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PMID:27642 | Biotin. Its place in evolution. | In the previous article we try to give an explanation for the success of models of enzymatic reactions in which coenzymes play a role. However, one vital cofactor that has thus far not yielded appreciably to this approach is biotin. We attempt to show that biotin presents a fundamentally new sort of problem to bioorganic chemistry; this problem requires consideration both of the origin of life and subsequent evolution in any attempt to understand the anomalies offered by this cofactor. | Biotin. Its place in evolution. In the previous article we try to give an explanation for the success of models of enzymatic reactions in which coenzymes play a role. However, one vital cofactor that has thus far not yielded appreciably to this approach is biotin. We attempt to show that biotin presents a fundamentally new sort of problem to bioorganic chemistry; this problem requires consideration both of the origin of life and subsequent evolution in any attempt to understand the anomalies offered by this cofactor. | [
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PMID:27644 | Covalent coupling of calf brain prolidase. | Calf brain prolidase covalently bound to CNBr-Sepharose 4B, retained about 32% of the activity of the uncoupled enzyme. The free enzyme showed slightly greater stability than the bound preparation when stored at 20 degrees C or at 0 degrees C. However, in either case the free and bound enzymes were more stable at the lower temperature. Greater thermal stability was shown by the free enzyme than by the bound preparation over a temperature range of 25 degrees C-60 degrees C. The free and bound prolidase, with and without Mn+2, had maximal activity at pH 4.0. Although the bound enzyme showed a single maximum, the free preparation exhibited three pH maxima of 4.0, 9.0, and 6.5, in decreasing order of activity. The ions Ag+, Cu+, Hg+2, and Zn+2 were strongly inhibitory on the free enzyme, whereas inhibition of the bound enzyme, with the exception of Zn+2 , was less. Unlike the coupled enzyme, a stimulatory effect was obtained on the free preparation with Co+3, Mg+2, and Mn+2. Various other compounds were studied and their effects were noted. | Covalent coupling of calf brain prolidase. Calf brain prolidase covalently bound to CNBr-Sepharose 4B, retained about 32% of the activity of the uncoupled enzyme. The free enzyme showed slightly greater stability than the bound preparation when stored at 20 degrees C or at 0 degrees C. However, in either case the free and bound enzymes were more stable at the lower temperature. Greater thermal stability was shown by the free enzyme than by the bound preparation over a temperature range of 25 degrees C-60 degrees C. The free and bound prolidase, with and without Mn+2, had maximal activity at pH 4.0. Although the bound enzyme showed a single maximum, the free preparation exhibited three pH maxima of 4.0, 9.0, and 6.5, in decreasing order of activity. The ions Ag+, Cu+, Hg+2, and Zn+2 were strongly inhibitory on the free enzyme, whereas inhibition of the bound enzyme, with the exception of Zn+2 , was less. Unlike the coupled enzyme, a stimulatory effect was obtained on the free preparation with Co+3, Mg+2, and Mn+2. Various other compounds were studied and their effects were noted. | [
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PMID:27645 | Characterization of an alkaline protease associated with a granulosis virus of Plodia interpunctella. | An alkaline protease was found to be associated with the granulosis virus of the Indian meal moth. Plodia interpunctella. The protease was located within the protein matrix of the occluded virus and hydrolyzed the major constituent of this matrix, a 28,000-dalton protein (granulin), to a mixture of polypeptides ranging in molecular weight from 10,000 to 27,000. A rapid, sensitive assay for the protease was developed using radioactively labeled granulosis virus as substrate. With this assay, the proteolytic activity could be detected by measuring the release of acid-soluble peptides from the labeled virus. The protease had a pH optimum of 10.5 and a temperature optimum of 40 degrees C and was inhibited by diisopropyl phosphorofluoridate, phenylmethylsulfonyl fluoride, and L-(1-tosylamido-2-phenyl) ethyl chloromethyl ketone. Purification of the protease from matrix protein was achieved by anion-exchange and gel permeation chromatography. The molecular weight of the isolated protease, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration, was approximately 14,000. | Characterization of an alkaline protease associated with a granulosis virus of Plodia interpunctella. An alkaline protease was found to be associated with the granulosis virus of the Indian meal moth. Plodia interpunctella. The protease was located within the protein matrix of the occluded virus and hydrolyzed the major constituent of this matrix, a 28,000-dalton protein (granulin), to a mixture of polypeptides ranging in molecular weight from 10,000 to 27,000. A rapid, sensitive assay for the protease was developed using radioactively labeled granulosis virus as substrate. With this assay, the proteolytic activity could be detected by measuring the release of acid-soluble peptides from the labeled virus. The protease had a pH optimum of 10.5 and a temperature optimum of 40 degrees C and was inhibited by diisopropyl phosphorofluoridate, phenylmethylsulfonyl fluoride, and L-(1-tosylamido-2-phenyl) ethyl chloromethyl ketone. Purification of the protease from matrix protein was achieved by anion-exchange and gel permeation chromatography. The molecular weight of the isolated protease, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration, was approximately 14,000. | [
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PMID:27646 | The urologic manifestations of XO/XY mosaicism. | The mosaic karyotype XO/XY is expressed by a spectrum of genital phenotypes, ranging from normal male through ambiguous genitalia to normal female. The urologist may see some of these patients because of the following clinical presentations: 1) ambiguous genitalia with a chromatin-negative buccal smear, 2) hypospadias with cryptorchidism or 3) cryptorchidism with müllerian remnants, discovered unexpectedly during inguinal operations. Reliable karyotyping is mandatory for diagnosis of XO/XY patients. Management should include laparotomy with excision of any intra-abdominal gonads (testis and/or streak gonad) because these are prone to develop malignancies that may occur before puberty. Female sex assignment and a reconstructive operation are advised in cases with severely deficient virilization of the genitalia. | The urologic manifestations of XO/XY mosaicism. The mosaic karyotype XO/XY is expressed by a spectrum of genital phenotypes, ranging from normal male through ambiguous genitalia to normal female. The urologist may see some of these patients because of the following clinical presentations: 1) ambiguous genitalia with a chromatin-negative buccal smear, 2) hypospadias with cryptorchidism or 3) cryptorchidism with müllerian remnants, discovered unexpectedly during inguinal operations. Reliable karyotyping is mandatory for diagnosis of XO/XY patients. Management should include laparotomy with excision of any intra-abdominal gonads (testis and/or streak gonad) because these are prone to develop malignancies that may occur before puberty. Female sex assignment and a reconstructive operation are advised in cases with severely deficient virilization of the genitalia. | [
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PMID:27648 | Bilateral trifid ureters associated with fused kidney, ureterovesical stenosis, left cryptorchidism and angioma of the bladder. | The first case of bilateral trifid ureters associated with fused kidney, ureterovesical stenosis, a left undescended testicle and angioma of the bladder is reported. Bilateral ureteroneocystostomy and left orchiopexy were done. The patient is well 3 months postoperatively with no urinary tract infection and stable renal function. | Bilateral trifid ureters associated with fused kidney, ureterovesical stenosis, left cryptorchidism and angioma of the bladder. The first case of bilateral trifid ureters associated with fused kidney, ureterovesical stenosis, a left undescended testicle and angioma of the bladder is reported. Bilateral ureteroneocystostomy and left orchiopexy were done. The patient is well 3 months postoperatively with no urinary tract infection and stable renal function. | [
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PMID:27659 | [The determination of a small amount of chlorine in the atmosphere by using 4-nitroaniline (author's transl)]. | The determination of small amount of chlorine in the atmosphere is carried on ordinarily by omicron-toluidine method at present. However, this method is not recommended because the issued colour is unstable and omicron-toluidine itself belongs in the first group member of the Ordinance on Prevention of Particular Chemical Hazards Substances. Authors recommend 4-nitroaniline method, reported by J. Gabbay etc., because this method is stable and more practical. Although the colour that issued from the reaction of chlorine with 4-nitroaniline is affected by the co-existence of reducing gas, e.g. SO2, H2S or organic gas, but this effect may be removed the co-existence of reducing gas, e.g. SO2, H2S or organic gas, but this effect may be removed by introducing the sample gas into the layer of H2SO4-52Cr2O7 mixture immersed in glassfiber filter for micro-analysis. In this paper, influence of pH of the issued colour, stability, stream velocity of samplegas and effect of reducing substance are discussed. | [The determination of a small amount of chlorine in the atmosphere by using 4-nitroaniline (author's transl)]. The determination of small amount of chlorine in the atmosphere is carried on ordinarily by omicron-toluidine method at present. However, this method is not recommended because the issued colour is unstable and omicron-toluidine itself belongs in the first group member of the Ordinance on Prevention of Particular Chemical Hazards Substances. Authors recommend 4-nitroaniline method, reported by J. Gabbay etc., because this method is stable and more practical. Although the colour that issued from the reaction of chlorine with 4-nitroaniline is affected by the co-existence of reducing gas, e.g. SO2, H2S or organic gas, but this effect may be removed the co-existence of reducing gas, e.g. SO2, H2S or organic gas, but this effect may be removed by introducing the sample gas into the layer of H2SO4-52Cr2O7 mixture immersed in glassfiber filter for micro-analysis. In this paper, influence of pH of the issued colour, stability, stream velocity of samplegas and effect of reducing substance are discussed. | [
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PMID:27664 | [Effect of adrenergic beta receptor blockaders on bronchial patency in ischemic heart disease]. | The effect of beta-adrenergic blocking agents inderal, trazicor, visken, benzoral and aptin on the bronchial patency was studied by means of four ventilation indices in 85 patients, 62 of whome had various diseases of the lungs; 44 of these patients had bronchial obstruction. It was established that all beta-blocking agents are detrimental to bronchial patency in patients with concomitant bronchial obstruction. In exacerbation of bronchial asthma, beta-blocking agents are contraindictaed. When it is necessary to prescribe beta-blocking agents for other patients with concomitant bronchial obstruction visken is the drug of choice. It should be given per os, with preliminary control of the function of external respiration. | [Effect of adrenergic beta receptor blockaders on bronchial patency in ischemic heart disease]. The effect of beta-adrenergic blocking agents inderal, trazicor, visken, benzoral and aptin on the bronchial patency was studied by means of four ventilation indices in 85 patients, 62 of whome had various diseases of the lungs; 44 of these patients had bronchial obstruction. It was established that all beta-blocking agents are detrimental to bronchial patency in patients with concomitant bronchial obstruction. In exacerbation of bronchial asthma, beta-blocking agents are contraindictaed. When it is necessary to prescribe beta-blocking agents for other patients with concomitant bronchial obstruction visken is the drug of choice. It should be given per os, with preliminary control of the function of external respiration. | [
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PMID:27665 | [Transient myopia with angle closure glaucoma. Case report and biometric findings (author's transl)]. | A 36-year-old man suffered from diarrhoea for some weeks and was treated with Salazosulphapyridie and Fluocortulon when he developed a transient myopia combined with an angle closure glaucoma. The refraction of his mild hyperopic eyes (+0,5 dpt) changed to -5,5 dpt and the intraocular pressure increased to 40 mm Hg in the right and 42 mm Hg in the left eye. Accommodation and pupillary reflexes were normal. Ultrasonic examination showed an increased axial diameter and a forward shifting of the lens. The resulting flattening of the anterior chamber induced the angle closure glaucoma. All symptoms disappeared within a week after the administration of Fluocortulon had been discontinued. | [Transient myopia with angle closure glaucoma. Case report and biometric findings (author's transl)]. A 36-year-old man suffered from diarrhoea for some weeks and was treated with Salazosulphapyridie and Fluocortulon when he developed a transient myopia combined with an angle closure glaucoma. The refraction of his mild hyperopic eyes (+0,5 dpt) changed to -5,5 dpt and the intraocular pressure increased to 40 mm Hg in the right and 42 mm Hg in the left eye. Accommodation and pupillary reflexes were normal. Ultrasonic examination showed an increased axial diameter and a forward shifting of the lens. The resulting flattening of the anterior chamber induced the angle closure glaucoma. All symptoms disappeared within a week after the administration of Fluocortulon had been discontinued. | [
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PMID:27691 | Semisynthetic derivatives of pyrrolizidine alkaloids of pharmacodynamic importance: a review. | Pyrrolizidine alkaloids occur in more than 40 genera. Among these are two important genera, Senecio and Crotalaria, which have been responsible for heavy losses of livestock and poisoning in man due to their hepatotoxicity. Pyrrolizidine alkaloids are also reported to possess a number of other biological activities. Attempts have been made to convert the pyrrolizidine alkaloids to new structures by synthetic modifications. One hundred and twenty semisynthetic compounds were developed and investigated pharmacologically. The range of activity exhibited was hypotensive, local anesthetic, ganglion blocking, neuromuscular blocking and antispasmodic. The five most promising compounds of these series were subjected to detailed pharmacological investigations. | Semisynthetic derivatives of pyrrolizidine alkaloids of pharmacodynamic importance: a review. Pyrrolizidine alkaloids occur in more than 40 genera. Among these are two important genera, Senecio and Crotalaria, which have been responsible for heavy losses of livestock and poisoning in man due to their hepatotoxicity. Pyrrolizidine alkaloids are also reported to possess a number of other biological activities. Attempts have been made to convert the pyrrolizidine alkaloids to new structures by synthetic modifications. One hundred and twenty semisynthetic compounds were developed and investigated pharmacologically. The range of activity exhibited was hypotensive, local anesthetic, ganglion blocking, neuromuscular blocking and antispasmodic. The five most promising compounds of these series were subjected to detailed pharmacological investigations. | [
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PMID:27696 | An adverse effect of insulin on the oxygen-release capacity of red blood cells in nonacidotic diabetics. | Oxyhemoglobin dissociation curves (ODC) were performed on blood from newly diagnosed, nonketotic diabetics prior to and following initial insulin treatment and from ambulatory juvenile diabetics before and after their usual morning insulin. In 10 newly discovered diabetics the average P50 at in vivo pH was normal prior to insulin (26.2 mm Hg), decreased to 24.5 mm Hg (p less than 0.005) on the day following the initial insulin administration, and was within normal limits (26.9 mm Hg) when the diabetes was finally well controlled and red cell 2,3-diphosphoglycerate (2,3-DPG) had risen to elevated levels. Oxygen affinity of hemoglobin was closely correlated with the content of red cell 2,3-DPG (r = 0.61, p less than 0.001) but was unrelated to the level of hemoglobin Alc. In 40 juvenile patients the average P50 was also normal prior to insulin administration but was significantly lower 3-4 hr after they had received their usual insulin dose (p less than 0.001). The study indicates that insulin administration to diabetics with high blood glucose levels may lead to transient decreases in red cell 2,3-DPG and in oxygen-releasing capacity of the red blood cells. | An adverse effect of insulin on the oxygen-release capacity of red blood cells in nonacidotic diabetics. Oxyhemoglobin dissociation curves (ODC) were performed on blood from newly diagnosed, nonketotic diabetics prior to and following initial insulin treatment and from ambulatory juvenile diabetics before and after their usual morning insulin. In 10 newly discovered diabetics the average P50 at in vivo pH was normal prior to insulin (26.2 mm Hg), decreased to 24.5 mm Hg (p less than 0.005) on the day following the initial insulin administration, and was within normal limits (26.9 mm Hg) when the diabetes was finally well controlled and red cell 2,3-diphosphoglycerate (2,3-DPG) had risen to elevated levels. Oxygen affinity of hemoglobin was closely correlated with the content of red cell 2,3-DPG (r = 0.61, p less than 0.001) but was unrelated to the level of hemoglobin Alc. In 40 juvenile patients the average P50 was also normal prior to insulin administration but was significantly lower 3-4 hr after they had received their usual insulin dose (p less than 0.001). The study indicates that insulin administration to diabetics with high blood glucose levels may lead to transient decreases in red cell 2,3-DPG and in oxygen-releasing capacity of the red blood cells. | [
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PMID:27701 | Kinetic properties of pyruvate kinase of Neurospora crassa at physiological pH. | The kinetic properties of pyruvate kinase (EC 2.7.1.40) extracted from the mycelia of Neurospora crassa were examined at physiological pH to determine the role of the enzyme in the regulation of glycolysis. The velocity curve with the substrates, phosphoenolpyruvate and adenosine diphosphate, are hyperbolic. The effect of magnesium, potassium, or calcium on the enzyme is influenced by the pH but not to the extent that would change their role as cofactor or inhibitor. Adenosine triphosphate and citrate remain strong inhibitors even with changes in pH. Fructose-1,6-diphosphate and glucose-6-phosphate are the dual positive effectors at physiological pH. Valine is the only amino acid that inhibits the enzyme at a concentration range of valine found in the mycelial juice. Thus, the properties of the enzyme at physiological pH are significantly different from those observed at neutral pH of the usual assay conditions, but its role as a key regulator of glycolysis is unchanged. | Kinetic properties of pyruvate kinase of Neurospora crassa at physiological pH. The kinetic properties of pyruvate kinase (EC 2.7.1.40) extracted from the mycelia of Neurospora crassa were examined at physiological pH to determine the role of the enzyme in the regulation of glycolysis. The velocity curve with the substrates, phosphoenolpyruvate and adenosine diphosphate, are hyperbolic. The effect of magnesium, potassium, or calcium on the enzyme is influenced by the pH but not to the extent that would change their role as cofactor or inhibitor. Adenosine triphosphate and citrate remain strong inhibitors even with changes in pH. Fructose-1,6-diphosphate and glucose-6-phosphate are the dual positive effectors at physiological pH. Valine is the only amino acid that inhibits the enzyme at a concentration range of valine found in the mycelial juice. Thus, the properties of the enzyme at physiological pH are significantly different from those observed at neutral pH of the usual assay conditions, but its role as a key regulator of glycolysis is unchanged. | [
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PMID:27702 | The influence of pH on the growth rate and viability of neutrophilic and acidophilic streptomycetes. | The influence of pH on the specific growth rates of two acidophilic and two neutrophilic soil streptomycetes was studied. The acidophiles had maximum growth rates over a broad range from pH 4.5 to 5.5, while the neutrophiles had clearly defined optima at pH 7.0. Mycelium of neutrophiles was less tolerant of acidity than that of acidophiles; both showed decreased viability at pH levels below those which allowed growth. Spores of neutrophiles and acidophiles were equally tolerant of acidity and this may allow the former to survive in acid soils. Both spores and mycelium of acidophiles remained viable at pH levels above those allowing growth. | The influence of pH on the growth rate and viability of neutrophilic and acidophilic streptomycetes. The influence of pH on the specific growth rates of two acidophilic and two neutrophilic soil streptomycetes was studied. The acidophiles had maximum growth rates over a broad range from pH 4.5 to 5.5, while the neutrophiles had clearly defined optima at pH 7.0. Mycelium of neutrophiles was less tolerant of acidity than that of acidophiles; both showed decreased viability at pH levels below those which allowed growth. Spores of neutrophiles and acidophiles were equally tolerant of acidity and this may allow the former to survive in acid soils. Both spores and mycelium of acidophiles remained viable at pH levels above those allowing growth. | [
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PMID:27703 | Cell wall autolysis in log phase cells of Micrococcus lysodeikticus (luteus). | Log phase cells of Micrococcus lysodeikticus (luteus) IFO 3333 autolyzed when incubated at 37 C in 0.01 M sodium-phosphate buffer pH 7.5. The enzyme involved in the autolysis was recovered mainly in an aqueous phase from cytoplasmic membranes and cytoplasmic materials treated with n-butanol, and proved to be an N-acetylmuramyl-L-alanine amidase. The autolysis of log phase cells suspended in autolyzing buffer was depressed by the addition of trypsin to the buffer. | Cell wall autolysis in log phase cells of Micrococcus lysodeikticus (luteus). Log phase cells of Micrococcus lysodeikticus (luteus) IFO 3333 autolyzed when incubated at 37 C in 0.01 M sodium-phosphate buffer pH 7.5. The enzyme involved in the autolysis was recovered mainly in an aqueous phase from cytoplasmic membranes and cytoplasmic materials treated with n-butanol, and proved to be an N-acetylmuramyl-L-alanine amidase. The autolysis of log phase cells suspended in autolyzing buffer was depressed by the addition of trypsin to the buffer. | [
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PMID:27704 | A new method for extraction of extravasated dye in the skin and the influence of fasting stress on passive cutaneous anaphylaxis in guinea pigs and rats. | A method for quantitative extraction of extravasated dye from the skin was studied in guinea pigs and rats. A simple method with a low cost and good recovery was established as follows; A piece of the skin containing extravasated dye was soaked overnight in a stoppered glass tube containing 1 ml of 1 N KOH at 37 C. Then, 9 ml of mixed solution of 0.6 N H3PO4 and acetone (5:13) was added to the tube. The tube was shaken vigorously for a few seconds and centrifuged at 3,000 rpm for 15 min. Absorbance of supernatant was measured at 620 nm. The recovery rate of the dye was about 95 per cent both in guinea pigs and rats. Using this method we observed that fasting stress significantly reduced the intensity of skin reaction induced by chemical mediators, heterologous PCA and especially homologous PCA in guinea pigs. | A new method for extraction of extravasated dye in the skin and the influence of fasting stress on passive cutaneous anaphylaxis in guinea pigs and rats. A method for quantitative extraction of extravasated dye from the skin was studied in guinea pigs and rats. A simple method with a low cost and good recovery was established as follows; A piece of the skin containing extravasated dye was soaked overnight in a stoppered glass tube containing 1 ml of 1 N KOH at 37 C. Then, 9 ml of mixed solution of 0.6 N H3PO4 and acetone (5:13) was added to the tube. The tube was shaken vigorously for a few seconds and centrifuged at 3,000 rpm for 15 min. Absorbance of supernatant was measured at 620 nm. The recovery rate of the dye was about 95 per cent both in guinea pigs and rats. Using this method we observed that fasting stress significantly reduced the intensity of skin reaction induced by chemical mediators, heterologous PCA and especially homologous PCA in guinea pigs. | [
