphite, interact with ferrous cytochrome P-450 and its denatured form, cytochrome P-420, to produce complexes having two peaks in the Soret region of their optical difference spectra. Careful evaluation of these spectra indicate that they arise for different reasons for each of the two cytochromes. Clear evidence shows that cytochrome P-450 is not denatured by these ligands. The high affinity of these ligands for heme iron is indicated by small Ks values. The experimental results are used to substantiate a theory of the origin of microsomal double Soret spectra and the nature of the environments available for microsomal cytochromes P-450 and P-420. | Complexes of trivalent oxygenated phosphorus compounds with cytochrome P-450 and cytochrome P-420: the origin of double Soret spectra. Trivalent oxygenated phosphorus ligands include alkyl and aryl phosphites, (RO)3P, phosphonites, (RO)2PR, and phosphinites, ROPR2. All such compounds tested, with the exception of triphenyl phosphite, interact with ferrous cytochrome P-450 and its denatured form, cytochrome P-420, to produce complexes having two peaks in the Soret region of their optical difference spectra. Careful evaluation of these spectra indicate that they arise for different reasons for each of the two cytochromes. Clear evidence shows that cytochrome P-450 is not denatured by these ligands. The high affinity of these ligands for heme iron is indicated by small Ks values. The experimental results are used to substantiate a theory of the origin of microsomal double Soret spectra and the nature of the environments available for microsomal cytochromes P-450 and P-420. | [
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PMID:28182 | The anaerobic dechlorination of trichlorofluoromethane by rat liver preparations in vitro. | Incubation of trichlorofluoromethane with a liver microsomal fraction and an NADPH generating system under anaerobic conditions produced a metabolite dichlorofluoromethane, characterised by gas chromatography and mass spectrometry. The metabolic reaction was carried out by liver microsomes from the mouse, rabbit, hamster and rat and was increased by phenobarbitone pre-treatment. The formation of dichlorofluoromethane in vitro was enhanced by the addition of FMN, but partially inhibited by the presence of air, oxygen, SK&F 525-A, metyrapone and carbon tetrachloride and totally inhibited by carbon monoxide. The consumption of NADPH in the reaction was greater than could be accounted for by the production of dichlorofluoromethane indicating the possible formation of other metabolic products. It is suggested that trichlorofluoromethane interacts with the reduced form of cytochrome P-450 at the oxygen binding site and a possible mechanism for its subsequent reductive dechlorination is proposed. | The anaerobic dechlorination of trichlorofluoromethane by rat liver preparations in vitro. Incubation of trichlorofluoromethane with a liver microsomal fraction and an NADPH generating system under anaerobic conditions produced a metabolite dichlorofluoromethane, characterised by gas chromatography and mass spectrometry. The metabolic reaction was carried out by liver microsomes from the mouse, rabbit, hamster and rat and was increased by phenobarbitone pre-treatment. The formation of dichlorofluoromethane in vitro was enhanced by the addition of FMN, but partially inhibited by the presence of air, oxygen, SK&F 525-A, metyrapone and carbon tetrachloride and totally inhibited by carbon monoxide. The consumption of NADPH in the reaction was greater than could be accounted for by the production of dichlorofluoromethane indicating the possible formation of other metabolic products. It is suggested that trichlorofluoromethane interacts with the reduced form of cytochrome P-450 at the oxygen binding site and a possible mechanism for its subsequent reductive dechlorination is proposed. | [
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PMID:28184 | A comparison of the effects of 5- and 6-hydroxydopamine on the isolated canine saphenous vein. | We studied and compared the effects of 5- and 6-hydroxydopamine (5- or 6-OHDA) on venous tone and on adrenergic and nonadrenergic responses of the isolated canine saphenous vein. In the tissue bath, both 5- and 6-OHDA caused increases in tone and abolished adrenergic responses to transmural nerve stimulation. Effects of 6-OHDA were blocked by desmethylimipramine. 6-OHDA reduced norepinephrine levels of venous strips to 15% of those in control strips. Neither 5- nor 6-OHDA markedly altered peak contractile responses to norepinephrine but 6-OHDA prolonged the response to norepinephrine. Both compounds reduced responses to tyramine, with 6-OHDA producing a greater reduction than 5-OHDA. Large contractile responses to 5-OHDA were blocked only partially by treatment of strips with 6-OHDA, suggesting that contractile responses to 5-OHDA were mediated by direct and indirect actions. These results suggest differences in the actions of 5- and 6-OHDA on adrenergic terminals and smooth muscle in saphenous veins. The results of the experiments suggest that both 5- and 6-OHDA may be useful pharmacological interventions for the study of adrenergic mechanisms in isolated blood vessels. | A comparison of the effects of 5- and 6-hydroxydopamine on the isolated canine saphenous vein. We studied and compared the effects of 5- and 6-hydroxydopamine (5- or 6-OHDA) on venous tone and on adrenergic and nonadrenergic responses of the isolated canine saphenous vein. In the tissue bath, both 5- and 6-OHDA caused increases in tone and abolished adrenergic responses to transmural nerve stimulation. Effects of 6-OHDA were blocked by desmethylimipramine. 6-OHDA reduced norepinephrine levels of venous strips to 15% of those in control strips. Neither 5- nor 6-OHDA markedly altered peak contractile responses to norepinephrine but 6-OHDA prolonged the response to norepinephrine. Both compounds reduced responses to tyramine, with 6-OHDA producing a greater reduction than 5-OHDA. Large contractile responses to 5-OHDA were blocked only partially by treatment of strips with 6-OHDA, suggesting that contractile responses to 5-OHDA were mediated by direct and indirect actions. These results suggest differences in the actions of 5- and 6-OHDA on adrenergic terminals and smooth muscle in saphenous veins. The results of the experiments suggest that both 5- and 6-OHDA may be useful pharmacological interventions for the study of adrenergic mechanisms in isolated blood vessels. | [
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PMID:28185 | Separation and analysis of arylsulfatase isoenzymes in body fluids of man. | Soluble arylsulfatase (EC 3.1.6.1) is present in the body fluids of man in the form of two isoenzymes, arylsulfatase A and B, which reportedly are useful biochemical markers for certain types of malignancy. However, rapid assay of the individual isoenzymes is extremely difficult; procedures based on differential inhibition or activation of the isoenzymes in a mixture yield only semiquantitative results. A feature of these isoenzymes is their inhibition by some common anions (notably phosphate) at physiologic concentrations. The isoenzymes can be separated by anion-exchange chromatography, the B isoenzyme being eluted in the void volume and the A isoenzyme and the anionic inhibitors retarded. Lead is used to sequester phosphate, enabling measurement of A in the salt-eluted fraction. Using this technique, we have found significant elevations of B in the sera of patients with colorectal cancer. The potential of rapid, chromatographic separation coupled with continuous monitoring for arylsulfatase activity is discussed. | Separation and analysis of arylsulfatase isoenzymes in body fluids of man. Soluble arylsulfatase (EC 3.1.6.1) is present in the body fluids of man in the form of two isoenzymes, arylsulfatase A and B, which reportedly are useful biochemical markers for certain types of malignancy. However, rapid assay of the individual isoenzymes is extremely difficult; procedures based on differential inhibition or activation of the isoenzymes in a mixture yield only semiquantitative results. A feature of these isoenzymes is their inhibition by some common anions (notably phosphate) at physiologic concentrations. The isoenzymes can be separated by anion-exchange chromatography, the B isoenzyme being eluted in the void volume and the A isoenzyme and the anionic inhibitors retarded. Lead is used to sequester phosphate, enabling measurement of A in the salt-eluted fraction. Using this technique, we have found significant elevations of B in the sera of patients with colorectal cancer. The potential of rapid, chromatographic separation coupled with continuous monitoring for arylsulfatase activity is discussed. | [
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PMID:28186 | Acid beta-glucosidase and the diagnosis of Gaucher's disease in liver and spleen. | Variable amounts of residual 4-methylumbelliferyl-beta-glucosidase activity gave rise to difficulties in the diagnosis of Gaucher's disease using spleen and particularly liver. Soluble and particulate components of beta-glucosidase, which interfere with the diagnosis, may be eliminated by preincubation of homogenates at pH 3.0 or with 100 mM sodium chloride at pH 4.0. After either of these treatments the optimum of acid beta-glucosidase was pH 4.5 and diagnosis of Gaucher's disease could be more easily made using homogenates of spleen and liver. There was residual acid beta-glucosidase activity in one of the Gaucher livers. | Acid beta-glucosidase and the diagnosis of Gaucher's disease in liver and spleen. Variable amounts of residual 4-methylumbelliferyl-beta-glucosidase activity gave rise to difficulties in the diagnosis of Gaucher's disease using spleen and particularly liver. Soluble and particulate components of beta-glucosidase, which interfere with the diagnosis, may be eliminated by preincubation of homogenates at pH 3.0 or with 100 mM sodium chloride at pH 4.0. After either of these treatments the optimum of acid beta-glucosidase was pH 4.5 and diagnosis of Gaucher's disease could be more easily made using homogenates of spleen and liver. There was residual acid beta-glucosidase activity in one of the Gaucher livers. | [
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PMID:28187 | Methylmalonic/beta-hydroxy-n-valeric aciduria due to methylmalonyl-CoA mutase deficiency. | A patient with methylmalonic and beta-hydroxy-n-valeric aciduria, apparently due to deficiency of methylmalonyl-CoA mutase, is described. The excretion of beta-hydroxy-n-valerate did not parallel that of beta-hydroxypropionate and methylmalonate but was observed, together with beta-keto-n-valerate, only during ketosis. beta-Hydroxy-n-valerate excretion thus correlates primarily not with the pool size of propionyl-CoA but with that of acetyl-CoA, and may occur during ketosis in any disorder causing accumulation of propionyl-CoA. | Methylmalonic/beta-hydroxy-n-valeric aciduria due to methylmalonyl-CoA mutase deficiency. A patient with methylmalonic and beta-hydroxy-n-valeric aciduria, apparently due to deficiency of methylmalonyl-CoA mutase, is described. The excretion of beta-hydroxy-n-valerate did not parallel that of beta-hydroxypropionate and methylmalonate but was observed, together with beta-keto-n-valerate, only during ketosis. beta-Hydroxy-n-valerate excretion thus correlates primarily not with the pool size of propionyl-CoA but with that of acetyl-CoA, and may occur during ketosis in any disorder causing accumulation of propionyl-CoA. | [
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PMID:28188 | Glycogenosis type II: the infantile- and late-onset acid maltase deficiency observed in one family. | The concurrence of the infantile and adult form of acid maltase deficiency in one family is presented. The muscle of both cases possesses residual activity. The glycogen amount in the infantile form is increased tremendously, while in the late-onset the amount of glycogen is normal. | Glycogenosis type II: the infantile- and late-onset acid maltase deficiency observed in one family. The concurrence of the infantile and adult form of acid maltase deficiency in one family is presented. The muscle of both cases possesses residual activity. The glycogen amount in the infantile form is increased tremendously, while in the late-onset the amount of glycogen is normal. | [
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] |
PMID:28189 | Considerations on physiopathological approaches to the treatment of hypertension. | 1. Two main physiopathological approaches to the treatment of hypertension are discussed, the first based on renin profiling and the second on haemodynamic measurements. 2. Reduction in plasma renin activity does not appear to be a clinically important mechanism in the hypotensive effect of beta-adrenergic blockers and of alpha-methyldopa. In particular, alpha-methyldopa has been found equally effective as a hypotensive agent both in normal renin and in low renin hypertensive patients. 3. Diuretics are certainly possessed of a renin-stimulating action, but in most patients this action does not obscure the hypotensive effect of these drugs. 4. Responders and non-responders to the hypotensive activity of beta-adrenergic blockers do not differ among them in their control haemodynamics. | Considerations on physiopathological approaches to the treatment of hypertension. 1. Two main physiopathological approaches to the treatment of hypertension are discussed, the first based on renin profiling and the second on haemodynamic measurements. 2. Reduction in plasma renin activity does not appear to be a clinically important mechanism in the hypotensive effect of beta-adrenergic blockers and of alpha-methyldopa. In particular, alpha-methyldopa has been found equally effective as a hypotensive agent both in normal renin and in low renin hypertensive patients. 3. Diuretics are certainly possessed of a renin-stimulating action, but in most patients this action does not obscure the hypotensive effect of these drugs. 4. Responders and non-responders to the hypotensive activity of beta-adrenergic blockers do not differ among them in their control haemodynamics. | [
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PMID:28190 | alpha-Methyldopa and beta-blockers in hypertension--a comparison of their haemodynamic effects. | 1. During acute injection of alpha-methyldopa there is a reduction in the blood pressure within a period of a few hours and a modest reduction in the cardiac output, sometimes due to a modest decrease in heart rate. Frequently the total peripheral resistance is decreased. In contrast, acute injection of beta-blockers induces a marked decrease in heart rate and cardiac output, a compensatory increase in the total peripheral resistance and no decrease in the blood pressure. 2. During long-term use alpha-methyldopa frequently reduces the total peripheral resistance and the reduction in cardiac output is usually modest, at rest as well as during exercise. The beta-blockers reduce the blood pressure, but induce a marked decrease in cardiac output and heart rate. The total peripheral resistance is little affected compared to the pre-treatment level. | alpha-Methyldopa and beta-blockers in hypertension--a comparison of their haemodynamic effects. 1. During acute injection of alpha-methyldopa there is a reduction in the blood pressure within a period of a few hours and a modest reduction in the cardiac output, sometimes due to a modest decrease in heart rate. Frequently the total peripheral resistance is decreased. In contrast, acute injection of beta-blockers induces a marked decrease in heart rate and cardiac output, a compensatory increase in the total peripheral resistance and no decrease in the blood pressure. 2. During long-term use alpha-methyldopa frequently reduces the total peripheral resistance and the reduction in cardiac output is usually modest, at rest as well as during exercise. The beta-blockers reduce the blood pressure, but induce a marked decrease in cardiac output and heart rate. The total peripheral resistance is little affected compared to the pre-treatment level. | [
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PMID:28191 | Immunotherapy of human acute leukaemia. | Conclusions are difficult to draw. In the six studies of immunotherapy of AML discussed, all the three employing BCG and cells showed a prolongation of survival and the major contributing factor to this prolongation of survival was extension of life after relapse. In the three studies using BCG alone only one shows a beneficial effect, but some more time must be allowed to elapse before this can be concluded with confidence. | Immunotherapy of human acute leukaemia. Conclusions are difficult to draw. In the six studies of immunotherapy of AML discussed, all the three employing BCG and cells showed a prolongation of survival and the major contributing factor to this prolongation of survival was extension of life after relapse. In the three studies using BCG alone only one shows a beneficial effect, but some more time must be allowed to elapse before this can be concluded with confidence. | [
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PMID:28193 | Pamatolol: phase I evaluation of the pharmacodynamics of a cardioselective beta adrenoceptor blocking drug. | A Phase I evaluation of a new adrenoceptor blocker, pamatolol, was performed in 10 healthy male volunteers. Minor reductions in standing and exercise and isoproterenol-induced increases in heart rate were observed with the 10-mg oral dose and appeared maximal with the 400-600 mg dose. The rate of decline of effect averaged 1.5% of the exercise heart rate/hr. Neither resting systolic time intervals nor post-exercise pulmonary function was affected by this dose range of pamatolol. Based on the latter responses and the isoproterenol dose response curve, we tentatively conclude that pamatolol is relatively cardioselective in man. | Pamatolol: phase I evaluation of the pharmacodynamics of a cardioselective beta adrenoceptor blocking drug. A Phase I evaluation of a new adrenoceptor blocker, pamatolol, was performed in 10 healthy male volunteers. Minor reductions in standing and exercise and isoproterenol-induced increases in heart rate were observed with the 10-mg oral dose and appeared maximal with the 400-600 mg dose. The rate of decline of effect averaged 1.5% of the exercise heart rate/hr. Neither resting systolic time intervals nor post-exercise pulmonary function was affected by this dose range of pamatolol. Based on the latter responses and the isoproterenol dose response curve, we tentatively conclude that pamatolol is relatively cardioselective in man. | [
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PMID:28194 | Assessing the subjective effects of stimulants in casual users. A methodology and preliminary results. | In order to assess the subjective effects of nefopam, a new non-opiate analgesic, a study was designed using highly educated, young, middle-to-upper class subjects in a naturalistic setting. Results suggest that the design is capable of differentiating variations in subjective drug effects. On a number of measures, 10 mg of d-amphetamine, a modest dosage, could be distinguished from placebo, showing changes in the direction expected for stimulant drugs. Nefopam (90 mg), on the other hand, showed few differences from placebo or caffeine (300 mg). Nefopam appeared mildly dysphoric, rather than stimulant, in subjective effects. | Assessing the subjective effects of stimulants in casual users. A methodology and preliminary results. In order to assess the subjective effects of nefopam, a new non-opiate analgesic, a study was designed using highly educated, young, middle-to-upper class subjects in a naturalistic setting. Results suggest that the design is capable of differentiating variations in subjective drug effects. On a number of measures, 10 mg of d-amphetamine, a modest dosage, could be distinguished from placebo, showing changes in the direction expected for stimulant drugs. Nefopam (90 mg), on the other hand, showed few differences from placebo or caffeine (300 mg). Nefopam appeared mildly dysphoric, rather than stimulant, in subjective effects. | [
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PMID:28195 | Analytical subcellular fractionation studies on enterocytes from the jejunum and ileum of the rat and some properties of brush-border alkaline phosphatase. | 1. Enterocytes, isolated from the proximal jejinum and distal ileum of the rat, were homogenized and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles, RNA and protein were determined in the sucrose gradients and related to the activities per entercocyte. 2. In the jejunum the modal equilibrium densities of the various organelles were: brush borders (1.20), lysosomes (1.20), peroxisomes (1.19), mitochondria (1.17) and basal-lateral membranes (1.13). The values were not significantly different in the ileum. The activities of brush-border enzymes, soluble and mitochondrial malate dehydrogenase, soluble and membrane-associated lactate dehydrogenase and particulate protein content, however, were greater in the jejunal than the ileal enterocytes. 3. Detergent exposed latent alkaline phosphatase activity in jejunal enterocytes and indicated that this enzyme is present not only in the brush border but also in the basal-lateral membrane and soluble fractions of the cell. 4. Isolated jejunal brush-border preprations showed latent activities of both alkaline phosphatase and gamma-glutamyltransferase whereas the activities of alpha-glucosidase and leucyl-beta-naphylamidase were not affected by detergent. Mechanical disruption of these preparations suggested the presence of two forms of alkaline phosphatase in the brush border and provides a technique to assess membrane fragility. | Analytical subcellular fractionation studies on enterocytes from the jejunum and ileum of the rat and some properties of brush-border alkaline phosphatase. 1. Enterocytes, isolated from the proximal jejinum and distal ileum of the rat, were homogenized and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles, RNA and protein were determined in the sucrose gradients and related to the activities per entercocyte. 2. In the jejunum the modal equilibrium densities of the various organelles were: brush borders (1.20), lysosomes (1.20), peroxisomes (1.19), mitochondria (1.17) and basal-lateral membranes (1.13). The values were not significantly different in the ileum. The activities of brush-border enzymes, soluble and mitochondrial malate dehydrogenase, soluble and membrane-associated lactate dehydrogenase and particulate protein content, however, were greater in the jejunal than the ileal enterocytes. 3. Detergent exposed latent alkaline phosphatase activity in jejunal enterocytes and indicated that this enzyme is present not only in the brush border but also in the basal-lateral membrane and soluble fractions of the cell. 4. Isolated jejunal brush-border preprations showed latent activities of both alkaline phosphatase and gamma-glutamyltransferase whereas the activities of alpha-glucosidase and leucyl-beta-naphylamidase were not affected by detergent. Mechanical disruption of these preparations suggested the presence of two forms of alkaline phosphatase in the brush border and provides a technique to assess membrane fragility. | [
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PMID:28196 | Urinary dopamine in man and rat: effects of inorganic salts on dopamine excretion. | 1. Plasma and urine free dopamine (3,4-dihydroxyphenethylamine) were measured in six normal male volunteer subjects and the urinary clearance of dopamine was calculated for each subject. 2. The excretion rates for free dopamine in man were greater than could be explained by simple renal clearance. It was concluded that free dopamine must, therefore, be formed in the kidney. 3. Changes in urinary dopamine excretion were studied in four groups of rats initially maintained on low sodium diet and then given equimolar dietary supplements of NaCl, NaHCO3, KCl or NH4Cl, to study the specificity of the previously observed increase in dopamine excretion after increased dietary NaCl. 4. The mean dopamine excretion increased significantly in rats given NaCl, KCl and NH4Cl, whereas dopamine excretion decreased in those given NaHCO3. 5. The failure of dopamine excretion to rise in response to loading with NaHCO3 was unexpected, and argues against a simple effect of volume expansion by the sodium ion. The increase in dopamine excretion with KCl and NH4Cl showed that this response was not specific to the sodium ion. | Urinary dopamine in man and rat: effects of inorganic salts on dopamine excretion. 1. Plasma and urine free dopamine (3,4-dihydroxyphenethylamine) were measured in six normal male volunteer subjects and the urinary clearance of dopamine was calculated for each subject. 2. The excretion rates for free dopamine in man were greater than could be explained by simple renal clearance. It was concluded that free dopamine must, therefore, be formed in the kidney. 3. Changes in urinary dopamine excretion were studied in four groups of rats initially maintained on low sodium diet and then given equimolar dietary supplements of NaCl, NaHCO3, KCl or NH4Cl, to study the specificity of the previously observed increase in dopamine excretion after increased dietary NaCl. 4. The mean dopamine excretion increased significantly in rats given NaCl, KCl and NH4Cl, whereas dopamine excretion decreased in those given NaHCO3. 5. The failure of dopamine excretion to rise in response to loading with NaHCO3 was unexpected, and argues against a simple effect of volume expansion by the sodium ion. The increase in dopamine excretion with KCl and NH4Cl showed that this response was not specific to the sodium ion. | [
