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20860412 | Expanded π-electron systems, tri(phenanthro)hexaazatriphenylenes and tri(phenanthrolino)hexaazatriphenylenes, that are self-assembled to form one-dimensional aggregates. | This paper reports the self-assembling and electrochemical nature of hexaazatriphenylene-based electron-deficient heteroaromatics with an expanded π-electron system. The tri(phenanthro)hexaazatriphenylenes (TPHAT-Cs) and tri(phenanthrolino)hexaazatriphenylenes (TPHAT-Ns) were prepared by condensation reactions of the corresponding phenanthrenequinones and phenanthrolinediones, respectively, with hexaaminobenzene. Their electron affinity was indicated from cyclic voltammetry measurements, in which the first reduction potentials were evaluated at around -1.7 V (vs Fc/Fc(+)) in dichloromethane. In nonpolar and polar solvents and in the film state, the TPHAT-Cs and TPHAT-Ns formed one-dimensional aggregates with an H-type parallel stacking mode. In the MALDI-TOF mass spectra, significant peaks were seen at several multiples of the parent ion up to tetramer aggregates. The (1)H NMR spectra indicated a line-broadening effect due to the aggregation. The UV-vis and fluorescence spectra showed a concentration dependence, which is attributed to a dynamic exchange between the monomer and aggregate species. The order of the aggregative nature was estimated from the concentration dependence and the fluorescence quantum yield. By replacement of the peripheral aromatic moieties instead of the phenanthrene (TPHAT-Cs) with the phenanthroline (TPHAT-Ns), the aggregative nature was enhanced. |
20860413 | A 50-week extension study on the safety and efficacy of colesevelam in adults with primary hypercholesterolemia. | Colesevelam is a bile acid sequestrant that differs structurally from traditional bile acid sequestrants, allowing it to bind bile acids with greater affinity. Studies have shown that colesevelam significantly reduces low-density lipoprotein cholesterol (LDL-C) levels and, in some cases, significantly increases high-density lipoprotein cholesterol (HDL-C) levels in adults with primary hypercholesterolemia. |
20860414 | The role of Angiotensin receptor blocker and calcium channel blocker combination therapy in treating hypertension: focus on recent studies. | Hypertension remains a significant health problem, affecting approximately 30% of the US population. Of these, only 36.8% have BP controlled to mended levels of <140/90 mmHg for plicated hypertension and <130/80 mmHg for patients with diabetes mellitus or renal disease. For those with uncontrolled hypertension, the risk of diabetes, renal disease, stroke, and cardiovascular disease is increased. Therapeutic options for the treatment of hypertension include several major classes of drugs: diuretics, β-adrenoceptor antagonists (β-blockers), ACE inhibitors, angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), renin inhibitors, calcium channel blockers, and central sympatholytics, alone or bination. Guidelines mend thiazide diuretics as preferred first-line monotherapy. However, only 50% of patients will respond adequately to this therapy and the rest will require two or more antihypertensive agents to achieve BP goals. Clinical evidence demonstrates that some drugs have advantages when used bination rather than as monotherapy. Drugs that block the renin-angiotensin-aldosterone system not only provide BP control but may also provide vascular protection and are metabolically neutral. This is a concise review of the safety and efficacy of ARBs bination with amlodipine for the treatment of hypertension, with focus on the bination. A MEDLINE search of the English literature from 2006 to 2009 of amlodipine bination with ARBs revealed six publications, which are included in this review. |
20860415 | Cardiovascular risk-benefit profile of sibutramine. | Sibutramine is bined norepinephrine and serotonin reuptake inhibitor used as an antiobesity agent to reduce appetite and promote weight loss bination with diet and exercise. At a daily dose of 10-20 mg, it was initially considered to have a good safety profile, as it does not induce primary pulmonary hypertension or adverse effects on cardiac valves, in contrast to previous reports relating to some other antiobesity agents. However, it exerts disparate effects on cardiovascular risk factors. On the one hand, sibutramine may have antiatherogenic activities, as it improves insulin resistance, glucose metabolism, dyslipidemia, and inflammatory markers, with most of these effects resulting from weight loss rather than from an intrinsic effect of the drug. On the other hand, because of its specific mode of action, sibutramine exerts a peripheral sympathomimetic effect, which induces a moderate increase in heart rate and attenuates the reduction in BP attributable to weight loss or even slightly increases BP. It may also prolong the QT interval, an effect that