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PMID:27709 | [Provocative gamma GT test in chronic pancreatitis? (author's transl)]. | The increase of serum gamma-GT after hormonal stimulation has been reported as a new provocative test in the diagnosis of chronic pancreatitis. The test was suggested to be more sensitive than the serum amylase provocation test. In a clinical study of both tests in 83 consecutive patients the unsensitivity and the high rate of false positive results were demonstrated. Thus these provocation tests do not seem to be valuable in the diagnosis of chronic pancreatitis. | [Provocative gamma GT test in chronic pancreatitis? (author's transl)]. The increase of serum gamma-GT after hormonal stimulation has been reported as a new provocative test in the diagnosis of chronic pancreatitis. The test was suggested to be more sensitive than the serum amylase provocation test. In a clinical study of both tests in 83 consecutive patients the unsensitivity and the high rate of false positive results were demonstrated. Thus these provocation tests do not seem to be valuable in the diagnosis of chronic pancreatitis. | [
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PMID:27705 | [Acetic acid, a catabolite repressor of cholinesterase synthesis by an Arthrobacter simplex culture]. | Acetic acid was found to repress cholinesterase synthesis in the cells of Arthrobacter simplex var. cholinesterasus even at very low concentrations (0.1%). The repression is very stable. It is not eliminated by glucose or an organic acid of the Krebs cycle being added to the medium with acetic acid. The combination of acetic and butyric acids decreases the repression but does not eliminate it. The kinetics of cholinesterase synthesis was different in the cells grown on the medium with acetic acid and the cells cultivated on the medium with acetic acid and glucose, then washed and transferred to a fresh growth medium with glucose and acetylcholine as the sources of carbon. | [Acetic acid, a catabolite repressor of cholinesterase synthesis by an Arthrobacter simplex culture]. Acetic acid was found to repress cholinesterase synthesis in the cells of Arthrobacter simplex var. cholinesterasus even at very low concentrations (0.1%). The repression is very stable. It is not eliminated by glucose or an organic acid of the Krebs cycle being added to the medium with acetic acid. The combination of acetic and butyric acids decreases the repression but does not eliminate it. The kinetics of cholinesterase synthesis was different in the cells grown on the medium with acetic acid and the cells cultivated on the medium with acetic acid and glucose, then washed and transferred to a fresh growth medium with glucose and acetylcholine as the sources of carbon. | [
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PMID:27710 | [Disorder of porphyrin metabolism in thallium intoxication (author's transl)]. | A 19-year old male ingested in suicidal attempt 750 mg of thallium. He developed the characteristic symptoms of thallium intoxication. During the acute phase the urinary excretion of porphyrins and porphyrin precursors was largely increased. The percentage distribution of the individual metabolites of heme synthesis revealed a preponderance of kopro- and uroporphyrin. This constellation (kopro- greater than uro- greater than tricarboxylic porphyrin) differs appreciably from that one in lead intoxication. The observation of increased urinary excretion of porphyrins and their precursors in a possibly particular spectrum in thallium intoxication is of special interest for differential-diagnostic reasoning. In each case of a toxic disorder of porphyrin metabolism thallium intoxication ought to be considered a possible cause. | [Disorder of porphyrin metabolism in thallium intoxication (author's transl)]. A 19-year old male ingested in suicidal attempt 750 mg of thallium. He developed the characteristic symptoms of thallium intoxication. During the acute phase the urinary excretion of porphyrins and porphyrin precursors was largely increased. The percentage distribution of the individual metabolites of heme synthesis revealed a preponderance of kopro- and uroporphyrin. This constellation (kopro- greater than uro- greater than tricarboxylic porphyrin) differs appreciably from that one in lead intoxication. The observation of increased urinary excretion of porphyrins and their precursors in a possibly particular spectrum in thallium intoxication is of special interest for differential-diagnostic reasoning. In each case of a toxic disorder of porphyrin metabolism thallium intoxication ought to be considered a possible cause. | [
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PMID:27706 | [Effect of pH values of the medium unfavorable for growth on the physiological, morphological and cytological characteristics of a chemostat culture of Candida utilis]. | The effect of growth inhibiting values of pH of the medium (pH 2.3 and 7.8) on physiological, morphological and cytological characteristics was studied with the chemostat culture of Candida utilis. Changes in the pH of the medium were accompanied with a decrease in the economic coefficient of the yeast cells, an increase in the respiratory quotient and the activity of phosphohydrolase. Phase-contrast micriscopy has shown that, at acid pH values, the cells were smaller than in the control (in the cells grown under optimal conditions) and rather uniform, oval or rounded, and contained large lipid granules. The presence of large lipid granules was confirmed by electron microscopy; vacuoles were smaller than in the control cells, but their number was greater than one; mitochondria stuck together and had one general outer membrane; the cell wall was 3--4 times thicker. At alkaline pH values of the medium, the whole cellular organization of C. utilis was disordered: the cells were larger, the size of vacuoles increased too much, and the structure became heterogeneous. | [Effect of pH values of the medium unfavorable for growth on the physiological, morphological and cytological characteristics of a chemostat culture of Candida utilis]. The effect of growth inhibiting values of pH of the medium (pH 2.3 and 7.8) on physiological, morphological and cytological characteristics was studied with the chemostat culture of Candida utilis. Changes in the pH of the medium were accompanied with a decrease in the economic coefficient of the yeast cells, an increase in the respiratory quotient and the activity of phosphohydrolase. Phase-contrast micriscopy has shown that, at acid pH values, the cells were smaller than in the control (in the cells grown under optimal conditions) and rather uniform, oval or rounded, and contained large lipid granules. The presence of large lipid granules was confirmed by electron microscopy; vacuoles were smaller than in the control cells, but their number was greater than one; mitochondria stuck together and had one general outer membrane; the cell wall was 3--4 times thicker. At alkaline pH values of the medium, the whole cellular organization of C. utilis was disordered: the cells were larger, the size of vacuoles increased too much, and the structure became heterogeneous. | [
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PMID:27707 | [Action of copper ions and of unfavorable medium pH values on protein and RNA synthesis by Candida utilis cells]. | The effect of copper ions and unfavourable pH values of the medium on the incorporation of labelled precursors of protein and RNA was studied in Candida utilis. Specific inhibition of protein synthesis by copper ions and alkaline conditions was found. No specific inhibition of protein or RNA was detected at low pH values of the medium. | [Action of copper ions and of unfavorable medium pH values on protein and RNA synthesis by Candida utilis cells]. The effect of copper ions and unfavourable pH values of the medium on the incorporation of labelled precursors of protein and RNA was studied in Candida utilis. Specific inhibition of protein synthesis by copper ions and alkaline conditions was found. No specific inhibition of protein or RNA was detected at low pH values of the medium. | [
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] |
PMID:27713 | Enlarged acid-base and blood gas calculations by electronical data computing in the blood gas laboratory. | A rapid anaysis of parameters of the acid-base equilibrium and blood gases during open heart surgery and emergency therapy is absolutely necessary. Computing of the several parameters of the acid-base status by slide rules or nomograms is time consuming and can be shortened by computer applications. The central blood gas laboratory consists of a blood gas analyzer for PO2, PCO2 and pH, an electronic desktop calculator, a four color X-Y-plotter and two data lines to the cardiac surgery unit and to the intensive care unit. The time needed for computing and feedback of the parameters could be decreased to one quarter. In addition to numerical data printout, a graphical representation of the several parameters is possible on a X-Y-plotter and includes the Rahn-Fenn-O2-CO2-Diagram with venous admixture, ventilation perfusion ratio, alveolar dead space ventilation and the standard and actual oxygen dissociation curve as well as the pH/HCO3- Acid-Base nomogram. Furthermore, a computer diagnosis of the actual disturbances can be plotted. | Enlarged acid-base and blood gas calculations by electronical data computing in the blood gas laboratory. A rapid anaysis of parameters of the acid-base equilibrium and blood gases during open heart surgery and emergency therapy is absolutely necessary. Computing of the several parameters of the acid-base status by slide rules or nomograms is time consuming and can be shortened by computer applications. The central blood gas laboratory consists of a blood gas analyzer for PO2, PCO2 and pH, an electronic desktop calculator, a four color X-Y-plotter and two data lines to the cardiac surgery unit and to the intensive care unit. The time needed for computing and feedback of the parameters could be decreased to one quarter. In addition to numerical data printout, a graphical representation of the several parameters is possible on a X-Y-plotter and includes the Rahn-Fenn-O2-CO2-Diagram with venous admixture, ventilation perfusion ratio, alveolar dead space ventilation and the standard and actual oxygen dissociation curve as well as the pH/HCO3- Acid-Base nomogram. Furthermore, a computer diagnosis of the actual disturbances can be plotted. | [
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PMID:27716 | Characterisation of ribosomal proteins from HeLa and Krebs II mouse ascites tumor cells by different two-dimensional polyacrylamide gel electrophoresis techniques. | Electrophoresis of ribosomal proteins according to Kaltschmidt and Wittmann, 1970a, b (pH 8.6/pH 4.5 urea system) yielded 29 proteins for the small subunits and 35 and 37 proteins for the large subunits of Krebs II ascites and HeLa ribosomes, respectively. Analysis of the proteins according to a modified technique by Mets and Bogorad (1974) (pH 4.5/pH 8.6 SDS system) revealed 28 and 29 proteins in the small subunits and 37 and 38 proteins in the large subunits of Krebs II ascites and HeLa ribosomes. The molecular weights of the individual proteins were determined by: 1. "three-dimensional" gel electrophoresis; 2. two-dimensional gel electrophoresis at pH 4.K/pH 8.6 in SDS. The molecular weights for 40S proteins ranged from 10,000 to 39,000 dalton (number average molecular weight: 21,000). The molecular weights for the 60S proteins ranged from 14,000 to 44,000 dalton (number average molecular weight: 23,000) using the "three-dimensional" technique. A molecular weight range from 10,000 to 38,000 dalton (number average molecular weight: 21,000) was obtained for the 40S subunits, whereas the molecular weights for the 60S ribosomal proteins (average molecular weight: 26,000) ranged from 12,000 to 69,000 dalton using the pH 4.5/pH 8.6 SDS system. The molecular weights Krebs II ascites and HeLa ribosomal proteins are compared with those obtained by other authors for different mammalian species. | Characterisation of ribosomal proteins from HeLa and Krebs II mouse ascites tumor cells by different two-dimensional polyacrylamide gel electrophoresis techniques. Electrophoresis of ribosomal proteins according to Kaltschmidt and Wittmann, 1970a, b (pH 8.6/pH 4.5 urea system) yielded 29 proteins for the small subunits and 35 and 37 proteins for the large subunits of Krebs II ascites and HeLa ribosomes, respectively. Analysis of the proteins according to a modified technique by Mets and Bogorad (1974) (pH 4.5/pH 8.6 SDS system) revealed 28 and 29 proteins in the small subunits and 37 and 38 proteins in the large subunits of Krebs II ascites and HeLa ribosomes. The molecular weights of the individual proteins were determined by: 1. "three-dimensional" gel electrophoresis; 2. two-dimensional gel electrophoresis at pH 4.K/pH 8.6 in SDS. The molecular weights for 40S proteins ranged from 10,000 to 39,000 dalton (number average molecular weight: 21,000). The molecular weights for the 60S proteins ranged from 14,000 to 44,000 dalton (number average molecular weight: 23,000) using the "three-dimensional" technique. A molecular weight range from 10,000 to 38,000 dalton (number average molecular weight: 21,000) was obtained for the 40S subunits, whereas the molecular weights for the 60S ribosomal proteins (average molecular weight: 26,000) ranged from 12,000 to 69,000 dalton using the pH 4.5/pH 8.6 SDS system. The molecular weights Krebs II ascites and HeLa ribosomal proteins are compared with those obtained by other authors for different mammalian species. | [
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PMID:27718 | Fidelity of conjugation in Saccharomyces cerevisiae. | An efficient method for the production of synchronous zygotes in Saccharomyces cerevisiae is described. Cells were synchronised under defined conditions in either an a, alpha mixed culture or by incubation of each mating type in cell-free medium in which cells of the opposite mating type had been grown. Synchronised cells were allowed to fuse under defined conditions on filter membranes. This method was used to test the fidelity of conjugation in S. cerevisiae. Under conditions where cells of a or alpha mating type were in contact with up to 6 cells of each of two strains of opposite mating type, less than 1 multiple mating in 10(4) diploid matings occurred. It is concluded that is sexual conjugation in S. cerevisiae some process distinct from cell contact restricts cell fusion to paired combinations of conjugant cells. | Fidelity of conjugation in Saccharomyces cerevisiae. An efficient method for the production of synchronous zygotes in Saccharomyces cerevisiae is described. Cells were synchronised under defined conditions in either an a, alpha mixed culture or by incubation of each mating type in cell-free medium in which cells of the opposite mating type had been grown. Synchronised cells were allowed to fuse under defined conditions on filter membranes. This method was used to test the fidelity of conjugation in S. cerevisiae. Under conditions where cells of a or alpha mating type were in contact with up to 6 cells of each of two strains of opposite mating type, less than 1 multiple mating in 10(4) diploid matings occurred. It is concluded that is sexual conjugation in S. cerevisiae some process distinct from cell contact restricts cell fusion to paired combinations of conjugant cells. | [
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PMID:27717 | Disturbance of the machinery for the gene expression by acidic pH in the repressible acid phosphatase system of Saccharomyces cerevisiae. | When the pH of growth medium containing a limited amount of inorganic phosphate is kept below 3.0, cells of Saccharomyces cerevisiae produce repressible alkaline phosphatase but no repressible acid phosphatase. The same cells produce acid phosphatase immediately on shifting the medium pH to 4.0 or above. Like intact cells, spheroplasts prepared from cells grown at pH 3.0 or 4.5 in medium with a limited amount of inorganic phosphate in suspension begin production of acid phosphatase immediately after pH shift from below 3.0 to 4.0 whereas sheroplasts from cells grown in inorganic phosphate-rich medium showed a prolonged lag period (3 h). The enzyme formation on the pH shift was sensitive to cycloheximide. No significant differences could be detected in cellular growth or in incorporation of 3H-L-lysine or 14C-adenine between cells cultivated at pH 3.0 and 4.5. These results along with the fact that the expression of structural genes of repressible acid and alkaline phosphatases is controlled by a common genetic regulatory system, at least in part, indicate that the genetic regulatory system operates to express the structural genes even at low pH, though the expression of repressible acid phosphatase is interrupted. Coupled experiments of temperature and pH shifts with the temperature-sensitive mutants of the regulatory genes suggest that the acidic pH affects the function of the cytoplasmic products of those genes in the expression of the structural gene. Based on these observations, a revised model involving the simultaneous functioning of the regulatory factors was suggested for the genetic regulation of repressible acid phosphatase synthesis. | Disturbance of the machinery for the gene expression by acidic pH in the repressible acid phosphatase system of Saccharomyces cerevisiae. When the pH of growth medium containing a limited amount of inorganic phosphate is kept below 3.0, cells of Saccharomyces cerevisiae produce repressible alkaline phosphatase but no repressible acid phosphatase. The same cells produce acid phosphatase immediately on shifting the medium pH to 4.0 or above. Like intact cells, spheroplasts prepared from cells grown at pH 3.0 or 4.5 in medium with a limited amount of inorganic phosphate in suspension begin production of acid phosphatase immediately after pH shift from below 3.0 to 4.0 whereas sheroplasts from cells grown in inorganic phosphate-rich medium showed a prolonged lag period (3 h). The enzyme formation on the pH shift was sensitive to cycloheximide. No significant differences could be detected in cellular growth or in incorporation of 3H-L-lysine or 14C-adenine between cells cultivated at pH 3.0 and 4.5. These results along with the fact that the expression of structural genes of repressible acid and alkaline phosphatases is controlled by a common genetic regulatory system, at least in part, indicate that the genetic regulatory system operates to express the structural genes even at low pH, though the expression of repressible acid phosphatase is interrupted. Coupled experiments of temperature and pH shifts with the temperature-sensitive mutants of the regulatory genes suggest that the acidic pH affects the function of the cytoplasmic products of those genes in the expression of the structural gene. Based on these observations, a revised model involving the simultaneous functioning of the regulatory factors was suggested for the genetic regulation of repressible acid phosphatase synthesis. | [
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PMID:27721 | Differential mutagenicity of reaction products of various pyrazolones with nitrite. | Four pyrazolones in frequent use, i.e. antipyrine (AP), aminopyrine (AMP), sulpyrine (SP) and isopropylantipyrine (IPA), were compared for their reactivity with nitrite and for the in vitro mutagenicity of their reaction products by Ames' reversion tests. In various acidic solutions at 37 degrees C, AP, AMP and SP were found to react easily with nitrite and yield various products including dimethylnitrosamine (DMNA) and 4-nitrosoantipyrine (4-NAP) in the cases of AMP and AP, respectively. When tested with Salmonella typhimurium TA100 and TA98 after lyophilization, the reaction products of AP (AP-N) were found to be mutagenic in both strains, while products of AMP and SP (AMP-N and SP-N) were mutagenic only in TA100. The presence of unknown ultimate mutagens, other than DMNA and 4-NAP, were evidenced in AP-N, AMP-N and SP-N. Incubation with S-9 mixture did not affect the mutagenicity of SP-N and decreased that of AP-N and AMP-N. In clear contrast to AP, AMP and SP, it was found that IPA remained essentially intact upon reaction with nitrite. No mutagenicity was detected with the reaction mixture (IPA-N) in either strain. | Differential mutagenicity of reaction products of various pyrazolones with nitrite. Four pyrazolones in frequent use, i.e. antipyrine (AP), aminopyrine (AMP), sulpyrine (SP) and isopropylantipyrine (IPA), were compared for their reactivity with nitrite and for the in vitro mutagenicity of their reaction products by Ames' reversion tests. In various acidic solutions at 37 degrees C, AP, AMP and SP were found to react easily with nitrite and yield various products including dimethylnitrosamine (DMNA) and 4-nitrosoantipyrine (4-NAP) in the cases of AMP and AP, respectively. When tested with Salmonella typhimurium TA100 and TA98 after lyophilization, the reaction products of AP (AP-N) were found to be mutagenic in both strains, while products of AMP and SP (AMP-N and SP-N) were mutagenic only in TA100. The presence of unknown ultimate mutagens, other than DMNA and 4-NAP, were evidenced in AP-N, AMP-N and SP-N. Incubation with S-9 mixture did not affect the mutagenicity of SP-N and decreased that of AP-N and AMP-N. In clear contrast to AP, AMP and SP, it was found that IPA remained essentially intact upon reaction with nitrite. No mutagenicity was detected with the reaction mixture (IPA-N) in either strain. | [
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PMID:27728 | Substance P: binding to lipids in the brain. | 1. Substance P (SP) could be extracted from brain homogenates with chloroform-methanol by a method which extracts all lipids. 2. SP could be transferred form this total lipid extract (TLE) into an aqueous solution at low pH values (2.0--3.0). 3. At higher pH values (5.5) SP could be transferred from an aqueous phase into an organic phase (chloroform:methanol, 2:1) and recombined with TLE (which was previously freed from endogenous SP) contained in this phase. The binding capacity of TLE for SP exceeded by far the amount of endogenous SP bound originally in the brain extracts. 4. Among the lipids present in TLE, phosphatidylserine was able to bind and release SP in a pH dependent manner. 5. It is suggested that SP bound to phosphatidylserine is the storage form of SP in the brain. The mechanisms by which it is released are still unknown. The possibility that the SP-receptor is also a phospholipid is considered. | Substance P: binding to lipids in the brain. 1. Substance P (SP) could be extracted from brain homogenates with chloroform-methanol by a method which extracts all lipids. 2. SP could be transferred form this total lipid extract (TLE) into an aqueous solution at low pH values (2.0--3.0). 3. At higher pH values (5.5) SP could be transferred from an aqueous phase into an organic phase (chloroform:methanol, 2:1) and recombined with TLE (which was previously freed from endogenous SP) contained in this phase. The binding capacity of TLE for SP exceeded by far the amount of endogenous SP bound originally in the brain extracts. 4. Among the lipids present in TLE, phosphatidylserine was able to bind and release SP in a pH dependent manner. 5. It is suggested that SP bound to phosphatidylserine is the storage form of SP in the brain. The mechanisms by which it is released are still unknown. The possibility that the SP-receptor is also a phospholipid is considered. | [
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PMID:27729 | The effect of some neuroleptics on the interaction of cortically and nigrally evoked potentials in the rat striatum. | The interaction of cortico- and nigrofugal inputs to the striatum of the rat was investigated using the technique of evoked potentials. Repetitive, unilateral stimulation of the substantia nigra inhibited potentials which were evoked from the ipsilateral rostral cortex and recorded from the ipsilateral striatum. The inhibition was antagonized by low doses of various intraperitoneally administered neuroleptics such as: pimozide (0.1 - 0.2 mg/kg), haloperidol (0.1 - 0.5 mg/kg), chlorpromazine (0.5 - 2.0 mg/kg) and thioridazine (0.5 - 4.0 mg/kg). These findings are discussed in view of the existing controversy regarding the mode of action of dopamine in the striatum. | The effect of some neuroleptics on the interaction of cortically and nigrally evoked potentials in the rat striatum. The interaction of cortico- and nigrofugal inputs to the striatum of the rat was investigated using the technique of evoked potentials. Repetitive, unilateral stimulation of the substantia nigra inhibited potentials which were evoked from the ipsilateral rostral cortex and recorded from the ipsilateral striatum. The inhibition was antagonized by low doses of various intraperitoneally administered neuroleptics such as: pimozide (0.1 - 0.2 mg/kg), haloperidol (0.1 - 0.5 mg/kg), chlorpromazine (0.5 - 2.0 mg/kg) and thioridazine (0.5 - 4.0 mg/kg). These findings are discussed in view of the existing controversy regarding the mode of action of dopamine in the striatum. | [