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PMID:28197 | Effect of varying PCO2 on intracellular pH and lactate consumption in the isolated perfused rat liver. | 1. The effects of varying PCO2 on lactate uptake and intracellular pH (pHi) were studied in the isolated rat liver perfused with differing concentration of lactate. 2. In general, pHi and lactate uptake are inversely related to PCO2, and pHi and lactate uptake are directly related to each other, but the quantitative aspects and significance of these relationships vary with the availability of lactate. A model of hepatic lactate metabolism is proposed which may account for the quantitative variation. 3. The metabolism of lactate within the hepatocyte exerts a destabilizing effect on hepatocyte cell pH, in contrast to the buffering effect seen in predominantly glycolytic tissues. 4. An attempt is made to relate the findings to the disturbances of lactate metabolism in clinical respiratory failure. | Effect of varying PCO2 on intracellular pH and lactate consumption in the isolated perfused rat liver. 1. The effects of varying PCO2 on lactate uptake and intracellular pH (pHi) were studied in the isolated rat liver perfused with differing concentration of lactate. 2. In general, pHi and lactate uptake are inversely related to PCO2, and pHi and lactate uptake are directly related to each other, but the quantitative aspects and significance of these relationships vary with the availability of lactate. A model of hepatic lactate metabolism is proposed which may account for the quantitative variation. 3. The metabolism of lactate within the hepatocyte exerts a destabilizing effect on hepatocyte cell pH, in contrast to the buffering effect seen in predominantly glycolytic tissues. 4. An attempt is made to relate the findings to the disturbances of lactate metabolism in clinical respiratory failure. | [
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PMID:28198 | Mechanism of the effect of varying PCO2 on gluconeogenesis from lactate in the perfused rat liver. | 1. The effects of varying PCO2 on glucose output and the intracellular concentrations of lactate, pyruvate, phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate were studied in the isolated rat liver perfused with differing concentrations of lactate. 2. When the perfusate lactate concentration is above 1.5 mmol/l respiratory acidosis (simulated by high perfusate PCO2) inhibits gluconeogenesis from lactate, whereas respiratory alkalosis stimulates gluconeogenesis. 3. In general there were significant positive correlations between intracellular pH (pHi) and hepatocyte phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate concentrations, and negative correlations between pHi and lactate and pyruvate concentrations; there were usually significant correlations in the opposite sense between these metabolites and log PCO2. 4. The results suggest that CO2 exerts an inhibitory effect on gluconeogenesis at a step between pyruvate and phosphoenolypruvate; however, this is not the only effect of CO2 on the gluconeogenic sequence. CO2 probably acts by changing pHi, but direct effects of CO2 and HCO-3 cannot be excluded. 5. Except at low lactate concentrations, nonionic diffusion probably does not play a major role in the entry of lactate into the hepatocyte. | Mechanism of the effect of varying PCO2 on gluconeogenesis from lactate in the perfused rat liver. 1. The effects of varying PCO2 on glucose output and the intracellular concentrations of lactate, pyruvate, phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate were studied in the isolated rat liver perfused with differing concentrations of lactate. 2. When the perfusate lactate concentration is above 1.5 mmol/l respiratory acidosis (simulated by high perfusate PCO2) inhibits gluconeogenesis from lactate, whereas respiratory alkalosis stimulates gluconeogenesis. 3. In general there were significant positive correlations between intracellular pH (pHi) and hepatocyte phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate concentrations, and negative correlations between pHi and lactate and pyruvate concentrations; there were usually significant correlations in the opposite sense between these metabolites and log PCO2. 4. The results suggest that CO2 exerts an inhibitory effect on gluconeogenesis at a step between pyruvate and phosphoenolypruvate; however, this is not the only effect of CO2 on the gluconeogenic sequence. CO2 probably acts by changing pHi, but direct effects of CO2 and HCO-3 cannot be excluded. 5. Except at low lactate concentrations, nonionic diffusion probably does not play a major role in the entry of lactate into the hepatocyte. | [
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PMID:28219 | [Crohn's disease: course and prognosis in 169 patients (author's transl)]. | The most common initial symptoms in 169 patients with Crohn's disease, followed from 1956 to 1973, were diffuse abdominal pain, diarrhoea without any blood admixture, loss of weight, and fever. At the onset of the disease 84% of patients were aged 10-39 years. The most important complications (in descending order of frequency) were fistulae and abscesses, ileus, anaemia, and malabsorption. A breakdown into active and passive phases indicated that the younger the patient at onset of the disease, the more severe its course. The disease seemed to take a more favourable course when only the colon, but not the terminal ileum, was involved. Recurrence occurred more frequently after a short than after a long preoperative history. Recurrences were more frequent in patients under than over 31 years of age at their first operation. | [Crohn's disease: course and prognosis in 169 patients (author's transl)]. The most common initial symptoms in 169 patients with Crohn's disease, followed from 1956 to 1973, were diffuse abdominal pain, diarrhoea without any blood admixture, loss of weight, and fever. At the onset of the disease 84% of patients were aged 10-39 years. The most important complications (in descending order of frequency) were fistulae and abscesses, ileus, anaemia, and malabsorption. A breakdown into active and passive phases indicated that the younger the patient at onset of the disease, the more severe its course. The disease seemed to take a more favourable course when only the colon, but not the terminal ileum, was involved. Recurrence occurred more frequently after a short than after a long preoperative history. Recurrences were more frequent in patients under than over 31 years of age at their first operation. | [
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PMID:28220 | Studies on the microsomal metabolism and binding of polybrominated biphenyls (PBBs). | The metabolism of polybrominated biphenyls (PBBs) was studied in vitro by using rat liver microsomes in the presence of NADPH and atmospheric O2. Quantitative recoveries of all PBBs were obtained after incubations with control or 3-methylcholanthrene (MC) induced microsomes. Of the twelve major components, losses of only peaks 1 (2,4,5,2',5'-pentabromobiphenyl) and 3 (a hexabromobiphenyl) were observed following incubations with microsomes from phenobarbital (PB)- or PBBS- pretreated rats. Of seven structurally identified PBB components, only peak 1 has a bromine-free para position. Peaks 1, 2, and 5 all have two adjacent unsubstituted carbons, yet only peak 1 is metabolized. Of two dibromobiphenyl model compounds studied, the 2,2'-congener was very rapidly metabolized by PB-induced microsomes whereas its 4,4'-isomer was not. These results suggest that the presence of a free para position is required for the metabolism of brominated biphenyls. Of lesser importance appears to be the number of bromines or the availability of two adjacent unsubstituted carbons. In vivo evidence for the metabolism of peaks 1 and 3 was also provided by their drastically diminished levels in liver and milk extracts. When a 14C-PBB mixture consisting almost exclusively of peaks 4 (2,4,5,2',4',5'-hexabromobiphenyl) and 8 (2,3,4,5,2',4',5'-heptabromobiphenyl) was incubated with PB- or PBBs- induced microsomes and NADPH, only traces of radioactivity remained with the microsomes after extensive extraction. However, less radioactivity was bound to microsomes from MC pretreated or especially control rats. No radioactivity was bound to exogenous DNA included in similar microsomal incubations, regardless of the type of microsomes used. Under the same conditions, [3H]-benzo[a]pyrene metabolites were bound to DNA, and PBB-induced microsomes enhanced this binding more than six-fold. | Studies on the microsomal metabolism and binding of polybrominated biphenyls (PBBs). The metabolism of polybrominated biphenyls (PBBs) was studied in vitro by using rat liver microsomes in the presence of NADPH and atmospheric O2. Quantitative recoveries of all PBBs were obtained after incubations with control or 3-methylcholanthrene (MC) induced microsomes. Of the twelve major components, losses of only peaks 1 (2,4,5,2',5'-pentabromobiphenyl) and 3 (a hexabromobiphenyl) were observed following incubations with microsomes from phenobarbital (PB)- or PBBS- pretreated rats. Of seven structurally identified PBB components, only peak 1 has a bromine-free para position. Peaks 1, 2, and 5 all have two adjacent unsubstituted carbons, yet only peak 1 is metabolized. Of two dibromobiphenyl model compounds studied, the 2,2'-congener was very rapidly metabolized by PB-induced microsomes whereas its 4,4'-isomer was not. These results suggest that the presence of a free para position is required for the metabolism of brominated biphenyls. Of lesser importance appears to be the number of bromines or the availability of two adjacent unsubstituted carbons. In vivo evidence for the metabolism of peaks 1 and 3 was also provided by their drastically diminished levels in liver and milk extracts. When a 14C-PBB mixture consisting almost exclusively of peaks 4 (2,4,5,2',4',5'-hexabromobiphenyl) and 8 (2,3,4,5,2',4',5'-heptabromobiphenyl) was incubated with PB- or PBBs- induced microsomes and NADPH, only traces of radioactivity remained with the microsomes after extensive extraction. However, less radioactivity was bound to microsomes from MC pretreated or especially control rats. No radioactivity was bound to exogenous DNA included in similar microsomal incubations, regardless of the type of microsomes used. Under the same conditions, [3H]-benzo[a]pyrene metabolites were bound to DNA, and PBB-induced microsomes enhanced this binding more than six-fold. | [
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PMID:28225 | Purification and properties of 5'-nucleotidase from lymphocyte plasma membranes. | 5'-Nucleotidase is purified from lymphocyte plasma membranes by two affinity chromatographies. The first one, on Lens culinaris lectin-Sepharose 4B yields a fraction of twelve lectin-binding glycoproteins (lectin-receptor fraction). The second one on 5'-AMP-Sepharose 4B leads to pure enzyme. This enzyme is a glycoprotein with a molecular weight of 130 000; it gives a single band in polyacrylamide/dodecylsulfate electrophoresis and displays a very high specific activity (2500-3000 mumol Pih-1mg-1). Some properties of purified 5'-nucleotidase are similar to those of membrane-bound enzyme: substrate specificity, temperature dependence, effects of ions and SH-blocking reagents. Others are completely different for the two systems and these differences result from an interaction between the enzyme molecule and other Lens culinaris lectin binding proteins. | Purification and properties of 5'-nucleotidase from lymphocyte plasma membranes. 5'-Nucleotidase is purified from lymphocyte plasma membranes by two affinity chromatographies. The first one, on Lens culinaris lectin-Sepharose 4B yields a fraction of twelve lectin-binding glycoproteins (lectin-receptor fraction). The second one on 5'-AMP-Sepharose 4B leads to pure enzyme. This enzyme is a glycoprotein with a molecular weight of 130 000; it gives a single band in polyacrylamide/dodecylsulfate electrophoresis and displays a very high specific activity (2500-3000 mumol Pih-1mg-1). Some properties of purified 5'-nucleotidase are similar to those of membrane-bound enzyme: substrate specificity, temperature dependence, effects of ions and SH-blocking reagents. Others are completely different for the two systems and these differences result from an interaction between the enzyme molecule and other Lens culinaris lectin binding proteins. | [
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PMID:28227 | Purification of aspartate transcarbamylase from Drosophila melanogaster. | A purification procedure is described by which aspartate transcarbamylase was obtained from cultured cells of Drosophila melanogaster as part of a high-molecular-weight enzyme complex. The complex is shown to contain several polypeptides. An antiserum directed against the complex enzyme inhibited in vitro the activity of aspartate transcarbamylase, carbamylphosphate synthetase and dihydro-orotase which were shown to copurify on a sucrose gradient and by gel electrophoresis. A fast preparation procedure using this antiserum yielded a 220 000-molecular-weight protein in addition to the polypeptides present in the complex. A purification procedure is also described to obtain aspartate transcarbamylase from second instar larvae of Drosophila. At this stage, the enzyme is not complexed with carbamylphosphate synthetase and dihydro-orotase but exhibits the same molecular weight as the aspartate transcarbamylase moiety found in the high-molecular-weight complex of cultured cells. | Purification of aspartate transcarbamylase from Drosophila melanogaster. A purification procedure is described by which aspartate transcarbamylase was obtained from cultured cells of Drosophila melanogaster as part of a high-molecular-weight enzyme complex. The complex is shown to contain several polypeptides. An antiserum directed against the complex enzyme inhibited in vitro the activity of aspartate transcarbamylase, carbamylphosphate synthetase and dihydro-orotase which were shown to copurify on a sucrose gradient and by gel electrophoresis. A fast preparation procedure using this antiserum yielded a 220 000-molecular-weight protein in addition to the polypeptides present in the complex. A purification procedure is also described to obtain aspartate transcarbamylase from second instar larvae of Drosophila. At this stage, the enzyme is not complexed with carbamylphosphate synthetase and dihydro-orotase but exhibits the same molecular weight as the aspartate transcarbamylase moiety found in the high-molecular-weight complex of cultured cells. | [
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PMID:28228 | Identification of the functional ionic groups of papain by pH/rate profile analysis. | The pH dependence of papain catalysis was analyzed by a scheme which evaluates the kinetic contribution of both protonated and unprotonated species of functional groups involved in catalysis. Kinetic measurements were made at constant pH, without buffers, by automatic titration. The rate-determining step for papain-catalyzed hydrolysis of alpha-N-benzoyl-L-arginine ethyl ester, determined by nucleophile competition, changed from acylation below pH 6.5 to mixed acylation-deacylation above pH 6.5. Kinetic analysis indicated that three prototropic groups governed the pH-specificity of alpha-N-benzoyl-L-arginine ethyl ester hydrolysis. These prototropic groups had pKa values of 4.8, 6.5 to 6.7, and 8.7. Theoretical treatment of the kinetics provided an excellent fit with the experimentally found profile when the contribution of all three prototropic groups was considered. Analysis showed that, in acid, the pathways of papain catalysis were functional with either two or three active-site protons. In base, a single functional ionic pathway is associated with an active site with only one proton. Pathways involving an unprotonated active site are catalytically inoperative in both acid and base. These results indicate that papain exhibits several catalytically functional ionic pathways. The results are discussed in terms of pKa assignments, and the mechanism of papain catalysis. | Identification of the functional ionic groups of papain by pH/rate profile analysis. The pH dependence of papain catalysis was analyzed by a scheme which evaluates the kinetic contribution of both protonated and unprotonated species of functional groups involved in catalysis. Kinetic measurements were made at constant pH, without buffers, by automatic titration. The rate-determining step for papain-catalyzed hydrolysis of alpha-N-benzoyl-L-arginine ethyl ester, determined by nucleophile competition, changed from acylation below pH 6.5 to mixed acylation-deacylation above pH 6.5. Kinetic analysis indicated that three prototropic groups governed the pH-specificity of alpha-N-benzoyl-L-arginine ethyl ester hydrolysis. These prototropic groups had pKa values of 4.8, 6.5 to 6.7, and 8.7. Theoretical treatment of the kinetics provided an excellent fit with the experimentally found profile when the contribution of all three prototropic groups was considered. Analysis showed that, in acid, the pathways of papain catalysis were functional with either two or three active-site protons. In base, a single functional ionic pathway is associated with an active site with only one proton. Pathways involving an unprotonated active site are catalytically inoperative in both acid and base. These results indicate that papain exhibits several catalytically functional ionic pathways. The results are discussed in terms of pKa assignments, and the mechanism of papain catalysis. | [
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PMID:28230 | Hyperphenylalaninaemia due to dihydropteridine reductase deficiency. | Two siblings with increased levels of serum phenylalanine were detected by newborn screening. The older sibling deteriorated neurologically and mentally, despite early dietary control, and died at the age of 6 1/2 years. In the younger sibling phenylalanine hydroxylase activity in liver tissue was normal. Further investigations revealed increased concentrations of biopterin derivatives in the blood, a low excretion of 5-hydroxyindole acetic acid in the urine, and a dihydropteridine reductase deficiency as the cause of hyperphenylalaninaemia. The parents of the siblings showed 50% of the normal dihydropteridine reductase activity in their fibroblasts grown in culture. Neurotransmitter therapy was started in the second child at the age of 6 months and this was followed by distinct neurological and mental improvement. | Hyperphenylalaninaemia due to dihydropteridine reductase deficiency. Two siblings with increased levels of serum phenylalanine were detected by newborn screening. The older sibling deteriorated neurologically and mentally, despite early dietary control, and died at the age of 6 1/2 years. In the younger sibling phenylalanine hydroxylase activity in liver tissue was normal. Further investigations revealed increased concentrations of biopterin derivatives in the blood, a low excretion of 5-hydroxyindole acetic acid in the urine, and a dihydropteridine reductase deficiency as the cause of hyperphenylalaninaemia. The parents of the siblings showed 50% of the normal dihydropteridine reductase activity in their fibroblasts grown in culture. Neurotransmitter therapy was started in the second child at the age of 6 months and this was followed by distinct neurological and mental improvement. | [
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PMID:28231 | Effects of stored and fresh blood transfusions on postoperative pulmonary function. A clinical study on patients following extracorporeal circulation in association with aortic valve surgery. | The effects on postoperative pulmonary function of fresh versus stored blood when priming the heart-lung machine were studied in 49 patients subjected to aortic valvular replacement. The onset of extracorporeal circulation was considered to mimic the conditions of massive blood transfusion. The patients receiving heparinized fresh blood required more oxygen in the respirator than those receiving stored blood, but still had a significantly lower arterial oxygen tension during the first and second postoperative days. The fresh blood patients also showed a tendency to require a larger amount of diuretics to maintain adequate urine output. Pre- and postoperative bleeding and changes in postoperative hematological variables did not differ in the two groups. The results imply that stored blood should be preferable when substituting blood losses. | Effects of stored and fresh blood transfusions on postoperative pulmonary function. A clinical study on patients following extracorporeal circulation in association with aortic valve surgery. The effects on postoperative pulmonary function of fresh versus stored blood when priming the heart-lung machine were studied in 49 patients subjected to aortic valvular replacement. The onset of extracorporeal circulation was considered to mimic the conditions of massive blood transfusion. The patients receiving heparinized fresh blood required more oxygen in the respirator than those receiving stored blood, but still had a significantly lower arterial oxygen tension during the first and second postoperative days. The fresh blood patients also showed a tendency to require a larger amount of diuretics to maintain adequate urine output. Pre- and postoperative bleeding and changes in postoperative hematological variables did not differ in the two groups. The results imply that stored blood should be preferable when substituting blood losses. | [
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PMID:28232 | Hemodynamic and metabolic changes induced by temporary clamping of the thoracic aorta. | Numerous authors reported a significant deterioration of heart function induced by aortic cross-clamping. Nevertheless, the aorta has been clamped during various surgical procedures without any complication. We studied the hemodynamic and metabolic variations induced by 20 min thoracic aorta cross-clamping in 6 open-chest dogs. During clamping the most striking modifications were an increase in coronary blood flow of over 65%, an increase in cardiac work of over 77% and an increase in total peripheral resistances of over 68% compared to base values. No significant variations were found in the heart rate and cardiac index. Metabolic parameters, such as O2 consumption and lactate consumption increased significantly during the clamping period. The increase in lactate consumption and the progressive and continuous improvement in oxygenation indexes (lactate/pyruvate, redox potential, excess of lactate) proved the absence of any myocardial anoxia during this period. Within 15--30 min after declamping all hemodynamic and metabolic parameters reverted to values close to basal values. These data strongly suggest that the mammalian heart can tolerate this procedure satisfactorily for a limited period of time. In clinical settings, one should consider the base conditions of the cardiovascular system before transposing these conclusions. | Hemodynamic and metabolic changes induced by temporary clamping of the thoracic aorta. Numerous authors reported a significant deterioration of heart function induced by aortic cross-clamping. Nevertheless, the aorta has been clamped during various surgical procedures without any complication. We studied the hemodynamic and metabolic variations induced by 20 min thoracic aorta cross-clamping in 6 open-chest dogs. During clamping the most striking modifications were an increase in coronary blood flow of over 65%, an increase in cardiac work of over 77% and an increase in total peripheral resistances of over 68% compared to base values. No significant variations were found in the heart rate and cardiac index. Metabolic parameters, such as O2 consumption and lactate consumption increased significantly during the clamping period. The increase in lactate consumption and the progressive and continuous improvement in oxygenation indexes (lactate/pyruvate, redox potential, excess of lactate) proved the absence of any myocardial anoxia during this period. Within 15--30 min after declamping all hemodynamic and metabolic parameters reverted to values close to basal values. These data strongly suggest that the mammalian heart can tolerate this procedure satisfactorily for a limited period of time. In clinical settings, one should consider the base conditions of the cardiovascular system before transposing these conclusions. | [