could induce arrhythmias. Because of plex effects, it is difficult to conclude what the final impact of sibutramine on cardiovascular es might be. Sibutramine has been shown to exert favorable effects on some surrogate cardiovascular endpoints such as reduction of left ventricular hypertrophy and improvement of endothelial dysfunction. A good cardiovascular safety profile was demonstrated in numerous 1- to 2-year controlled trials, in both diabetic and nondiabetic well selected patients, as well as in several observational studies. However, since 2002, several cardiovascular adverse events (hypertension, tachycardia, arrhythmias, and myocardial infarction) have been reported in sibutramine-treated patients. This led to a contraindication of the use of this antiobesity agent in patients with established coronary heart disease, previous stroke, heart failure, or cardiac arrhythmias. SCOUT (Sibutramine Cardiovascular and Diabetes e Study) was designed to prospectively evaluate the efficacy/safety ratio of sibutramine in a high-risk population. The efficacy/safety results of the first 6-week lead-in open period of treatment with sibutramine 10 mg/day were reassuring in 10 742 overweight/obese high-risk subjects (97% had cardiovascular disease, 88% had hypertension, and 84% had type 2 diabetes mellitus). However, the final results of SCOUT showed that long-term (5 years') treatment with sibutramine (10-15 mg/day) exposed subjects with pre-existing cardiovascular disease to a significantly increased risk for nonfatal myocardial infarction and nonfatal stroke, but not cardiovascular death or all-cause mortality. Because the benefit of sibutramine as a weight-loss aid seems not to outweigh the cardiovascular risks, the European Medicines Agency mended the suspension of marketing authorizations for sibutramine across the EU. The US FDA stated that the drug should carry a 'black box' warning due to an increased risk of stroke and heart attack in patients with a history of cardiovascular disease. In conclusion, concern still persists about the safety profile of sibutramine regarding cardiovascular es, and the drug should not be prescribed for overweight/obese patients with a high cardiovascular risk profile. |
20860416 | Candesartan cilexetil: in children and adolescents aged 1 to <17 years with hypertension. | Candesartan cilexetil is the orally administered prodrug of candesartan, an angiotensin II subtype 1 receptor antagonist. The pharmacokinetics (area under the plasma concentration-time curve and maximum plasma concentration) of candesartan do not appear to be affected by age, sex, or weight, with a similar exposure observed in children aged 1 to <6 years or >6 years and adults. Therapy with candesartan cilexetil 0.05, 0.20, and 0.40 mg/kg/day for 4 weeks was effective in the treatment of hypertension in children aged 1 to <6 years, inducing significant dose-dependent reductions from baseline in sitting SBP (SSBP) [primary endpoint] and sitting DBP (SDBP) in the double-blind phase of a randomized, parallel-group, multinational, dose-ranging clinical study. The criteria for antihypertensive response (SBP and DBP values that were less than the 95th percentile) were met by 28-66% of patients. The beneficial antihypertensive effects of candesartan cilexetil therapy were sustained for up to 160 weeks. No significant difference from zero in the slope of the placebo-adjusted change in SSBP (primary endpoint) and SDBP was observed across the three candesartan cilexetil treatment groups (candesartan cilexetil 2, 8, or 16 mg/day in patients weighing <50 kg and candesartan cilexetil 4, 16, or 32 mg/day in patients weighing ≥50 kg) during the double-blind phase of a randomized, double-blind, parallel-group, placebo-controlled, multinational, dose-ranging study in children and adolescents aged 6 to <17 years. Nonetheless, candesartan cilexetil demonstrated significantly greater changes from baseline to the end of the double-blind phase than placebo in SSBP and SDBP, with a significantly higher proportion of patients receiving candesartan cilexetil meeting the criteria for antihypertensive response than those receiving placebo. Antihypertensive response rates were sustained for 52 weeks. Candesartan cilexetil therapy for up to 160 weeks was generally well tolerated in clinical studies in children and adolescents aged 1 to <17 years with hypertension. |
20860417 | Riferminogene pecaplasmide. | Sanofi-aventis is developing riferminogene pecaplasmide, a fibroblast growth factor 1 (FGF-1; NV1FGF) gene therapy for the treatment of peripheral arterial disorders (PAD) such as critical limb ischemia. Following intramuscular injection into an area of restricted blood flow, riferminogene pecaplasmide is taken up by muscle cells resulting in increased expression of FGF protein, which in turn promotes blood vessel growth. Riferminogene pecaplasmide is currently being evaluated in a randomized, double-blind, placebo-controlled phase III trial (TAMARIS) in patients with PAD in 32 countries, including the US, EU, Canada, Japan and Australia. This review discusses the development history and scientific profile of this pound. |