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PMID:27734 | The treatment of anxiety with a polyfluorinated benzodiazepine derivative. | Following 4 weeks of treatment with ORF-8063 a polyfluorinated benzodiazepine derivative, 8 hospitalized patients manifesting a primary pathology of anxiety showed marked general improvement. 2 other persons were treated, but for shorter periods: 9 and 14 days. Both are included in the pre-post analysis. Mean optimal dosage was 66.5 mg. The five instruments used to measure therapeutic effect showed pre- to posttreatment change with high level of statistical significance in serveral of the pathological factors. When measures of change are considered, patients showed more improvement related to psychic than somatic components of anxiety. Change data also indicates more patients improvement in anxiety than depression. Side effects reported more were dizziness, faintness and insomnia; these were reported in 8 patients. 6 patients noted drowsiness, and 4 noted excitement. 5 persons tolerated optimum dosages with no extreme reactions; 5 others (including the 2 subjects who terminated treatment early) were unable to maintain optimum dosages because of side effects. | The treatment of anxiety with a polyfluorinated benzodiazepine derivative. Following 4 weeks of treatment with ORF-8063 a polyfluorinated benzodiazepine derivative, 8 hospitalized patients manifesting a primary pathology of anxiety showed marked general improvement. 2 other persons were treated, but for shorter periods: 9 and 14 days. Both are included in the pre-post analysis. Mean optimal dosage was 66.5 mg. The five instruments used to measure therapeutic effect showed pre- to posttreatment change with high level of statistical significance in serveral of the pathological factors. When measures of change are considered, patients showed more improvement related to psychic than somatic components of anxiety. Change data also indicates more patients improvement in anxiety than depression. Side effects reported more were dizziness, faintness and insomnia; these were reported in 8 patients. 6 patients noted drowsiness, and 4 noted excitement. 5 persons tolerated optimum dosages with no extreme reactions; 5 others (including the 2 subjects who terminated treatment early) were unable to maintain optimum dosages because of side effects. | [
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PMID:27735 | Duration of apnea needed to confirm brain death. | To determine the duration of respiratory arrest needed to attain a PaCO2 level high enough to provide maximal stimulation of respiration, we evaluated changes in PaCO2, PaO2 and apH during periods of apnea lasting as long as 10 minutes in 10 apparently brain-dead subjects. Before apnea, mean PaCO2 was 33 mm Hg. In seven subjects who did not breathe for 10 minutes, the mean rate of rise of PaCO2 was 3.2 mm Hg per minute. PaCO2 at 4 minutes was 50 mm Hg and at 10 minutes was 67 mm Hg. Three subjects breathed, two after less than 2 minutes of apnea, when PaCO2 was 47 and 54 mm Hg, and one after 4.5 minutes, when PaCO2 was 47 mm Hg. These data indicate: (1) that the threshold for respiratory stimulation may approach a PaCO2 of 60 mm Hg in patients with brain damage; (2) that the rate of increase in PaCO2 is such that, even in a normocapnic subject after 3 minutes of apnea, the PaCO2 may not be sufficiently high to stimulate respiration; and (3) if a patient is hypocapnic prior to the onset of apnea, PaCO2 may not reach 60 mm Hg even after 15 minutes. To confirm absolute apnea, then, blood gas monitoring is necessary for verification of normocapnia prior to the beginning of apnea. In the absence of blood gas determinations, no fixed period of apnea, sufficient in all cases to establish absolute apnea, can be ascertained. | Duration of apnea needed to confirm brain death. To determine the duration of respiratory arrest needed to attain a PaCO2 level high enough to provide maximal stimulation of respiration, we evaluated changes in PaCO2, PaO2 and apH during periods of apnea lasting as long as 10 minutes in 10 apparently brain-dead subjects. Before apnea, mean PaCO2 was 33 mm Hg. In seven subjects who did not breathe for 10 minutes, the mean rate of rise of PaCO2 was 3.2 mm Hg per minute. PaCO2 at 4 minutes was 50 mm Hg and at 10 minutes was 67 mm Hg. Three subjects breathed, two after less than 2 minutes of apnea, when PaCO2 was 47 and 54 mm Hg, and one after 4.5 minutes, when PaCO2 was 47 mm Hg. These data indicate: (1) that the threshold for respiratory stimulation may approach a PaCO2 of 60 mm Hg in patients with brain damage; (2) that the rate of increase in PaCO2 is such that, even in a normocapnic subject after 3 minutes of apnea, the PaCO2 may not be sufficiently high to stimulate respiration; and (3) if a patient is hypocapnic prior to the onset of apnea, PaCO2 may not reach 60 mm Hg even after 15 minutes. To confirm absolute apnea, then, blood gas monitoring is necessary for verification of normocapnia prior to the beginning of apnea. In the absence of blood gas determinations, no fixed period of apnea, sufficient in all cases to establish absolute apnea, can be ascertained. | [
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PMID:27736 | Thiamine deficiency: selective impairment of the cerebellar serotonergic system. | To explore the role of thiamine deficiency in synaptic transmission, the high-affinity uptake and release systems for putative neurotransmitters were studied in synaptosomal preparations isolated from the telencephalon, hypothalamus, and cerebellum of rats made thiamine deficient by diet or pyrithiamine. There was significant decrease in the uptake of serotonin by the synaptosomal preparations of the cerebellum. Although thiamine and its phosphorylated forms added in vitro did not restore the decreased serotonin uptake, the administration of the vitamin in vivo resulted in a significant reversibility of the inhibition of serotonin uptake, coinciding with dramatic clinical improvement. The study supports the possibility of an important serotonergic innervation of the cerebellum and suggests a selective involvement of this system in the pathogenesis of some of the neurologic manifestations of thiamine deficiency. | Thiamine deficiency: selective impairment of the cerebellar serotonergic system. To explore the role of thiamine deficiency in synaptic transmission, the high-affinity uptake and release systems for putative neurotransmitters were studied in synaptosomal preparations isolated from the telencephalon, hypothalamus, and cerebellum of rats made thiamine deficient by diet or pyrithiamine. There was significant decrease in the uptake of serotonin by the synaptosomal preparations of the cerebellum. Although thiamine and its phosphorylated forms added in vitro did not restore the decreased serotonin uptake, the administration of the vitamin in vivo resulted in a significant reversibility of the inhibition of serotonin uptake, coinciding with dramatic clinical improvement. The study supports the possibility of an important serotonergic innervation of the cerebellum and suggests a selective involvement of this system in the pathogenesis of some of the neurologic manifestations of thiamine deficiency. | [
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PMID:27745 | [Infestation of mosquitoes from the Maritime Territory by the entomopathogenic fungus, Coelomomyces iliensis, under laboratory conditions]. | The infection of larvae of Culex pipiens molestus, C. vagans and C. tritaeniorhynchus (the vector of the virus of Japanese encephalitis) with the entomopathogenic fungus Coelomomyces iliensis from Kazakhstan was carried out in the Primorje Territory in 1973--1974. At the infection of larvae of C. tritaeniorhynchus with the suspension of infected larvae the mortality was recorded only from 60% of individuals, while at the infection with a content of sporangia--from 36.6% of larvae. Somewhat less mortality (27.5%) was observed among larvae of C. pipiens molestus and C. pipiens. In control the mortali larvae did not exceed 5%. | [Infestation of mosquitoes from the Maritime Territory by the entomopathogenic fungus, Coelomomyces iliensis, under laboratory conditions]. The infection of larvae of Culex pipiens molestus, C. vagans and C. tritaeniorhynchus (the vector of the virus of Japanese encephalitis) with the entomopathogenic fungus Coelomomyces iliensis from Kazakhstan was carried out in the Primorje Territory in 1973--1974. At the infection of larvae of C. tritaeniorhynchus with the suspension of infected larvae the mortality was recorded only from 60% of individuals, while at the infection with a content of sporangia--from 36.6% of larvae. Somewhat less mortality (27.5%) was observed among larvae of C. pipiens molestus and C. pipiens. In control the mortali larvae did not exceed 5%. | [
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PMID:27752 | Interaction of peripheral and central respiratory drives in cats. I. Effects of sodium cyanide as a peripheral chemoreceptor stimulus at different levels of CSF pH. | In cats anesthetized with chloralose-urethane, the central respiratory chemoreceptors were exposed to mock CSF of pH 7.02, 7.02, or 7.57. The right carotid body was simultaneously stimulated by intracarotid injections of 40, 80, or 160 microgram sodium cyanide in 200 microliter Ringer solution. The left carotid nerve and, in some animals, both vagosympathetic truncs were dissected. It could be demonstrated that the increase in ventilation produced by application of NaCN to the peripheral chemoreceptors is significantly larger at high than at low mock CSF pH (i.e. at low than at high central stimulus intensity). In vagotomized cats the responses of VT and V to NaCN similarly depend upon CSF pH; they are somewhat larger, though, than in intact animals. These results are discussed as compared with results reported by different authors. | Interaction of peripheral and central respiratory drives in cats. I. Effects of sodium cyanide as a peripheral chemoreceptor stimulus at different levels of CSF pH. In cats anesthetized with chloralose-urethane, the central respiratory chemoreceptors were exposed to mock CSF of pH 7.02, 7.02, or 7.57. The right carotid body was simultaneously stimulated by intracarotid injections of 40, 80, or 160 microgram sodium cyanide in 200 microliter Ringer solution. The left carotid nerve and, in some animals, both vagosympathetic truncs were dissected. It could be demonstrated that the increase in ventilation produced by application of NaCN to the peripheral chemoreceptors is significantly larger at high than at low mock CSF pH (i.e. at low than at high central stimulus intensity). In vagotomized cats the responses of VT and V to NaCN similarly depend upon CSF pH; they are somewhat larger, though, than in intact animals. These results are discussed as compared with results reported by different authors. | [
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PMID:27756 | [Gastric acid secretion by vagal electrostimulation (author's transl)]. | In the operative verification of vagotomy, electrical stimulation of the vagus nerves with the study of pH should seem to be a reliable method. On the basis of an experiment in the cat, the authors emphasise the effectiveness of electrical stimulation of gastric acid secretion, confirmed by 16 clinical cases. Stimulation of the proximal end of the divided right nerve may be used to detect a nervous strand arising above the level of the section and to confirm the completeness of left vagotomy. | [Gastric acid secretion by vagal electrostimulation (author's transl)]. In the operative verification of vagotomy, electrical stimulation of the vagus nerves with the study of pH should seem to be a reliable method. On the basis of an experiment in the cat, the authors emphasise the effectiveness of electrical stimulation of gastric acid secretion, confirmed by 16 clinical cases. Stimulation of the proximal end of the divided right nerve may be used to detect a nervous strand arising above the level of the section and to confirm the completeness of left vagotomy. | [
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PMID:27761 | Protonated polynucleotides structures - 22.CD study of the acid-base titration of poly(dG).poly(dC). | The acid-base titration (pH 8 --> pH 2.5 --> pH 8) of eleven mixing curve samples of the poly(dG) plus poly(dC) system has been performed in 0.15 M NaCl. Upon protonation, poly(dG).poly(dC) gives rise to an acid complex, in various amounts according to the origin of the sample. We have established that the hysteresis of the acid-base titration is due to the non-reversible formation of an acid complex, and the liberation of the homopolymers at the end of the acid titration and during the base titration: the homopolymer mixtures remain stable up to pH 7. A 1G:1C stoichiometry appears to be the most probable for the acid complex, a 1G:2C stoichiometry, as found in poly(C(+)).poly(I).poly(C) or poly(C(+)).poly(G).poly(C), cannot be rejected. In the course of this study, evidence has been found that the structural consequences of protonation could be similar for both double stranded poly(dG).poly(dC) and G-C rich DNA's: 1) protonation starts near pH 6, dissociation of the acid complex of poly(dG).poly(dC) and of protonated DNA take place at pH 3; 2) the CD spectrum computed for the acid polymer complex displays a positive peak at 255 nm as found in the acid spectra of DNA's; 3) double stranded poly(dG).poly(dC) embedded in triple-stranded poly(dG).poly(dG).poly(dC) should be in the A-form and appears to be prevented from the proton induced conformational change. The neutral triple stranded poly(dG).poly(dG).poly(dC) appears therefore responsible, although indirectly, for the complexity and variability of the acid titration of poly(dG).poly(dC) samples. | Protonated polynucleotides structures - 22.CD study of the acid-base titration of poly(dG).poly(dC). The acid-base titration (pH 8 --> pH 2.5 --> pH 8) of eleven mixing curve samples of the poly(dG) plus poly(dC) system has been performed in 0.15 M NaCl. Upon protonation, poly(dG).poly(dC) gives rise to an acid complex, in various amounts according to the origin of the sample. We have established that the hysteresis of the acid-base titration is due to the non-reversible formation of an acid complex, and the liberation of the homopolymers at the end of the acid titration and during the base titration: the homopolymer mixtures remain stable up to pH 7. A 1G:1C stoichiometry appears to be the most probable for the acid complex, a 1G:2C stoichiometry, as found in poly(C(+)).poly(I).poly(C) or poly(C(+)).poly(G).poly(C), cannot be rejected. In the course of this study, evidence has been found that the structural consequences of protonation could be similar for both double stranded poly(dG).poly(dC) and G-C rich DNA's: 1) protonation starts near pH 6, dissociation of the acid complex of poly(dG).poly(dC) and of protonated DNA take place at pH 3; 2) the CD spectrum computed for the acid polymer complex displays a positive peak at 255 nm as found in the acid spectra of DNA's; 3) double stranded poly(dG).poly(dC) embedded in triple-stranded poly(dG).poly(dG).poly(dC) should be in the A-form and appears to be prevented from the proton induced conformational change. The neutral triple stranded poly(dG).poly(dG).poly(dC) appears therefore responsible, although indirectly, for the complexity and variability of the acid titration of poly(dG).poly(dC) samples. | [
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PMID:27762 | Protonated polynucleotides structures - 23. The acid-base hysteresis of poly(dG).poly(dC). | The large hysteresis observed during the acid-base titration of poly(dG). poly (dC) was studied by CD and potentiometric scanning curves. Intermediate scanning loops as well as the equilibrium and metastable branches of the hysteresis loop have been determined. The potentiometric titrations showed, however, that the various complexes were not discrete entities, but were linked in "polycomplexes" as had been already suggested. This prevented a thermodynamic study of the system. The acid-base titration was further investigated as a function of ionic strength and temperature. The pK's showed considerably lower ionic strength dependence than observed for polyribonucleotide complexes. The thermal transitions permitted to establish the relative stabilities of the various complexes between pH 2.5 and pH 12.0. | Protonated polynucleotides structures - 23. The acid-base hysteresis of poly(dG).poly(dC). The large hysteresis observed during the acid-base titration of poly(dG). poly (dC) was studied by CD and potentiometric scanning curves. Intermediate scanning loops as well as the equilibrium and metastable branches of the hysteresis loop have been determined. The potentiometric titrations showed, however, that the various complexes were not discrete entities, but were linked in "polycomplexes" as had been already suggested. This prevented a thermodynamic study of the system. The acid-base titration was further investigated as a function of ionic strength and temperature. The pK's showed considerably lower ionic strength dependence than observed for polyribonucleotide complexes. The thermal transitions permitted to establish the relative stabilities of the various complexes between pH 2.5 and pH 12.0. | [
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PMID:27763 | Cross-linking of nucleosomal histones with monofunctional imidoesters. | Cross-linking experiments with the MONOfunctional imidoester methyl-acetimidate, in the pH range 7.0 - 8.0, on rat liver nucleosomes generate a cross-linking pattern almost identical with the one observed for much longer BIfunctional reagents (e.g. dimethylsuberimidate). Combined cross-linking and trypsin digestion experiments suggest that all or at least the great majority of this cross-linking occurs on trypsin digestible segments (or "tails") of the histones. The formation of oligomers over such extremely short distances and especially the observation of an H3 homodimer suggests a very close proximity of half-nucleosomes. | Cross-linking of nucleosomal histones with monofunctional imidoesters. Cross-linking experiments with the MONOfunctional imidoester methyl-acetimidate, in the pH range 7.0 - 8.0, on rat liver nucleosomes generate a cross-linking pattern almost identical with the one observed for much longer BIfunctional reagents (e.g. dimethylsuberimidate). Combined cross-linking and trypsin digestion experiments suggest that all or at least the great majority of this cross-linking occurs on trypsin digestible segments (or "tails") of the histones. The formation of oligomers over such extremely short distances and especially the observation of an H3 homodimer suggests a very close proximity of half-nucleosomes. | [
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PMID:27764 | An efficient in vitro total reconstitution of the Escherichia coli 50S ribosomal subunit. | A new, relatively simple technique for the total invitro reconstitution of E. coli 50S ribosomes has been developed. It is a two-step procedure like that previously reported by Nierhaus and Dohme [Proc. Natl. Acad. Sci. 71, 4713 (1974)], but it differs in a number of important aspects. Ribosomal RNA is prepared by direct phenol extraction of 70S particles to minimize nuclease fragmentation. A mixture of 50S proteins is prepared by acetic acid extraction and immediate removal of the acetic acid by thin film dialysis. The resulting protein mixture is soluble and stable. Separate RNA and protein fractions are mixed, incubated first at 44 degrees C in 7.5 mM Mg(2+), and then at 50 degrees C in 20 mM Mg(2+). The resulting 50S particles comigrate with native 50S particles in analytical gradients. They range from 50 to 100% active in five different functional assays. This is a fairly stringent test of the effectiveness of reconstitution since 50S particles derived from highly active vacant couples were used as a control.Images | An efficient in vitro total reconstitution of the Escherichia coli 50S ribosomal subunit. A new, relatively simple technique for the total invitro reconstitution of E. coli 50S ribosomes has been developed. It is a two-step procedure like that previously reported by Nierhaus and Dohme [Proc. Natl. Acad. Sci. 71, 4713 (1974)], but it differs in a number of important aspects. Ribosomal RNA is prepared by direct phenol extraction of 70S particles to minimize nuclease fragmentation. A mixture of 50S proteins is prepared by acetic acid extraction and immediate removal of the acetic acid by thin film dialysis. The resulting protein mixture is soluble and stable. Separate RNA and protein fractions are mixed, incubated first at 44 degrees C in 7.5 mM Mg(2+), and then at 50 degrees C in 20 mM Mg(2+). The resulting 50S particles comigrate with native 50S particles in analytical gradients. They range from 50 to 100% active in five different functional assays. This is a fairly stringent test of the effectiveness of reconstitution since 50S particles derived from highly active vacant couples were used as a control.Images | [
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PMID:27765 | The isolation of duplex DNA fragments containing (dG.dC) clusters by chromatography on poly(rC)-Sephadex. | Duplex DNA containing oligo(dG.dC)-rich clusters can be isolated by specific binding to poly(rC)-Sephadex. This binding, probably mediated by the formation of an oligo(dG.dC)rC+ triple helix, is optimal at pH 5 in 50% formamide, 2 M LiCl; the bound DNA is recovered by elution at pH 7.5. Using this method we find that the viral DNAs PM2, lambda and SV40 contain at least 1, 1 and 2 sites for binding to poly(rC)-Sephadex, respectively. These binding sites have been mapped in the case of SV40; the binding sites can in turn be used for physical mapping studies of DNAs containing (dG.dC) clusters. Inspection of the sequence of the bound fragments of SV40 DNA shows that a (dG.dC)6-7 tract is required for the binding of duplex DNA to poly(rC)-Sephadex. Although about 60% of rabbit DNA cleaved with restriction endonuclease KpnI binds to poly(rC)-Sephadex, no binding is observed for the 5.1 kb DNA fragment generated by KpnI digestion, which contains the rabbit beta-globin gene. This indicates that oligo(dG.dC) clusters are not found close to the rabbit beta-globin gene. | The isolation of duplex DNA fragments containing (dG.dC) clusters by chromatography on poly(rC)-Sephadex. Duplex DNA containing oligo(dG.dC)-rich clusters can be isolated by specific binding to poly(rC)-Sephadex. This binding, probably mediated by the formation of an oligo(dG.dC)rC+ triple helix, is optimal at pH 5 in 50% formamide, 2 M LiCl; the bound DNA is recovered by elution at pH 7.5. Using this method we find that the viral DNAs PM2, lambda and SV40 contain at least 1, 1 and 2 sites for binding to poly(rC)-Sephadex, respectively. These binding sites have been mapped in the case of SV40; the binding sites can in turn be used for physical mapping studies of DNAs containing (dG.dC) clusters. Inspection of the sequence of the bound fragments of SV40 DNA shows that a (dG.dC)6-7 tract is required for the binding of duplex DNA to poly(rC)-Sephadex. Although about 60% of rabbit DNA cleaved with restriction endonuclease KpnI binds to poly(rC)-Sephadex, no binding is observed for the 5.1 kb DNA fragment generated by KpnI digestion, which contains the rabbit beta-globin gene. This indicates that oligo(dG.dC) clusters are not found close to the rabbit beta-globin gene. | [
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PMID:27766 | Histone H1--DNA interaction. On the mechanism of DNA strands crosslinking by histone H1. | Crosslinking of DNA fibers by histone H1 or phosphorylated on Ser-37 histone H1, and by the individual fragments of the H1 polypeptide chain was studied by the method of turbidimetry. The dependence of the turbidity of DNA-protein complexes on the ionic strength in solution suggests that the condensation of H1.DNA complexes in vitro is apparently due to both specific histone-DNA interactions with the contribution of hydrogen and/or hydrophobic bonds and the formation of polycationic "bridges" fastening the DNA fibers. The effectiveness of the condensation is postulated to be a function of a proportion between the two mechanisms which in turn can be controlled by slight changes in ionic surroundings. The sharp dependence of shrinkage of H1.DNA complexes on ionic strength at "physiological" salt concentrations could provide a mechanism to regulate density and consequently the total activity of chromatin in the cell nuclei. The phosphorylation of histone H1 on Ser-37 by a specific histone kinase does not noticeably affect the pattern of DNA crosslinking by the H1. | Histone H1--DNA interaction. On the mechanism of DNA strands crosslinking by histone H1. Crosslinking of DNA fibers by histone H1 or phosphorylated on Ser-37 histone H1, and by the individual fragments of the H1 polypeptide chain was studied by the method of turbidimetry. The dependence of the turbidity of DNA-protein complexes on the ionic strength in solution suggests that the condensation of H1.DNA complexes in vitro is apparently due to both specific histone-DNA interactions with the contribution of hydrogen and/or hydrophobic bonds and the formation of polycationic "bridges" fastening the DNA fibers. The effectiveness of the condensation is postulated to be a function of a proportion between the two mechanisms which in turn can be controlled by slight changes in ionic surroundings. The sharp dependence of shrinkage of H1.DNA complexes on ionic strength at "physiological" salt concentrations could provide a mechanism to regulate density and consequently the total activity of chromatin in the cell nuclei. The phosphorylation of histone H1 on Ser-37 by a specific histone kinase does not noticeably affect the pattern of DNA crosslinking by the H1. | [