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PMID:28233 | Climbing behaviour induced by apomorphine in mice: a potential model for the detection of neuroleptic activity. | Apomorphine and the putative dopamine agonist, 2-(N, N-dipropyl)-amino-5, 6-dihydroxytetralin induced dose-dependent climbing behaviour in the mouse which was measured in wire mesh lined cages as the percentage of time spent climbing in the 30 min period following the first climb and as the maximum time spent in a single climb throughout the drug effect. These These two measures were generally found to parallel excepting when the interacting agent caused muscular hypotonia. All potential interacting agents were given as pretreatments to determine changes in motor function which may interfere with the climbing induced by 1.0 mg/kg s.c. apomorphine. The possibility of a change in the apomorphine response to a sterotyped biting, which would also interfere with climbing, was also considered. Excluding these non-specific changes, climbing behaviour was shown to be antagonised, dose-dependently, by low doses of typical and atypical neuroleptic agents (haloperidol, fluphenazine, loxapine, pimozide, oxiperomide, clozapin, thioridazine, sulpiride, tiapride and metoclopramide) but not specifically by other psychoactive agents. Climbing behaviour was modified by serotonergic agents; the agonist quipazine reduced or abolished, whilst the antagonists, methysergide and cyproheptadine, enhanced the response. Picrotoxin specifically reduced climbing behaviour but sodium valproate exerted non-specific effects, precluding conclusions as to a GABA involvement. Cholinergic and noradrenergic involvements with climbing were also apparently eliminated by the ineffectiveness of atropine, aceperone, piperoxan and propranolol. The involvement of serotonin with climbing was extended to the actions of the neuroleptics: the antagonistic effects of typical neuroleptics (haloperidol, fluphenazine, loxapine) were markedly enhanced by combination with methysergide or cyproheptadine whilst the effects of clozapine, sulpiride and thioridazine were significantly reduced. The actions of metoclopramide, oxiperomide, pimozide and tiapride were not generally modified by such combinations. These differences are discussed in terms of differential abilities to induce extrapyramidal disturbances and the mouse climbing model is forwarded as a test with potential to detect antipsychotic agents of different activity spectra. | Climbing behaviour induced by apomorphine in mice: a potential model for the detection of neuroleptic activity. Apomorphine and the putative dopamine agonist, 2-(N, N-dipropyl)-amino-5, 6-dihydroxytetralin induced dose-dependent climbing behaviour in the mouse which was measured in wire mesh lined cages as the percentage of time spent climbing in the 30 min period following the first climb and as the maximum time spent in a single climb throughout the drug effect. These These two measures were generally found to parallel excepting when the interacting agent caused muscular hypotonia. All potential interacting agents were given as pretreatments to determine changes in motor function which may interfere with the climbing induced by 1.0 mg/kg s.c. apomorphine. The possibility of a change in the apomorphine response to a sterotyped biting, which would also interfere with climbing, was also considered. Excluding these non-specific changes, climbing behaviour was shown to be antagonised, dose-dependently, by low doses of typical and atypical neuroleptic agents (haloperidol, fluphenazine, loxapine, pimozide, oxiperomide, clozapin, thioridazine, sulpiride, tiapride and metoclopramide) but not specifically by other psychoactive agents. Climbing behaviour was modified by serotonergic agents; the agonist quipazine reduced or abolished, whilst the antagonists, methysergide and cyproheptadine, enhanced the response. Picrotoxin specifically reduced climbing behaviour but sodium valproate exerted non-specific effects, precluding conclusions as to a GABA involvement. Cholinergic and noradrenergic involvements with climbing were also apparently eliminated by the ineffectiveness of atropine, aceperone, piperoxan and propranolol. The involvement of serotonin with climbing was extended to the actions of the neuroleptics: the antagonistic effects of typical neuroleptics (haloperidol, fluphenazine, loxapine) were markedly enhanced by combination with methysergide or cyproheptadine whilst the effects of clozapine, sulpiride and thioridazine were significantly reduced. The actions of metoclopramide, oxiperomide, pimozide and tiapride were not generally modified by such combinations. These differences are discussed in terms of differential abilities to induce extrapyramidal disturbances and the mouse climbing model is forwarded as a test with potential to detect antipsychotic agents of different activity spectra. | [
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PMID:28234 | The influence of heart rate on ouabain cardiotoxicity in cats with spinal cord transection. | The dose, serum level and ventricular content of ouabain needed to produce cardiotoxicity were examined in control cats, cats with transected spinal cords and cats with transected spinal cords whose heart rates were restored to control values by artificial pacing. The lethal dose of ouabain was higher in cats with transected spinal cords and not paced than it was in the control group. However, the lethal dose of ouabain in spinal-sectioned cats with ventricular pacing was no different from that in controls. However, in both groups of spinal-sectioned cats, death was associated with higher ventricular and serum levels of ouabain than in controls. The ventricular ouabain content of paced animals with transected spinal cords was higher than that of controls and lower than that of unpaced spinal cats. Thus, restoration of heart rate to control levels in spinal animals appeared to accelerate myocardial ouabain uptake. The lower myocardial ouabain content in the spinal-sectioned animals which were paced suggests that pacing sensitizes the heart to cardiotoxicity. Spinal section itself appears to decrease the sensitivity to ouabain partly through a decrease in cardiac rate and partly through a loss of neurogenic influence. | The influence of heart rate on ouabain cardiotoxicity in cats with spinal cord transection. The dose, serum level and ventricular content of ouabain needed to produce cardiotoxicity were examined in control cats, cats with transected spinal cords and cats with transected spinal cords whose heart rates were restored to control values by artificial pacing. The lethal dose of ouabain was higher in cats with transected spinal cords and not paced than it was in the control group. However, the lethal dose of ouabain in spinal-sectioned cats with ventricular pacing was no different from that in controls. However, in both groups of spinal-sectioned cats, death was associated with higher ventricular and serum levels of ouabain than in controls. The ventricular ouabain content of paced animals with transected spinal cords was higher than that of controls and lower than that of unpaced spinal cats. Thus, restoration of heart rate to control levels in spinal animals appeared to accelerate myocardial ouabain uptake. The lower myocardial ouabain content in the spinal-sectioned animals which were paced suggests that pacing sensitizes the heart to cardiotoxicity. Spinal section itself appears to decrease the sensitivity to ouabain partly through a decrease in cardiac rate and partly through a loss of neurogenic influence. | [
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PMID:28236 | Halothane-induced sleeping time in the mouse: its modification by benzodiazepines. | The conditions under which prolongation of halothane-induced sleeping time in the mouse may be used as a test for centrally acting drugs are described. The test can be recommended for its practical advantages over methods using barbiturates to induce hypnosis; due cognizance must be taken of a diurnal variation in the response of mice to halothane. To assess the usefulness of the test the effects of amphetamine, chlorpromazine, histamine, morphine, nikethamide, pentobarbitone and SKF 525A have been investigated. The interaction between 5 benzodiazepines and halothane has been studied in particular. Results from sleeping time experiments, measurements of body temperature and of brain halothane concentrations suggest that the halothane-benzodiazepine interaction is due to additive CNS depressant effects. It was found that nitrazepam and diazepam were clearly more potent than chlorodiazepoxide, medazepam and oxazepam in respect of their interactions with halothane. | Halothane-induced sleeping time in the mouse: its modification by benzodiazepines. The conditions under which prolongation of halothane-induced sleeping time in the mouse may be used as a test for centrally acting drugs are described. The test can be recommended for its practical advantages over methods using barbiturates to induce hypnosis; due cognizance must be taken of a diurnal variation in the response of mice to halothane. To assess the usefulness of the test the effects of amphetamine, chlorpromazine, histamine, morphine, nikethamide, pentobarbitone and SKF 525A have been investigated. The interaction between 5 benzodiazepines and halothane has been studied in particular. Results from sleeping time experiments, measurements of body temperature and of brain halothane concentrations suggest that the halothane-benzodiazepine interaction is due to additive CNS depressant effects. It was found that nitrazepam and diazepam were clearly more potent than chlorodiazepoxide, medazepam and oxazepam in respect of their interactions with halothane. | [
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PMID:28237 | Relaxation of depolarized guinea pig taenia caecum induced by some antispasmodics. | Taenia isolated from the guinea pig caecum were used for the experiments. No inhibitory response of the depolarized taenia to isoprenaline was observed during the significant increase of cyclic AMP level. These observations suggest that the total tissue level of cyclic AMP is not an important determinant of relaxation in the depolarized taenia. Antispasmodics, such as papaverine, benactyzine and Aspaminol (1,1-diphenyl-3-piperidino-butanol hydrochloride) relaxed the depolarized taenia, while the depolarized taenia was not relaxed by concentrations of dibutyryl cyclic AMP sufficient to relax the polarized taenia. Ca uptake by the depolarized taenia was inhibited by papaverine, benactyzine and Aspaminol but not by isoprenaline and dibutyryl cyclic AMP. These results indicate that relaxation of the depolarized taenia induced by the antispasmodics used was mainly due to inhibition of Ca uptake. | Relaxation of depolarized guinea pig taenia caecum induced by some antispasmodics. Taenia isolated from the guinea pig caecum were used for the experiments. No inhibitory response of the depolarized taenia to isoprenaline was observed during the significant increase of cyclic AMP level. These observations suggest that the total tissue level of cyclic AMP is not an important determinant of relaxation in the depolarized taenia. Antispasmodics, such as papaverine, benactyzine and Aspaminol (1,1-diphenyl-3-piperidino-butanol hydrochloride) relaxed the depolarized taenia, while the depolarized taenia was not relaxed by concentrations of dibutyryl cyclic AMP sufficient to relax the polarized taenia. Ca uptake by the depolarized taenia was inhibited by papaverine, benactyzine and Aspaminol but not by isoprenaline and dibutyryl cyclic AMP. These results indicate that relaxation of the depolarized taenia induced by the antispasmodics used was mainly due to inhibition of Ca uptake. | [
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PMID:28250 | Steric aspects of dopaminergic drugs. | There are a variety of molecule species of dopamine avaialable at physiological pH. The predominant form available at physiological pH is the phenolic ammonium salt. However, at the present time the molecular form that is optimum for producing dopaminergic activity is unknown. In attempting to delineate the conformational requirements of dopaminergic agonists, a variety of conformationally restricted analogs and complex molecules possessing a dopaminergic segment have been investigated. It appears at this time that the trans extended form of dopamine is the optimum form for binding to dopamine receptors. The rotameric forms of dopamine are also important considerations when examining a molecule for dopaminergic agonist activity. A high degree of stereospecificity has been shown in different dopaminergic systems. | Steric aspects of dopaminergic drugs. There are a variety of molecule species of dopamine avaialable at physiological pH. The predominant form available at physiological pH is the phenolic ammonium salt. However, at the present time the molecular form that is optimum for producing dopaminergic activity is unknown. In attempting to delineate the conformational requirements of dopaminergic agonists, a variety of conformationally restricted analogs and complex molecules possessing a dopaminergic segment have been investigated. It appears at this time that the trans extended form of dopamine is the optimum form for binding to dopamine receptors. The rotameric forms of dopamine are also important considerations when examining a molecule for dopaminergic agonist activity. A high degree of stereospecificity has been shown in different dopaminergic systems. | [
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PMID:28254 | [Several new inhibitors of gastric secretion]. | In experiments on dogs, milid (proglymid) entailed a weak inhibition of the 2nd phase of the gastric secretion leaving intact the 1st phase. The action of LS-519 was obvious in the 1st phase, having entailed a significant inhibition. The glycomacropeptid exerted a strong inhibiting effect both on the 1st and the 2nd phases, the effect lasting longer than that of the first two drugs. All the three drugs not only inhibited the gastric secretion but increased pH, reduced the gastric juice acidity while exerting no significan effect on concentration of common proteinases. | [Several new inhibitors of gastric secretion]. In experiments on dogs, milid (proglymid) entailed a weak inhibition of the 2nd phase of the gastric secretion leaving intact the 1st phase. The action of LS-519 was obvious in the 1st phase, having entailed a significant inhibition. The glycomacropeptid exerted a strong inhibiting effect both on the 1st and the 2nd phases, the effect lasting longer than that of the first two drugs. All the three drugs not only inhibited the gastric secretion but increased pH, reduced the gastric juice acidity while exerting no significan effect on concentration of common proteinases. | [
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PMID:28255 | Ergonomics. Reducing mental and physical fatigue in the dental operatory. | The work output and the mental and physical fatigue generated by a dental procedure is affected by the length and type of operation, physical facilities, the amount of cooperation given by the patient, operating techniques, and the effective teamwork and rapport of the operatory dental team. Fatigue is also generated by stresses that arise outside of the office and which, when superimposed over the normal operating stresses of the office, can have a cumulative effect of decreasing output and increasing mental and physical fatigue for the dentist, the assistant, and the patient. Probably the three most important means to compensate for both routine and nonroutine physical and mental stresses of any type or origin are: (1) learn to cope with or resolve the origin of the stress; (2) develop a pattern of healthy living; (3) cultivate job satisfaction. | Ergonomics. Reducing mental and physical fatigue in the dental operatory. The work output and the mental and physical fatigue generated by a dental procedure is affected by the length and type of operation, physical facilities, the amount of cooperation given by the patient, operating techniques, and the effective teamwork and rapport of the operatory dental team. Fatigue is also generated by stresses that arise outside of the office and which, when superimposed over the normal operating stresses of the office, can have a cumulative effect of decreasing output and increasing mental and physical fatigue for the dentist, the assistant, and the patient. Probably the three most important means to compensate for both routine and nonroutine physical and mental stresses of any type or origin are: (1) learn to cope with or resolve the origin of the stress; (2) develop a pattern of healthy living; (3) cultivate job satisfaction. | [
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PMID:28260 | Adenylate cyclase of human gastric mucosa. Stimulation of enzyme activity by histamine and catecholamines. | Human gastric mucosal adenylate cyclase has been shown to be sensitive to histamine and catecholamines. Stimulation of enzyme activity by histamine and catecholamines were selectively blocked by cimetidine and propranolol, respectively. Combination of both hormones at maximally effective concentrations were additive, indicating that human gastric mucosa contains at least two separate hormone-sensitive adenylate cyclases. | Adenylate cyclase of human gastric mucosa. Stimulation of enzyme activity by histamine and catecholamines. Human gastric mucosal adenylate cyclase has been shown to be sensitive to histamine and catecholamines. Stimulation of enzyme activity by histamine and catecholamines were selectively blocked by cimetidine and propranolol, respectively. Combination of both hormones at maximally effective concentrations were additive, indicating that human gastric mucosa contains at least two separate hormone-sensitive adenylate cyclases. | [
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PMID:28261 | Fecal chymotrypsin: study on some characteristics of the enzyme. | A Lineweaver-Burk plot demonstrated that the apparent Michaelis constants are identical for chymotrypsin (CT) in duodenal juice and in feces of the same patient. CT in fecal homogenates exhibits exhibits a remarkable stability and is bound to particles to a considerable but variable extent. The pH optimum of CT in human feces is somewhat higher as compared to pure bovine pancreatic CT. All measurements of fecal CT activity should, therefore, be performed at pH 9.0. The distribution of CT among the fecal mass has been investigated. There were considerable differences between CT activities in random fecal specimens and in the corresponding stool collections. However, if the results were expressed in terms of 'normal' and 'abnormal', 113 out of 120 random fecal specimens gave the same results as the corresponding stool collections. It is concluded that the risk of 'false-normal' values cannot be effectively reduced by determination of CT outputs in stool collections (or by using continuous markers) instead of CT activities in random stool specimens. | Fecal chymotrypsin: study on some characteristics of the enzyme. A Lineweaver-Burk plot demonstrated that the apparent Michaelis constants are identical for chymotrypsin (CT) in duodenal juice and in feces of the same patient. CT in fecal homogenates exhibits exhibits a remarkable stability and is bound to particles to a considerable but variable extent. The pH optimum of CT in human feces is somewhat higher as compared to pure bovine pancreatic CT. All measurements of fecal CT activity should, therefore, be performed at pH 9.0. The distribution of CT among the fecal mass has been investigated. There were considerable differences between CT activities in random fecal specimens and in the corresponding stool collections. However, if the results were expressed in terms of 'normal' and 'abnormal', 113 out of 120 random fecal specimens gave the same results as the corresponding stool collections. It is concluded that the risk of 'false-normal' values cannot be effectively reduced by determination of CT outputs in stool collections (or by using continuous markers) instead of CT activities in random stool specimens. | [
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PMID:28263 | Polyarteritis nodosa causing severe intestinal bleeding. | Rupture of an aneurysm of the mesentergic artery caused severe intestinal hemorrhage in a 50-year-old woman with polyarteritis nodosa. Abdominal angiography not only established diagnosis of polyarteritis nodosa by demonstrating multiple visceral aneurysms but also localized the site of bleeding. | Polyarteritis nodosa causing severe intestinal bleeding. Rupture of an aneurysm of the mesentergic artery caused severe intestinal hemorrhage in a 50-year-old woman with polyarteritis nodosa. Abdominal angiography not only established diagnosis of polyarteritis nodosa by demonstrating multiple visceral aneurysms but also localized the site of bleeding. | [
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PMID:28264 | Non-beta islet cell tumor calcification assoicated with Zollinger-Ellison syndrome and multiple endocrine adenomatosis. | The radiographic triad of a calcified pancreatic mass, duodenal ulcers, and nephrocalcinosis should suggest the Zollinger-Ellison syndrome, as part of the multiple endocrine adenomatosis complex. The clinical and radiographic features of the entity are described in this case report. | Non-beta islet cell tumor calcification assoicated with Zollinger-Ellison syndrome and multiple endocrine adenomatosis. The radiographic triad of a calcified pancreatic mass, duodenal ulcers, and nephrocalcinosis should suggest the Zollinger-Ellison syndrome, as part of the multiple endocrine adenomatosis complex. The clinical and radiographic features of the entity are described in this case report. | [
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PMID:28269 | Recognition of alcoholic liver disease in a district general hospital. | Two-hundred-and-two patients with alcoholic liver disease whose investigations included a liver biopsy were seen in a district general hospital over a seven year period. Thirty-five percent presented with general gastrointestinal symptoms rather than with overt liver disease or previously recognised excess consumption of alcohol. Recognition of the alcohol problem was assisted by the finding of a raised mean corpuscular volume (MCV) and/or gammaglutamyl transpeptidase (GGTP). The use of these methods of detection is discussed in relation to the rapid rise in alcohol consumption in the United Kingdom, and the high mortality of cirrhosis reported from special centres. Twnety-two per cent of the patients were found to have an established cirrhosis, and there was some evidence that the women were more susceptible to some of the toxic effects of alcohol. Early detection can be enhanced by a high level of suspicion, wider recognition of the significance of a high MCV, and the greater use of GGTP estimations. | Recognition of alcoholic liver disease in a district general hospital. Two-hundred-and-two patients with alcoholic liver disease whose investigations included a liver biopsy were seen in a district general hospital over a seven year period. Thirty-five percent presented with general gastrointestinal symptoms rather than with overt liver disease or previously recognised excess consumption of alcohol. Recognition of the alcohol problem was assisted by the finding of a raised mean corpuscular volume (MCV) and/or gammaglutamyl transpeptidase (GGTP). The use of these methods of detection is discussed in relation to the rapid rise in alcohol consumption in the United Kingdom, and the high mortality of cirrhosis reported from special centres. Twnety-two per cent of the patients were found to have an established cirrhosis, and there was some evidence that the women were more susceptible to some of the toxic effects of alcohol. Early detection can be enhanced by a high level of suspicion, wider recognition of the significance of a high MCV, and the greater use of GGTP estimations. | [