20860418 | Outcomes of children and adolescents with well-differentiated thyroid carcinoma and pulmonary metastases following ¹³¹I treatment: a systematic review. | The optimal dose and efficacy of ¹³¹I treatment of children and adolescents with well-differentiated thyroid carcinoma (WDTC) and pulmonary metastases are not well established. A therapeutic challenge is to achieve the maximum benefit of ¹³¹I to decrease disease-related morbidity and obtain disease-free survival while avoiding the plications of ¹³¹I therapy. |
20860419 | The relationship of preconception thyrotropin levels to requirements for increasing the levothyroxine dose during pregnancy in women with primary hypothyroidism. | Most women with hypothyroidism require an increase in their dose of levothyroxine (LT4) after conception. To minimize fetal and plications of maternal hypothyroidism, it is thought that women should be rapidly restored to the euthyroid state. The objectives of this study was to determine the percentage of hypothyroid women who would need to increase their dose of LT4 dose even if they had a preconception (pre-C) serum thyrotropin (TSH) of <2.5 mIU/L as mended by the Endocrine Society's guidelines and to ascertain whether there was a relationship between the pre-C TSH value and the need to increase the LT4 dose during pregnancy. |
20860420 | Dietary iodine restriction in preparation for radioactive iodine treatment or scanning in well-differentiated thyroid cancer: a systematic review. | Dietary iodine is often restricted before radioactive iodine (RAI) scanning or treatment of well-differentiated thyroid cancer. Our objective was to examine the impact of a low-iodine diet (LID) before RAI treatment or scanning on the following es: (i) the efficacy of thyroid remnant ablation (or residual disease elimination), (ii) urinary iodine measurements, (iii) RAI kinetics, and (iv) long-term thyroid cancer es. |
20860422 | Real-time elastography for the differentiation of benign and malignant thyroid nodules: a meta-analysis. | Work-up of thyroid nodules remains challenging. Fine-needle aspiration (FNA) has been shown to be the most cost-effective way to select patients for surgery with sensitivities of 54%–90% and specificities of 60%–96% for the detection of malignant lesions. Ultrasound-based real-time elastography (RTE) enables the determination of tissue elasticity and has shown promising results for the differentiation of thyroid nodules. A meta-analysis was performed to assess the overall performance of RTE for the differentiation of thyroid nodules. |
20860423 | Impact of pregnancy on outcome and prognosis of survivors of papillary thyroid cancer. | Papillary thyroid cancer monly affects women of child-bearing age. During normal pregnancy, several factors may have a stimulatory effect on normal and nodular thyroid growth. The aim of the study was to determine whether pregnancy in thyroid-cancer survivors poses a risk of progression or recurrence of the disease. |
20860424 | Thyroid cancer resistance to vitamin D receptor activation is associated with 24-hydroxylase levels but not the ff FokI polymorphism. | The vitamin D receptor (VDR) has been studied as a novel target for cancer therapy in many tissue types as VDR ligands decrease cell proliferation in vitro and decrease tumor growth in vivo in sensitive cells. The objective of this study was to analyze the response to VDR agonist therapy in a panel of validated thyroid cancer cells and assess genetic markers predicting sensitivity and resistance to calcitriol and the noncalcemic analog DP006. |
20860425 | Variable suppression of serum thyroxine in female mice of different inbred strains by triiodothyronine administered in drinking water. | binant-inbred mouse strains differ in their susceptibility to Graves'-like hyperthyroidism induced by immunization with adenovirus expressing the human thyrotropin (TSH) receptor. Because one ponent contributing to this susceptibility is altered thyroid sensitivity to TSH receptor agonist stimulation, we wished to quantify thyroid responsiveness to TSH. For such studies, it is necessary to suppress endogenous TSH by administering L-3,5,3′-triiodothyronine (L-T3), with the subsequent decrease in serum thyroxine (T4) reflecting endogenous TSH suppression. Our two objectives were to assess in different inbred strains of mice (i) the extent of serum T4 suppression after L-T3 administration and (ii) the magnitude of serum T4 increase induced by TSH. |