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PMID:27767 | In vitro transcription in E. coli crude lysates prepared on cellophane discs. | An in vitro RNA-synthesizing system consisting of gently lysed E. coli cells on cellophane discs is described. The system has been optimalized with respect to total RNA synthesis. Under certain standard conditions DNA dependent RNA polymerase (EC 2.7.7.6) is responsible for the majority of the RNA synthesis. The extensive rifampicin sensitivity of the synthesis indicates that most of the transcripts are initiated in vitro. The RNA synthesizing system described here has been developed with the aim of studying phage transcription in vitro. We show here that lysates of a P4 infected P2 lysogen support initiation and propagation of transcription from the P2 prophage. | In vitro transcription in E. coli crude lysates prepared on cellophane discs. An in vitro RNA-synthesizing system consisting of gently lysed E. coli cells on cellophane discs is described. The system has been optimalized with respect to total RNA synthesis. Under certain standard conditions DNA dependent RNA polymerase (EC 2.7.7.6) is responsible for the majority of the RNA synthesis. The extensive rifampicin sensitivity of the synthesis indicates that most of the transcripts are initiated in vitro. The RNA synthesizing system described here has been developed with the aim of studying phage transcription in vitro. We show here that lysates of a P4 infected P2 lysogen support initiation and propagation of transcription from the P2 prophage. | [
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PMID:27775 | Hospital phobia: a rapid desensitization technique. | The less disabling phobias do not normally present a problem in that the stimulus may be avoided. This would also apply to hospital phobia until an acute medical or surgical problem might arise, when avoidance could constitute a direct threat to life. Although phobic illness is a common problem the small number of cases of hospital phobia recorded may represent the tip of the iceberg beneath which could be many phobic patients who deny their symptoms and risk their health because of their irrational fear. A case of hopsital phobia in a pregnant patient with suspected disproportion was treated by a rapid desensitization technique using hypnosis. After five sessions of 30 min each, the patient was symptom free. This simple method of desensitization, if more widely known would considerably minimize the risk caused by concealment of the phobic problem. | Hospital phobia: a rapid desensitization technique. The less disabling phobias do not normally present a problem in that the stimulus may be avoided. This would also apply to hospital phobia until an acute medical or surgical problem might arise, when avoidance could constitute a direct threat to life. Although phobic illness is a common problem the small number of cases of hospital phobia recorded may represent the tip of the iceberg beneath which could be many phobic patients who deny their symptoms and risk their health because of their irrational fear. A case of hopsital phobia in a pregnant patient with suspected disproportion was treated by a rapid desensitization technique using hypnosis. After five sessions of 30 min each, the patient was symptom free. This simple method of desensitization, if more widely known would considerably minimize the risk caused by concealment of the phobic problem. | [
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PMID:27779 | [Effect of cultivation temperature and pH on the biosynthesis of extracellular phosphohydrolases by the culture Penicillium brevi-compactum]. | The effect of cultivation temperature and pH on growth of the culture Penicillium brevi-compactum and biosynthesis of extracellular phosphohydrolases (acid and alkaline RNases and acid PMEase) involved in RNA degradation was studied. The maximum growth of the culture was seen at 30 degrees and pA-7.0 and its maximum physiological activity with respect to the above enzymes was noted at 24 degrees and pH = 3.0, i.e. optimal conditions for the biosynthesis of phosphohydrolases did not coincide with those for the culture growth. The cultivation temperature and pH produced an effect on the oxygen consumption and synthesis of extracellular phosphohydrolases by the culture. | [Effect of cultivation temperature and pH on the biosynthesis of extracellular phosphohydrolases by the culture Penicillium brevi-compactum]. The effect of cultivation temperature and pH on growth of the culture Penicillium brevi-compactum and biosynthesis of extracellular phosphohydrolases (acid and alkaline RNases and acid PMEase) involved in RNA degradation was studied. The maximum growth of the culture was seen at 30 degrees and pA-7.0 and its maximum physiological activity with respect to the above enzymes was noted at 24 degrees and pH = 3.0, i.e. optimal conditions for the biosynthesis of phosphohydrolases did not coincide with those for the culture growth. The cultivation temperature and pH produced an effect on the oxygen consumption and synthesis of extracellular phosphohydrolases by the culture. | [
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PMID:27783 | Hydrolysis of poly (A) to adenine nucleotides by purified poly (A) polymerase. | Highly purified poly(A) polymerase (polynucleotide adenylyltransferase, EC 2.7.7.19), which synthesizes poly(A) from ATP substrate, can also catalyze hydrolysis of poly(A). The enzyme, designated as poly(A) hydrolase, requires either Mn2+ or Mg2+ for activity. Although AMP is the predominant product of the reaction, ADP and ATP are also formed. The enzyme is a 3'-exonuclease that does not degrade poly(A) associated with poly(A) poly(U) helical structure. AMP, ADP, and ATP inhibit the hydrolytic reaction. These data suggest that (i) the levels of adenine nucleotides regulate synthesis and degradation of poly(A), (ii) poly(A) itself is a storage form of adenine nucleotides, (iii) the hydrolytic reaction is responsible for poly(A) shortening or turnover observed in vivo, and (iv) the synthetic and hydrolytic activities are functions of the same protein molecule. | Hydrolysis of poly (A) to adenine nucleotides by purified poly (A) polymerase. Highly purified poly(A) polymerase (polynucleotide adenylyltransferase, EC 2.7.7.19), which synthesizes poly(A) from ATP substrate, can also catalyze hydrolysis of poly(A). The enzyme, designated as poly(A) hydrolase, requires either Mn2+ or Mg2+ for activity. Although AMP is the predominant product of the reaction, ADP and ATP are also formed. The enzyme is a 3'-exonuclease that does not degrade poly(A) associated with poly(A) poly(U) helical structure. AMP, ADP, and ATP inhibit the hydrolytic reaction. These data suggest that (i) the levels of adenine nucleotides regulate synthesis and degradation of poly(A), (ii) poly(A) itself is a storage form of adenine nucleotides, (iii) the hydrolytic reaction is responsible for poly(A) shortening or turnover observed in vivo, and (iv) the synthetic and hydrolytic activities are functions of the same protein molecule. | [
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PMID:27780 | [Examination of the action of effectors after storing glutamine synthetase from the fodder yeast Candida tropicalis at room temperature]. | The pattern of action of effectors (AMP, IMP, CMP, anthranilic acid, tryptophane, alanine, glutamine, glycine, histidine) and glutamine synthetase (GS) extracted from the fodder yeast Candida tropicalis and stored at room temperature for 1.5-2 hrs was examined. As regards the action of effectors on GS after its exposure at room temperature, they can be subdivided into four groups: 1) the effector loses completely its inhibitory effect (glutamine, CMP, anthranilic acid in the synthetase reaction); 2) the inhibitory effect on the enzyme increases (AMP, IMP, anthranilic acid in the transferase reaction); 3) at low concentrations of the effector the peak of activation appears (tryptophane, GMP, alanine, glycine); 4) at low concentrations of the enzyme two peaks of activation appear (histidine). Similar results were obtained with the purified preparation of GS. | [Examination of the action of effectors after storing glutamine synthetase from the fodder yeast Candida tropicalis at room temperature]. The pattern of action of effectors (AMP, IMP, CMP, anthranilic acid, tryptophane, alanine, glutamine, glycine, histidine) and glutamine synthetase (GS) extracted from the fodder yeast Candida tropicalis and stored at room temperature for 1.5-2 hrs was examined. As regards the action of effectors on GS after its exposure at room temperature, they can be subdivided into four groups: 1) the effector loses completely its inhibitory effect (glutamine, CMP, anthranilic acid in the synthetase reaction); 2) the inhibitory effect on the enzyme increases (AMP, IMP, anthranilic acid in the transferase reaction); 3) at low concentrations of the effector the peak of activation appears (tryptophane, GMP, alanine, glycine); 4) at low concentrations of the enzyme two peaks of activation appear (histidine). Similar results were obtained with the purified preparation of GS. | [
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PMID:27781 | [Kinetics and stability of glucooxidase from Penicillium vitale]. | The kinetics, thermal stability and ultrasonic resistance of glucosoxidase from Penicillium vitale have been investigated. Its oxidative constant is close to, catalytic constant is 1.7 times less and the reductive constant is 5.4 times more than the respective constants of the enzyme from Aspergillus niger. The relationship between the thermal inactivation constant (k(i)=2.1 pT 15.3. The same relationship is true of the ultrasonic inactivation constant and pH in the pH range of 6.5-8.0. In a more acidic medium the rate of ultrasonic inactivation shows an insignificant dependence on pH. The mechanism of enzyme inactivation is discussed. | [Kinetics and stability of glucooxidase from Penicillium vitale]. The kinetics, thermal stability and ultrasonic resistance of glucosoxidase from Penicillium vitale have been investigated. Its oxidative constant is close to, catalytic constant is 1.7 times less and the reductive constant is 5.4 times more than the respective constants of the enzyme from Aspergillus niger. The relationship between the thermal inactivation constant (k(i)=2.1 pT 15.3. The same relationship is true of the ultrasonic inactivation constant and pH in the pH range of 6.5-8.0. In a more acidic medium the rate of ultrasonic inactivation shows an insignificant dependence on pH. The mechanism of enzyme inactivation is discussed. | [
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PMID:27784 | Isolation of a low molecular weight Ca2+ carrier from calf heart inner mitochondrial membrane. | A protein was isolated from calf heart inner mitochondrial membrane with the aid of an electron paramagnetic resonance assay based on the relative binding properties of Ca2+, Mn2+, and Mg2+ to the protein. The molecular weight of this protein has been estimated to be about 3000 by urea/sodium dodecyl sulfate gel electrophoresis and amino acid analysis. The protein is shown to have two classes of binding sites for Ca2+ by flow dialysis studies and can extract Ca2+ into an organic phase. The selectivity sequence of this protein determined from the organic solvent extraction experiments shows that it favors divalent cations over monovalent cations. Also, the relative selectivity sequence for divalent cations is Ca2+, Sr2+ greater than Mn2+ greater than Mg2+. Ruthenium red and La3+ are shown to inhibit the protein-mediated extraction of Ca2+ into the organic solvent. The calcium translocation in a Pressman cell by this protein is selectively driven by a hydrogen ion gradient. Control experiments indicate that the Ca2+ trnsport properties of the protein are not due to the contaminating phospholipids. It appears that we have isolated from the inner mitochondrial membrane a calcium carrier, which we have named "calciphorin." | Isolation of a low molecular weight Ca2+ carrier from calf heart inner mitochondrial membrane. A protein was isolated from calf heart inner mitochondrial membrane with the aid of an electron paramagnetic resonance assay based on the relative binding properties of Ca2+, Mn2+, and Mg2+ to the protein. The molecular weight of this protein has been estimated to be about 3000 by urea/sodium dodecyl sulfate gel electrophoresis and amino acid analysis. The protein is shown to have two classes of binding sites for Ca2+ by flow dialysis studies and can extract Ca2+ into an organic phase. The selectivity sequence of this protein determined from the organic solvent extraction experiments shows that it favors divalent cations over monovalent cations. Also, the relative selectivity sequence for divalent cations is Ca2+, Sr2+ greater than Mn2+ greater than Mg2+. Ruthenium red and La3+ are shown to inhibit the protein-mediated extraction of Ca2+ into the organic solvent. The calcium translocation in a Pressman cell by this protein is selectively driven by a hydrogen ion gradient. Control experiments indicate that the Ca2+ trnsport properties of the protein are not due to the contaminating phospholipids. It appears that we have isolated from the inner mitochondrial membrane a calcium carrier, which we have named "calciphorin." | [
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PMID:27785 | 31P nuclear magnetic resonance studies of bioenergetics and glycolysis in anaerobic Escherichia coli cells. | 31P nuclear magnetic resonance spectra of glycolyzing, anaerobic Escherichia coli cells and their perchloric acid extracts were obtained at 145.7 MHz. Time-dependent intracellular concentrations of nucleoside di- and triphosphates, Pi, and sugar phosphates were measured during glycolysis with 2-min resolution, while intracellular and extra-cellular pH values were monitored simultaneously. Upon glucose addition, anaerobic E. coli cells rapidly produce acids and develop a transmembrane pH gradient (delta pH). Glycolysis rates were calculated from the changes in the external pH. It was found that glycolysis rates are strongly dependent on internal pH, sharply decreasing when the pH drops below approximately 7.2. The ATPase inhibitor, dicyclohexylcarbodiimide (DCCD), prevented NTP hydrolysis and inhibited delta pH formation. The uncoupler, carbonyl cyanide p-triflouromethoxyphenyl hydrazone (FCCP), drastically reduced both the delta pH and the NTP level. When the cells were previously treated with DCCD, FCCP collapsed the delta pH while the NTP levels remained high. It is concluded that ATP produced by glycolysis is hydrolyzed by the membrane ATPase to generate a delta pH and that FCCP stimulates ATP hydrolysis by ATPase and collapses the proton gradient. | 31P nuclear magnetic resonance studies of bioenergetics and glycolysis in anaerobic Escherichia coli cells. 31P nuclear magnetic resonance spectra of glycolyzing, anaerobic Escherichia coli cells and their perchloric acid extracts were obtained at 145.7 MHz. Time-dependent intracellular concentrations of nucleoside di- and triphosphates, Pi, and sugar phosphates were measured during glycolysis with 2-min resolution, while intracellular and extra-cellular pH values were monitored simultaneously. Upon glucose addition, anaerobic E. coli cells rapidly produce acids and develop a transmembrane pH gradient (delta pH). Glycolysis rates were calculated from the changes in the external pH. It was found that glycolysis rates are strongly dependent on internal pH, sharply decreasing when the pH drops below approximately 7.2. The ATPase inhibitor, dicyclohexylcarbodiimide (DCCD), prevented NTP hydrolysis and inhibited delta pH formation. The uncoupler, carbonyl cyanide p-triflouromethoxyphenyl hydrazone (FCCP), drastically reduced both the delta pH and the NTP level. When the cells were previously treated with DCCD, FCCP collapsed the delta pH while the NTP levels remained high. It is concluded that ATP produced by glycolysis is hydrolyzed by the membrane ATPase to generate a delta pH and that FCCP stimulates ATP hydrolysis by ATPase and collapses the proton gradient. | [
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PMID:27786 | Selective labeling of alpha-adrenergic receptors in caudate nucleus by [3H] dihydroergocryptine in the presence of spiperone-blocked dopamine receptors. | Because it was known that [(3)H]dihydroergocryptine can label alpha-adrenergic receptors as well as dopamine receptors, this study was done to establish the conditions under which [(3)H]dihydroergocryptine would be a reliable ligand for selective labeling of alpha-adrenergic receptors. The calf caudate was chosen because it contains both dopamine and adrenergic receptors, and 5 nM spiperone (spiroperidol) was used to block the neuroleptic/dopamine receptors. Thus, in the presence of spiperone, [(3)H]dihydroergocryptine exhibited saturable binding with a K(d) of 0.73 nM and a total number of sites of 150 fmol/mg of protein. The catechol neurotransmitters competed for [(3)H]dihydroergocryptine binding in the potencies order epinephrine > (-)-norepinephrine > dopamine, indicating that [(3)H]dihydroergocryptine (in the presence of 5 nM spiperone) was revealing alpha receptors. The alpha-adrenergic antagonists also competed for binding in the appropriate order: phentolamine > phenoxybenzamine > dibenamine. Finally, chlorpromazine was more potent than haloperidol in competing for [(3)H]dihydroergocryptine, also in accord with the properties of alpha receptors. These results with [(3)H]dihydroergocryptine as an alpha-adrenergic receptor ligand correlate well with those published by others for [(3)H]WB-4101. | Selective labeling of alpha-adrenergic receptors in caudate nucleus by [3H] dihydroergocryptine in the presence of spiperone-blocked dopamine receptors. Because it was known that [(3)H]dihydroergocryptine can label alpha-adrenergic receptors as well as dopamine receptors, this study was done to establish the conditions under which [(3)H]dihydroergocryptine would be a reliable ligand for selective labeling of alpha-adrenergic receptors. The calf caudate was chosen because it contains both dopamine and adrenergic receptors, and 5 nM spiperone (spiroperidol) was used to block the neuroleptic/dopamine receptors. Thus, in the presence of spiperone, [(3)H]dihydroergocryptine exhibited saturable binding with a K(d) of 0.73 nM and a total number of sites of 150 fmol/mg of protein. The catechol neurotransmitters competed for [(3)H]dihydroergocryptine binding in the potencies order epinephrine > (-)-norepinephrine > dopamine, indicating that [(3)H]dihydroergocryptine (in the presence of 5 nM spiperone) was revealing alpha receptors. The alpha-adrenergic antagonists also competed for binding in the appropriate order: phentolamine > phenoxybenzamine > dibenamine. Finally, chlorpromazine was more potent than haloperidol in competing for [(3)H]dihydroergocryptine, also in accord with the properties of alpha receptors. These results with [(3)H]dihydroergocryptine as an alpha-adrenergic receptor ligand correlate well with those published by others for [(3)H]WB-4101. | [
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PMID:27787 | Multiple glycosidase deficiencies in a case of juvenile (type 3) Gaucher disease. | Biochemical investigations were performed on autopsy tissues obtained from an 11-year-old girl who died with the juvenile, subacute neuropathic form of Gaucher disease. In addition to the expected deficiency of glucocerebrosidase activity, extracts of both liver and kidney from this individual displayed a profound (greater than or equal to 90%) deficiency of "soluble" beta-glucosidase, beta-xylosidase, and beta-galactosidase activities. Fibroblasts obtained from this individual also contained markedly reduced levels of beta-xylosidase activity but normal levels of beta-D-fucosidase and beta-galactosidase activity. Because the soluble beta-glucosidase, beta-xylosidase, and a portion of the beta-galactosidase activities from control human liver all cochromatographed on a gel filtration column of Sephadex G-200, it is suggested that these activities all reside in a single enzyme, analogous to the situation described in a number of nonhuman, mammalian tissues. This demonstration of multiple glycosidase deficiencies in addition to the deficiency of glucocerebrosidase in a case of subacute neuropathic Gaucher disease suggests that other biochemical aberrations, in addition to a deficiency of glucocerebrosidase, might contribute to pathology in some cases of Gaucher disease. | Multiple glycosidase deficiencies in a case of juvenile (type 3) Gaucher disease. Biochemical investigations were performed on autopsy tissues obtained from an 11-year-old girl who died with the juvenile, subacute neuropathic form of Gaucher disease. In addition to the expected deficiency of glucocerebrosidase activity, extracts of both liver and kidney from this individual displayed a profound (greater than or equal to 90%) deficiency of "soluble" beta-glucosidase, beta-xylosidase, and beta-galactosidase activities. Fibroblasts obtained from this individual also contained markedly reduced levels of beta-xylosidase activity but normal levels of beta-D-fucosidase and beta-galactosidase activity. Because the soluble beta-glucosidase, beta-xylosidase, and a portion of the beta-galactosidase activities from control human liver all cochromatographed on a gel filtration column of Sephadex G-200, it is suggested that these activities all reside in a single enzyme, analogous to the situation described in a number of nonhuman, mammalian tissues. This demonstration of multiple glycosidase deficiencies in addition to the deficiency of glucocerebrosidase in a case of subacute neuropathic Gaucher disease suggests that other biochemical aberrations, in addition to a deficiency of glucocerebrosidase, might contribute to pathology in some cases of Gaucher disease. | [
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PMID:27788 | Reduction of membrane potential, an immediate effect of colicin K. | Colicin K causes a rapid and drastic reduction of the membrane potential of Escherichia coli cells, as measured by the uptake of the lipophilic cation triphenylmethylphosphonium. The colicin causes no major changes in the pH gradient, as measured by the uptake of butyric acid. The decrease in membrane potential following addition of colicin K to the cells is a prompt response that parallels or precedes known physiological effects such as efflux of accumulated substrates. Hence the loss of membrane potential qualifies as the primary action by which the colicin uncouples membrane-associated function from respiration. Certain peculiarities of bacterial cells pretreated with EDTA in their response to uncoupling agents and lipophilic ions are described. | Reduction of membrane potential, an immediate effect of colicin K. Colicin K causes a rapid and drastic reduction of the membrane potential of Escherichia coli cells, as measured by the uptake of the lipophilic cation triphenylmethylphosphonium. The colicin causes no major changes in the pH gradient, as measured by the uptake of butyric acid. The decrease in membrane potential following addition of colicin K to the cells is a prompt response that parallels or precedes known physiological effects such as efflux of accumulated substrates. Hence the loss of membrane potential qualifies as the primary action by which the colicin uncouples membrane-associated function from respiration. Certain peculiarities of bacterial cells pretreated with EDTA in their response to uncoupling agents and lipophilic ions are described. | [
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PMID:27820 | Neurochemical and operant behavioral studies of a strain of alcohol-preferring rats. | The levels of serotonin (5-HT), 5-hydroxyindoleacetic acid, tyrosine (TYR), norepinephrine (NE), acetylcholine, GABA, glutamate (GLU), aspartate (ASP), alanine, glycine (GLY) and taurine were measured in the CNS of adult male rats selectively inbred to the F8 generation for alcohol preference (P) and non-preference (NP). With respect to the values found in the NP group, higher levels of 5-HT, GABA, GLU and GLY and lower levels of ASP were found in the diencephalon-mesencephalon (D-M) and higher levels of NE were found in the telencephalon (TEL) of the P group. The animals in the P and NP strains were further subdivided into two additional groups, one given only H2O (W) and the second given 10% ethanol (A) during a one week period, thereby producing four groups (NP-W, NP-A, P-W and P-A). With these conditions, the level of (a) TYR in the D-M was higher in the P-A and NP-A animals than in the P-W and NP-W groups respectively; (b) 5-HT in the TEL was higher in the NP-A group than NP-W group; and (c) GABA in the TEL was higher in the P-A than P-W animals. No differences were observed in the cerebellum between the two strains or between the subgroups within each strain. The present study also demonstrated that the P animals will work in an operant situation to obtain 10% ethanol, even when H2O is freely available, and will voluntarily bar-press up to 6-7 times for each ethanol reinforcement. | Neurochemical and operant behavioral studies of a strain of alcohol-preferring rats. The levels of serotonin (5-HT), 5-hydroxyindoleacetic acid, tyrosine (TYR), norepinephrine (NE), acetylcholine, GABA, glutamate (GLU), aspartate (ASP), alanine, glycine (GLY) and taurine were measured in the CNS of adult male rats selectively inbred to the F8 generation for alcohol preference (P) and non-preference (NP). With respect to the values found in the NP group, higher levels of 5-HT, GABA, GLU and GLY and lower levels of ASP were found in the diencephalon-mesencephalon (D-M) and higher levels of NE were found in the telencephalon (TEL) of the P group. The animals in the P and NP strains were further subdivided into two additional groups, one given only H2O (W) and the second given 10% ethanol (A) during a one week period, thereby producing four groups (NP-W, NP-A, P-W and P-A). With these conditions, the level of (a) TYR in the D-M was higher in the P-A and NP-A animals than in the P-W and NP-W groups respectively; (b) 5-HT in the TEL was higher in the NP-A group than NP-W group; and (c) GABA in the TEL was higher in the P-A than P-W animals. No differences were observed in the cerebellum between the two strains or between the subgroups within each strain. The present study also demonstrated that the P animals will work in an operant situation to obtain 10% ethanol, even when H2O is freely available, and will voluntarily bar-press up to 6-7 times for each ethanol reinforcement. | [