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PMID:28270 | Postprandial duodenal function in man. | Duodenal function was studied in 11 healthy volunteers after intragastric instillation of a mixed semi-elemental meal. The duodenum accepted chyme of varying pH, osmolality, and nutrient concentration; and, as a result of biliary, pancreatic, and enteric secretion as well as absorption, it delivered chyme with nearly constant pH, osmolality, and nutrient concentration to the jejunum. The flow rate and nutrient load of jejunal chyme varied. The duodenum absorbed more carbohydrate than lipid and less protein, taking up each nutrient at a constant rate during most of the postprandial period. The percentage of nutrient load absorbed was greatest in the late postprandial period, when flow rate, nutrient load, and concentrations were low. | Postprandial duodenal function in man. Duodenal function was studied in 11 healthy volunteers after intragastric instillation of a mixed semi-elemental meal. The duodenum accepted chyme of varying pH, osmolality, and nutrient concentration; and, as a result of biliary, pancreatic, and enteric secretion as well as absorption, it delivered chyme with nearly constant pH, osmolality, and nutrient concentration to the jejunum. The flow rate and nutrient load of jejunal chyme varied. The duodenum absorbed more carbohydrate than lipid and less protein, taking up each nutrient at a constant rate during most of the postprandial period. The percentage of nutrient load absorbed was greatest in the late postprandial period, when flow rate, nutrient load, and concentrations were low. | [
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PMID:28271 | Acid microclimate in coeliac and Crohn's disease: a model for folate malabsorption. | The surface pH of human proximal jejunum was measured in biopsy samples and found to be more acid than the phosphate buffer in which they were incubated. The in vitro jejunal surface pH was 5.93 +/- 0.05 in control subjects and 6.19 +/- 0.09 in treated coeliac patients. A group of untreated coeliac patients with a surface pH of 6.56 +/- 0.14 had a significantly less acid surface pH compared to controls, as did a group of Crohn's patients with a surface pH of 6.21 +/- 0.04. These two groups with a significantly raised surface pH were subdivisible into 'high' and 'low'groups. Surface pH was found to remain low in the treated coeliac and control groups but became more acid over the incubation period reaching almost normal values in the Crohn's group and the untreated coelic initial surface pH. The raised surface pH in untreated coeliac disease and Crohn's disease would alter the amount of a weak acid available for non-ionic diffusion. Therefore the present results may help to explain the folate malabsorption known to occur in untreated coeliac disease and the frequently seen low serum folate levels in Crohn's disease. | Acid microclimate in coeliac and Crohn's disease: a model for folate malabsorption. The surface pH of human proximal jejunum was measured in biopsy samples and found to be more acid than the phosphate buffer in which they were incubated. The in vitro jejunal surface pH was 5.93 +/- 0.05 in control subjects and 6.19 +/- 0.09 in treated coeliac patients. A group of untreated coeliac patients with a surface pH of 6.56 +/- 0.14 had a significantly less acid surface pH compared to controls, as did a group of Crohn's patients with a surface pH of 6.21 +/- 0.04. These two groups with a significantly raised surface pH were subdivisible into 'high' and 'low'groups. Surface pH was found to remain low in the treated coeliac and control groups but became more acid over the incubation period reaching almost normal values in the Crohn's group and the untreated coelic initial surface pH. The raised surface pH in untreated coeliac disease and Crohn's disease would alter the amount of a weak acid available for non-ionic diffusion. Therefore the present results may help to explain the folate malabsorption known to occur in untreated coeliac disease and the frequently seen low serum folate levels in Crohn's disease. | [
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PMID:28272 | Effects of phospholipase A and triton x-100 on guanylate cyclase activity in mammary gland homogenates from mice. | The effects of a variety of agents on guanylate cyclase activity were tested in broken cell preparations of mammary glands from midpregnant mice. Of the agents tested, only phospholipase A, triton X-100, and an impure egg lysolecithin preparation enhanced the activity of guanylate cyclase in mammary gland homogenates; other agents, including sodium azide and phospholipase C, and purified egg lysolecithin had no effect. Phospholipase A increased the activity of guanylate cyclase in the 150,000 g pellet fractions of mammary gland homogenates, bud did not consistently enhance guanylate cyclase in the 150,000 g supernatant fractions. Phospholipase A did not appear to enhance guanylate cyclase activity by solublizing the enzyme from the 150,000 g pellet. Triton X-100, in contrast, appeared to act by solubilizing guanylate cyclase from the material present in the 150,000 g pellet. Triton X-100 increased by several fold guanylate cyclase activity in the tissue homogenates and the 150,000 g pellets, but did not consistently enhance enzyme activity in the 150,000 g supernatant. Triton X-100 had no effect on the apparent Km of guanylate cyclase. | Effects of phospholipase A and triton x-100 on guanylate cyclase activity in mammary gland homogenates from mice. The effects of a variety of agents on guanylate cyclase activity were tested in broken cell preparations of mammary glands from midpregnant mice. Of the agents tested, only phospholipase A, triton X-100, and an impure egg lysolecithin preparation enhanced the activity of guanylate cyclase in mammary gland homogenates; other agents, including sodium azide and phospholipase C, and purified egg lysolecithin had no effect. Phospholipase A increased the activity of guanylate cyclase in the 150,000 g pellet fractions of mammary gland homogenates, bud did not consistently enhance guanylate cyclase in the 150,000 g supernatant fractions. Phospholipase A did not appear to enhance guanylate cyclase activity by solublizing the enzyme from the 150,000 g pellet. Triton X-100, in contrast, appeared to act by solubilizing guanylate cyclase from the material present in the 150,000 g pellet. Triton X-100 increased by several fold guanylate cyclase activity in the tissue homogenates and the 150,000 g pellets, but did not consistently enhance enzyme activity in the 150,000 g supernatant. Triton X-100 had no effect on the apparent Km of guanylate cyclase. | [
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PMID:28274 | Rapid formation of N-nitrosamines from nitrogen oxides under neutral and alkaline conditions. | The formation of carcinogenic N-nitrosamines in neutral and alkaline aqueous solutions (pH 6-14) at 25 degrees C is reported using dissolved N2O3 and N2O4 gases. These reactions are very much faster than those with acidified nitrite: typically, 2 X 10(-3) M amine gives ca. 10-50% N-nitrosamine in a few seconds with 5-20 fold excess of nitrogen oxide. The N-nitrosamine yield in 0.1 M sodium hydroxide is independent of amine basicity from pKA 11.2-0.99, but decreases with decreasing pH of the reaction solution for the more basic amines. Significantly, N-nitrosamine yields are not lowered with diluted nitrogen oxides (1000 ppm) and moderately basic amines (eg. N-methylpiperazine) react readily at physiological pH. The mechanism by which these reactions occur is discussed, with particular reference to the existence of two reactive tautomeric forms of N2O3 and N2O4. The formation of carcinogenic N-nitrosamines from NO in ethanol at 25 degrees C is also reported. These reactions are slow in the absence of air (oxygen), I2 or metal salts. Oxygen accelerates nitrosation by converting NO via NO2 to either N2O3 or N2O4, but both I2 and metal salts are effective under anaerobic conditions, where reaction rates are virtually independent of amine basicity but depend on the nature of the added reagent. The most effective substance is I2, which gives quantitative yields of N-nitrosamine in a few minutes at 25 degrees C by forming the reactive nitrosyl iodide (NOI) reagent. Acceleration in ethanol at 25 degrees C is also observed with AgI, CuI, CuII, ZnII, FeIII and CoII salts, among others, with substantial amounts of N-nitrosamine being produced in ca. 30-300 min. Metal iodides intervene by way of the NOI reagent, as for I2, but other salts require a mechanism involving reaction between a metal-amine complex and NO, itself. The results show that carcinogenic N-nitrosamines may form under a much wider range of experimental conditions than suspected hitherto. Their relevance to human exposure is discussed, with particular reference to urban pollution and the effect of dietary antioxidants. | Rapid formation of N-nitrosamines from nitrogen oxides under neutral and alkaline conditions. The formation of carcinogenic N-nitrosamines in neutral and alkaline aqueous solutions (pH 6-14) at 25 degrees C is reported using dissolved N2O3 and N2O4 gases. These reactions are very much faster than those with acidified nitrite: typically, 2 X 10(-3) M amine gives ca. 10-50% N-nitrosamine in a few seconds with 5-20 fold excess of nitrogen oxide. The N-nitrosamine yield in 0.1 M sodium hydroxide is independent of amine basicity from pKA 11.2-0.99, but decreases with decreasing pH of the reaction solution for the more basic amines. Significantly, N-nitrosamine yields are not lowered with diluted nitrogen oxides (1000 ppm) and moderately basic amines (eg. N-methylpiperazine) react readily at physiological pH. The mechanism by which these reactions occur is discussed, with particular reference to the existence of two reactive tautomeric forms of N2O3 and N2O4. The formation of carcinogenic N-nitrosamines from NO in ethanol at 25 degrees C is also reported. These reactions are slow in the absence of air (oxygen), I2 or metal salts. Oxygen accelerates nitrosation by converting NO via NO2 to either N2O3 or N2O4, but both I2 and metal salts are effective under anaerobic conditions, where reaction rates are virtually independent of amine basicity but depend on the nature of the added reagent. The most effective substance is I2, which gives quantitative yields of N-nitrosamine in a few minutes at 25 degrees C by forming the reactive nitrosyl iodide (NOI) reagent. Acceleration in ethanol at 25 degrees C is also observed with AgI, CuI, CuII, ZnII, FeIII and CoII salts, among others, with substantial amounts of N-nitrosamine being produced in ca. 30-300 min. Metal iodides intervene by way of the NOI reagent, as for I2, but other salts require a mechanism involving reaction between a metal-amine complex and NO, itself. The results show that carcinogenic N-nitrosamines may form under a much wider range of experimental conditions than suspected hitherto. Their relevance to human exposure is discussed, with particular reference to urban pollution and the effect of dietary antioxidants. | [
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PMID:28275 | Mechanism of N-nitrosodimethylamine formation from trimethylamine and trimethylaminoxide. | The kinetics of nitrosation of trimethylamine (TMA) and trimethylaminoxide (TMAO) to give N-nitrosodimethylamine (NDMA) have been studied. The nitrosation rates of TMA and TMAO, when determined at 100 degrees C in sealed tubes, showed maximum values at about pH 3, while at temperatures lower than 75 degrees C the pH dependence of the nitrosation of these compounds was similar to that observed with alkylamides. The initial rate of NDMA formation from TMAO determined at pH 3.0 and 25 degrees C was found to be proportional to the TMAO and nitrite concentrations, not to the square of the nitrite concentration. In contrast, the rates of NDMA formation from TMA and TMAO when reacted at pH 3.0 and 100 degrees C in sealed tubes were found to be proportional to the square and the cube, respectively, of the nitrite concentration. These results strongly suggest that the NDMA formation at higher temperatures involves the oxidative cleavage of tertiary amines to produce secondary amines (dimethylamine, DMA) which may react with nitrite to form NDMA. On the other hand, at lower temperatures, NDMA may be formed from TMA or TMAO by a pathway not involving DMA. | Mechanism of N-nitrosodimethylamine formation from trimethylamine and trimethylaminoxide. The kinetics of nitrosation of trimethylamine (TMA) and trimethylaminoxide (TMAO) to give N-nitrosodimethylamine (NDMA) have been studied. The nitrosation rates of TMA and TMAO, when determined at 100 degrees C in sealed tubes, showed maximum values at about pH 3, while at temperatures lower than 75 degrees C the pH dependence of the nitrosation of these compounds was similar to that observed with alkylamides. The initial rate of NDMA formation from TMAO determined at pH 3.0 and 25 degrees C was found to be proportional to the TMAO and nitrite concentrations, not to the square of the nitrite concentration. In contrast, the rates of NDMA formation from TMA and TMAO when reacted at pH 3.0 and 100 degrees C in sealed tubes were found to be proportional to the square and the cube, respectively, of the nitrite concentration. These results strongly suggest that the NDMA formation at higher temperatures involves the oxidative cleavage of tertiary amines to produce secondary amines (dimethylamine, DMA) which may react with nitrite to form NDMA. On the other hand, at lower temperatures, NDMA may be formed from TMA or TMAO by a pathway not involving DMA. | [
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PMID:28276 | Some effects of phenol- and thiol-nitrosation reactions on N-nitrosamine formation. | C-Nitrosophenols, produced by the nitrosation of phenols, catalyse N-nitrosamine formation. The rate of N-nitrosation of pyrrolidine, catalysed by p-nitroso-o-cresol, is fastest at about pH 5. The catalytic species is thought to be the quinone monoxime tautomer of the nitrosophenol. A possible mechanism for the catalysis is proposed. A reaction of pyrrolidine with nitrite at pH 5.0 is described, which gives enhanced N-nitrosation in the presence of p-cresol. The yield of N-nitrosopyrrolidine (NPYR) is further enhanced when this reaction is carried out under anaerobic conditions. Nitrosocysteine hydrochloride reacts with N-methylaniline at pH 2.65, 5.5 and 9.75 in the absence of nitrite to give N-nitroso N-methylaniline. The N-nitrosation of morpholine and pyrrolidine at pH 9.75 is also effected by nitrosocysteine hydrochloride. The rate of N-nitrosation at this pH decreases with increasing amine basicity. The reaction of nitrosocysteine with N-methylaniline at pH 9.75 under anaerobic conditions leads to a significant reduction in the yield of N-nitroso-N-methylaniline. | Some effects of phenol- and thiol-nitrosation reactions on N-nitrosamine formation. C-Nitrosophenols, produced by the nitrosation of phenols, catalyse N-nitrosamine formation. The rate of N-nitrosation of pyrrolidine, catalysed by p-nitroso-o-cresol, is fastest at about pH 5. The catalytic species is thought to be the quinone monoxime tautomer of the nitrosophenol. A possible mechanism for the catalysis is proposed. A reaction of pyrrolidine with nitrite at pH 5.0 is described, which gives enhanced N-nitrosation in the presence of p-cresol. The yield of N-nitrosopyrrolidine (NPYR) is further enhanced when this reaction is carried out under anaerobic conditions. Nitrosocysteine hydrochloride reacts with N-methylaniline at pH 2.65, 5.5 and 9.75 in the absence of nitrite to give N-nitroso N-methylaniline. The N-nitrosation of morpholine and pyrrolidine at pH 9.75 is also effected by nitrosocysteine hydrochloride. The rate of N-nitrosation at this pH decreases with increasing amine basicity. The reaction of nitrosocysteine with N-methylaniline at pH 9.75 under anaerobic conditions leads to a significant reduction in the yield of N-nitroso-N-methylaniline. | [
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PMID:28277 | Alpha-tocopherol: uses in preventing nitrosamine formation. | alpha-Tocopherol has been evaluated as a nitrite scavenger for the prevention of nitrosamine formation in a model system and under practical conditions. alpha-Tocopherol was found to react with nitrosating agents in both lipophilic and aqueous environments. The use of alpha-tocopherol was shown to inhibit aminopyrene-nitrite induced hepatotoxicity in rats and to reduce the amount of NDMA formed in cigarette smoke. Of primary interest is the finding of a significant reduction of NPYR formation in fried bacon. Nitrosamine inhibition was greater with alpha-tocopherol used in combination with sodium ascorbate than with sodium ascorbate alone. | Alpha-tocopherol: uses in preventing nitrosamine formation. alpha-Tocopherol has been evaluated as a nitrite scavenger for the prevention of nitrosamine formation in a model system and under practical conditions. alpha-Tocopherol was found to react with nitrosating agents in both lipophilic and aqueous environments. The use of alpha-tocopherol was shown to inhibit aminopyrene-nitrite induced hepatotoxicity in rats and to reduce the amount of NDMA formed in cigarette smoke. Of primary interest is the finding of a significant reduction of NPYR formation in fried bacon. Nitrosamine inhibition was greater with alpha-tocopherol used in combination with sodium ascorbate than with sodium ascorbate alone. | [
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PMID:28279 | Acceleration of nitrosamine formation at pH 3.5 by microorganisms. | Rate enhancements of from 12 to 49-fold occurred when dihexylamine was nitrosated at pH 3.5 in the presence of bacteria and yeast cells at a concentration of 12 mg/ml. Rates were similar in the presence of either boiled or unheated cells. The magnitude of the rate enhancement for nitrosation of other amines depended on the alkyl chain length. A nonenzymatic mechanism involving hydrophobic interactions of the precursor amines and cellular constituents is proposed. | Acceleration of nitrosamine formation at pH 3.5 by microorganisms. Rate enhancements of from 12 to 49-fold occurred when dihexylamine was nitrosated at pH 3.5 in the presence of bacteria and yeast cells at a concentration of 12 mg/ml. Rates were similar in the presence of either boiled or unheated cells. The magnitude of the rate enhancement for nitrosation of other amines depended on the alkyl chain length. A nonenzymatic mechanism involving hydrophobic interactions of the precursor amines and cellular constituents is proposed. | [
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PMID:28282 | Preliminary observations on amines and nitrosamines in non-normal human gastric contents. | Gastric contents from fasting humans were pooled and analysed for amines. Volatile amines present were dimethylamine, trimethylamine and histamine; non-volatile amines found were cadaverine, putrescine, ethanolamine and tryptamine. Gastric contents from 35 patients, some before and/or after gastric stimulation with histamine or pentagastrin, were analysed for nitrosamines. N-Nitrosodiethylamine (NDEA) (5-30 microgram/kg) was present in four samples, N-nitrosodimethylamine (NDMA) (2 microgram/kg) in two samples and N-nitrosopyrrolidine (NPYR) (6 microgram/kg) in one sample. pH, nitrite and nitrate determinations were made on some samples. Medical diagnosis of patients could not be correlated with the presence of nitrosamines in the gastric contents. | Preliminary observations on amines and nitrosamines in non-normal human gastric contents. Gastric contents from fasting humans were pooled and analysed for amines. Volatile amines present were dimethylamine, trimethylamine and histamine; non-volatile amines found were cadaverine, putrescine, ethanolamine and tryptamine. Gastric contents from 35 patients, some before and/or after gastric stimulation with histamine or pentagastrin, were analysed for nitrosamines. N-Nitrosodiethylamine (NDEA) (5-30 microgram/kg) was present in four samples, N-nitrosodimethylamine (NDMA) (2 microgram/kg) in two samples and N-nitrosopyrrolidine (NPYR) (6 microgram/kg) in one sample. pH, nitrite and nitrate determinations were made on some samples. Medical diagnosis of patients could not be correlated with the presence of nitrosamines in the gastric contents. | [
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PMID:28285 | Homologous and cross-reactive precipitins in anti-pneumococcal sera raised in mules. | Serial bleedings were obtained from two mules during prolonged immunization, one with type XXV the other with type VIII pneumococcal vaccine. IgGa, IgGb, IgGc, IgB, IgG(T) and IgM present among purified Pn anti-XXV and Pn anti-VIII immunoglobulin isolated from various bleedings were identified by use of rabbit anti-equine heavy chain specific reagents. Radioimmunodiffusion with 14C-labelled type XXV pneumococcal capsular polysaccharide and horse and donkey reagents with species specificity directed against donkey or horse IgGa respectively, demonstrated both parental horse and donkey IgGa heavy chain isotypes among the anti-PnXXV antibodies of the interspecies hybrid. Qualtitative and quantitative examination of the cross-precipitation of mule anti-PnXXV sera with the capsular polysaccharides of pneumococcal types IV, X and XA, with birch sap, ketha gum, and with polysaccharides of E. coli, Klebsiella and Rhizobium was carried out and compared with data obtained with anti-PnXXV raised in a horse. Analysis of supernatants from the cross-reactions showed that distinct subfractions had reacted. indicating a marked heterogeneity of the antibodies. | Homologous and cross-reactive precipitins in anti-pneumococcal sera raised in mules. Serial bleedings were obtained from two mules during prolonged immunization, one with type XXV the other with type VIII pneumococcal vaccine. IgGa, IgGb, IgGc, IgB, IgG(T) and IgM present among purified Pn anti-XXV and Pn anti-VIII immunoglobulin isolated from various bleedings were identified by use of rabbit anti-equine heavy chain specific reagents. Radioimmunodiffusion with 14C-labelled type XXV pneumococcal capsular polysaccharide and horse and donkey reagents with species specificity directed against donkey or horse IgGa respectively, demonstrated both parental horse and donkey IgGa heavy chain isotypes among the anti-PnXXV antibodies of the interspecies hybrid. Qualtitative and quantitative examination of the cross-precipitation of mule anti-PnXXV sera with the capsular polysaccharides of pneumococcal types IV, X and XA, with birch sap, ketha gum, and with polysaccharides of E. coli, Klebsiella and Rhizobium was carried out and compared with data obtained with anti-PnXXV raised in a horse. Analysis of supernatants from the cross-reactions showed that distinct subfractions had reacted. indicating a marked heterogeneity of the antibodies. | [
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PMID:28293 | Ionic binding of aminoglycosides to human serum albumin in the absence of divalent cations. IV. Effect of structure, ph and concentration. | The binding of sisomicin and streptomycin to human serum albumin was studied in the absence of divalent cations by means of the dialysis method. Hydrophobic bonds between albumin and sisomicin or streptomycin can be excluded by nuclear magnetic resonance measurements. The presence of hydrogen bonds is made unlikely according to the result that the binding of the aminoglycosides decreases with increasing number of OH groups in the aminoglycoside molecule. The pH dependence of protein binding suggests that ionic bonds are involved in the binding of aminoglycosides. On the basis of the concentration dependence of the albumin binding of sisomicin and streptomycin we determined the binding affinities delta F degrees, the binding constants K1, and the maximum number n of aminoglycoside molecules that can be bound by a molecule of albumin in the absence of Ca++ ions. The results were as follows: Sisomicin: delta F degrees = -4189 cal/mole, K1 = 900 1/mole, n = 12; Streptomycin: delta F degrees = 3512 cal/mole, K1 = 300 1/mole, n = 17. | Ionic binding of aminoglycosides to human serum albumin in the absence of divalent cations. IV. Effect of structure, ph and concentration. The binding of sisomicin and streptomycin to human serum albumin was studied in the absence of divalent cations by means of the dialysis method. Hydrophobic bonds between albumin and sisomicin or streptomycin can be excluded by nuclear magnetic resonance measurements. The presence of hydrogen bonds is made unlikely according to the result that the binding of the aminoglycosides decreases with increasing number of OH groups in the aminoglycoside molecule. The pH dependence of protein binding suggests that ionic bonds are involved in the binding of aminoglycosides. On the basis of the concentration dependence of the albumin binding of sisomicin and streptomycin we determined the binding affinities delta F degrees, the binding constants K1, and the maximum number n of aminoglycoside molecules that can be bound by a molecule of albumin in the absence of Ca++ ions. The results were as follows: Sisomicin: delta F degrees = -4189 cal/mole, K1 = 900 1/mole, n = 12; Streptomycin: delta F degrees = 3512 cal/mole, K1 = 300 1/mole, n = 17. | [