20860426 | Short-term exposure of umbilical cord blood CD34+ cells to granulocyte-macrophage colony-stimulating factor early in culture improves ex vivo expansion of neutrophils. | Despite the availability of modern antibiotics/antimycotics and cytokine support, neutropenic infection accounts for the majority of chemotherapy-associated deaths. While transfusion support with donor neutrophils is possible, cost plicated logistics make such an option unrealistic on a routine basis. A manufactured neutrophil product could enable routine prophylactic administration of neutrophils, preventing the onset of neutropenia and substantially reducing the risk of infection. We examined the use of pre-culture strategies and various binations to improve neutrophil expansion from umbilical cord blood (UCB) hematopoietic stem and progenitor cells (HPC). |
20860427 | Isolation and characterization of equine amniotic fluid-derived multipotent stem cells. | Amniotic fluid (AF) is a well-known source of stem cells. However, there have been no reports regarding equine AF stem cells. We have isolated equine AF-derived multipotent stem cells (MSC) (eAF-MSC) and show that these cells exhibit self-renewal ability and multilineage differentiation. |
20860428 | Dental erosive wear among Norwegian wine tasters. | To assess the prevalence and severity of dental erosive wear among a group of professional wine tasters. |
20860429 | Sense of coherence and oral health status in an adult Swedish population. | To investigate sense of coherence in relation to oral health status in an adult Swedish population in order to better understand the determinants of positive oral health-promoting behavior and differences in oral health. |
20860430 | Molecular, morphologic, and outcome analysis of thyroid carcinomas according to degree of extrathyroid extension. | The impact of varying degrees of extrathyroid extension (ETE), especially microscopic ETE (METE), on survival in thyroid carcinomas (TC) has not been well established. Our objective was to analyze ETE at the molecular and histologic levels and assess the effect of its extent on e. |
20860431 | Quality improvement in palliative care services and networks: preliminary results of a benchmarking process in Catalonia, Spain. | A wide range of palliative care services has been implemented in Catalonia over the past 20 years. Quantitative and qualitative differences in the organization of palliative care services between districts and settings can result in wide variability in the quality of these services, and their accessibility. |
20860432 | Socioeconomic disparities in trajectories of adiposity across childhood. | Socioeconomic inequalities in obesity are consistently observed in e countries. The development of such inequalities across childhood; however, has not been studied using longitudinal data. |
20860433 | What factors are important in increasing junior doctors' willingness to provide palliative care in Taiwan? An educational intervention study. | To explore the factors that influence the willingness of junior doctors to provide palliative care in future clinical practice and to evaluate the effect of palliative care education in ameliorating these factors. |
20860434 | Simultaneous methylation profiling of tumor suppressor genes in head and neck cancer. | Head and neck cancer (HNC) is mon cancer, and its prognosis has not changed during the last decades. Detection of the disease at an early stage is crucial for successful treatment, as early diagnosis can significantly increase the survival rate. Methylation of tumor suppressor genes is an early event in cancer responsible for incorrect gene silencing. Since methylation changes are reversible, they also provide a promising target for therapy. So far, only individual genes have been analyzed for aberrant methylation in HNC. In this study, we analyzed the methylation status of 24 tumor suppressor genes simultaneously by methylation-specific multiplex ligation-dependent probe amplification in matched tumor and normal tissue samples from patients with HNC. CHFR, RARβ, DAPK1, and RASFF1 genes were the most frequently methylated genes in tumor tissue. Eight genes were not methylated in any sample. The methylation frequencies for individual genes ranged from 0% to 19%. Our results indicate that methylation of tumor suppressor genes is not high as previously reported by methylation-specific polymerase chain reaction and is confined to a smaller but significant fraction of the tumors. Whether this group represents a unique entity in the disease spectrum warrants further studies. |
20860436 | Antianxiety activity of Gelsemium sempervirens. | The clinical applications of well-known benzodiazepines as anxiolytic agents are limited because of their side effects. Therefore, the development of new pharmacological agents, from medicinal plants, is well justified. |
20860437 | The antinociceptive and anti-inflammatory effects of Salvia officinalis leaf aqueous and butanol extracts. | The leaf of sage Salvia officinalis L. (Lamiaceae) is reputed in the folk medicine of Arabia, and Jordan in particular, to relieve pain associated with gastrointestinal disturbance. |