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PMID:27827 | [Anxiety- an approach to defining terms and formulating a methodological concept for measuring anxiety states within the framework of clinical trials with anxiolytic substances (author's transl)]. | A methodological concept for measuring anxiety states and changes in anxiety states in clinical studies with anxiolytic substances is presented: Effectivity should be evaluated on several levels which include emotions, objects of anxiety, psychophysiology, biochemistry, and observed behavior. This test concept is based on new knowledge from behavior psychology, learning theory, psychology of testing, psychophysiology, biochemistry, neuroendocrinology, and psychiatry. In diagrams, important mechanisms of thr origin of experimental, stress-induced and pathological anxiety states are depicted. The point is stressed that anxiety is situational and fluctuates. | [Anxiety- an approach to defining terms and formulating a methodological concept for measuring anxiety states within the framework of clinical trials with anxiolytic substances (author's transl)]. A methodological concept for measuring anxiety states and changes in anxiety states in clinical studies with anxiolytic substances is presented: Effectivity should be evaluated on several levels which include emotions, objects of anxiety, psychophysiology, biochemistry, and observed behavior. This test concept is based on new knowledge from behavior psychology, learning theory, psychology of testing, psychophysiology, biochemistry, neuroendocrinology, and psychiatry. In diagrams, important mechanisms of thr origin of experimental, stress-induced and pathological anxiety states are depicted. The point is stressed that anxiety is situational and fluctuates. | [
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PMID:27823 | Determination of mepyramine, aminophenazone, nialamide and chloroquine using the deltapj method. | Mepyramine maleate, aminophenazone, nialamide and chloroquine phosphate are examples of compounds which do not fulfil the requirements of the delta A method. By the proper choice of polynomial and wavelengths, the deltapj method has been successfully applied to their determination. The mean percentage recoveries were found to be 100.2 +/- 0.8, 99.6 +/- 0.6, 99.1 +/- 1.7 and 100.4 +/- 1.3, respectively. | Determination of mepyramine, aminophenazone, nialamide and chloroquine using the deltapj method. Mepyramine maleate, aminophenazone, nialamide and chloroquine phosphate are examples of compounds which do not fulfil the requirements of the delta A method. By the proper choice of polynomial and wavelengths, the deltapj method has been successfully applied to their determination. The mean percentage recoveries were found to be 100.2 +/- 0.8, 99.6 +/- 0.6, 99.1 +/- 1.7 and 100.4 +/- 1.3, respectively. | [
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PMID:27828 | Autonomic perception and responses in anxiety-inducing situations. | The anxiolytic and sedative properties of a thienodiazepine (clotiazepam) were investigated in 40 healthy subjects with varying degrees of arousal and with the aid of specific anxiety-inducing conditions. A cross-over design with a double blind technique was used. EEG, heart and respiratory rate, peripheral pulse volume and skin resistance were measured during the anxiety-inducing conditions with the visualization of neutral and fearful situations as well as with the threat of shock. The mood, physical sensations and behaviour tendencies of the test subjects were determined by self-rating questionnaires. The anxiolytic and sedative effects of the thienodiazepine under study were able to be differentiated as far as subjective perception and autonomic responses were concerned. The development of sedative and anxiolytic effects is dependent on the subject's state of arousal. Situations involving the anticipation of anxiety are sufficient as proof of pharmacogenic anxiolysis. The tranquilizer reduces anxiety and physical tension, but does not influence the timing of autonomic readiness responses, and thus does not affect the coping strategies. | Autonomic perception and responses in anxiety-inducing situations. The anxiolytic and sedative properties of a thienodiazepine (clotiazepam) were investigated in 40 healthy subjects with varying degrees of arousal and with the aid of specific anxiety-inducing conditions. A cross-over design with a double blind technique was used. EEG, heart and respiratory rate, peripheral pulse volume and skin resistance were measured during the anxiety-inducing conditions with the visualization of neutral and fearful situations as well as with the threat of shock. The mood, physical sensations and behaviour tendencies of the test subjects were determined by self-rating questionnaires. The anxiolytic and sedative effects of the thienodiazepine under study were able to be differentiated as far as subjective perception and autonomic responses were concerned. The development of sedative and anxiolytic effects is dependent on the subject's state of arousal. Situations involving the anticipation of anxiety are sufficient as proof of pharmacogenic anxiolysis. The tranquilizer reduces anxiety and physical tension, but does not influence the timing of autonomic readiness responses, and thus does not affect the coping strategies. | [
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PMID:27829 | [Treatment of pain with psychotropic drugs (author's transl)]. | 30 patients suffering from therapy-resistant chronic pain were divided into three groups according to drive and mood: I. psychomotor inhibition combined with depressive mood, II. agitation and depressive mood, III. agitation combined normal mood. The psychopharmacological treatment of pain showed sufficient results, when the drugs were directed to the target symptoms "agitation", "lack of drive", and "depression". The differentiated administration of activating or sedative antidepressants and neuroleptics caused reduction or absence of pain while the routine administration of neuroleptics (i.e. chlorpromazine) was less effective. | [Treatment of pain with psychotropic drugs (author's transl)]. 30 patients suffering from therapy-resistant chronic pain were divided into three groups according to drive and mood: I. psychomotor inhibition combined with depressive mood, II. agitation and depressive mood, III. agitation combined normal mood. The psychopharmacological treatment of pain showed sufficient results, when the drugs were directed to the target symptoms "agitation", "lack of drive", and "depression". The differentiated administration of activating or sedative antidepressants and neuroleptics caused reduction or absence of pain while the routine administration of neuroleptics (i.e. chlorpromazine) was less effective. | [
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PMID:27832 | Early diagnosis of crepitant gangrene caused by Bacteroides melaninogenicus. | A rapid non-invasive test for the presence of B. melaninogenicus in the wounds of crepitant non-clostridial gangrene is described. The wounds are viewed under an ultraviolet light, and the presence of bright red fluorescene indicates the probable presence of B. melaninogenicus. | Early diagnosis of crepitant gangrene caused by Bacteroides melaninogenicus. A rapid non-invasive test for the presence of B. melaninogenicus in the wounds of crepitant non-clostridial gangrene is described. The wounds are viewed under an ultraviolet light, and the presence of bright red fluorescene indicates the probable presence of B. melaninogenicus. | [
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PMID:27830 | The effects of TAB and of adrenergic blocking drugs on the course of the experimental irradiation disease. | The experiment is aimed at establishing the consequences of the endotoxic stress (TAB) associated with alpha- or beta-adrenergic selective blocking drugs on the course of the acute irradiation disease in rats (700R, gamma rad Co60). TAB administered before or after irradiation, alone or associated with propranolol, increases the surviving rate at 30 and 60 days from exposure as compared to the controls (LD 95/30 days). Generally, dibenzyline has unfavourable effects on mortality and survival rate at the mentioned intervals. Based on the data obtained, an adrenergic component is analysed in achieving the survival increase by TAB and beta-adrenergic blocking substances; a hypothesis about the mechanisms involved is advanced. | The effects of TAB and of adrenergic blocking drugs on the course of the experimental irradiation disease. The experiment is aimed at establishing the consequences of the endotoxic stress (TAB) associated with alpha- or beta-adrenergic selective blocking drugs on the course of the acute irradiation disease in rats (700R, gamma rad Co60). TAB administered before or after irradiation, alone or associated with propranolol, increases the surviving rate at 30 and 60 days from exposure as compared to the controls (LD 95/30 days). Generally, dibenzyline has unfavourable effects on mortality and survival rate at the mentioned intervals. Based on the data obtained, an adrenergic component is analysed in achieving the survival increase by TAB and beta-adrenergic blocking substances; a hypothesis about the mechanisms involved is advanced. | [
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PMID:27831 | Some neural effects of adenosin. | The possible neural effects of adenosine were investigated by using electrophysiological techniques at the level of some central and peripheral synapses. The evoked potentials in the somatosensorial cerebral cortex are influenced according to both the type of administration and the level of the electrical stimulation. While the local application does not induce significant alterations, the intrathalamic injections and the perfusion of the IIIrd cerebral ventricle do change the distribution of activated units at the level of different cortical layers especially during the peripheral stimulation. The frequency of spontaneous miniature discharges intracellularly recorded in the neuromuscular junction (mepp) is significantly depressed by adenosine. This effect is calcium- and dose-dependent. The end plate potentials (EPP) were also depressed. The statistical binomial analysis of the phenomenon indicated that adenosine induces a decrease if the presynaptic pool of the available transmitter. The data obtained demonstrate a presynaptic inhibitory action of adenosine beside its known vascular and metaholic effects. | Some neural effects of adenosin. The possible neural effects of adenosine were investigated by using electrophysiological techniques at the level of some central and peripheral synapses. The evoked potentials in the somatosensorial cerebral cortex are influenced according to both the type of administration and the level of the electrical stimulation. While the local application does not induce significant alterations, the intrathalamic injections and the perfusion of the IIIrd cerebral ventricle do change the distribution of activated units at the level of different cortical layers especially during the peripheral stimulation. The frequency of spontaneous miniature discharges intracellularly recorded in the neuromuscular junction (mepp) is significantly depressed by adenosine. This effect is calcium- and dose-dependent. The end plate potentials (EPP) were also depressed. The statistical binomial analysis of the phenomenon indicated that adenosine induces a decrease if the presynaptic pool of the available transmitter. The data obtained demonstrate a presynaptic inhibitory action of adenosine beside its known vascular and metaholic effects. | [
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PMID:27835 | Use of antianxiety agents in anxious outpatients. | The present paper reviews the role of antianxiety agents in the treatment of nonpsychotic anxious patients. Major emphasis is placed on findings from clinical trials conducted by this research group. Consideration is given to the relative efficacy of available antianxiety agents, to patients response in relation to patterns of symptomatology, and to the degree of symptom relief experienced by drug-treated anxious patients. Also discussed are some of the many nonspecific factors that affect improvement with drug treatment in general and with the benzodiazepines in particular. It is concluded that many anxious patients are not currently receiving adequate drug treatment, and may require longer periods of drug therapy or supplemental nondrug intervention. | Use of antianxiety agents in anxious outpatients. The present paper reviews the role of antianxiety agents in the treatment of nonpsychotic anxious patients. Major emphasis is placed on findings from clinical trials conducted by this research group. Consideration is given to the relative efficacy of available antianxiety agents, to patients response in relation to patterns of symptomatology, and to the degree of symptom relief experienced by drug-treated anxious patients. Also discussed are some of the many nonspecific factors that affect improvement with drug treatment in general and with the benzodiazepines in particular. It is concluded that many anxious patients are not currently receiving adequate drug treatment, and may require longer periods of drug therapy or supplemental nondrug intervention. | [
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PMID:27836 | Neuropharmacological profile of clobazam, a new 1',5'-benzodiazepine. | The effect of the new 1,5-benzodiazepine clobazam on visual evoked potentials (VEP) and spontaneous EEG in the conscious rabbit and on spinal polysynaptic reflexes in the decerebrated cat was studied in comparison to the 1,4-benzodiazepine diazepam. Clobazam was half as potent as diazepam in depressing the amplitude of visual evoked potentials in the nonanaesthetized rabbit, whereas the depressing effect on spinal polysynaptic reflexes in the decerebrated cat was only 1/7 --1/30 of the diazepam effect. The action of clobazam and diazepam on VEP also showed differences in time course, i.e., the peak effect of clobazam lasted from 1 to 6 h after application, whereas the effect of diazepam appeared after 10 min and declined already after 1 h. Both compounds had similar effects on computer-analyzed spontaneous EEG in the rabbit (power spectrum analysis), with an increase of power in the beta-band (13-39Hz) and a decrease in the alpha (8-13 Hz) and theta (4-8Hz) bands. | Neuropharmacological profile of clobazam, a new 1',5'-benzodiazepine. The effect of the new 1,5-benzodiazepine clobazam on visual evoked potentials (VEP) and spontaneous EEG in the conscious rabbit and on spinal polysynaptic reflexes in the decerebrated cat was studied in comparison to the 1,4-benzodiazepine diazepam. Clobazam was half as potent as diazepam in depressing the amplitude of visual evoked potentials in the nonanaesthetized rabbit, whereas the depressing effect on spinal polysynaptic reflexes in the decerebrated cat was only 1/7 --1/30 of the diazepam effect. The action of clobazam and diazepam on VEP also showed differences in time course, i.e., the peak effect of clobazam lasted from 1 to 6 h after application, whereas the effect of diazepam appeared after 10 min and declined already after 1 h. Both compounds had similar effects on computer-analyzed spontaneous EEG in the rabbit (power spectrum analysis), with an increase of power in the beta-band (13-39Hz) and a decrease in the alpha (8-13 Hz) and theta (4-8Hz) bands. | [
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PMID:27846 | Studies on cholesterol esterification in human tissues. | In vitro cholesteryl synthesis from oleic acid [1-14C] was studied with enzyme preparations from human thoracic aorta and liver. Results from studies on the properties of the esterifying system provide good evidence that the mechanism involves fatty acyl-CoA-cholesterol acyl transferase. In studies on human thoracic aorta with varying degrees of atherosclerotic disease, and pairs of normal and diseased aorta from the same subject, there was no obvious relationship between aortic cholesteryl esterifying activity and severity of atheroma. Normal aorta from two young males, presumably free of atherosclerosis, had relatively very low esterifying activity. In the six liver samples tested, there was negligible esterifying activity, in contrast to the high activity seen in the case of rat liver. For the thin layer chromatographic isolation of the labeled cholesteryl oleate a solvent system of isooctane:diethyl ether (100:6) was found to give a better separation of the ester than the petroleum ether: diethylether:acetic acid system generally used. | Studies on cholesterol esterification in human tissues. In vitro cholesteryl synthesis from oleic acid [1-14C] was studied with enzyme preparations from human thoracic aorta and liver. Results from studies on the properties of the esterifying system provide good evidence that the mechanism involves fatty acyl-CoA-cholesterol acyl transferase. In studies on human thoracic aorta with varying degrees of atherosclerotic disease, and pairs of normal and diseased aorta from the same subject, there was no obvious relationship between aortic cholesteryl esterifying activity and severity of atheroma. Normal aorta from two young males, presumably free of atherosclerosis, had relatively very low esterifying activity. In the six liver samples tested, there was negligible esterifying activity, in contrast to the high activity seen in the case of rat liver. For the thin layer chromatographic isolation of the labeled cholesteryl oleate a solvent system of isooctane:diethyl ether (100:6) was found to give a better separation of the ester than the petroleum ether: diethylether:acetic acid system generally used. | [
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PMID:27847 | Inhibition of acute anaphylaxis in the chicken by anti-allergic drugs. | The anti-anaphylactic effects of four potential anti-allergic agents (DSCG: disodium cromoglycate, PRD-92-EA, M&B 22,948 and DECC: diethylcarbamazine citrate) were studied on cardiovascular responses of acute systemic anaphylaxis and chemical mediators of immediate hypersensitivity in chickens. Compounds M&B 22,948, PRD-92-EA, DSCG and DECC all inhibited cardiovascular manifestations of systemic anaphylaxis in domestic fowl. High doses of Compounds PRD-92 EA, M&B 22,948 and DECC also exhibited a nonspecific receptor blocking activity towards exogenously administered chemical mediators of anaphylaxis. | Inhibition of acute anaphylaxis in the chicken by anti-allergic drugs. The anti-anaphylactic effects of four potential anti-allergic agents (DSCG: disodium cromoglycate, PRD-92-EA, M&B 22,948 and DECC: diethylcarbamazine citrate) were studied on cardiovascular responses of acute systemic anaphylaxis and chemical mediators of immediate hypersensitivity in chickens. Compounds M&B 22,948, PRD-92-EA, DSCG and DECC all inhibited cardiovascular manifestations of systemic anaphylaxis in domestic fowl. High doses of Compounds PRD-92 EA, M&B 22,948 and DECC also exhibited a nonspecific receptor blocking activity towards exogenously administered chemical mediators of anaphylaxis. | [
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PMID:27848 | Comparison of the mechanisms controlling intracellular pH and sodium in snail neurones. | Ion-sensitive microelectrodes were used to record intracellular pH, Na+ and Cl- in snail neurones. NaCl or HCl was injected iontophoretically to compare the Na pump with the pHi regulating system. The Na pump was inhibited by ouabain, carbonyl cyanide m-chlorophenyl hydrazone and increasing the membrane potential, whereas the pHi regulating system was relatively unaffected. Activation of the Na pump had no effect on pHi whereas activation of the pHi recovery process increased internal Na+. Activation of the pHi recovery process by CO2 application increased internal Na+ and also decreased internal Cl-. The results show that there is no direct connexion between the Na pump and the pHi recovery process, and that the pHi recovery process is electroneutral, and appears not to require metabolic energy. The results also confirm that the pHi recovery process involves the influx of Na+ ions and the efflux of Cl- ions. | Comparison of the mechanisms controlling intracellular pH and sodium in snail neurones. Ion-sensitive microelectrodes were used to record intracellular pH, Na+ and Cl- in snail neurones. NaCl or HCl was injected iontophoretically to compare the Na pump with the pHi regulating system. The Na pump was inhibited by ouabain, carbonyl cyanide m-chlorophenyl hydrazone and increasing the membrane potential, whereas the pHi regulating system was relatively unaffected. Activation of the Na pump had no effect on pHi whereas activation of the pHi recovery process increased internal Na+. Activation of the pHi recovery process by CO2 application increased internal Na+ and also decreased internal Cl-. The results show that there is no direct connexion between the Na pump and the pHi recovery process, and that the pHi recovery process is electroneutral, and appears not to require metabolic energy. The results also confirm that the pHi recovery process involves the influx of Na+ ions and the efflux of Cl- ions. | [
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PMID:27849 | Intracellular acid-base state at a variable temperature in air-breathing vertebrates and its representation. | When temperature changes are superimposed on changes in the control variables of acid-base state (PCO2, strong ion difference), the understanding of acid-base changes becomes difficult. A solution has recently been proposed for blood (Malan, 1977); it was based on the assumption that closed system conditions correspond to a minimal change in the overall acid-base state when temperature varies. The feasibility of extending these concepts to muscle intracellular acid-base vs temperature relationships is evaluated on the basis of a model study; the errors made by replacing closed conditions (which require knowledge of chemical composition) by more convenient approximations are estimated. A representation of both extracellular and intracellular acid-base data on a temperature-corrected bicarbonate-pH diagram is derived. It allows the interpretation of variable-temperature intracellular acid-base changes in terms of changes in control variables, 'respiratory (PCO2) or 'metabolic' (strong ion difference). | Intracellular acid-base state at a variable temperature in air-breathing vertebrates and its representation. When temperature changes are superimposed on changes in the control variables of acid-base state (PCO2, strong ion difference), the understanding of acid-base changes becomes difficult. A solution has recently been proposed for blood (Malan, 1977); it was based on the assumption that closed system conditions correspond to a minimal change in the overall acid-base state when temperature varies. The feasibility of extending these concepts to muscle intracellular acid-base vs temperature relationships is evaluated on the basis of a model study; the errors made by replacing closed conditions (which require knowledge of chemical composition) by more convenient approximations are estimated. A representation of both extracellular and intracellular acid-base data on a temperature-corrected bicarbonate-pH diagram is derived. It allows the interpretation of variable-temperature intracellular acid-base changes in terms of changes in control variables, 'respiratory (PCO2) or 'metabolic' (strong ion difference). | [