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PMID:28288 | Factors affecting in vitro lipid peroxidation of rat brain homogenate. | Peroxidation of the unsaturated lipid of tissue homogenates is an established method to assess the antioxidant or vitamin E status of animals. In the present study the spontaneous lipid peroxidation in air of rat brain homogenates is reported. The effects of various factors like pH, time, concentration of tissues, temperature, ferrocompounds and catalysis by added tissues like liver are described. Rat brain homogenates appear to be a suitable preparation for in vitro studies of lipid peroxidation. | Factors affecting in vitro lipid peroxidation of rat brain homogenate. Peroxidation of the unsaturated lipid of tissue homogenates is an established method to assess the antioxidant or vitamin E status of animals. In the present study the spontaneous lipid peroxidation in air of rat brain homogenates is reported. The effects of various factors like pH, time, concentration of tissues, temperature, ferrocompounds and catalysis by added tissues like liver are described. Rat brain homogenates appear to be a suitable preparation for in vitro studies of lipid peroxidation. | [
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PMID:28289 | Enhancement of insulin hypoglycaemia by beta adrenoceptor antagonists. | Interaction of insulin with beta-adrenoceptor antagonists was studied in conscious rabbits. Propranolol and metoprolol did not modify the peak of insulin hypoglycaemia but delayed its recovery. Practolol, sotalol and 1-INPEA enhanced the peak effect and delayed the recovery of insulin-induced hypoglycaemia. H 35/25 and d-INPEA did not modify insulin hypoglycaemia. The beta-blockers did not produce significant hypoglycaemia per se. Since sotalol, 1-INPEA (specific beta-adrenoceptor antagonists devoid of local anaesthetic activity); practolol and metoprolol (selective cardiac beta-1 adrenoceptor antagonists) enhanced hypoglycaemic action of insulin and H 35/25 (a selective beta-2 adrenoceptor antagonist) failed to affect it, it seems that selective beta-adrenoceptor blockade (similar to cardiac beta-1 adrenoceptors) mediates enhancement of insulin hypoglycaemia. Caution should, therefore, be exercised in administering beta-adrenoceptor antagonists and insulin together. A reduction in the dose of insulin may be necessary. | Enhancement of insulin hypoglycaemia by beta adrenoceptor antagonists. Interaction of insulin with beta-adrenoceptor antagonists was studied in conscious rabbits. Propranolol and metoprolol did not modify the peak of insulin hypoglycaemia but delayed its recovery. Practolol, sotalol and 1-INPEA enhanced the peak effect and delayed the recovery of insulin-induced hypoglycaemia. H 35/25 and d-INPEA did not modify insulin hypoglycaemia. The beta-blockers did not produce significant hypoglycaemia per se. Since sotalol, 1-INPEA (specific beta-adrenoceptor antagonists devoid of local anaesthetic activity); practolol and metoprolol (selective cardiac beta-1 adrenoceptor antagonists) enhanced hypoglycaemic action of insulin and H 35/25 (a selective beta-2 adrenoceptor antagonist) failed to affect it, it seems that selective beta-adrenoceptor blockade (similar to cardiac beta-1 adrenoceptors) mediates enhancement of insulin hypoglycaemia. Caution should, therefore, be exercised in administering beta-adrenoceptor antagonists and insulin together. A reduction in the dose of insulin may be necessary. | [
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PMID:28290 | Acetylcholine: a possible neurotransmitter in Setaria cervi. | The total and free acetylcholine (Ach) and cholinesterase (CHE) content of adult Setaria cervi were estimated. The Ach was estimated by bioassay on rectus abdominis muscle of frog and the CHE by measuring the drop in pH following incubation of worm homogenate with Ach chloride. The free and total Ach contents (4.0 +/- 0.57 and 6.0 +/- 0.48 microgram/g wet weight of worms respectively) were as high as found in mammalian brain cortex. The cholinesterase activity was found to be 5.57 +/- 0.6 units/g wet weight of worms. It is possible that there may exist a well developed system responsible for the synthesis, storage, release and destruction of Ach and that Ach may be acting as an excitatory neurohormone in S. cervi. | Acetylcholine: a possible neurotransmitter in Setaria cervi. The total and free acetylcholine (Ach) and cholinesterase (CHE) content of adult Setaria cervi were estimated. The Ach was estimated by bioassay on rectus abdominis muscle of frog and the CHE by measuring the drop in pH following incubation of worm homogenate with Ach chloride. The free and total Ach contents (4.0 +/- 0.57 and 6.0 +/- 0.48 microgram/g wet weight of worms respectively) were as high as found in mammalian brain cortex. The cholinesterase activity was found to be 5.57 +/- 0.6 units/g wet weight of worms. It is possible that there may exist a well developed system responsible for the synthesis, storage, release and destruction of Ach and that Ach may be acting as an excitatory neurohormone in S. cervi. | [
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PMID:28295 | Inhibition of allergic reactions by a new antiallergic drug, LC-6 (trans-2,3b,4,5,7,8b,9,10-octahydronaphthol[1,2-c:5,6-c'] dipyrazole). I. Inhibition of the rat reaginic passive cutaneous anaphylaxis. | A new synthetic compound, LC-6, has been shown to inhibit the passive cutaneous anaphylaxis reactions induced in rats by mouse reaginic antibody. In this system, the ED50 was 35 mg/kg body weight of LC-6 administered per os. LC-6 prevented neither histamine skin reactions nor the reactions to histamine and other chemical mediators released by 48/80. Therefore, its inhibitory activity is comparable to that of the model anti-allergic compound, disodium cromoglycate (DSCG). In contrast to DSCG, the new drug exhibits the distinct advantage of being active per os and over prolonged periods of time. Its activity has been shown to persist for at least 6 h when doses 4 times higher than the ED50 were administered. The duration of the drug effect was clearly dose-dependent. Predoses of the compound increased its effectiveness. The long-lasting association of LC-6 with mast cells, as indicated by its prolonged inhibitory activity, makes it a valuable tool in the search for receptors involved in anaphylactic reactions. | Inhibition of allergic reactions by a new antiallergic drug, LC-6 (trans-2,3b,4,5,7,8b,9,10-octahydronaphthol[1,2-c:5,6-c'] dipyrazole). I. Inhibition of the rat reaginic passive cutaneous anaphylaxis. A new synthetic compound, LC-6, has been shown to inhibit the passive cutaneous anaphylaxis reactions induced in rats by mouse reaginic antibody. In this system, the ED50 was 35 mg/kg body weight of LC-6 administered per os. LC-6 prevented neither histamine skin reactions nor the reactions to histamine and other chemical mediators released by 48/80. Therefore, its inhibitory activity is comparable to that of the model anti-allergic compound, disodium cromoglycate (DSCG). In contrast to DSCG, the new drug exhibits the distinct advantage of being active per os and over prolonged periods of time. Its activity has been shown to persist for at least 6 h when doses 4 times higher than the ED50 were administered. The duration of the drug effect was clearly dose-dependent. Predoses of the compound increased its effectiveness. The long-lasting association of LC-6 with mast cells, as indicated by its prolonged inhibitory activity, makes it a valuable tool in the search for receptors involved in anaphylactic reactions. | [
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PMID:28291 | Effect of light and exhaustive ergometric exercise on blood sugar, total cholesterol and pH in untrained young human subjects. | Light and exhaustive ergometric exercise in untrained male and female medical students in the age group 18-21 years resulted in significant lowering of the blood sugar, cholesterol and pH. Females exhibited hypoglycemia of slightly greater magnitude as compared to male subjects and during both the exercises, however, such sex differences were not observed for changes in cholesterol and pH. | Effect of light and exhaustive ergometric exercise on blood sugar, total cholesterol and pH in untrained young human subjects. Light and exhaustive ergometric exercise in untrained male and female medical students in the age group 18-21 years resulted in significant lowering of the blood sugar, cholesterol and pH. Females exhibited hypoglycemia of slightly greater magnitude as compared to male subjects and during both the exercises, however, such sex differences were not observed for changes in cholesterol and pH. | [
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PMID:28296 | Immunological nature of the inhibition of BLV-induced early polykaryocytosis by bovine sera. | A quantitative in vitro assay (EPI) was developed for the serological detection of bovine leukemia virus (BLV) infection in cattle. Positive sera inhibit early polykaryocytosis (EP) induced by BLV. We report herein experiments which demonstrate that BLV-induced antibodies are responsible for this inhibition. Serum fractionation by gel filtration and affinity chromatography indicate that EP-inhibiting activity is mediated only by immunoglobulins of the IgG class. Furthermore, on the basis of their ion-exchange chromatographic behaviour, these antibodies were classified as IgG1. We also ruled out the participation in the EP inhibition reaction of the other compounds such as polypeptides, including serum complement and interferon or DNA and RNA. These results demonstrate that EP inhibition by bovine sera is specific to BLV-induced antibodies. | Immunological nature of the inhibition of BLV-induced early polykaryocytosis by bovine sera. A quantitative in vitro assay (EPI) was developed for the serological detection of bovine leukemia virus (BLV) infection in cattle. Positive sera inhibit early polykaryocytosis (EP) induced by BLV. We report herein experiments which demonstrate that BLV-induced antibodies are responsible for this inhibition. Serum fractionation by gel filtration and affinity chromatography indicate that EP-inhibiting activity is mediated only by immunoglobulins of the IgG class. Furthermore, on the basis of their ion-exchange chromatographic behaviour, these antibodies were classified as IgG1. We also ruled out the participation in the EP inhibition reaction of the other compounds such as polypeptides, including serum complement and interferon or DNA and RNA. These results demonstrate that EP inhibition by bovine sera is specific to BLV-induced antibodies. | [
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PMID:28297 | The dissociation of b-TSH. The effect of sodium dodecyl sulfate, pH, urea and temperature. | In the present study SDS polyacrylamide gel electrophoresis was used to reinvestigate the conditions under which b-TSH dissociates into its constituent subunits. The effects of SDS, itself, urea, acid pH and temperature were assessed by the decrease in the amount of undissociated TSH and the increase in the dissociated components as revealed by SDS gel electrophoresis. In SDS alone 25--30% dissociation occurred. Pre-treatment with increasing concentrations of urea up to 7.1 M increased the degree of dissociation to 70% after h at room temperature. Maximum dissociation was achieved by treatment at pH 2.5 and 37 degree C for 1 h. In 1 M propionic acid approximately 10% of the TSH was still undissociated after 18 h at 25 degree C. | The dissociation of b-TSH. The effect of sodium dodecyl sulfate, pH, urea and temperature. In the present study SDS polyacrylamide gel electrophoresis was used to reinvestigate the conditions under which b-TSH dissociates into its constituent subunits. The effects of SDS, itself, urea, acid pH and temperature were assessed by the decrease in the amount of undissociated TSH and the increase in the dissociated components as revealed by SDS gel electrophoresis. In SDS alone 25--30% dissociation occurred. Pre-treatment with increasing concentrations of urea up to 7.1 M increased the degree of dissociation to 70% after h at room temperature. Maximum dissociation was achieved by treatment at pH 2.5 and 37 degree C for 1 h. In 1 M propionic acid approximately 10% of the TSH was still undissociated after 18 h at 25 degree C. | [
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PMID:28300 | Assessment of long-acting neuroleptics. Methods and problems. | Long-acting neuroleptics, without offering a therapeutic breakthrough in the treatment of schizophrenia, are nevertheless a definite step in the management of patients with this disorder. The adequate assessment of these agents necessitates methodological considerations to ensure first, just and adequate patient selection, secondly, adaptations to the drug's characteristics, thridly, sufficient duration of the study and finally, special precautions in the assessment of toxicity. Furthermore, the patient management in these studies must ensure continued and easy accessibility of the simultaneously investigating and treating team. | Assessment of long-acting neuroleptics. Methods and problems. Long-acting neuroleptics, without offering a therapeutic breakthrough in the treatment of schizophrenia, are nevertheless a definite step in the management of patients with this disorder. The adequate assessment of these agents necessitates methodological considerations to ensure first, just and adequate patient selection, secondly, adaptations to the drug's characteristics, thridly, sufficient duration of the study and finally, special precautions in the assessment of toxicity. Furthermore, the patient management in these studies must ensure continued and easy accessibility of the simultaneously investigating and treating team. | [
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PMID:28301 | The pH dependency of sodium and chloride transport in the isolated human cornea. | Sodium and chloride net transport in isolated human cornea preparations were found to be pH dependent. Sodium net transport was directed from aqueous humor to tear side at pH 7.6 and 8.6. At pH 7.4, net sodium flux did not differ significantly from zero, and at pH 7.0, net sodium transport was directed toward the aqueous humor side. Chloride net flux at pH 8.6 and 7.6 was also directed from aqueous humor to tear side. Acidification of the bathing solution to pH 7.4 and 7.0 was followed by a decrease in chloride net fluxes to values not significantly different from zero. | The pH dependency of sodium and chloride transport in the isolated human cornea. Sodium and chloride net transport in isolated human cornea preparations were found to be pH dependent. Sodium net transport was directed from aqueous humor to tear side at pH 7.6 and 8.6. At pH 7.4, net sodium flux did not differ significantly from zero, and at pH 7.0, net sodium transport was directed toward the aqueous humor side. Chloride net flux at pH 8.6 and 7.6 was also directed from aqueous humor to tear side. Acidification of the bathing solution to pH 7.4 and 7.0 was followed by a decrease in chloride net fluxes to values not significantly different from zero. | [
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PMID:28307 | Variability of oxygen affinity of normal blood: an automated method of measurement. | Oxygen equilibrium curves of 48 healthy adult subjects have been measured by the method of Rossi-Bernardi et al. (Clin. Chem. 21: 1747, 1975), in which H2O2 is gradually added to a sample of deoxygenated blood that contains an excess of catalase. The mean P50 for nonsmokers was 26.9 Torr and the distribution of values was slightly skewed to the right (range 24.2--29.9 Torr). The method differs from others previously available in that pH, PCO2, and HCO3-- are constant during oxygenation. The system for control of the experiment and data collection and processing has been automated by the use of a microprocessor so that the equilibrium curve can be obtained quickly, reproducibly, and relatively simply. With the aid of a digital computer, the parameters of the generalized Adair equation can also be estimated. | Variability of oxygen affinity of normal blood: an automated method of measurement. Oxygen equilibrium curves of 48 healthy adult subjects have been measured by the method of Rossi-Bernardi et al. (Clin. Chem. 21: 1747, 1975), in which H2O2 is gradually added to a sample of deoxygenated blood that contains an excess of catalase. The mean P50 for nonsmokers was 26.9 Torr and the distribution of values was slightly skewed to the right (range 24.2--29.9 Torr). The method differs from others previously available in that pH, PCO2, and HCO3-- are constant during oxygenation. The system for control of the experiment and data collection and processing has been automated by the use of a microprocessor so that the equilibrium curve can be obtained quickly, reproducibly, and relatively simply. With the aid of a digital computer, the parameters of the generalized Adair equation can also be estimated. | [
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PMID:28308 | Alpha-adrenergic receptors in human and canine tracheal and bronchial smooth muscle. | We studied the reactions of human tracheal and bronchial smooth muscle and canine trachealis muscle to adrenergic agonists. Human tissue was obtained from recent autopsies of patients with normal lungs and patients with respiratory disorders, and canine tissue was obtained from animals used in other experiments. The muscle was mounted in tissue baths fitted with platinum wire electrodes and the mechanical activity was recorded. Norepinephrine added to the normal human or canine tissue in concentrations up to 10(-5) M caused no reaction. In the normal human and in the dog, pretreatment with histamine or KCl changed this response and when norepinephrine was added the tissue contracted. This contraction was blocked by phentolamine or N,N'-bis-(O-methoxybenzylaminohexyl)-cystamine tetrahydrochloride (BHC). In diseased tissue, the addition of norepinephrine resulted in a contraction that was blocked by phentolamine or BHC and no pretreatment with histamine or KCl was required. These findings demonstrate alpha-receptors in human and canine airway smooth muscle, and there is a difference between normal and diseased human tissue in the reaction of these tissues to alpha-adrenergic agonists. | Alpha-adrenergic receptors in human and canine tracheal and bronchial smooth muscle. We studied the reactions of human tracheal and bronchial smooth muscle and canine trachealis muscle to adrenergic agonists. Human tissue was obtained from recent autopsies of patients with normal lungs and patients with respiratory disorders, and canine tissue was obtained from animals used in other experiments. The muscle was mounted in tissue baths fitted with platinum wire electrodes and the mechanical activity was recorded. Norepinephrine added to the normal human or canine tissue in concentrations up to 10(-5) M caused no reaction. In the normal human and in the dog, pretreatment with histamine or KCl changed this response and when norepinephrine was added the tissue contracted. This contraction was blocked by phentolamine or N,N'-bis-(O-methoxybenzylaminohexyl)-cystamine tetrahydrochloride (BHC). In diseased tissue, the addition of norepinephrine resulted in a contraction that was blocked by phentolamine or BHC and no pretreatment with histamine or KCl was required. These findings demonstrate alpha-receptors in human and canine airway smooth muscle, and there is a difference between normal and diseased human tissue in the reaction of these tissues to alpha-adrenergic agonists. | [
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PMID:28309 | Rapamycin (AY-22,989), a new antifungal antibiotic. III. In vitro and in vivo evaluation. | The activity of rapamycin, a new anti-Candida antibiotic, was not affected by pH values between 6 and 8; at pH 4, however, activity was abolished. The MIC of rapamycin did not vary drastically with the size of inoculum: a ten-fold dilution of the inoculum reduced the MIC only two-fold. Serum binding was extensive. Serum levels obtained in mice were higher on subcutaneous injection than with oral administration. Dogs absorbed rapamycin after oral administration. Rapamycin cured systemic candidosis in mice: PD50 s.c. was 9.5 mg/kg: PD50 p.o. was 11 mg/kg. In the same experimental infections amphotericin B and nystatin exhibited PD50 values of less than 0.25 mg and greater than 4,000 units/kg respectively. Rapamycin and amphotericin B, administered at 1, 4 and 24 hours after infection, gave approximately the same percent survival after 30 days of observation. When the above treatment was extended by an additional daily treatment for 6 days, rapamycin by the subcutaneous route yielded a higher percentage of survival than either rapamycin or amphotericin B, administered orally, after a 30-day observation period. Vaginal candidosis in female rats was treated efficiently (91% cure) by rapamycin administered orally. No increase of resistance of C. albicans was observed during treatment. | Rapamycin (AY-22,989), a new antifungal antibiotic. III. In vitro and in vivo evaluation. The activity of rapamycin, a new anti-Candida antibiotic, was not affected by pH values between 6 and 8; at pH 4, however, activity was abolished. The MIC of rapamycin did not vary drastically with the size of inoculum: a ten-fold dilution of the inoculum reduced the MIC only two-fold. Serum binding was extensive. Serum levels obtained in mice were higher on subcutaneous injection than with oral administration. Dogs absorbed rapamycin after oral administration. Rapamycin cured systemic candidosis in mice: PD50 s.c. was 9.5 mg/kg: PD50 p.o. was 11 mg/kg. In the same experimental infections amphotericin B and nystatin exhibited PD50 values of less than 0.25 mg and greater than 4,000 units/kg respectively. Rapamycin and amphotericin B, administered at 1, 4 and 24 hours after infection, gave approximately the same percent survival after 30 days of observation. When the above treatment was extended by an additional daily treatment for 6 days, rapamycin by the subcutaneous route yielded a higher percentage of survival than either rapamycin or amphotericin B, administered orally, after a 30-day observation period. Vaginal candidosis in female rats was treated efficiently (91% cure) by rapamycin administered orally. No increase of resistance of C. albicans was observed during treatment. | [
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PMID:28310 | Specificity and regulation of gamma-aminobutyrate transport in Escherichia coli. | A specific gamma-aminobutyrate (GABA) transport system in Escherichia coli K-12 cells with a K(m) of 12 muM and a V(max) of 278 nmol/ml of intracellular water per min is described. Membrane vesicles contained d-lactate-dependent activity of the system. Mutants defective in GABA transport were isolated; they lost the ability to utilize GABA as a nitrogen source, although the activities of glutamate-succinylsemialdehyde transaminase (GSST) (EC 2.6.1.19) and succinylsemialdehyde dehydrogenase (SSDH) (EC 1.2.1.16), the enzymes that catalyze GABA utilization, remained as high as in the parental CS101B strain. The ability to utilize l-ornithine, l-arginine, putrescine, l-proline, and glycine as a nitrogen source was preserved in the mutants. The genetic lesions resulting in the loss of GABA transport, gabP5 and gabP9, mapped in the gab gene cluster in close linkage to gabT and gabD, the structural genes of GSST and SSDH, and to gabC, a gene controlling the utilization of GABA, arginine, putrescine, and ornithine. The synthesis of the GABA transport carrier is subject to dual physiological control by (i) catabolite repression and (ii) nitrogen availability. Experiments with glutamine synthetase (EC 6.3.1.2)-negative and with glutamine synthetase-constitutive strains strongly indicate that this enzyme is the effector in the regulation of GABA carrier synthesis by route (ii). | Specificity and regulation of gamma-aminobutyrate transport in Escherichia coli. A specific gamma-aminobutyrate (GABA) transport system in Escherichia coli K-12 cells with a K(m) of 12 muM and a V(max) of 278 nmol/ml of intracellular water per min is described. Membrane vesicles contained d-lactate-dependent activity of the system. Mutants defective in GABA transport were isolated; they lost the ability to utilize GABA as a nitrogen source, although the activities of glutamate-succinylsemialdehyde transaminase (GSST) (EC 2.6.1.19) and succinylsemialdehyde dehydrogenase (SSDH) (EC 1.2.1.16), the enzymes that catalyze GABA utilization, remained as high as in the parental CS101B strain. The ability to utilize l-ornithine, l-arginine, putrescine, l-proline, and glycine as a nitrogen source was preserved in the mutants. The genetic lesions resulting in the loss of GABA transport, gabP5 and gabP9, mapped in the gab gene cluster in close linkage to gabT and gabD, the structural genes of GSST and SSDH, and to gabC, a gene controlling the utilization of GABA, arginine, putrescine, and ornithine. The synthesis of the GABA transport carrier is subject to dual physiological control by (i) catabolite repression and (ii) nitrogen availability. Experiments with glutamine synthetase (EC 6.3.1.2)-negative and with glutamine synthetase-constitutive strains strongly indicate that this enzyme is the effector in the regulation of GABA carrier synthesis by route (ii). | [
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PMID:28311 | Structural basis of the thermostability of monomeric malate synthase from a thermophilic Bacillus. | Malate synthases from a thermophilic Bacillus and Escherichia coli have been isolated in a high state of purity. Molecular weights of these two proteins determined in the native state and after denaturation in sodium dodecyl sulfate-mercaptoethanol show that the enzymes are monomeric. This conclusion is supported, for the thermophile enzyme, by the result of an electrophoretic analysis of that protein after treatment with dimethylsuberimidate and denaturation. The thermophilic Bacillus malate synthase is considerably more thermostable than its mesophilic counterparts from E. coli, Bacillus licheniformis, and Pseudomonas indigofera. It is, however, markedly labilized by an increase in the ionic strength of the medium brought about by the addition of 0.2 M potassium chloride or in pH above 9. Increased ionic strength has little effect on the thermostability of the mesophilic bacterial malate synthases. These observations provide strong support for the idea that monomeric proteins in thermophiles owe their unusual heat stability to the presence of salt bridges in their tertiary structure. | Structural basis of the thermostability of monomeric malate synthase from a thermophilic Bacillus. Malate synthases from a thermophilic Bacillus and Escherichia coli have been isolated in a high state of purity. Molecular weights of these two proteins determined in the native state and after denaturation in sodium dodecyl sulfate-mercaptoethanol show that the enzymes are monomeric. This conclusion is supported, for the thermophile enzyme, by the result of an electrophoretic analysis of that protein after treatment with dimethylsuberimidate and denaturation. The thermophilic Bacillus malate synthase is considerably more thermostable than its mesophilic counterparts from E. coli, Bacillus licheniformis, and Pseudomonas indigofera. It is, however, markedly labilized by an increase in the ionic strength of the medium brought about by the addition of 0.2 M potassium chloride or in pH above 9. Increased ionic strength has little effect on the thermostability of the mesophilic bacterial malate synthases. These observations provide strong support for the idea that monomeric proteins in thermophiles owe their unusual heat stability to the presence of salt bridges in their tertiary structure. | [
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PMID:28312 | High-dose benzodiazepines in the treatment of severe neurotic anxiety. | There has been a paucity of research in the use of high-dose benzodiazepines in the treatment of severe neurotic anxiety. The author presents five cases, three with excellent and two with poor outcomes. The English and Fench language literature is reviewed and reveals evidence that high-dose benzodiazepines may be useful in the treatment of certain neurotic patients. However, the lack of controlled studies is noted. The author poses several questions important to the future of research on benzodiazepines. | High-dose benzodiazepines in the treatment of severe neurotic anxiety. There has been a paucity of research in the use of high-dose benzodiazepines in the treatment of severe neurotic anxiety. The author presents five cases, three with excellent and two with poor outcomes. The English and Fench language literature is reviewed and reveals evidence that high-dose benzodiazepines may be useful in the treatment of certain neurotic patients. However, the lack of controlled studies is noted. The author poses several questions important to the future of research on benzodiazepines. | [
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PMID:28313 | Multi-clinic double-blind comparison of triazolam (Halcion) and placebo administered for 14 consecutive nights in outpatients with insomnia. | In this multi-clinic double-blind study, patients suffering from insomnia were treated with triazolam 0.5 mg (Halcion) or placebo for 14 days. Four investigators treated 239 patients, 122 on triazolam and 117 on placebo. Thirty-nine patients, 10 on triazolam and 29 on placebo, dropped out for ineffectiveness of the medication and 32 patients, 16 in each group, dropped out for side effects. Analysis of pooled efficacy data showed that triazolam was significantly better than placebo on all efficacy parameters measured, including how much the medication helped the patients sleep, onset of sleep, duration of sleep, duration compared to usual, number of nocturnal awakenings, and feeling of restfulness in the morning. Triazolam did not produce evidence of tolerance development after 2 weeks of treatment. The same variety of side effects occurred on each treatment and primarily included drowsiness, grogginess, headaches, impaired coordination nausea, and dizziness. | Multi-clinic double-blind comparison of triazolam (Halcion) and placebo administered for 14 consecutive nights in outpatients with insomnia. In this multi-clinic double-blind study, patients suffering from insomnia were treated with triazolam 0.5 mg (Halcion) or placebo for 14 days. Four investigators treated 239 patients, 122 on triazolam and 117 on placebo. Thirty-nine patients, 10 on triazolam and 29 on placebo, dropped out for ineffectiveness of the medication and 32 patients, 16 in each group, dropped out for side effects. Analysis of pooled efficacy data showed that triazolam was significantly better than placebo on all efficacy parameters measured, including how much the medication helped the patients sleep, onset of sleep, duration of sleep, duration compared to usual, number of nocturnal awakenings, and feeling of restfulness in the morning. Triazolam did not produce evidence of tolerance development after 2 weeks of treatment. The same variety of side effects occurred on each treatment and primarily included drowsiness, grogginess, headaches, impaired coordination nausea, and dizziness. | [
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] |
PMID:28314 | A microelectronic pH sensor. | This paper presents preliminary data on a new integrated circuit microelectronic pH sensor. The device is extremely miniaturized by the use of integrated circuit technology, and uses the intrinsic hydrogen ion selective properties of the gate insulator material. In order to make the device compatible with aqueous solution monitoring, the silicon dioxide-silicon nitride gate insulator structure is used. The integrated circuit chip was designed, processed, and packaged by a variety of techniques which protect all metal parts from the aqueous solution. Test data are reported on leakage current, sensitivity, reproducibility, linearity, stability, response time, and life. The results indicate that this type of pH sensor may have many significant advantages for biomedical research and application. | A microelectronic pH sensor. This paper presents preliminary data on a new integrated circuit microelectronic pH sensor. The device is extremely miniaturized by the use of integrated circuit technology, and uses the intrinsic hydrogen ion selective properties of the gate insulator material. In order to make the device compatible with aqueous solution monitoring, the silicon dioxide-silicon nitride gate insulator structure is used. The integrated circuit chip was designed, processed, and packaged by a variety of techniques which protect all metal parts from the aqueous solution. Test data are reported on leakage current, sensitivity, reproducibility, linearity, stability, response time, and life. The results indicate that this type of pH sensor may have many significant advantages for biomedical research and application. | [
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PMID:28315 | Fabrication of pH-sensitive implantable electrode by thick film hybrid technology. | We report preliminary results of our experiments directed at fabricating pH-sensitive electrodes suitable for in vivo use by means of thick film screening techniques. Our results show that glass membranes of suitable thickness and possessing nearly theoretical sensitivity to pH can be fabricated by this process. A hybrid electrode structure permits the incorporation of a source follower FET amplifier directly adjacent to the pH membrane, significantly reducing response time and noise pick-up. Extension of the basic electrode structure to accommodate membranes sensitive to other ions is discussed. | Fabrication of pH-sensitive implantable electrode by thick film hybrid technology. We report preliminary results of our experiments directed at fabricating pH-sensitive electrodes suitable for in vivo use by means of thick film screening techniques. Our results show that glass membranes of suitable thickness and possessing nearly theoretical sensitivity to pH can be fabricated by this process. A hybrid electrode structure permits the incorporation of a source follower FET amplifier directly adjacent to the pH membrane, significantly reducing response time and noise pick-up. Extension of the basic electrode structure to accommodate membranes sensitive to other ions is discussed. | [
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PMID:28317 | Use of enzymolysis techniques in studying the mechanical properties of connective tissue components. | The optimum conditions for the selective removal of elastin from connective tissues are described. The process, elastolysis, consists of incubating small samples of connective tissue in buffered saline at ph=8.6 containing 300 microgram/me of a 50-50% mixture of elastase with trypsin inhibitor, for 5-6 hours at room temperature. This process, complimented with other processes for selective removal of lipids, or mucopolysaccharides, or collagen, enables one to examine the contribution of the various components of the connective tissue to its mechanical function. The elastolysis was tested with aortic, valvular and tendon tissues from human, bovine and canine species and it was found that in tensile stress experiments, collagen was unaffected while the low-stress contribution of elastin disappeared. | Use of enzymolysis techniques in studying the mechanical properties of connective tissue components. The optimum conditions for the selective removal of elastin from connective tissues are described. The process, elastolysis, consists of incubating small samples of connective tissue in buffered saline at ph=8.6 containing 300 microgram/me of a 50-50% mixture of elastase with trypsin inhibitor, for 5-6 hours at room temperature. This process, complimented with other processes for selective removal of lipids, or mucopolysaccharides, or collagen, enables one to examine the contribution of the various components of the connective tissue to its mechanical function. The elastolysis was tested with aortic, valvular and tendon tissues from human, bovine and canine species and it was found that in tensile stress experiments, collagen was unaffected while the low-stress contribution of elastin disappeared. | [
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PMID:28318 | Diffusion of fluoride ions in dental enamel at pH 7. | The penetration and uptake of both radioactive (18F) and stable fluoride (19F) in bovine enamel were investigated. Buffered pH 7 NaF solutions were employed. Penetration profiles of both 18F and 19F in enamel were determined by using a sectioning technique. 18F and 19F concentrations decreased exponentially with increasing penetration distance. The uptake of 18F in enamel can be described by a power function of the immersion time, with an average power of 0.76. The results agree reasonably with our previously published theoretical model for the diffusion in enamel, based on simultaneous diffusion in enamel pores and in the hydroxyapatite crystallites. The diffusion coefficients of fluoride ions in enamel obtained from the application of the model to the results presented here, were: D = 0.9 x 10(-17) cm2/s in the crystallites and D' = 3.3 x 10(-10) cm2/s in the enamel pores. An average penetration depth of fluoride ions at pH 7.0 of 8 micron in 4 hours has been calculated. | Diffusion of fluoride ions in dental enamel at pH 7. The penetration and uptake of both radioactive (18F) and stable fluoride (19F) in bovine enamel were investigated. Buffered pH 7 NaF solutions were employed. Penetration profiles of both 18F and 19F in enamel were determined by using a sectioning technique. 18F and 19F concentrations decreased exponentially with increasing penetration distance. The uptake of 18F in enamel can be described by a power function of the immersion time, with an average power of 0.76. The results agree reasonably with our previously published theoretical model for the diffusion in enamel, based on simultaneous diffusion in enamel pores and in the hydroxyapatite crystallites. The diffusion coefficients of fluoride ions in enamel obtained from the application of the model to the results presented here, were: D = 0.9 x 10(-17) cm2/s in the crystallites and D' = 3.3 x 10(-10) cm2/s in the enamel pores. An average penetration depth of fluoride ions at pH 7.0 of 8 micron in 4 hours has been calculated. | [
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PMID:28319 | Characterization of ionomycin as a calcium ionophore. | The ionophorous properties of a new antibiotic, ionomycin, have been studied. It was found that the antibiotic is capable of extracting calcium ion from the bulk of an aqueous phase into an organic phase. The antibiotic also acts as a mobile ion carrier to transport the cation across a solvent barrier. The divalent cation selectivity order for ionomycin as determined by ion competition experiments was found to be: Ca greater than Mg greater than Sr = Ba, where the binding of strontium and barium by the antibiotic is insignificant. The antibiotic also binds La3+ to some extent, but its complexation with monovalent alkali metal ions is negligible. Measurement of the binding of ionomycin with Ca2+ indicates that ionomycin complexes and transports calcium ion in a one to one stoichiometry. | Characterization of ionomycin as a calcium ionophore. The ionophorous properties of a new antibiotic, ionomycin, have been studied. It was found that the antibiotic is capable of extracting calcium ion from the bulk of an aqueous phase into an organic phase. The antibiotic also acts as a mobile ion carrier to transport the cation across a solvent barrier. The divalent cation selectivity order for ionomycin as determined by ion competition experiments was found to be: Ca greater than Mg greater than Sr = Ba, where the binding of strontium and barium by the antibiotic is insignificant. The antibiotic also binds La3+ to some extent, but its complexation with monovalent alkali metal ions is negligible. Measurement of the binding of ionomycin with Ca2+ indicates that ionomycin complexes and transports calcium ion in a one to one stoichiometry. | [
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PMID:28320 | Evidence for thyroid hormone-dependent and independent glucocorticoid actions in cultured cells. Studies on the induction of growth hormone and glutamine synthetase in GH1 cells and tyrosine aminotransferase in Reuber H-35 cells. | The induction of growth hormone synthesis and mRNA by thyroid hormone in cultured GH1 cells is mediated by the thyroid hormone nuclear receptor. In addition, the regulation of the growth hormone response by glucocorticoid is highly dependent on the action of thyroid hormone. To clarify whether thyroid hormone has a general influence on glucocorticoid action in GH1 cells, the glucocorticoid induction of growth hormone and glutamine synthetase was simultaneously examined. In contrast to the growth hormone response, the induction of glutamine synthetase by glucocorticoid was not influenced by thyroid hormone. Both responses appear to be modulated by the glucocorticoid receptor, and thyroid hormone had no influence on nuclear-associated glucocorticoid receptor levels. These results suggest that the thyroid hormone control of glucocorticoid induction of growth hormone may be a selective process, and the nuclear associated receptors for both thyroid and glucocorticoid hormones interrelate to control the growth hormone response. | Evidence for thyroid hormone-dependent and independent glucocorticoid actions in cultured cells. Studies on the induction of growth hormone and glutamine synthetase in GH1 cells and tyrosine aminotransferase in Reuber H-35 cells. The induction of growth hormone synthesis and mRNA by thyroid hormone in cultured GH1 cells is mediated by the thyroid hormone nuclear receptor. In addition, the regulation of the growth hormone response by glucocorticoid is highly dependent on the action of thyroid hormone. To clarify whether thyroid hormone has a general influence on glucocorticoid action in GH1 cells, the glucocorticoid induction of growth hormone and glutamine synthetase was simultaneously examined. In contrast to the growth hormone response, the induction of glutamine synthetase by glucocorticoid was not influenced by thyroid hormone. Both responses appear to be modulated by the glucocorticoid receptor, and thyroid hormone had no influence on nuclear-associated glucocorticoid receptor levels. These results suggest that the thyroid hormone control of glucocorticoid induction of growth hormone may be a selective process, and the nuclear associated receptors for both thyroid and glucocorticoid hormones interrelate to control the growth hormone response. | [
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PMID:28321 | Purification and properties of prolylcarboxypeptidase (angiotensinase C) from human kidney. | Prolylcarboxypeptidase was purified from human kidney 1200-fold with 18% yield. The enzyme had no cathepsin A activity and appeared to be homogeneous in gel electrophoresis. The molecular weight of prolylcarboxypeptidase was estimated to be 115,000 by gel filtration. Under denaturing conditions the enzyme dissociated into subunits of 45,000 and 66,500 molecular weight. The enzyme cleaved benzyloxycarbonyl (Cbz)-Pro-Phe, representing the COOH-terminal end of angiotensin II and des-Asp1-angiotensin II (angiotensin III), at a rate of 31 micronmol/h/mg of protein. The rate of hydrolysis increased when phenylalanine in the N-protected dipeptide was replaced with alanine, valine, or leucine or when the octapeptide angiotensin II or the heptapeptide angiotensin III were the substrates. The enzyme also cleaved the angiotensin II antagonist saralasin (Sar1-Ala8-angiotensin II). The Km values were 1 mM, 2mM, and 0.77 mM with Cbz-Pro-Phe, angiotensin II, and angiotensin III, respectively. The enzyme had an acid pH optimum (4.5 to 5.5), but hydrolyzed angiotensin III at pH 7 at 50% of the optimal rate. Prolylcarboxypeptidase was inhibited by diisopropyl phosphorofluoridate and pepstatin, but not by sequestering agents or -SH reagents. | Purification and properties of prolylcarboxypeptidase (angiotensinase C) from human kidney. Prolylcarboxypeptidase was purified from human kidney 1200-fold with 18% yield. The enzyme had no cathepsin A activity and appeared to be homogeneous in gel electrophoresis. The molecular weight of prolylcarboxypeptidase was estimated to be 115,000 by gel filtration. Under denaturing conditions the enzyme dissociated into subunits of 45,000 and 66,500 molecular weight. The enzyme cleaved benzyloxycarbonyl (Cbz)-Pro-Phe, representing the COOH-terminal end of angiotensin II and des-Asp1-angiotensin II (angiotensin III), at a rate of 31 micronmol/h/mg of protein. The rate of hydrolysis increased when phenylalanine in the N-protected dipeptide was replaced with alanine, valine, or leucine or when the octapeptide angiotensin II or the heptapeptide angiotensin III were the substrates. The enzyme also cleaved the angiotensin II antagonist saralasin (Sar1-Ala8-angiotensin II). The Km values were 1 mM, 2mM, and 0.77 mM with Cbz-Pro-Phe, angiotensin II, and angiotensin III, respectively. The enzyme had an acid pH optimum (4.5 to 5.5), but hydrolyzed angiotensin III at pH 7 at 50% of the optimal rate. Prolylcarboxypeptidase was inhibited by diisopropyl phosphorofluoridate and pepstatin, but not by sequestering agents or -SH reagents. | [
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PMID:28325 | Regulation of glutamine synthetase by dexamethasone in hepatoma tissue culture cells. | In certain lines of hepatoma tissue culture (HTC) cells, glutamine synthetase (EC 6.3.1.2) specific activity is increased 2.5- to 3-fold by the addition of glucocorticoids to the growth media. Actinomycin D blocks both the induction and deinduction of glutamine synthetase by glucocorticoids, suggesting a requirement of RNA synthesis for both processes. Using an antiserum raised against purified rat liver glutamine synthetase, we have precipitated radiolabeled glutamine synthetase from HTC cells. Electrophoresis of the immunoprecipitates on sodium didecyl sulfate-acrylamide gels isolates the subunit of glutamine synthetase and permits the radioactivity in the glutamine synthetase band to be quantitated. Using this technique, we have investigated the effect of dexamethasone, a synthetic glucocorticoid, on the rates of synthesis and degradation of glutamine synthetase. Dexamethasone (10(-7) M) increases the rate of synthesis of glutamine synthetase 2- to 3-fold but has no effect on the rate of glutamine synthetase degradation. The rates of total cell protein synthesis and degradation are not significantly affected by dexamethasone. The presence of actinomycin D at the time of removal of dexamethasone from induced cells prevents the fall in the induced rate of synthesis of glutamine synthetase normally seen when the inhibitor is removed from the culture medium. The regulation of glutamine synthetase by dexamethasone has been compared to the regulation of another dexamethasone-inducible enzyme in HTC cells, tyrosine aminotransferase, and been found to be similar in all parameters studied. | Regulation of glutamine synthetase by dexamethasone in hepatoma tissue culture cells. In certain lines of hepatoma tissue culture (HTC) cells, glutamine synthetase (EC 6.3.1.2) specific activity is increased 2.5- to 3-fold by the addition of glucocorticoids to the growth media. Actinomycin D blocks both the induction and deinduction of glutamine synthetase by glucocorticoids, suggesting a requirement of RNA synthesis for both processes. Using an antiserum raised against purified rat liver glutamine synthetase, we have precipitated radiolabeled glutamine synthetase from HTC cells. Electrophoresis of the immunoprecipitates on sodium didecyl sulfate-acrylamide gels isolates the subunit of glutamine synthetase and permits the radioactivity in the glutamine synthetase band to be quantitated. Using this technique, we have investigated the effect of dexamethasone, a synthetic glucocorticoid, on the rates of synthesis and degradation of glutamine synthetase. Dexamethasone (10(-7) M) increases the rate of synthesis of glutamine synthetase 2- to 3-fold but has no effect on the rate of glutamine synthetase degradation. The rates of total cell protein synthesis and degradation are not significantly affected by dexamethasone. The presence of actinomycin D at the time of removal of dexamethasone from induced cells prevents the fall in the induced rate of synthesis of glutamine synthetase normally seen when the inhibitor is removed from the culture medium. The regulation of glutamine synthetase by dexamethasone has been compared to the regulation of another dexamethasone-inducible enzyme in HTC cells, tyrosine aminotransferase, and been found to be similar in all parameters studied. | [