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PMID:27850 | Regulation of blood pH in teleost fish. | The nature of pH changes with temperature is similar in both air-breathing and water-breathing poikilotherms having a pH-temperature slope of -0.015 to 0.020 U/degrees C. The means by which this is accomplished are quite different in the two groups. The air-breather behaves in vivo as a Rosenthal, or constant CO2 content system, with PaCO2 increasing at higher temperatures. The increase in PaCO2 is brought about by a reduction in the ration VE/MCO2. The water-breather, on the other hand, does not change VG/MO2, so as not to sacrifice oxygen delivery, and consequently does not control PaCO2 by ventilation and perhaps does not control it at all. Instead, the ratio of CT/SCO2 is controlled by altering blood bicarbonate concentration. Since alteraction of Na+ and Cl- uptake rates affects blood pH, and alterations of blood pH affect uptake of Na+ and Cl- at the gills, the carrier-mediated Na+/H+(NH4+) and Cl-/HCO3-(OH-) mechanisms now known to occur in gills appear to be the primary pH-regulating mechanism in water-breathers. Our knowledge of the role of gut and kidney in pH regulation is incomplete, but on the basis of preliminary information the kidney does not appear to respond to acid challenge. | Regulation of blood pH in teleost fish. The nature of pH changes with temperature is similar in both air-breathing and water-breathing poikilotherms having a pH-temperature slope of -0.015 to 0.020 U/degrees C. The means by which this is accomplished are quite different in the two groups. The air-breather behaves in vivo as a Rosenthal, or constant CO2 content system, with PaCO2 increasing at higher temperatures. The increase in PaCO2 is brought about by a reduction in the ration VE/MCO2. The water-breather, on the other hand, does not change VG/MO2, so as not to sacrifice oxygen delivery, and consequently does not control PaCO2 by ventilation and perhaps does not control it at all. Instead, the ratio of CT/SCO2 is controlled by altering blood bicarbonate concentration. Since alteraction of Na+ and Cl- uptake rates affects blood pH, and alterations of blood pH affect uptake of Na+ and Cl- at the gills, the carrier-mediated Na+/H+(NH4+) and Cl-/HCO3-(OH-) mechanisms now known to occur in gills appear to be the primary pH-regulating mechanism in water-breathers. Our knowledge of the role of gut and kidney in pH regulation is incomplete, but on the basis of preliminary information the kidney does not appear to respond to acid challenge. | [
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PMID:27851 | Weak acids, weak bases and intracellular pH. | Against the background of classical observations made 50 years ago, a brief review is offered of some of the work performed in the author's laboratory on the behavior of weak acids and bases towards living animal cells. The significance of membrane permeability of the charged partner of these electrolytes is pointed out, and the existence of an active process of H+ extrusion (or its equivalent) in response to acid loading is demonstrated. The effect of intracellular inhomogeneity on weak acid and base transmembrane distribution is examined. The significance of these variables for weak acid- or base-derived intracellular pH is discussed. | Weak acids, weak bases and intracellular pH. Against the background of classical observations made 50 years ago, a brief review is offered of some of the work performed in the author's laboratory on the behavior of weak acids and bases towards living animal cells. The significance of membrane permeability of the charged partner of these electrolytes is pointed out, and the existence of an active process of H+ extrusion (or its equivalent) in response to acid loading is demonstrated. The effect of intracellular inhomogeneity on weak acid and base transmembrane distribution is examined. The significance of these variables for weak acid- or base-derived intracellular pH is discussed. | [
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PMID:27852 | Evaluation of the DMO method for measuring intracellular pH. | Intracellular pH in single muscle fibres from Balanus nubilus was determined, both by the weak acid distribution method (using 5,5-dimethyl-2,4-oxazolidine dione) and by means of a glass pH microelectrode, following prolonged equilibrations in normal, acid or alkaline Ringer solutions. In the DMO method [3H]inulin was combined with [14C]DMO so that an extracellular space could be calculated for each 'DMO space' on each fibre. Less than ideal uptake curves were obtained both for [14C]DMO and [3H]inulin, yet the calculated pHi compared favourably with the microelectrode pHi, especially when the DMO-pHi was calculated from [14C]DMO and [3H]inulin values obtained by extrapolating the 'plateaus' of the uptake curves to time zero. The Waddell and Butler equation was examined to determine why acceptable pHi values should be forthcoming from less than ideal uptake data. | Evaluation of the DMO method for measuring intracellular pH. Intracellular pH in single muscle fibres from Balanus nubilus was determined, both by the weak acid distribution method (using 5,5-dimethyl-2,4-oxazolidine dione) and by means of a glass pH microelectrode, following prolonged equilibrations in normal, acid or alkaline Ringer solutions. In the DMO method [3H]inulin was combined with [14C]DMO so that an extracellular space could be calculated for each 'DMO space' on each fibre. Less than ideal uptake curves were obtained both for [14C]DMO and [3H]inulin, yet the calculated pHi compared favourably with the microelectrode pHi, especially when the DMO-pHi was calculated from [14C]DMO and [3H]inulin values obtained by extrapolating the 'plateaus' of the uptake curves to time zero. The Waddell and Butler equation was examined to determine why acceptable pHi values should be forthcoming from less than ideal uptake data. | [
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PMID:27853 | Intracellular pH transients induced by Co2 or NH3. | Experiments are reviewed in which intracellular pH (pHi), during exposure of a cell to CO2- or NH3-containing solutions, not only undergoes an acidification of alkalinization, respectively, but tends to return toward its original value and, upon removal of the test solution, rebounds to a value more alkaline or acid, respectively, than the initial one. A simple physiochemical model is discussed which interprets these observations both qualitatively and quantitatively. In the case of NH3-induced transients, only passive movements seem to take place; in the CO2-induced transients one must postulate an active 'proton pump'. Experimentally verifiable predictions can be made from these models. It is suggested that many physiological effects follow exposure to CO2 or NH3 may be subject to similar transients and rebounds. | Intracellular pH transients induced by Co2 or NH3. Experiments are reviewed in which intracellular pH (pHi), during exposure of a cell to CO2- or NH3-containing solutions, not only undergoes an acidification of alkalinization, respectively, but tends to return toward its original value and, upon removal of the test solution, rebounds to a value more alkaline or acid, respectively, than the initial one. A simple physiochemical model is discussed which interprets these observations both qualitatively and quantitatively. In the case of NH3-induced transients, only passive movements seem to take place; in the CO2-induced transients one must postulate an active 'proton pump'. Experimentally verifiable predictions can be made from these models. It is suggested that many physiological effects follow exposure to CO2 or NH3 may be subject to similar transients and rebounds. | [
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PMID:27854 | Intracellular buffering. | In the quantification of buffering the distinct roles of bicarbonate and of other buffers must be taken into account. The determination of the total non-bicarbonate buffer value, betaa, in intact tissues is complicated by active pH regulation and by heterogeneity of cytoplasm with respect to betaa, while heterogeneity with respect to pH in vivo could cause errors in estimates made with homogenates. Available estimates of betaa are discussed, as are the individual contributions of proteins, dipeptides and phosphates. A high betaa is appropriate in cells which sometimes have high rates of glycolysis, or which buffer extracellular fluid, but non-protein buffer concentrations can be well below the limits imposed by osmolarity, perhaps because buffering can upset ionic gradients. | Intracellular buffering. In the quantification of buffering the distinct roles of bicarbonate and of other buffers must be taken into account. The determination of the total non-bicarbonate buffer value, betaa, in intact tissues is complicated by active pH regulation and by heterogeneity of cytoplasm with respect to betaa, while heterogeneity with respect to pH in vivo could cause errors in estimates made with homogenates. Available estimates of betaa are discussed, as are the individual contributions of proteins, dipeptides and phosphates. A high betaa is appropriate in cells which sometimes have high rates of glycolysis, or which buffer extracellular fluid, but non-protein buffer concentrations can be well below the limits imposed by osmolarity, perhaps because buffering can upset ionic gradients. | [
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] |
PMID:27855 | Active control of intracellular pH. | When the interior of a squid giant axon is loaded with acid, the cell responds by extruding that acid in an energy-requiring process. Our results indicate that this acid extrusion is accomplished by exchanging external HCO3- for internal Cl- at the expense of ATP. | Active control of intracellular pH. When the interior of a squid giant axon is loaded with acid, the cell responds by extruding that acid in an energy-requiring process. Our results indicate that this acid extrusion is accomplished by exchanging external HCO3- for internal Cl- at the expense of ATP. | [
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PMID:27856 | Measurement of intracellular pH and aspects of its control in higher plant cells cultivated in liquid medium. | The 5,5-dimethyloxazolidine-2,4-dione (DMO) method for the determination of intracellular pH has been adapted to Acer pseudoplatanus cells cultivated in liquid medium. DMO is metabolized by these cells and this parameter has to be taken into account in the measurement of the intracellular concentration of free DMO. As the cells contain a large acidic vacuolar compartment, the intracellular pH estimated from the DMO technique is an overall pHi', the dependence of which on various cytoplasmic and vacuolar characteristics has been discussed. Important modifications of these overall pHi values under the influence of CO2 or NH4+ have been measured. These pHi modifications strongly affect the regulation of cell division through the control of the intracellular concentration of hormones of the auxin type. | Measurement of intracellular pH and aspects of its control in higher plant cells cultivated in liquid medium. The 5,5-dimethyloxazolidine-2,4-dione (DMO) method for the determination of intracellular pH has been adapted to Acer pseudoplatanus cells cultivated in liquid medium. DMO is metabolized by these cells and this parameter has to be taken into account in the measurement of the intracellular concentration of free DMO. As the cells contain a large acidic vacuolar compartment, the intracellular pH estimated from the DMO technique is an overall pHi', the dependence of which on various cytoplasmic and vacuolar characteristics has been discussed. Important modifications of these overall pHi values under the influence of CO2 or NH4+ have been measured. These pHi modifications strongly affect the regulation of cell division through the control of the intracellular concentration of hormones of the auxin type. | [
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PMID:27857 | Independent and dependent variables of acid-base control. | Basic physical principles and concepts plus computer-implemented numberical techniques now make possible a thorough quantitative analysis of acid-base systems. Some important conclusions from that analysis are presented: 1. Acid-base balance for physiological solutions hould be defined as the value of [OH-]/[H+]. 2. pH is a dangerously misleading indirect representation of [H+]. 3. Strong electrolytes affect [H+] and other deendent acid-base variables primarily through their resultant, the strong ion difference. 4 Hydrogen ion concentration in biological solutions is determined by the strong ion difference, the carbon dioxide partial pressure, and the total weak acid present. Changes in hydrogen ion concentration can be broght about only by changing one or more of these three independent variables. The same statements apply to all the other dependent variables, notably bicarbonate ion concentration. None of the dependent variables determines any other dependent variable, although their quantitative behaviors are necessarily correlected. 5. Solutions separated by membranes can interact in acid-base terms only by processes which alter the values of their independent variables. Interaction of intra- and extracellular acid-base balance can only occur by the cell membrane altering these independent variables in the extracellular fluid and in the cytosol. | Independent and dependent variables of acid-base control. Basic physical principles and concepts plus computer-implemented numberical techniques now make possible a thorough quantitative analysis of acid-base systems. Some important conclusions from that analysis are presented: 1. Acid-base balance for physiological solutions hould be defined as the value of [OH-]/[H+]. 2. pH is a dangerously misleading indirect representation of [H+]. 3. Strong electrolytes affect [H+] and other deendent acid-base variables primarily through their resultant, the strong ion difference. 4 Hydrogen ion concentration in biological solutions is determined by the strong ion difference, the carbon dioxide partial pressure, and the total weak acid present. Changes in hydrogen ion concentration can be broght about only by changing one or more of these three independent variables. The same statements apply to all the other dependent variables, notably bicarbonate ion concentration. None of the dependent variables determines any other dependent variable, although their quantitative behaviors are necessarily correlected. 5. Solutions separated by membranes can interact in acid-base terms only by processes which alter the values of their independent variables. Interaction of intra- and extracellular acid-base balance can only occur by the cell membrane altering these independent variables in the extracellular fluid and in the cytosol. | [
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PMID:27860 | [Pathological and compensatory processes in the cerebral circulation during blood transfusion shock]. | In experiments on dogs the intravenous injection of heterogenous blood resulted in a decrease of total arterial pressure, weakening of the brain blood flow, fall of Po2 and pH in the brain cortex. A simultaneous constriction if inner carotid arteries is depending on direct action on the vascular wall of heterogenous proteins and on a release in it of physiologically active substances, such as serotonin. Fine pial arteries were dilated by the compensatory mechanism that was not associated with a decrease of intravascular and with direct action of hypoxia or acid metabolites on vascular walls. It was proposed that the trigger mechanism of this vasodilatation is hypoxic changes of metabolism in the nervous tissue. | [Pathological and compensatory processes in the cerebral circulation during blood transfusion shock]. In experiments on dogs the intravenous injection of heterogenous blood resulted in a decrease of total arterial pressure, weakening of the brain blood flow, fall of Po2 and pH in the brain cortex. A simultaneous constriction if inner carotid arteries is depending on direct action on the vascular wall of heterogenous proteins and on a release in it of physiologically active substances, such as serotonin. Fine pial arteries were dilated by the compensatory mechanism that was not associated with a decrease of intravascular and with direct action of hypoxia or acid metabolites on vascular walls. It was proposed that the trigger mechanism of this vasodilatation is hypoxic changes of metabolism in the nervous tissue. | [
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] |
PMID:27862 | [Gastric secretion and gastrin values following portocaval and splenocaval shunts in the rat]. | The basal and gastrin-stimulated gastric acid output was measured in rats with a distal splenocaval shunt. In addition, serum gastrin levels were determined in rats with splenocaval and portacaval shunts. The rise in gastric acid output with increasing gastrin dosage was the same in rats with splenocaval shunt as in the controls. Serum gastrin levels were not influenced by portocaval or splenocaval shunting. | [Gastric secretion and gastrin values following portocaval and splenocaval shunts in the rat]. The basal and gastrin-stimulated gastric acid output was measured in rats with a distal splenocaval shunt. In addition, serum gastrin levels were determined in rats with splenocaval and portacaval shunts. The rise in gastric acid output with increasing gastrin dosage was the same in rats with splenocaval shunt as in the controls. Serum gastrin levels were not influenced by portocaval or splenocaval shunting. | [
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PMID:27863 | [Preventive practice in dentistry and its current meaning]. | Improvements in the field of sealants and of adhesive restorations based thereon represent the most important new development in preventive dentistry. Caries prevention by means of better nutritional habits is greatly enhanced by newly developed and marketed sugar-free and tooth sparing products. Statistical mortality studies have again demonstrated that prevention by means of fluorides constitutes no danger to public health. Considerable advances have been made in the field of fluoridation of domestic salt. Newer Scandinavian studies revealed that intensive care programs with children including dental hygiene sessions every 3-5 weeks resulted in moderate decreases of caries incidence. By contrast, intensive care programs with adults were extremely successful. By means of 4-6 recall sessions with dental hygienists it was possible to completely stop periodontal destruction for 4, even for 7 years. Apart from initial restorative and conservative dental work, the success of periodontal treatment may be guaranteed only by prevention of recurring gingivitis. Extensive dental statistics from Switzerland reveal a marked success of applied preventive dental medicine. The work of dental practitioners is by now greatly influenced by the new scientific insight gained from research in the prevention of dental disease. | [Preventive practice in dentistry and its current meaning]. Improvements in the field of sealants and of adhesive restorations based thereon represent the most important new development in preventive dentistry. Caries prevention by means of better nutritional habits is greatly enhanced by newly developed and marketed sugar-free and tooth sparing products. Statistical mortality studies have again demonstrated that prevention by means of fluorides constitutes no danger to public health. Considerable advances have been made in the field of fluoridation of domestic salt. Newer Scandinavian studies revealed that intensive care programs with children including dental hygiene sessions every 3-5 weeks resulted in moderate decreases of caries incidence. By contrast, intensive care programs with adults were extremely successful. By means of 4-6 recall sessions with dental hygienists it was possible to completely stop periodontal destruction for 4, even for 7 years. Apart from initial restorative and conservative dental work, the success of periodontal treatment may be guaranteed only by prevention of recurring gingivitis. Extensive dental statistics from Switzerland reveal a marked success of applied preventive dental medicine. The work of dental practitioners is by now greatly influenced by the new scientific insight gained from research in the prevention of dental disease. | [
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PMID:27864 | Lymphocyte ecto-5'-nucleotidase deficiency in agammaglobulinemia. | Fresh peripheral blood lymphocytes from eight patients with congenital agammaglobulinemia demonstrate reduced ecto-5'-nucleotidase activity when compared to the mean activity of normal subjects and patients with other forms of immunoglobulin deficiency. A specific defect of ecto-5'-nucleotidase is further suggested by normal values for lymphocyte ecto-adenosinetriphosphatase and ecto-nonspecific phosphatase. The data provide evidence for an enzyme deficiency in this X-linked, B lymphocyte deficiency syndrome. | Lymphocyte ecto-5'-nucleotidase deficiency in agammaglobulinemia. Fresh peripheral blood lymphocytes from eight patients with congenital agammaglobulinemia demonstrate reduced ecto-5'-nucleotidase activity when compared to the mean activity of normal subjects and patients with other forms of immunoglobulin deficiency. A specific defect of ecto-5'-nucleotidase is further suggested by normal values for lymphocyte ecto-adenosinetriphosphatase and ecto-nonspecific phosphatase. The data provide evidence for an enzyme deficiency in this X-linked, B lymphocyte deficiency syndrome. | [
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PMID:27879 | The abnormalities of beta-galactosidase in GM1-gangliosidoses. | The activity of GM1 beta-galactosidase in the brain and liver of patients with GM1-gangliosidosis was assayed using GM1-ganglioside tritiated in the terminal galactose. In the cases of GM1-gangliosidosis Types 1 and 2A the activity was less than 0.5% of the control. In the liver of GM1-gangliosidosis Type 2B the activity was observed to be much higher than that of Types 1 and 2A. On Sephadex G-150 gel filtration, three active fractions (I, II and III) for 4-methylumbelliferyl beta-galactopyranoside (4MU) and two active fractions (I and II) for GM1-ganglioside were obtained in the control liver. There was no active fraction for GM1-ganglioside in spite of the preserved fraction I for 4MU in the liver of GM1-gangliosidosis Type 1 or Type 2A. In any of the three cases fraction II for both 4MU and G71-ganglioside was not detected. | The abnormalities of beta-galactosidase in GM1-gangliosidoses. The activity of GM1 beta-galactosidase in the brain and liver of patients with GM1-gangliosidosis was assayed using GM1-ganglioside tritiated in the terminal galactose. In the cases of GM1-gangliosidosis Types 1 and 2A the activity was less than 0.5% of the control. In the liver of GM1-gangliosidosis Type 2B the activity was observed to be much higher than that of Types 1 and 2A. On Sephadex G-150 gel filtration, three active fractions (I, II and III) for 4-methylumbelliferyl beta-galactopyranoside (4MU) and two active fractions (I and II) for GM1-ganglioside were obtained in the control liver. There was no active fraction for GM1-ganglioside in spite of the preserved fraction I for 4MU in the liver of GM1-gangliosidosis Type 1 or Type 2A. In any of the three cases fraction II for both 4MU and G71-ganglioside was not detected. | [
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PMID:27884 | Effects of phenobarbital in cerebral ischemia. Part I: cerebral energy metabolism during pronounced incomplete ischemia. | Changes in cerebral cortex concentrations of high-energy phosphates, glycolytic metabolites, citric acid cycle intermediates, associated amino acids, and ammonia, were studied after 5, 15 and 30 min of incomplete ischemia in rats anesthetized with 70% N2O or 150 mg.kg-1 of phenobartibal. Previous results have shown that with this type of ischemia (bilateral carotid artery occlusion combined with reduction in blood pressure to 50 mm Hg) cortical blood flow is reduced to below 10% of nitrous oxide values, whether animals are anesthetized with 70% N2O or 150 mg.kg-1 of phenobarbital. In animals under 70% N2O, changes in tissue concentrations of phosphocreatine, ATP, ADP and AMP were similar to those previously obtained in complete ischemia. However, some glucose remained in the tissue, and the lactate concentrations gradually rose to reach excessive values. Changes occuring in glycolytic and citric acid cycle intermediates were similar to those seen in complete ischemia but, after 30 min, there was some reduction in the pool size of amino acids. In those animals given phenobarbital and which lost all EEG activity during ischemia, changes in cerebral metabolites were virtually identical to those observed in nitrous oxide-anesthetized animals. However, some animals exposed to 5 or 15 min of ischemia had some remaining EEG activity. In these, cerebral energy state was significantly less deranged, and levels of glycogen, glucose and pyruvate were higher. | Effects of phenobarbital in cerebral ischemia. Part I: cerebral energy metabolism during pronounced incomplete ischemia. Changes in cerebral cortex concentrations of high-energy phosphates, glycolytic metabolites, citric acid cycle intermediates, associated amino acids, and ammonia, were studied after 5, 15 and 30 min of incomplete ischemia in rats anesthetized with 70% N2O or 150 mg.kg-1 of phenobartibal. Previous results have shown that with this type of ischemia (bilateral carotid artery occlusion combined with reduction in blood pressure to 50 mm Hg) cortical blood flow is reduced to below 10% of nitrous oxide values, whether animals are anesthetized with 70% N2O or 150 mg.kg-1 of phenobarbital. In animals under 70% N2O, changes in tissue concentrations of phosphocreatine, ATP, ADP and AMP were similar to those previously obtained in complete ischemia. However, some glucose remained in the tissue, and the lactate concentrations gradually rose to reach excessive values. Changes occuring in glycolytic and citric acid cycle intermediates were similar to those seen in complete ischemia but, after 30 min, there was some reduction in the pool size of amino acids. In those animals given phenobarbital and which lost all EEG activity during ischemia, changes in cerebral metabolites were virtually identical to those observed in nitrous oxide-anesthetized animals. However, some animals exposed to 5 or 15 min of ischemia had some remaining EEG activity. In these, cerebral energy state was significantly less deranged, and levels of glycogen, glucose and pyruvate were higher. | [