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PMID:28326 | Biosynthesis in Escherichia coli of sn-glycerol 3-phosphate, a precursor of phospholipid. Kinetic characterization of wild type and feedback-resistant forms of the biosynthetic sn-glycerol-3-phosphate dehydrogenase. | Homogeneous wild type and feedback-resistant forms of the biosynthetic sn-glycerol 3-phosphate (glycerol-P) dehydrogenase of Escherichia coli (EC1.1.1.8) were subjected to two-substrate kinetic analysis. The kinetics of the NADPH-dependent reduction of dihydroxyacetone phosphate (dihydroxyacetone-P) and of the NADP-dependent oxidation of glycerol-P indicate that these reactions proceed by a sequential mechanism. Glycerol-P was a competitive inhibitor with respect to dihydroxyacetone-P for both enzymes. The wild type and feedback-resistant glycerol-P dehydrogenases had Ki values for glycerol-P of 4.4 micrometer and 43 micrometer, respectively. Therefore, the sensitivity of the wild type activity and reduced sensitivity of the feedback-resistant activity, both noted previously in crude extracts, were inherent properties of the enzymes. The patterns of product inhibition for both enzymes were identical, and the difference in the inhibition constants for glycerol-P occurred without significant alteration of any other kinetic constant determined. Kinetic mechanisms consistent with the patterns of product inhibition violated Haldane relationships and other kinetic relationships. These discrepancies suggest that glycerol-P inhibition occurs at a site distinct from the active site. The pH dependencies of the Km for dihydroxyacetone-P and the Ki for glycerol-P were markedly different suggesting the existence of an allosteric site. The addition of glycerol-P in the presence of NADPH stabilized both enzymes against thermal inactivation. Half-maximal stabilization was provided by 5 micrometer and 50 micrometer glycerol-P for the wild type and feedback-resistant enzymes, respectively. These kinetic data, considered in conjunction with previous physiologic and genetic data, indicate that the synthesis of glycerol-P is regulated in vivo by glycerol-P inhibition of the glycerol-P dehydrogenase. The data suggest that glycerol-P inhibition occurs at an allosteric, regulatory site. | Biosynthesis in Escherichia coli of sn-glycerol 3-phosphate, a precursor of phospholipid. Kinetic characterization of wild type and feedback-resistant forms of the biosynthetic sn-glycerol-3-phosphate dehydrogenase. Homogeneous wild type and feedback-resistant forms of the biosynthetic sn-glycerol 3-phosphate (glycerol-P) dehydrogenase of Escherichia coli (EC1.1.1.8) were subjected to two-substrate kinetic analysis. The kinetics of the NADPH-dependent reduction of dihydroxyacetone phosphate (dihydroxyacetone-P) and of the NADP-dependent oxidation of glycerol-P indicate that these reactions proceed by a sequential mechanism. Glycerol-P was a competitive inhibitor with respect to dihydroxyacetone-P for both enzymes. The wild type and feedback-resistant glycerol-P dehydrogenases had Ki values for glycerol-P of 4.4 micrometer and 43 micrometer, respectively. Therefore, the sensitivity of the wild type activity and reduced sensitivity of the feedback-resistant activity, both noted previously in crude extracts, were inherent properties of the enzymes. The patterns of product inhibition for both enzymes were identical, and the difference in the inhibition constants for glycerol-P occurred without significant alteration of any other kinetic constant determined. Kinetic mechanisms consistent with the patterns of product inhibition violated Haldane relationships and other kinetic relationships. These discrepancies suggest that glycerol-P inhibition occurs at a site distinct from the active site. The pH dependencies of the Km for dihydroxyacetone-P and the Ki for glycerol-P were markedly different suggesting the existence of an allosteric site. The addition of glycerol-P in the presence of NADPH stabilized both enzymes against thermal inactivation. Half-maximal stabilization was provided by 5 micrometer and 50 micrometer glycerol-P for the wild type and feedback-resistant enzymes, respectively. These kinetic data, considered in conjunction with previous physiologic and genetic data, indicate that the synthesis of glycerol-P is regulated in vivo by glycerol-P inhibition of the glycerol-P dehydrogenase. The data suggest that glycerol-P inhibition occurs at an allosteric, regulatory site. | [
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PMID:28329 | Bovine thymus poly(adenosine diphosphate ribose) polymerase. | About 1,300-fold purification of poly(adenosine diphosphate ribose) polymerase has been achieved from the extract of bovine thymus with a recovery of 10 to 20%. The final preparation has a purity of 99%, and the enzyme is composed of a single peptide with a molecular weight of 130,000. The purified enzyme required NAD+, Mg2+, a thiol compound, DNA, and histones for full activity. Whereas DNA is essential for activation of the enzyme, histones are not. The observed stimulation of the reaction by histones is shown to be due to masking of the inhibitory effect of contaminating denartured DNA in native DNA preparation. The concentration of DNA required for half-maximal enzyme activity (apparent Km for DNA) is proportional to the concentration of enzyme in the reaction mixture. The minimum estimation of the number of nucleotide pairs of DNA required for half-maximal activation of one enzyme molecule is 220 to 240 for bulk of calf thymus DNA, while the value is 10 for a calf thymus DNA fraction, "active DNA," which was separated from the enzyme fraction in a stage of the purification. These results suggest that the enzyme is activated by binding to a specific site on calf thymus DNA. The apparent Km for NAD+ and the maximum velocity of the enzyme are estimated to be 60 micrometer and 0.91 mumolper min per mg, respectively. | Bovine thymus poly(adenosine diphosphate ribose) polymerase. About 1,300-fold purification of poly(adenosine diphosphate ribose) polymerase has been achieved from the extract of bovine thymus with a recovery of 10 to 20%. The final preparation has a purity of 99%, and the enzyme is composed of a single peptide with a molecular weight of 130,000. The purified enzyme required NAD+, Mg2+, a thiol compound, DNA, and histones for full activity. Whereas DNA is essential for activation of the enzyme, histones are not. The observed stimulation of the reaction by histones is shown to be due to masking of the inhibitory effect of contaminating denartured DNA in native DNA preparation. The concentration of DNA required for half-maximal enzyme activity (apparent Km for DNA) is proportional to the concentration of enzyme in the reaction mixture. The minimum estimation of the number of nucleotide pairs of DNA required for half-maximal activation of one enzyme molecule is 220 to 240 for bulk of calf thymus DNA, while the value is 10 for a calf thymus DNA fraction, "active DNA," which was separated from the enzyme fraction in a stage of the purification. These results suggest that the enzyme is activated by binding to a specific site on calf thymus DNA. The apparent Km for NAD+ and the maximum velocity of the enzyme are estimated to be 60 micrometer and 0.91 mumolper min per mg, respectively. | [
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PMID:28332 | Actin filament destruction by osmium tetroxide. | We have studied the destruction of purified muscle actin filaments by osmium tetroxide (OsO4) to develop methods to preserve actin filaments during preparation for electron microscopy. Actin filaments are fragmented during exposure to OsO4. This causes the viscosity of solutions of actin filaments to decrease, ultimately to zero, and provides a convenient quantitative assay to analyze the reaction. The rate of filament destruction is determined by the OsO4 concentration, temperature, buffer type and concentration, and pH. Filament destruction is minimized by treatment with a low concentration of OsO4 in sodium phosphate buffer, pH 6.0, at 0 degrees C. Under these conditions, the viscosity of actin filament solutions is stable and actin filaments retain their straight, unbranched structure, even after dehydration and embedding. Under more severe conditions, the straight actin filaments are converted into what look like the microfilament networks commonly observed in cells fixed with OsO4. Destruction of actin filaments can be inhibited by binding tropomyosin to the actin. Cross-linking the actin molecules within a filament with glutaraldehyde does not prevent their destruction by OsO4. The viscosity decrease requires the continued presence of free OsO4. During the time of the viscosity change, OsO4 is reduced and the sulfur-containing amino acids of actin are oxidized, but little of the osmium is bound to the actin. Over a much longer time span, the actin molecules are split into discrete peptides. | Actin filament destruction by osmium tetroxide. We have studied the destruction of purified muscle actin filaments by osmium tetroxide (OsO4) to develop methods to preserve actin filaments during preparation for electron microscopy. Actin filaments are fragmented during exposure to OsO4. This causes the viscosity of solutions of actin filaments to decrease, ultimately to zero, and provides a convenient quantitative assay to analyze the reaction. The rate of filament destruction is determined by the OsO4 concentration, temperature, buffer type and concentration, and pH. Filament destruction is minimized by treatment with a low concentration of OsO4 in sodium phosphate buffer, pH 6.0, at 0 degrees C. Under these conditions, the viscosity of actin filament solutions is stable and actin filaments retain their straight, unbranched structure, even after dehydration and embedding. Under more severe conditions, the straight actin filaments are converted into what look like the microfilament networks commonly observed in cells fixed with OsO4. Destruction of actin filaments can be inhibited by binding tropomyosin to the actin. Cross-linking the actin molecules within a filament with glutaraldehyde does not prevent their destruction by OsO4. The viscosity decrease requires the continued presence of free OsO4. During the time of the viscosity change, OsO4 is reduced and the sulfur-containing amino acids of actin are oxidized, but little of the osmium is bound to the actin. Over a much longer time span, the actin molecules are split into discrete peptides. | [
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PMID:28335 | Interference in word associations in schizophrenia. | Assessed the effect of response interference on the word associations of male and female process and reactive schizophrenics in two studies that used the difference in associative disturbances between high and low interference (low and high commonality stimulus words) as the measure. The reactives showed a significantly greater increase in disturbances in the high interference condition than did process schizophrenics in both studies. These results occurred in process and reactive groups that did not differ in age, IQ, institutionalization, and current level of physiological arousal and symptom severity in Study I. Findings supported predictions from a qualitative differences theory of cognitive deficit in schizophrenia. | Interference in word associations in schizophrenia. Assessed the effect of response interference on the word associations of male and female process and reactive schizophrenics in two studies that used the difference in associative disturbances between high and low interference (low and high commonality stimulus words) as the measure. The reactives showed a significantly greater increase in disturbances in the high interference condition than did process schizophrenics in both studies. These results occurred in process and reactive groups that did not differ in age, IQ, institutionalization, and current level of physiological arousal and symptom severity in Study I. Findings supported predictions from a qualitative differences theory of cognitive deficit in schizophrenia. | [
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PMID:28336 | Psychophysiological responses to presentation of a caged snake among behaviorally avoidant and non-avoidant college students. | Sixty-six coeds who reported fear of snakes on a paper-and-pencil fear inventory were exposed to a Physiological Response Test, during which their electrodermal and cardiac responses to a neutral stimulus and a caged snake were recorded. Half of these coeds then were exposed to a representative Behavioral Avoidance Test, on the basis of which they were classified as avoidant, as non-avoidant, or as neither. Those remaining were classified similarly with an Incentive Behavioral Avoidation Test, before which each was offered an incentive for displaying non-fearfulness. The electrodermal response data showed that students classifed as avoidant had not been more responsive to snake confrontation than the the students classified as non-avoidant. The cardiac response data showed that avoidant Ss had been relatively more responsive to the snake cue, but that differential responsiveness was not robust. These results held for both behavioral avoidance tests. | Psychophysiological responses to presentation of a caged snake among behaviorally avoidant and non-avoidant college students. Sixty-six coeds who reported fear of snakes on a paper-and-pencil fear inventory were exposed to a Physiological Response Test, during which their electrodermal and cardiac responses to a neutral stimulus and a caged snake were recorded. Half of these coeds then were exposed to a representative Behavioral Avoidance Test, on the basis of which they were classified as avoidant, as non-avoidant, or as neither. Those remaining were classified similarly with an Incentive Behavioral Avoidation Test, before which each was offered an incentive for displaying non-fearfulness. The electrodermal response data showed that students classifed as avoidant had not been more responsive to snake confrontation than the the students classified as non-avoidant. The cardiac response data showed that avoidant Ss had been relatively more responsive to the snake cue, but that differential responsiveness was not robust. These results held for both behavioral avoidance tests. | [
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PMID:28337 | Facilitating and debilitating test anxiety among college students and volunteers for desensitization workshops. | Administered the Alpert-Haber Achievement Anxiety Test (AAT) to 54 students who expressed interest in participating in a test anxiety desensitization workshop. In addition, 182 students from the general college population were tested. Results indicated that both the debilitating and facilitating (AAT) scales were higher for the self-referred volunteer group. These data indicate that these scales are useful in distinguishing self-referred volunteers for behavior modification workshops from a general college population. In addition, the scales of the AAT were correlated with the number of sessions attended by those students who enrolled in the desensitization groups. Results indicated no relationship between attrition and debilitating anxiety. There was a correlation of r = .318 p less than .15 between facilitating anxiety scores and number of sessions attended. It is suggested that facilitating anxiety can function as a measure of S's ego strength in predicting workshop attendance. | Facilitating and debilitating test anxiety among college students and volunteers for desensitization workshops. Administered the Alpert-Haber Achievement Anxiety Test (AAT) to 54 students who expressed interest in participating in a test anxiety desensitization workshop. In addition, 182 students from the general college population were tested. Results indicated that both the debilitating and facilitating (AAT) scales were higher for the self-referred volunteer group. These data indicate that these scales are useful in distinguishing self-referred volunteers for behavior modification workshops from a general college population. In addition, the scales of the AAT were correlated with the number of sessions attended by those students who enrolled in the desensitization groups. Results indicated no relationship between attrition and debilitating anxiety. There was a correlation of r = .318 p less than .15 between facilitating anxiety scores and number of sessions attended. It is suggested that facilitating anxiety can function as a measure of S's ego strength in predicting workshop attendance. | [
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PMID:28339 | Reduction in enamel dissolution by liquorice and glycyrrhizinic acid. | Liquorice extracts and confections reduced enamel dissolution in acidic buffers and saliva/glucose incubations by a direct effect on solubility, and by inhibiting the fall in pH on incubation. These actions may be attributed to the solubility-reducing, glycolysis-inhibiting, and buffering properties of glycyrrhizinic acid, a constituent of liquorice. | Reduction in enamel dissolution by liquorice and glycyrrhizinic acid. Liquorice extracts and confections reduced enamel dissolution in acidic buffers and saliva/glucose incubations by a direct effect on solubility, and by inhibiting the fall in pH on incubation. These actions may be attributed to the solubility-reducing, glycolysis-inhibiting, and buffering properties of glycyrrhizinic acid, a constituent of liquorice. | [
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PMID:28340 | An electrochemical study on the human dental enamel with special reference to isoelectric point. | In an attempt to make a dynamic study of the isoelectric point and the chargeability of human dental enamel, an electrochemical approach was utilized. Zeta potential of three kinds of the enamel was measured by a streaming potential method. As a result, these isoelectric points could be decided. | An electrochemical study on the human dental enamel with special reference to isoelectric point. In an attempt to make a dynamic study of the isoelectric point and the chargeability of human dental enamel, an electrochemical approach was utilized. Zeta potential of three kinds of the enamel was measured by a streaming potential method. As a result, these isoelectric points could be decided. | [
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PMID:28341 | Effect of 4.5--year use of xylitol and sorbitol on plaque. | The pH values of xylitol-containing plaque suspensions of persons who habitually used xylitol and sorbitol during 3.2 to 4.5 years did not significantly differ from those observed with suspensions containing no added carbohydrates. Sorbitol produced in 22-hour incubations pH values as low as 3.9 to 5.5. The activity of plaque xylitol dehydrogenase was almost nil, whereas sorbitol dehydrogenase activity was higher. The nonacidogenic nature of xylitol in relation to plaque did not change in prolonged use of xylitol. | Effect of 4.5--year use of xylitol and sorbitol on plaque. The pH values of xylitol-containing plaque suspensions of persons who habitually used xylitol and sorbitol during 3.2 to 4.5 years did not significantly differ from those observed with suspensions containing no added carbohydrates. Sorbitol produced in 22-hour incubations pH values as low as 3.9 to 5.5. The activity of plaque xylitol dehydrogenase was almost nil, whereas sorbitol dehydrogenase activity was higher. The nonacidogenic nature of xylitol in relation to plaque did not change in prolonged use of xylitol. | [
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PMID:28342 | Effect of progestins on androgen delta4-3-ketosteroid-5alpha-A-ring reductase system in rat oral mucosa. | Rat oral mucosa microsomal delta4-3-ketosteroid-5alpha-A-ring reductase enzyme system, reducing testosterone and 4-androstenedione, was found to be inducible by systemic administration of medroxyprogesterone acetate (MPA). MPA, when used in a mixture with testosterone and/or 4-androstenedione in vitro, acted as a competitive inhibitor of the reduction of these substrates. | Effect of progestins on androgen delta4-3-ketosteroid-5alpha-A-ring reductase system in rat oral mucosa. Rat oral mucosa microsomal delta4-3-ketosteroid-5alpha-A-ring reductase enzyme system, reducing testosterone and 4-androstenedione, was found to be inducible by systemic administration of medroxyprogesterone acetate (MPA). MPA, when used in a mixture with testosterone and/or 4-androstenedione in vitro, acted as a competitive inhibitor of the reduction of these substrates. | [
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PMID:28343 | Child abuse and dentistry: orofacial trauma and its recognition by dentists. | Orofacial trauma was found in 49% of 260 documented cases of child abuse seen during of five-year period at the Children's Hospital Medical Center, Boston. An additional 16% of the cases involved head trauma; the total percentage of head and facial trauma was 65%. Head or facial trauma was the principal reason for admission to the hospital in 45% of the cases. A survey of 537 dentists in Massachusetts showed that the majority were unaware of their legal and social responsibilities to report suspected cases of child abuse. Eleven percent of all dentists surveyed saw orofacial trauma cases that were of a suspicious nature, by only 22 confirmed cases of child abuse were noted by the dentists. Of these, only four were reported to social agencies. In general, oral surgeons and pedodontists saw a higher percentage of these cases and were more aware of their responsibilities than were general practitioners. | Child abuse and dentistry: orofacial trauma and its recognition by dentists. Orofacial trauma was found in 49% of 260 documented cases of child abuse seen during of five-year period at the Children's Hospital Medical Center, Boston. An additional 16% of the cases involved head trauma; the total percentage of head and facial trauma was 65%. Head or facial trauma was the principal reason for admission to the hospital in 45% of the cases. A survey of 537 dentists in Massachusetts showed that the majority were unaware of their legal and social responsibilities to report suspected cases of child abuse. Eleven percent of all dentists surveyed saw orofacial trauma cases that were of a suspicious nature, by only 22 confirmed cases of child abuse were noted by the dentists. Of these, only four were reported to social agencies. In general, oral surgeons and pedodontists saw a higher percentage of these cases and were more aware of their responsibilities than were general practitioners. | [
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PMID:28346 | [A new instrument for measurement of actual instantaneous pH in obstetric (author's transl)]. | The authors present a new instrument for measurement of actual instantaneous pH in obstetrics. It has been developped to avoid most errors of the usual scalp-blood sampling. Its advantages are:--Aspiration is manual and controlled.--Results are obtained within 10--15 seconds. A comparative study with two other pH-meters has demonstrated an excellent correlation and reliability of this new instrument. The authors consider the method as simple, functional and reliable, all favourable factors for routine use. | [A new instrument for measurement of actual instantaneous pH in obstetric (author's transl)]. The authors present a new instrument for measurement of actual instantaneous pH in obstetrics. It has been developped to avoid most errors of the usual scalp-blood sampling. Its advantages are:--Aspiration is manual and controlled.--Results are obtained within 10--15 seconds. A comparative study with two other pH-meters has demonstrated an excellent correlation and reliability of this new instrument. The authors consider the method as simple, functional and reliable, all favourable factors for routine use. | [