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PMID:27891 | Inhibition of 3'-methyl-4-dimethylaminoazobenezene-induced hepatocarcinogenesis by portacaval shunt. | Adult male Sprague Dalwey rats on which end-to-side portacaval shunt (PCS) operation was performed did not hyperplastic nodules and hepatoms when they were fed 3'-methyl-4-dimethylaminoazobenzene in semisynthetic basal diet for periods of up to 169 days. In contrast, all the intact rats fed the same diet for only 75 days, developed hyperplastic nodules in the liver. Transferred to normal pellet for another 25 days, hepatomas developed in 100% of these animals. The amount of protein-bond 3'-Me-DAB was found to be much smaller in operated rats than in intact animals. The glutathione (GSH) level in PCS-operated rats was lower than in intact controsl. A single large dose of 3'-Me-DAB led to the increase of only about 30% in the concentration of GSH during the period of 24-48 h, compared to the increase of 50-100% in non-operated rats. No clear tendency to a gradual increase in the activity of gamma-glutamyl transpeptidase was noted in PCS-operated rats during the period of 5 1/2 months of 3'-Me-DAB feeding. The increase in GT-ase activity never exceeded 30% above the level of GT-ase in the livers of PCS-operated rats fed basal diet without the carcinogen. This striking inhibibiton of GT-ase increase induced by 3'Me-DAB in PCS-operated rats contrasted with an increase of GI-ase activity by 5,000% found in livers of non-operated rats with hyperplastic nodules after 75 days of 3'-Me-DAB feeding and the increase by up to 10,000% in developed hepatomas. These effects and the inhibition of 3'Me-DAB-induced hepatocarcinogenesis, manifested by lack preneoplastic morphologic changes and the absecnce of hepatomas in rats after PCS, can best be explained by functional deficiency of the liver to metabolize the procarcinogen 3'-Me-DAB into an activated carcinogen. | Inhibition of 3'-methyl-4-dimethylaminoazobenezene-induced hepatocarcinogenesis by portacaval shunt. Adult male Sprague Dalwey rats on which end-to-side portacaval shunt (PCS) operation was performed did not hyperplastic nodules and hepatoms when they were fed 3'-methyl-4-dimethylaminoazobenzene in semisynthetic basal diet for periods of up to 169 days. In contrast, all the intact rats fed the same diet for only 75 days, developed hyperplastic nodules in the liver. Transferred to normal pellet for another 25 days, hepatomas developed in 100% of these animals. The amount of protein-bond 3'-Me-DAB was found to be much smaller in operated rats than in intact animals. The glutathione (GSH) level in PCS-operated rats was lower than in intact controsl. A single large dose of 3'-Me-DAB led to the increase of only about 30% in the concentration of GSH during the period of 24-48 h, compared to the increase of 50-100% in non-operated rats. No clear tendency to a gradual increase in the activity of gamma-glutamyl transpeptidase was noted in PCS-operated rats during the period of 5 1/2 months of 3'-Me-DAB feeding. The increase in GT-ase activity never exceeded 30% above the level of GT-ase in the livers of PCS-operated rats fed basal diet without the carcinogen. This striking inhibibiton of GT-ase increase induced by 3'Me-DAB in PCS-operated rats contrasted with an increase of GI-ase activity by 5,000% found in livers of non-operated rats with hyperplastic nodules after 75 days of 3'-Me-DAB feeding and the increase by up to 10,000% in developed hepatomas. These effects and the inhibition of 3'Me-DAB-induced hepatocarcinogenesis, manifested by lack preneoplastic morphologic changes and the absecnce of hepatomas in rats after PCS, can best be explained by functional deficiency of the liver to metabolize the procarcinogen 3'-Me-DAB into an activated carcinogen. | [
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PMID:27892 | [Neurohumoral correlations and the effect of hydrocortisone on respiratory function in experimental pancreatitis]. | From the observations on 18 patients and the experiments on 77 dogs with experimental pancreatitis neuro-humoral interrelations and hydrocortisone effect upon the respiratory function have been studied. Both in the clinic and in the experiment the authors have found the intermediate metabolism disturbed: adrenaline-like substances blood level rises, while the cholinergic complex blood level drops dramatically. The conclusion on a vital importance of a consecutive neuro-humoral correction with the use of cholinomimetics and corticosteroids in pancreatitis is drawn. | [Neurohumoral correlations and the effect of hydrocortisone on respiratory function in experimental pancreatitis]. From the observations on 18 patients and the experiments on 77 dogs with experimental pancreatitis neuro-humoral interrelations and hydrocortisone effect upon the respiratory function have been studied. Both in the clinic and in the experiment the authors have found the intermediate metabolism disturbed: adrenaline-like substances blood level rises, while the cholinergic complex blood level drops dramatically. The conclusion on a vital importance of a consecutive neuro-humoral correction with the use of cholinomimetics and corticosteroids in pancreatitis is drawn. | [
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PMID:27893 | [Comparative assessment of the methods for surgical treatment of cryptorchism]. | The experience with the surgical treatment of 305 cases of cryptorchism is presented. 108 Keetly and Torek's operations and 22 Mixter's operations have proved that in surgical technic the main emphasis should be transferred to the mobilization of the spermatic cord elements, but the orchoifixation should be simple and atraumatic. The Fowler's method of the descent of the testicles (107) in superficial inguinal ectopy and various modifications of the Petriwalsky's method of the descent of the testicles (43) in high inguinal retention and abdominal cryptorchism have made a favorable impression. | [Comparative assessment of the methods for surgical treatment of cryptorchism]. The experience with the surgical treatment of 305 cases of cryptorchism is presented. 108 Keetly and Torek's operations and 22 Mixter's operations have proved that in surgical technic the main emphasis should be transferred to the mobilization of the spermatic cord elements, but the orchoifixation should be simple and atraumatic. The Fowler's method of the descent of the testicles (107) in superficial inguinal ectopy and various modifications of the Petriwalsky's method of the descent of the testicles (43) in high inguinal retention and abdominal cryptorchism have made a favorable impression. | [
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PMID:27895 | [The localisation of endocrine cells in the distal esophagus (author's transl)]. | At the esophago-cardiac junction squamous epithelium is intermingled with gastric epithelium. Within the lamina propria of the distal 3 cm of the esophagus we found cardiac glands with many argyrophil cells in 60% of cases. Electron microscopy revealed seven well knonwn types and two further forms which we could not identify: EC, ECL, D, D1, AL, I eg. M, S. It is supposed that these cells are modified neurotransmitters with a local activity. Their function is local regulation of the lower esophageal sphincter (LES). | [The localisation of endocrine cells in the distal esophagus (author's transl)]. At the esophago-cardiac junction squamous epithelium is intermingled with gastric epithelium. Within the lamina propria of the distal 3 cm of the esophagus we found cardiac glands with many argyrophil cells in 60% of cases. Electron microscopy revealed seven well knonwn types and two further forms which we could not identify: EC, ECL, D, D1, AL, I eg. M, S. It is supposed that these cells are modified neurotransmitters with a local activity. Their function is local regulation of the lower esophageal sphincter (LES). | [
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PMID:27901 | Maintenance of 2,3-DPG and ATP levels in blood stored for 30 days at a constant pH obtained by variation of CO2. | A novel procedure for storing blood at a controlled pH consists in collecting blood in a pH 8.20, Tris-CPD solution and storing it in a special recipient including a gas permeable membrane under a CO2 atmosphere. The recipient is placed in an atmosphere of variable CO2 content, so that the initial alkalinity of the preservative is balanced by dissolved CO2, the proportion of which is diminished when lactate production increases with storage. 2,3-DPG and ATP were studied at three different pH levels of approximately 7.25, 7.45, and 7.65 at 4 degrees C. The best pH for the simultaneous maintenance of 2,3-DPG and ATP was 7.65. Under these conditions, 2,3-DPG is maintained at its initial level and ATP at 55% of its initial level at the 30th day. Lactate production is linear and hemolysis moderate. | Maintenance of 2,3-DPG and ATP levels in blood stored for 30 days at a constant pH obtained by variation of CO2. A novel procedure for storing blood at a controlled pH consists in collecting blood in a pH 8.20, Tris-CPD solution and storing it in a special recipient including a gas permeable membrane under a CO2 atmosphere. The recipient is placed in an atmosphere of variable CO2 content, so that the initial alkalinity of the preservative is balanced by dissolved CO2, the proportion of which is diminished when lactate production increases with storage. 2,3-DPG and ATP were studied at three different pH levels of approximately 7.25, 7.45, and 7.65 at 4 degrees C. The best pH for the simultaneous maintenance of 2,3-DPG and ATP was 7.65. Under these conditions, 2,3-DPG is maintained at its initial level and ATP at 55% of its initial level at the 30th day. Lactate production is linear and hemolysis moderate. | [
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PMID:27903 | Production of valine by a Bacillus sp. | A bacterium isolated from Burdwan (India) soil was found to accumulate L-valine in the growth medium and identified to be a strain of Bacillus subtilis. The strain is able to grow and accumulate valine in a purely synthetic medium, but supplementation of the synthetic medium with either Casamino acids or yeast extract or with both, significantly improves the yield. The entire fermentation period can be divided into a growth phase and a production phase, which can be prolonged by adjustment of pH to the neutral range. Among the different carbon and nitrogen sources tested glucose at 8.5% and L-glutamic acid at 0.8%, respectively, were found most suitable. Cane sugar molasses tested as a substitute for glucose significantly stimulated growth but valine production was less. Different vitamins tested stimulated growth and valine yield and an inoculum level of 10% (v/v) of the medium was found to be optimal. The yield of valine under optimal conditions was found to be 4.53 g per litre of the medium. Valine has been isolated in crystalline form from the fermented broth by ion exchange resin chromatography and found to be a pure sample of the L-isomer. | Production of valine by a Bacillus sp. A bacterium isolated from Burdwan (India) soil was found to accumulate L-valine in the growth medium and identified to be a strain of Bacillus subtilis. The strain is able to grow and accumulate valine in a purely synthetic medium, but supplementation of the synthetic medium with either Casamino acids or yeast extract or with both, significantly improves the yield. The entire fermentation period can be divided into a growth phase and a production phase, which can be prolonged by adjustment of pH to the neutral range. Among the different carbon and nitrogen sources tested glucose at 8.5% and L-glutamic acid at 0.8%, respectively, were found most suitable. Cane sugar molasses tested as a substitute for glucose significantly stimulated growth but valine production was less. Different vitamins tested stimulated growth and valine yield and an inoculum level of 10% (v/v) of the medium was found to be optimal. The yield of valine under optimal conditions was found to be 4.53 g per litre of the medium. Valine has been isolated in crystalline form from the fermented broth by ion exchange resin chromatography and found to be a pure sample of the L-isomer. | [
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PMID:27909 | [Circulating immune complexes in acute viral hepatitis, chronic active hepatitis, and periarteritis nodosa (author's transl)]. | Circulating immune complexes were determined in patients with acute viral hepatitis, chronic active hepatitis and periarteriitis nodosa with the Raji cell technique. Circulating immune complexes were found in 11/18 HBsAg positive and HBsAg negative cases of acute viral hepatitis. In HBsAg positive chronic active hepatitis immune complexes were detectable in 42/43 cases but only in 1/27 HBsAg negative cases. Ten healthy HBsAg carriers demonstrated no detectable immune complexes. Using FITC conjugated antisera against HBs, HBc, and e antigen, immune complexes could not be found in any case of acute viral hepatitis or chronic active hepatitis. Elution of immune complexes from Raji demonstrated IgG, C'3 and a lack of HBsAg, HBc or e antigen. Immune complexes were present in 4/8 cases with periarteriitis nodosa. Viral components were detectable in one case. | [Circulating immune complexes in acute viral hepatitis, chronic active hepatitis, and periarteritis nodosa (author's transl)]. Circulating immune complexes were determined in patients with acute viral hepatitis, chronic active hepatitis and periarteriitis nodosa with the Raji cell technique. Circulating immune complexes were found in 11/18 HBsAg positive and HBsAg negative cases of acute viral hepatitis. In HBsAg positive chronic active hepatitis immune complexes were detectable in 42/43 cases but only in 1/27 HBsAg negative cases. Ten healthy HBsAg carriers demonstrated no detectable immune complexes. Using FITC conjugated antisera against HBs, HBc, and e antigen, immune complexes could not be found in any case of acute viral hepatitis or chronic active hepatitis. Elution of immune complexes from Raji demonstrated IgG, C'3 and a lack of HBsAg, HBc or e antigen. Immune complexes were present in 4/8 cases with periarteriitis nodosa. Viral components were detectable in one case. | [
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PMID:27927 | [Psychophysiologic characteristics of the individual psychotropic activity of benzodiazepine derivatives under experimental conditions]. | In 156 experiments performed on 41 cats with adequate experimental models of pseudoneurotic conditions, states of anxiety due to an electrostimulation of the hypothalamus through implanted electrodes and an emotional stress due to a conflict situation the authors compared the individual traits of the psychotropic activity of lorazepam, diazepam, chlordiazepoxide, oxazepam, nirazepam. These experiments permitted to display significant differences of psychophysiological structures in the tranquilizing effect of 5 benzodiazepine derivatives. | [Psychophysiologic characteristics of the individual psychotropic activity of benzodiazepine derivatives under experimental conditions]. In 156 experiments performed on 41 cats with adequate experimental models of pseudoneurotic conditions, states of anxiety due to an electrostimulation of the hypothalamus through implanted electrodes and an emotional stress due to a conflict situation the authors compared the individual traits of the psychotropic activity of lorazepam, diazepam, chlordiazepoxide, oxazepam, nirazepam. These experiments permitted to display significant differences of psychophysiological structures in the tranquilizing effect of 5 benzodiazepine derivatives. | [
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] |
PMID:27929 | A direct lead technique for histochemical demonstration of leucocyte alkaline phosphatase activity in blood smears. | A histochemical technique for demonstrating leucocyte alkaline phosphatase activity (LAP), based on direct precipitation of lead phosphate at pH 9.5, is described. The effect of fixative, temperature and stability of the medium on the activity of the enzyme and stability of the colour reaction was thoroughly studied. Peripheral blood smears obtained from both normal humans and pathological cases were studied and the results were compared with these obtained by the azo-dye method. | A direct lead technique for histochemical demonstration of leucocyte alkaline phosphatase activity in blood smears. A histochemical technique for demonstrating leucocyte alkaline phosphatase activity (LAP), based on direct precipitation of lead phosphate at pH 9.5, is described. The effect of fixative, temperature and stability of the medium on the activity of the enzyme and stability of the colour reaction was thoroughly studied. Peripheral blood smears obtained from both normal humans and pathological cases were studied and the results were compared with these obtained by the azo-dye method. | [
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PMID:27930 | Effect of beta-sympatholytic agents on vascular responses to noradrenaline and potassium chloride. | Vasoconstrictory responses to noradrenaline (NA) or high potassium chloride (130 mM) usually show a biphasic behaviour: an initial peak is followed by a lower steady state level. The influence of three beta-sympatholytic agents (propranolol, pindolol, practolol) and a "Ca-antagonist" (verapamil) on this particular behaviour of KCl-induced vasoconstrictions was compared with responses to NA. Studies were performed on the intact vascular bed of an isolated intestinal preparation of the rat. 1. Increases in the concentration of propranolol and pindolol from 10(-10) to 10(-6) M attenuated the vascular responses to high KCl. Practolol, however, distinctly enhanced the KCl-responses. NA (1.3 microgram/ml)-elicited vasoconstriction was found to be influenced in a similar manner by the beta-receptor antagonists used, though lower concentrations of pindolol had an enhancing, higher concentrations a reducing effect on the constrictory responses to NA. 2. The extent to which the biphasic response adjusted to the steady state level was concentration-dependently increased KCl-responses and significantly decreased to a monophasic response to NA, in the presence of the beta-sympatholytic agents. 3. By using a quotient of deltaPs (steady-state phase) to deltaPi (initial vasoconstriction) and by comparing the effect of the three beta-sympatholytic agents with that of verapamil on this quotient showed a concentration-dependent decrease in presence of the beta-sympatholytic as well as of the Ca-antagonistic agents. These myotropic actions, i.e. negative influences on the mechanism of vascular smooth muscle activation ranged in the following sequence: Verapamil greater than propranolol greater than pindolol greater than practolol. 4. The mechanism underlying the biphasic responses to high potassium chloride are concluded to be basically different from the NA-responses because they are inversely affected by beta-sympatholytic agents. The steady-state response to KCl was found to be very sensitive to non-specific pharmacological actions of beta-sympatholytic substances. The myotropic action of the beta-receptor antagonists is compared with that of the Ca-antagonist verapamil and the role of calcium in the mechanism of activation of vascular smooth muscle is discussed. | Effect of beta-sympatholytic agents on vascular responses to noradrenaline and potassium chloride. Vasoconstrictory responses to noradrenaline (NA) or high potassium chloride (130 mM) usually show a biphasic behaviour: an initial peak is followed by a lower steady state level. The influence of three beta-sympatholytic agents (propranolol, pindolol, practolol) and a "Ca-antagonist" (verapamil) on this particular behaviour of KCl-induced vasoconstrictions was compared with responses to NA. Studies were performed on the intact vascular bed of an isolated intestinal preparation of the rat. 1. Increases in the concentration of propranolol and pindolol from 10(-10) to 10(-6) M attenuated the vascular responses to high KCl. Practolol, however, distinctly enhanced the KCl-responses. NA (1.3 microgram/ml)-elicited vasoconstriction was found to be influenced in a similar manner by the beta-receptor antagonists used, though lower concentrations of pindolol had an enhancing, higher concentrations a reducing effect on the constrictory responses to NA. 2. The extent to which the biphasic response adjusted to the steady state level was concentration-dependently increased KCl-responses and significantly decreased to a monophasic response to NA, in the presence of the beta-sympatholytic agents. 3. By using a quotient of deltaPs (steady-state phase) to deltaPi (initial vasoconstriction) and by comparing the effect of the three beta-sympatholytic agents with that of verapamil on this quotient showed a concentration-dependent decrease in presence of the beta-sympatholytic as well as of the Ca-antagonistic agents. These myotropic actions, i.e. negative influences on the mechanism of vascular smooth muscle activation ranged in the following sequence: Verapamil greater than propranolol greater than pindolol greater than practolol. 4. The mechanism underlying the biphasic responses to high potassium chloride are concluded to be basically different from the NA-responses because they are inversely affected by beta-sympatholytic agents. The steady-state response to KCl was found to be very sensitive to non-specific pharmacological actions of beta-sympatholytic substances. The myotropic action of the beta-receptor antagonists is compared with that of the Ca-antagonist verapamil and the role of calcium in the mechanism of activation of vascular smooth muscle is discussed. | [
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PMID:27932 | Effects of alpha-adrenergic stimulation and blockade of plasma parathyroid hormone concentrations in cows. | Experiments were designed to investigate responses of immunoreactive parathyroid hormone (PTH) during alpha-adrenergic stimulation and blockade in cows. Alpha-adrenergic agonists (methoxamine, phenylephrine and noradrenaline, the beta-adrenergic action of which was blocked by propranolol) did not change PTH and free fatty acid levels, whereas they characteristically increased the blood pressure and decreased the heart rate. In contrast, alpha-adrenergic blockade by phentolamine progressively increased PTH levels. The elevated PTH concentrations, associated with increased plasma noradrenaline and free fatty acid levels, rising heart rate and decreasing blood pressure, indicated that all these changes can be related to a beta-adrenergic stimulatory mechanism. Beta-adrenergic stimulation was presumably responsible for the initial elevation of PTH concentrations, whereas, during the later phase of the phentolamine infusions, a concomitant hypocalcaemia probably also produced a stimulatory effect. | Effects of alpha-adrenergic stimulation and blockade of plasma parathyroid hormone concentrations in cows. Experiments were designed to investigate responses of immunoreactive parathyroid hormone (PTH) during alpha-adrenergic stimulation and blockade in cows. Alpha-adrenergic agonists (methoxamine, phenylephrine and noradrenaline, the beta-adrenergic action of which was blocked by propranolol) did not change PTH and free fatty acid levels, whereas they characteristically increased the blood pressure and decreased the heart rate. In contrast, alpha-adrenergic blockade by phentolamine progressively increased PTH levels. The elevated PTH concentrations, associated with increased plasma noradrenaline and free fatty acid levels, rising heart rate and decreasing blood pressure, indicated that all these changes can be related to a beta-adrenergic stimulatory mechanism. Beta-adrenergic stimulation was presumably responsible for the initial elevation of PTH concentrations, whereas, during the later phase of the phentolamine infusions, a concomitant hypocalcaemia probably also produced a stimulatory effect. | [
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PMID:27933 | Testicular blood flow and testosterone concentrations in the spermatic venous blood in rats with experimental cryptorchidism. | Testicular blood flow and testosterone concentrations in the spermatic venous plasma were measured on unilaterally cryptorchid rats. Blood flow to the cryptorchid testis was 31.4 +/- 11.7 (SD) ml/100 g X min which was significantly higher thant that of the scrotal testis (17.7 +/- 4.4 ml/100 g X min). Stereological analysis showed a relative increase of blood vessel containing interstitial tissue in the cryptorchid testis, which was probably the main factor responsible for the relative increase of blood flow to the cryptorchid testis. The increase of interstitial tissue was greater than the increase of blood vessels and thus, the interstitium in the cryptorchid testis contained a number of vessels which was smaller than that of the interstitium in the scrotally located testis. The concentration of testosterone in the spermatic vein of the abdominal testis was 18.0 +/- 5.5 (SD) ng/ml and the corresponding value for the scrotal testis was 41.2 +/- 7.0 ng/ml. Calculations based on functional and morphological data indicate that the function of the Leydig cells in the abdominal testis was impaired. It was concluded that the outflow of testosterone from the cryptorchid testis was highly reduced. | Testicular blood flow and testosterone concentrations in the spermatic venous blood in rats with experimental cryptorchidism. Testicular blood flow and testosterone concentrations in the spermatic venous plasma were measured on unilaterally cryptorchid rats. Blood flow to the cryptorchid testis was 31.4 +/- 11.7 (SD) ml/100 g X min which was significantly higher thant that of the scrotal testis (17.7 +/- 4.4 ml/100 g X min). Stereological analysis showed a relative increase of blood vessel containing interstitial tissue in the cryptorchid testis, which was probably the main factor responsible for the relative increase of blood flow to the cryptorchid testis. The increase of interstitial tissue was greater than the increase of blood vessels and thus, the interstitium in the cryptorchid testis contained a number of vessels which was smaller than that of the interstitium in the scrotally located testis. The concentration of testosterone in the spermatic vein of the abdominal testis was 18.0 +/- 5.5 (SD) ng/ml and the corresponding value for the scrotal testis was 41.2 +/- 7.0 ng/ml. Calculations based on functional and morphological data indicate that the function of the Leydig cells in the abdominal testis was impaired. It was concluded that the outflow of testosterone from the cryptorchid testis was highly reduced. | [
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PMID:27934 | Erythrocyte acetylcholinesterase activity changes in the early stages of anemic and hypobaric hypoxia or after CoCl2 treatment in rabbits. | The authors studied the changes of erythrocyte acetylcholinesterase (AChE) activity in rabbits respectively subjected to bleeding, hypobaric hypoxia and CoCl2 treatment; in such conditions a rise of the enzyme activity was observed. Similar increases take place also as a consequence of intravenous infusions carried out by using lactic or hydrochloric acid. The authors suggest that these increases in the erythrocyte AChE activity are connected with the decrease of the pCO2 that occurs in the various experimental conditions achieved. | Erythrocyte acetylcholinesterase activity changes in the early stages of anemic and hypobaric hypoxia or after CoCl2 treatment in rabbits. The authors studied the changes of erythrocyte acetylcholinesterase (AChE) activity in rabbits respectively subjected to bleeding, hypobaric hypoxia and CoCl2 treatment; in such conditions a rise of the enzyme activity was observed. Similar increases take place also as a consequence of intravenous infusions carried out by using lactic or hydrochloric acid. The authors suggest that these increases in the erythrocyte AChE activity are connected with the decrease of the pCO2 that occurs in the various experimental conditions achieved. | [
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PMID:27935 | The adrenergic mechanism of the haemodynamic effects of massive doses of hydrocortisone in controlled haemorrhagic shock in the dog. | Haemorrhagic shock was induced in anaesthetized dogs by bleeding them into a blood reservoir system. By adjusting the blood level of the reservoir at a certain distance over the heart level the mean arterial blood pressure was kept at 6.7 kPa (50 mmHg). As has been found earlier, massive doses of hydrocortisone (80-560 mg.kg-1 body weight) caused a dose-dependent decrease in the total peripheral resistance. The degree of vasodilation distinctly increased during concomitant alpha-receptor blockade induced by phenoxybenzamine. The beta-receptor blocking drug propranolol efficiently inhibited the vasodilation caused by hydrocortisone and phenoxybenzamine. The findings fit with the hypothesis that massive doses of hydrocortisone induce an increased stimulation of the adrenergic beta2-receptors of the vascular smooth muscles. | The adrenergic mechanism of the haemodynamic effects of massive doses of hydrocortisone in controlled haemorrhagic shock in the dog. Haemorrhagic shock was induced in anaesthetized dogs by bleeding them into a blood reservoir system. By adjusting the blood level of the reservoir at a certain distance over the heart level the mean arterial blood pressure was kept at 6.7 kPa (50 mmHg). As has been found earlier, massive doses of hydrocortisone (80-560 mg.kg-1 body weight) caused a dose-dependent decrease in the total peripheral resistance. The degree of vasodilation distinctly increased during concomitant alpha-receptor blockade induced by phenoxybenzamine. The beta-receptor blocking drug propranolol efficiently inhibited the vasodilation caused by hydrocortisone and phenoxybenzamine. The findings fit with the hypothesis that massive doses of hydrocortisone induce an increased stimulation of the adrenergic beta2-receptors of the vascular smooth muscles. | [
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PMID:27936 | Neuromuscular blockade of fazadinium bromide (AH 8165) in renal failure patients. | Fazadinium bromide (AH 8165) is a new non-depolarizing neuromuscular blocking agent with rapid onset of action and intermediate duration of effect. The characteristics of the neuromuscular blockade induced were compared in normal and renal failure patients by monitoring the mechanical responses of thumb adductor muscle to ulnar nerve stimulation. The data suggest that renal failure, even in anephric patients, does not influence the depth of neuromuscular relaxation when judged from the identical dose-effect curves in both groups of patients. Moreover, the duration of the neuromuscular block was not significantly increased in end-stage kidney failure patients, whether the initial or late phases of the spontaneous recovery of neuromuscular transmission were considered, and this occurred over the entire therapeutic range. However, additional incremental injections of fazadinium bromide should be used cautiously, as evidence appeared of prolonged duration of action. This agent, fazadinium bromide, may therefore present useful advantages to other non-depolarizing neuromuscular blocking agents as to clinical safety and effects in patients with renal insufficiency. | Neuromuscular blockade of fazadinium bromide (AH 8165) in renal failure patients. Fazadinium bromide (AH 8165) is a new non-depolarizing neuromuscular blocking agent with rapid onset of action and intermediate duration of effect. The characteristics of the neuromuscular blockade induced were compared in normal and renal failure patients by monitoring the mechanical responses of thumb adductor muscle to ulnar nerve stimulation. The data suggest that renal failure, even in anephric patients, does not influence the depth of neuromuscular relaxation when judged from the identical dose-effect curves in both groups of patients. Moreover, the duration of the neuromuscular block was not significantly increased in end-stage kidney failure patients, whether the initial or late phases of the spontaneous recovery of neuromuscular transmission were considered, and this occurred over the entire therapeutic range. However, additional incremental injections of fazadinium bromide should be used cautiously, as evidence appeared of prolonged duration of action. This agent, fazadinium bromide, may therefore present useful advantages to other non-depolarizing neuromuscular blocking agents as to clinical safety and effects in patients with renal insufficiency. | [
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PMID:27937 | Cerebral metabolic rate of oxygen (CMRO2) in the acute phase of brain injury. | In 22 comatose patients with acute brain injury, the cerebral metabolic rate of oxygen (CMRO2) was calculated as the product of the hemispheric cerebral blood flow (CBF) and the arteriovenous oxygen content difference. All patients were subjected to moderate sedation without barbiturates, normothermia and respiratory treatment. The CBF was calculated by the 133xenon washout method as the average of 16 regions. The results indicate high jugular venous oxygen tension and, in some studies, very low oxygen consumption. A critical, low CMRO2 was not found, and values of about 0.4 ml/100 g/min were compatible with restitution of intellectual function. The CMRO2 was unrelated to the clinical outcome and to the time after the trauma. In bilateral studies, the lowest values were measured in the most severely injured hemisphere. | Cerebral metabolic rate of oxygen (CMRO2) in the acute phase of brain injury. In 22 comatose patients with acute brain injury, the cerebral metabolic rate of oxygen (CMRO2) was calculated as the product of the hemispheric cerebral blood flow (CBF) and the arteriovenous oxygen content difference. All patients were subjected to moderate sedation without barbiturates, normothermia and respiratory treatment. The CBF was calculated by the 133xenon washout method as the average of 16 regions. The results indicate high jugular venous oxygen tension and, in some studies, very low oxygen consumption. A critical, low CMRO2 was not found, and values of about 0.4 ml/100 g/min were compatible with restitution of intellectual function. The CMRO2 was unrelated to the clinical outcome and to the time after the trauma. In bilateral studies, the lowest values were measured in the most severely injured hemisphere. | [
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PMID:27938 | Cerebral autoregulation in unconscious patients with brain injury. | In 18 unconscious patients with traumatic brain injury, the cerebral autoregulation was tested during the first 2-3 weeks after the acute trauma. Regional cerebral blood flow (rCBF) was measured by the intra-arterial 133xenon washout method before and after an increase of about 20% in the mean arterial blood pressure (MABP) by angiotensin. The difference between MABP and intraventricular pressure (IVP) was used as cerebral perfusion pressure (PP). Simultaneously, ventricular fluid pH, lactate and pyruvate were measured. Regional loss of autoregulation indicated by a 20% flow increase was observed in 29 out of 35 studies (83%), while hemispheric loss of autoregulation was observed in only one study. The results of the autoregulation tests were unrelated to the clinical outcome, the presence of brain-stem lesion, and the ventricular fluid pH, lactate and lactate/pyruvate ratio. In repeated studies, a gradual normalization of the autoregulation was observed about 5 days after the acute trauma. | Cerebral autoregulation in unconscious patients with brain injury. In 18 unconscious patients with traumatic brain injury, the cerebral autoregulation was tested during the first 2-3 weeks after the acute trauma. Regional cerebral blood flow (rCBF) was measured by the intra-arterial 133xenon washout method before and after an increase of about 20% in the mean arterial blood pressure (MABP) by angiotensin. The difference between MABP and intraventricular pressure (IVP) was used as cerebral perfusion pressure (PP). Simultaneously, ventricular fluid pH, lactate and pyruvate were measured. Regional loss of autoregulation indicated by a 20% flow increase was observed in 29 out of 35 studies (83%), while hemispheric loss of autoregulation was observed in only one study. The results of the autoregulation tests were unrelated to the clinical outcome, the presence of brain-stem lesion, and the ventricular fluid pH, lactate and lactate/pyruvate ratio. In repeated studies, a gradual normalization of the autoregulation was observed about 5 days after the acute trauma. | [
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PMID:27939 | Haemodynamic effects of different corticosteroids in controlled haemorrhagic shock in the dog. | The haemodynamic effects of massive doses of hydrocortisone (80-320 mg.kg-1), methylprednisolone (4-32 mg.kg-1), betamethasone (1.6-12.8 mg.kg-1) and aldosterone (0.1-0.8 mg.kg-1) and the interaction with phenoxybenzamine and propranolol have been studied during controlled haemorrhagic shock in the anaesthetized dog. Hydrocortisone was the only steroid which showed any significant vasodilating ability when given alone. The alpha-receptor blocking agent phenoxybenzamine distinctly decreased the total peripheral resistance. The effect of the phenoxybenzamine was increased in combination with hydrocortisone or methylprednisolone, especially if the steroid was given as the first drug. The vasodilation found was efficiently abolished by the beta-receptor blocking agent propranolol. The ability of hydrocortisone or methylprednisolone to potentiate phenoxybenzamine was not shared by betamethasone or aldosterone. Thus, the haemodynamic effect of the steroid does not seem to be correlated to either a glucocorticoid nor a mineralocorticoid effect. It is suggested that the steroid effect studied is related to the ability of hydrocortisone or methylprednisolone to block the extra neuronal amine uptake which decreases the rate of elimination of the sympathetic transmitter from the vicinity of the adrenergic receptor of the vascular smooth muscle. | Haemodynamic effects of different corticosteroids in controlled haemorrhagic shock in the dog. The haemodynamic effects of massive doses of hydrocortisone (80-320 mg.kg-1), methylprednisolone (4-32 mg.kg-1), betamethasone (1.6-12.8 mg.kg-1) and aldosterone (0.1-0.8 mg.kg-1) and the interaction with phenoxybenzamine and propranolol have been studied during controlled haemorrhagic shock in the anaesthetized dog. Hydrocortisone was the only steroid which showed any significant vasodilating ability when given alone. The alpha-receptor blocking agent phenoxybenzamine distinctly decreased the total peripheral resistance. The effect of the phenoxybenzamine was increased in combination with hydrocortisone or methylprednisolone, especially if the steroid was given as the first drug. The vasodilation found was efficiently abolished by the beta-receptor blocking agent propranolol. The ability of hydrocortisone or methylprednisolone to potentiate phenoxybenzamine was not shared by betamethasone or aldosterone. Thus, the haemodynamic effect of the steroid does not seem to be correlated to either a glucocorticoid nor a mineralocorticoid effect. It is suggested that the steroid effect studied is related to the ability of hydrocortisone or methylprednisolone to block the extra neuronal amine uptake which decreases the rate of elimination of the sympathetic transmitter from the vicinity of the adrenergic receptor of the vascular smooth muscle. | [
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PMID:27942 | Effects of isoprenaline and dibutyryl-C-AMP on the electrical and mechanical activity of the rabbit myometrium. | Mechanical and electrical responses of spontaneously contracting muscle strips from oestrogen dominated rabbit uterus were investigated by the sucrose gap method. The effects of isoprenaline and dibutyryl-c-AMP in the presence and absence of propranolol were tested. It has been shown previously that the beta-adrenoceptor agonist isoprenaline inhibits the spontaneously contracting uterus even in the presence of the beta-blocker propranolol. The rise in c-amp which is caused by isoprenaline, is, however, blocked by propranolol. The aim of this investigation was to study further the role of c-AMP in the isoprenaline-induced relaxation of the uterus. Isoprenaline (10(-6) M) consistently abolished spikes and mechanical contractions, usually accompanied by hyperpolarization. Propranolol (3 X 10(-6) M) markedly reduced the incidence of hyperpolarization, but did not affect the other actions of isoprenaline. Hyperpolarization does not seem to be a prerequisite for inhibition of uterine contraction. Dibutyryl-c-AMP mimicked the actions of isoprenaline. No positive evidence to support a hypothesis of a c-AMP-independent mechanism was found. Therefore a possible explanation of the results could be that isoprenaline increases c-AMP in a small intracellular pool, mediating electrical and mechanical responses but not influenced by propranolol. | Effects of isoprenaline and dibutyryl-C-AMP on the electrical and mechanical activity of the rabbit myometrium. Mechanical and electrical responses of spontaneously contracting muscle strips from oestrogen dominated rabbit uterus were investigated by the sucrose gap method. The effects of isoprenaline and dibutyryl-c-AMP in the presence and absence of propranolol were tested. It has been shown previously that the beta-adrenoceptor agonist isoprenaline inhibits the spontaneously contracting uterus even in the presence of the beta-blocker propranolol. The rise in c-amp which is caused by isoprenaline, is, however, blocked by propranolol. The aim of this investigation was to study further the role of c-AMP in the isoprenaline-induced relaxation of the uterus. Isoprenaline (10(-6) M) consistently abolished spikes and mechanical contractions, usually accompanied by hyperpolarization. Propranolol (3 X 10(-6) M) markedly reduced the incidence of hyperpolarization, but did not affect the other actions of isoprenaline. Hyperpolarization does not seem to be a prerequisite for inhibition of uterine contraction. Dibutyryl-c-AMP mimicked the actions of isoprenaline. No positive evidence to support a hypothesis of a c-AMP-independent mechanism was found. Therefore a possible explanation of the results could be that isoprenaline increases c-AMP in a small intracellular pool, mediating electrical and mechanical responses but not influenced by propranolol. | [
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PMID:27945 | The release of serotonin from rat duodenal enterochromaffin cells by adrenoceptor agonists studied in vitro. | The serotonin (5-HT) content of enterochromaffin cells (EC) was studied by a cytofluorimetric method in biopsies from rat duodenal mucosa after in vitro incubation with different adrenoceptor agonists and antagonists and acetylcholine (ACh). Noradrenaline (NA), Adrenaline (A) and Isoprenaline (IP) caused a decrease of 5-HT in EC down to 40--60% and for NA and A this effect was concentration-dependent. The effect was antagonized by d,1-propranolol but not by d-propranolol, metoprolol, phentolamine or phenoxybenzamine indicating that the 5-HT release from EC is probably mediated via a true beta-adrenoceptor mechanism possibly of the beta2 type. ACh also decreased the 5-HT content of EC but was much less potent than the adrenergic substances. Dopamine (DA) had no effect. | The release of serotonin from rat duodenal enterochromaffin cells by adrenoceptor agonists studied in vitro. The serotonin (5-HT) content of enterochromaffin cells (EC) was studied by a cytofluorimetric method in biopsies from rat duodenal mucosa after in vitro incubation with different adrenoceptor agonists and antagonists and acetylcholine (ACh). Noradrenaline (NA), Adrenaline (A) and Isoprenaline (IP) caused a decrease of 5-HT in EC down to 40--60% and for NA and A this effect was concentration-dependent. The effect was antagonized by d,1-propranolol but not by d-propranolol, metoprolol, phentolamine or phenoxybenzamine indicating that the 5-HT release from EC is probably mediated via a true beta-adrenoceptor mechanism possibly of the beta2 type. ACh also decreased the 5-HT content of EC but was much less potent than the adrenergic substances. Dopamine (DA) had no effect. | [
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PMID:27948 | Comparative evaluation of hypnotic efficacy of flunitrazepam in psychiatric in-patients. | Flunitrazepam in 2-mg and 4-mg doses was compared with flurazepam 30 mg and nitrazepam 10 mg for hypnotic efficacy in a double-blind, multiple cross-over trial involving 41 psychiatric in-patients. In the vast majority of comparisons involving a number of sleep parameters differences did not reach significance level. Flunitrazepam 4 mg tended to produce the shortest latency time and the longest duration of sleep but also the most side-effects. Nitrazepam 10 mg appeared to have a slight advantage over the other drugs in terms of patient preference. For severe sleep disturbance flunitrazepam 2 mg tended to be the most satisfactory drug in terms of efficacy and paucity of side-effects. | Comparative evaluation of hypnotic efficacy of flunitrazepam in psychiatric in-patients. Flunitrazepam in 2-mg and 4-mg doses was compared with flurazepam 30 mg and nitrazepam 10 mg for hypnotic efficacy in a double-blind, multiple cross-over trial involving 41 psychiatric in-patients. In the vast majority of comparisons involving a number of sleep parameters differences did not reach significance level. Flunitrazepam 4 mg tended to produce the shortest latency time and the longest duration of sleep but also the most side-effects. Nitrazepam 10 mg appeared to have a slight advantage over the other drugs in terms of patient preference. For severe sleep disturbance flunitrazepam 2 mg tended to be the most satisfactory drug in terms of efficacy and paucity of side-effects. | [
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PMID:27949 | Neuroendocrine disorders in depressions and their significance for the monoamine hypothesis of depression. | This article discusses the results of recent neuroendocrinological research in depressions. The abnormalities found in a given category of vital depressive patients--cortisol hypersecretion, decreased growth hormone response to insulin hypoglycaemia and decreased luteinizing hormone secretion in menopause--are believed to be due to deficient noradrenalin-(NA)-ergic activity in the hypothalmus. Thus explained, they support the so-called MA (monoamine) hypothesis, which postulates that a functional NA deficiency in the brain plays a role in the pathogenesis of certain types of vital depression. Disorders in certain central MA-ergic systems are predictive of disorders in the hormone secretion of the anterior pituitary. Inversely, disorders in the hormone secretion of the anterior pituitary can be indicative of disorders in the MA-ergic transmission in the hypothalamus. Consequently we can expect a convergence of transmitter research and neuroendocrinological research--two lines of research which have so far been largely separated in studies of human individuals. | Neuroendocrine disorders in depressions and their significance for the monoamine hypothesis of depression. This article discusses the results of recent neuroendocrinological research in depressions. The abnormalities found in a given category of vital depressive patients--cortisol hypersecretion, decreased growth hormone response to insulin hypoglycaemia and decreased luteinizing hormone secretion in menopause--are believed to be due to deficient noradrenalin-(NA)-ergic activity in the hypothalmus. Thus explained, they support the so-called MA (monoamine) hypothesis, which postulates that a functional NA deficiency in the brain plays a role in the pathogenesis of certain types of vital depression. Disorders in certain central MA-ergic systems are predictive of disorders in the hormone secretion of the anterior pituitary. Inversely, disorders in the hormone secretion of the anterior pituitary can be indicative of disorders in the MA-ergic transmission in the hypothalamus. Consequently we can expect a convergence of transmitter research and neuroendocrinological research--two lines of research which have so far been largely separated in studies of human individuals. | [
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PMID:27950 | Primary culture of adult rat liver cells. III. Hormonal effects on cytological and biochemical properties of primary cultured cells. | The effect of various hormones on cytological and biochemical properties of cultured hepatic cells were investigated in order to obtain long-term survival of the hepatocytes with adult liver functions in primary culture. Insulin supplementation of the culture medium enhanced the attachemnt efficiency of cells in primary culture without affecting either maintenance of morphological characters of epithelial cells or retention of liver-specific functions in cultured cells. A combination of dexamethasone and insulin was apparently effective in stimulating the formation of a monolayer of polygonal cells with granular cytoplasm and in maintenance of liver-specific functions for relatively longer periods. Supplementation with either dexamethasone or hydrocortisone alone enhanced tyrosine aminotransferase activities in cultured cells for at least 4 days postinoculation. These steroid hormones also allowed growth of small epithelial cells with clear cytoplasm and maintenance of increased albumin production for 8 days after inoculation. The roles of these hormones in the primary culture of isolated hepatic cells are discussed in the present paper. | Primary culture of adult rat liver cells. III. Hormonal effects on cytological and biochemical properties of primary cultured cells. The effect of various hormones on cytological and biochemical properties of cultured hepatic cells were investigated in order to obtain long-term survival of the hepatocytes with adult liver functions in primary culture. Insulin supplementation of the culture medium enhanced the attachemnt efficiency of cells in primary culture without affecting either maintenance of morphological characters of epithelial cells or retention of liver-specific functions in cultured cells. A combination of dexamethasone and insulin was apparently effective in stimulating the formation of a monolayer of polygonal cells with granular cytoplasm and in maintenance of liver-specific functions for relatively longer periods. Supplementation with either dexamethasone or hydrocortisone alone enhanced tyrosine aminotransferase activities in cultured cells for at least 4 days postinoculation. These steroid hormones also allowed growth of small epithelial cells with clear cytoplasm and maintenance of increased albumin production for 8 days after inoculation. The roles of these hormones in the primary culture of isolated hepatic cells are discussed in the present paper. | [
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-0.04871930927038193
] |
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