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PMID:28350 | Polyarteritis: A cause of nerve palsy in the extremity. | The association between polyarteritis and peripheral neuropathy may be overlooked in the clinical assessment of nerve lesions in the extremity. Nerve palsy may be the initial presenting complaint in polyarteritis nodosa. A case is presented which demonstrates the pathological process. A method for early recognition and treatment is suggested. | Polyarteritis: A cause of nerve palsy in the extremity. The association between polyarteritis and peripheral neuropathy may be overlooked in the clinical assessment of nerve lesions in the extremity. Nerve palsy may be the initial presenting complaint in polyarteritis nodosa. A case is presented which demonstrates the pathological process. A method for early recognition and treatment is suggested. | [
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PMID:28369 | Low molecular weight C1q-precipitins in hypocomplementemic vasculitis-urticaria syndrome: partial purification and characterization as immunoglobulin. | A lupus-like syndrome involving chronic urticaria with cutaneous vasculitis, systemic symptoms, hypocomplementemia with preferential depletion of C1q, and low m.w. (7S) C1q-precipitins has recently been defined. The C1q-precipitin activity (C1q-p) seems to represent a diagnostic marker of the disease, but its chemical nature is not yet clear. We have partially purified and characterized C1q-p from the serum of two patients with this syndrome and compared its activity with the C1q-precipitating activity of aggregated human gamma-globulin (AHGG) anti-C1q antibodies, and several polynucleotides including DNA and polyinosinic acid. C1q-p was found to partition with IgG during precipitation by ammonium sulfate and low ionic strength buffer as well as during column chromatography on DEAE-cellulose and G-200 Sephadex. Like AHGG, but in complete contrast to the polynucleotides, the C1q-precipitating activity of C1q-p was sensitive to pepsin, trypsin, and acidic conditions, but unaffected by DNAse or RNAse; the C1q-precipitating activity of anti-C1q antibody was not diminished by any of these procedures. Thus, C1q-p consists of gamma-migrating protein of low m.w., and its C1q-precipitating activity is indistinguishable from that of AHGG. These results are consistent with the concept that C1q-p is comprised, at least in part, of IgG that binds C1q via the Fc portion of the molecule. | Low molecular weight C1q-precipitins in hypocomplementemic vasculitis-urticaria syndrome: partial purification and characterization as immunoglobulin. A lupus-like syndrome involving chronic urticaria with cutaneous vasculitis, systemic symptoms, hypocomplementemia with preferential depletion of C1q, and low m.w. (7S) C1q-precipitins has recently been defined. The C1q-precipitin activity (C1q-p) seems to represent a diagnostic marker of the disease, but its chemical nature is not yet clear. We have partially purified and characterized C1q-p from the serum of two patients with this syndrome and compared its activity with the C1q-precipitating activity of aggregated human gamma-globulin (AHGG) anti-C1q antibodies, and several polynucleotides including DNA and polyinosinic acid. C1q-p was found to partition with IgG during precipitation by ammonium sulfate and low ionic strength buffer as well as during column chromatography on DEAE-cellulose and G-200 Sephadex. Like AHGG, but in complete contrast to the polynucleotides, the C1q-precipitating activity of C1q-p was sensitive to pepsin, trypsin, and acidic conditions, but unaffected by DNAse or RNAse; the C1q-precipitating activity of anti-C1q antibody was not diminished by any of these procedures. Thus, C1q-p consists of gamma-migrating protein of low m.w., and its C1q-precipitating activity is indistinguishable from that of AHGG. These results are consistent with the concept that C1q-p is comprised, at least in part, of IgG that binds C1q via the Fc portion of the molecule. | [
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PMID:28370 | Characterization of human hairbulb tyrosinase: properties of normal and albino enzyme. | Human hairbulb tyrosinase from normally pigmented and tyrosinase-positive oculocutaneous albino (TPA) hairbulbs was studied by single hairbulb and by pooled hairbulb assay procedures. The response to temperature and pH was the same for TPA and normal enzyme. The Km for tyrosine as substrate and the Km or dopa as cofactor was the same for TPA and normal enzyme. These studies show that TPA tyrosinase is kinetically normal and that the defect with this form of albinism must be elsewhere in the melanin pathway. | Characterization of human hairbulb tyrosinase: properties of normal and albino enzyme. Human hairbulb tyrosinase from normally pigmented and tyrosinase-positive oculocutaneous albino (TPA) hairbulbs was studied by single hairbulb and by pooled hairbulb assay procedures. The response to temperature and pH was the same for TPA and normal enzyme. The Km for tyrosine as substrate and the Km or dopa as cofactor was the same for TPA and normal enzyme. These studies show that TPA tyrosinase is kinetically normal and that the defect with this form of albinism must be elsewhere in the melanin pathway. | [
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PMID:28372 | Endogenous angiotensin I concentration in human plasma. | A reliable radioimmunoassay of endogenous angiotensin I concentration in plasma, extracted on a Dowex-resin at pH 7.4, is described. The concentration of angiotensin I in the pH 7.4-extracted plasma samples is significantly correlated with the angiotensin I concentration in the samples extracted at pH 5.5, the pH optimum of the in vitro reaction of human renin with human renin substrate. The presence of immunoreactive angiotensin I-like material in plasma and the relatively high cross-reaction of renin substrate with the anti-angiotensin I antiserum necessitates a chromatographic purification on a Dowex resin. The normal range found for angiotensin I in venous blood of apparently normal, male subjects was 25 to 143 pg/ml. A significant correlation (r = 0.78; p less than 0.001) between PA-I and PRA was found in normal subjects. No differences (p greater than 0.10) between arterial and venous angiotensin I concentration were observed in hypertensive patients. | Endogenous angiotensin I concentration in human plasma. A reliable radioimmunoassay of endogenous angiotensin I concentration in plasma, extracted on a Dowex-resin at pH 7.4, is described. The concentration of angiotensin I in the pH 7.4-extracted plasma samples is significantly correlated with the angiotensin I concentration in the samples extracted at pH 5.5, the pH optimum of the in vitro reaction of human renin with human renin substrate. The presence of immunoreactive angiotensin I-like material in plasma and the relatively high cross-reaction of renin substrate with the anti-angiotensin I antiserum necessitates a chromatographic purification on a Dowex resin. The normal range found for angiotensin I in venous blood of apparently normal, male subjects was 25 to 143 pg/ml. A significant correlation (r = 0.78; p less than 0.001) between PA-I and PRA was found in normal subjects. No differences (p greater than 0.10) between arterial and venous angiotensin I concentration were observed in hypertensive patients. | [
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PMID:28373 | Supersaturation of urine with uric acid and urate: response to a uricosuric diuretic. | In order to assess the possibility that treatment with the uricosuric diuretic ticrynafen (tienilic acid) could lead to UA or MSU crystalluria, the degree of urinary supersaturation with respect to these crystalloids was assessed in persons receiving the diuretic for 1 week, and the results were compared with similar data generated from the use of probenecid. Initially, only probenecid significantly increased the degree of urinary suspersaturation with respect to MSU, and after adjustment of urine pH values to 5.5, probenecid also increased the degree of urinary supersaturation with respect to nonionized UA. At a pH of 5.5, the urine was significantly more supersaturated with nonionized UA after a single dose of probenecid than after ticrynafen (tienilic acid). Ticrynafen never significantly affected the degree of urinary supersaturation with respect to UA or MSU. Neither agent affected small amounts of "colloidal" or "bound" urinary urate. Insofar as the degree of urinary supersaturation with these crystalloids predisposes to crystalluria and calculus formation, ticrynafen (tienilic acid) appears to present no increased risk. | Supersaturation of urine with uric acid and urate: response to a uricosuric diuretic. In order to assess the possibility that treatment with the uricosuric diuretic ticrynafen (tienilic acid) could lead to UA or MSU crystalluria, the degree of urinary supersaturation with respect to these crystalloids was assessed in persons receiving the diuretic for 1 week, and the results were compared with similar data generated from the use of probenecid. Initially, only probenecid significantly increased the degree of urinary suspersaturation with respect to MSU, and after adjustment of urine pH values to 5.5, probenecid also increased the degree of urinary supersaturation with respect to nonionized UA. At a pH of 5.5, the urine was significantly more supersaturated with nonionized UA after a single dose of probenecid than after ticrynafen (tienilic acid). Ticrynafen never significantly affected the degree of urinary supersaturation with respect to UA or MSU. Neither agent affected small amounts of "colloidal" or "bound" urinary urate. Insofar as the degree of urinary supersaturation with these crystalloids predisposes to crystalluria and calculus formation, ticrynafen (tienilic acid) appears to present no increased risk. | [
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PMID:28376 | Renal regulation of acid-base balance in a freshwater fish (1). | Intra-arterial injection of a fixed acid load caused only a short-lived (less than 2h) disturbance of blood pH but a long lived (2-3 days) elevation of urinary acid excretion in freshwater trout (Salmo gairdneri). The renal response comprised an immediate increase in acid output in the form of titratable acidity minus bicarbonate, and a slower rise in acid output in the form of ammonia. The total elevation in urinary acid efflux over 72h was such that no other mechanism besides renal function is needed to explain the ultimate compensation of this experimental acid-base disturbance. | Renal regulation of acid-base balance in a freshwater fish (1). Intra-arterial injection of a fixed acid load caused only a short-lived (less than 2h) disturbance of blood pH but a long lived (2-3 days) elevation of urinary acid excretion in freshwater trout (Salmo gairdneri). The renal response comprised an immediate increase in acid output in the form of titratable acidity minus bicarbonate, and a slower rise in acid output in the form of ammonia. The total elevation in urinary acid efflux over 72h was such that no other mechanism besides renal function is needed to explain the ultimate compensation of this experimental acid-base disturbance. | [
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PMID:28377 | The isolation of a Bwamba virus variant from man in Western Kenya. | A bwamba group virus was isolated from the blood of a febrile child on the Kano Plain, Kenya. The isolate (NY-45), closely resembling Bwamba, established infection in both Anopheles gambiae and Mansonia uniformis. Neither the Bwamba nor the Pongola prototype strains grew in both species. In gel-diffusion tests NY-45 virus passaged through mosquitoes exhibited a line of identity with Pongola antiserum. In contrast no cross-reaction was observed with NY-45 virus which had not previously been passaged through mosquitoes. | The isolation of a Bwamba virus variant from man in Western Kenya. A bwamba group virus was isolated from the blood of a febrile child on the Kano Plain, Kenya. The isolate (NY-45), closely resembling Bwamba, established infection in both Anopheles gambiae and Mansonia uniformis. Neither the Bwamba nor the Pongola prototype strains grew in both species. In gel-diffusion tests NY-45 virus passaged through mosquitoes exhibited a line of identity with Pongola antiserum. In contrast no cross-reaction was observed with NY-45 virus which had not previously been passaged through mosquitoes. | [
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PMID:28378 | Effect of a new benzodiazepine bromazepam on locomotor performance and brain monoamine metabolism. | Administration of a single dose (10 mg/kg) of a relatively new benzodiazepine, bromazepam to rats markedly suppressed their spontaneous locomotor activity. Hypomobility became apparent 15 min after the injection and remained significantly lower during the period of observation for 6 hours when locomotor activity was 27% of controls. Following 2 hours after bromazepam treatment, no change was noted in tyrosine levels and tyrosine hydroxylase activity in striatum or rate of catecholamine synthesis in synaptosomal preparation (P2 pellet). However, the endogenous levels of norepinephrine, dopamine and 5-hydroxytryptamine were significantly increased not only in several brain areas examined, but also in P2 pellet. Bromazepam failed to change 3H-norepinephrine and 3H-5-hydroxytryptamine uptake in synaptosomes suggesting that the increased levels of monoamines are not related to laterations in uptake mechanisms, but probably to a diminished release. This is supported by the data on striatal homovanillic acid and whole brain 4-hydroxy-3-methoxyphenyl glycol whose concentrations were significantly lowered following a single injection of this benzodiazepine. However, bromazepam increased 5-hydroxyindole-acetic acid levels in hypothalamus, mid-brain and pons-medulla. The present study demonstrates that bromazepam elicits its tranquilizing action by lowering the release of catecholamines in brain; however, its anti-anxiety action might be associated with a reduction in 5-hydroxytryptamine turn over. Our data also suggest that bromazepam is almost as potent as diazepam in altering the metabolism of certain putative neurotransmitters in brain. | Effect of a new benzodiazepine bromazepam on locomotor performance and brain monoamine metabolism. Administration of a single dose (10 mg/kg) of a relatively new benzodiazepine, bromazepam to rats markedly suppressed their spontaneous locomotor activity. Hypomobility became apparent 15 min after the injection and remained significantly lower during the period of observation for 6 hours when locomotor activity was 27% of controls. Following 2 hours after bromazepam treatment, no change was noted in tyrosine levels and tyrosine hydroxylase activity in striatum or rate of catecholamine synthesis in synaptosomal preparation (P2 pellet). However, the endogenous levels of norepinephrine, dopamine and 5-hydroxytryptamine were significantly increased not only in several brain areas examined, but also in P2 pellet. Bromazepam failed to change 3H-norepinephrine and 3H-5-hydroxytryptamine uptake in synaptosomes suggesting that the increased levels of monoamines are not related to laterations in uptake mechanisms, but probably to a diminished release. This is supported by the data on striatal homovanillic acid and whole brain 4-hydroxy-3-methoxyphenyl glycol whose concentrations were significantly lowered following a single injection of this benzodiazepine. However, bromazepam increased 5-hydroxyindole-acetic acid levels in hypothalamus, mid-brain and pons-medulla. The present study demonstrates that bromazepam elicits its tranquilizing action by lowering the release of catecholamines in brain; however, its anti-anxiety action might be associated with a reduction in 5-hydroxytryptamine turn over. Our data also suggest that bromazepam is almost as potent as diazepam in altering the metabolism of certain putative neurotransmitters in brain. | [
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PMID:28379 | Biosynthesis and processing of presumed neurosecretory proteins in single identified neurons of Aplysia californica. | The biosynthesis and processing of low molecular weight protein (presumed neurosecretory protein) in cells R15, R14 and L11 of Aplysia californica was studied at high resolution by polyacrylamide slab gel electrophoresis in sodium dodecylsulfate. The number of low molecular weight proteins detected in each cell ranges from 3 in R14 and L11 to 5 to 6 in R15. In each of the cells studied, the low molecular weight protein consists of a primary precursor of ca. 12,000 daltons, and its proteolytic processing products. In each cell, the smallest protein, or in the case of R14, one of the two smallest proteins, accumulates to a significant extent, suggesting that it might correspond to a final processed neurohormone. In cell R15, the biosynthesis of the primary precursor and its subsequent processing to smaller peptides is largely unaffected by removal of extracellular calcium, by replacement of calcium with cobalt or by inhibition of spontaneous bursting via stimulation of the brachial nerve. | Biosynthesis and processing of presumed neurosecretory proteins in single identified neurons of Aplysia californica. The biosynthesis and processing of low molecular weight protein (presumed neurosecretory protein) in cells R15, R14 and L11 of Aplysia californica was studied at high resolution by polyacrylamide slab gel electrophoresis in sodium dodecylsulfate. The number of low molecular weight proteins detected in each cell ranges from 3 in R14 and L11 to 5 to 6 in R15. In each of the cells studied, the low molecular weight protein consists of a primary precursor of ca. 12,000 daltons, and its proteolytic processing products. In each cell, the smallest protein, or in the case of R14, one of the two smallest proteins, accumulates to a significant extent, suggesting that it might correspond to a final processed neurohormone. In cell R15, the biosynthesis of the primary precursor and its subsequent processing to smaller peptides is largely unaffected by removal of extracellular calcium, by replacement of calcium with cobalt or by inhibition of spontaneous bursting via stimulation of the brachial nerve. | [
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PMID:28387 | Evidence for a change in neurotransmitter affecting oesophageal motility in Parkinson's disease. | In a study of oesophageal motility in 20 patients with Parkinson's disease, intravenous atropine produced marked disruption of co-ordination in response to swallows, when compared with control subjects. This suggests that cholinergic rather than dopaminergic mechanisms are more important in the control of swallowing in patients with Parkinsonism. No conclusive evidence of peripheral dopamine depletion or autonomic neuropathy was found, although minor changes suggestive of the former were found in severely affected patients. | Evidence for a change in neurotransmitter affecting oesophageal motility in Parkinson's disease. In a study of oesophageal motility in 20 patients with Parkinson's disease, intravenous atropine produced marked disruption of co-ordination in response to swallows, when compared with control subjects. This suggests that cholinergic rather than dopaminergic mechanisms are more important in the control of swallowing in patients with Parkinsonism. No conclusive evidence of peripheral dopamine depletion or autonomic neuropathy was found, although minor changes suggestive of the former were found in severely affected patients. | [
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PMID:28388 | Radioiodinated derivatives of beta adrenoceptor blockers for myocardial imaging. | Four new beta-adrenoceptor blocking agents carrying tyramine as the amino moiety were synthesized and the distribution of their I-125-tagged derivatives evaluated in rats. This distribution was compared with the distribution of various agonists and antagonists labeled with H-3 and C-14, and with the in vitro binding affinity of the new derivatives. A radioiodinated derivative of a cardioselective blocker, alprenolol, showed poor blood clearance and no cardiac selectivity. A derivative of another cardioselective blocker, practolol, showed a promising heart-to-blood ratio (ca. 19) and cardioselectivity with a heart-to-lung ratio of ca. 2. Two additional practolol analogs showed no improvement over the practolol derivative; because of the increased lipophilicity of these derivatives, blood clearance and cardioselectivity were diminished. An inverse correlation is suggested between the dissociation constant for the beta adrenoceptor in the lung and the heart-to-blood and heart-to-lung values. We conclude that polarity plays an important role in the blood clearance and cardioselectivity of these beta-adrenoceptor derivatives. | Radioiodinated derivatives of beta adrenoceptor blockers for myocardial imaging. Four new beta-adrenoceptor blocking agents carrying tyramine as the amino moiety were synthesized and the distribution of their I-125-tagged derivatives evaluated in rats. This distribution was compared with the distribution of various agonists and antagonists labeled with H-3 and C-14, and with the in vitro binding affinity of the new derivatives. A radioiodinated derivative of a cardioselective blocker, alprenolol, showed poor blood clearance and no cardiac selectivity. A derivative of another cardioselective blocker, practolol, showed a promising heart-to-blood ratio (ca. 19) and cardioselectivity with a heart-to-lung ratio of ca. 2. Two additional practolol analogs showed no improvement over the practolol derivative; because of the increased lipophilicity of these derivatives, blood clearance and cardioselectivity were diminished. An inverse correlation is suggested between the dissociation constant for the beta adrenoceptor in the lung and the heart-to-blood and heart-to-lung values. We conclude that polarity plays an important role in the blood clearance and cardioselectivity of these beta-adrenoceptor derivatives. | [
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PMID:28389 | Experimental cross infections of Fasciola hepatica in lambs and calves. | The effects of experimental infections with Fasciola hepatica of ovine and bovine origin in homologous and heterologous hosts and in uninfected controls were compared; groups comprised 5 animals each. The effects of the infections were monitored by biweekly determinations of packed cell volumes (PCV), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma glutamyl transpeptidase (GGT), serum iron, bilirubin levels, alkaline phosphatase (AlP) and total serum protein levels. Infected animals showed changes in SGOT, SGPT and GGT activity levels, and GGT activity levels, and infected lambs showed changes in PCV and AlP. However, no no significant differences in these serum levels between infected host groups were attributable to fluke strain. At necropsy, calves infected with ovine and bovine strains on an average had about the same number of flukes, but lambs infected with a high dose of the bovine strain on the average had nearly twice the number of flukes as those infected with ovine strain. Weight gains did not differ within host groups; liver damage was extensive in all infected animals. On the basis of these experiments, the pathogenicity of the ovine and the bovine strains of F. hepatica appears to be the same. | Experimental cross infections of Fasciola hepatica in lambs and calves. The effects of experimental infections with Fasciola hepatica of ovine and bovine origin in homologous and heterologous hosts and in uninfected controls were compared; groups comprised 5 animals each. The effects of the infections were monitored by biweekly determinations of packed cell volumes (PCV), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma glutamyl transpeptidase (GGT), serum iron, bilirubin levels, alkaline phosphatase (AlP) and total serum protein levels. Infected animals showed changes in SGOT, SGPT and GGT activity levels, and GGT activity levels, and infected lambs showed changes in PCV and AlP. However, no no significant differences in these serum levels between infected host groups were attributable to fluke strain. At necropsy, calves infected with ovine and bovine strains on an average had about the same number of flukes, but lambs infected with a high dose of the bovine strain on the average had nearly twice the number of flukes as those infected with ovine strain. Weight gains did not differ within host groups; liver damage was extensive in all infected animals. On the basis of these experiments, the pathogenicity of the ovine and the bovine strains of F. hepatica appears to be the same. | [
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0.07011712342500687,
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0.0924406498670578,
0.013553264550864697
] |
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