20860438 | Protective effect of Amaranthus spinosus against D-galactosamine/lipopolysaccharide-induced hepatic failure. | The current study is an effort to identify the hepatoprotective activity of the 50% ethanol extract of the whole plant of Amaranthus spinosus Linn. (Amaranthaceae) against d-galactosamine/lipopolysaccharide (d-GalN/LPS)-induced liver injury in rats. d-GalN/LPS (300 mg/kg body weight/30 µg/kg body weight)-induced hepatic damage was manifested by a significant (p <0.05) increase in the activities of marker enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase and gamma glutamyl transferase) and bilirubin level in serum while phospholipids significantly decreased. All other parameters, i.e. cholesterol, triglycerides and free fatty acids were increased significantly in both serum and pared to the control group. Pretreatment of rats with A. spinosus extract (400 mg/kg) significantly (p <0.05) reversed these altered parameters to pared to the intoxicated group. The biochemical observations were supplemented by histopathological examination of liver sections. There were no significant changes in the activities of marker enzymes, bilirubin level and lipids in the rats treated with A. spinosus extract alone. Results of this study revealed that A. spinosus extract could afford a significant protection against d-GalN/LPS-induced hepatocellular injury. |
20860440 | Hip resurfacing arthroplasty. | Hip resurfacing arthroplasty is claimed to allow higher activity levels and to give better quality of life than total hip arthroplasty. In this literature review, we assessed the therapeutic value of hip resurfacing arthroplasty as measured by functional e. |
20860441 | Neuropeptide Y innervation during fracture healing and remodeling. A study of angulated tibial fractures in the rat. | Autonomic neuropeptide Y (NPY) is involved in local bone remodeling via the central nervous system. However, the role of peripheral neuronal NPY in fracture healing is not known. We investigated the relationship between bone healing and side-specific occurrence of NPY in angular and straight fractures. |
20860439 | Immunosuppressive activity on the murine immune responses of glycyrol from Glycyrrhiza uralensis via inhibition of calcineurin activity. | Calcineurin (CN), a unique protein phosphatase, plays an important role in immune regulation. Our laboratory has established an effective molecular drug-screening model based on CN activity. |
20860442 | More intramedullary nails and arthroplasties for treatment of hip fractures in Sweden. | The surgical methods for treatment of femoral neck fractures and trochanteric hip fractures vary. We describe the changes in Sweden over the period 1998–2007 and the regional differences in treatment. Patients and methods Data on 144,607 patients were drawn from the National Patient Register. |
20860443 | The final follow-up plain radiograph is sufficient for clinical evaluation of polyethylene wear in total hip arthroplasty. A study of validity and reliability. | Radiostereometric analysis (RSA) is a highly accurate tool for assessment of polyethylene (PE) wear in total hip arthroplasty (THA); however, PE wear measurements in clinical studies are often limited to plain radiographs. We evaluated the agreement between PE wear measured with PolyWare software, which uses plain radiographs, and by model-based RSA, which uses stereo radiographs. |
20860444 | An important Norwegian contribution to the study of the bursae of the upper and lower extremities. | We present a critical analysis of the monograph of A.S.D. Synnestvedt (1869) “En anatomisk beskrivelse af de paa over- og underestremiteterne forekommende Bursae mucosae”. The analysis pleted using anatomical information from the historically oldest publications dealing with the bursae of the extremities: Albinus (1734) , Monro (1788) , Rosenmüller (1799) . We are of the opinion that Synnestvedt's publication is important, not only historically but also as a source of information for recent medical practitioners. Synnestvedt's monograph has a wealth of literary citations, unambiguous opinions of seasoned anatomists regarding the structure and function of the synovial membrane, and detailed descriptions of dissections he performed on fetal and adult cadavers. The information in this publication may enhance the diagnosis of bursopathies and enthesopathies of the extremities. |
20860445 | Measurement of femoral head penetration in polyethylene using a 3-dimensional CT-scan technique. | Current techniques for measuring in vivo polyethylene wear suffer from a range of problems, resulting in an unacceptable lack of repeatability and/or insufficient accuracy when they are used to measure the low wear rates associated with new, highly crosslinked polyethylene. We describe an improved CT method for measurement of 3D femoral head penetration in PE acetabular cups that has sufficient accuracy and repeatability to allow assessment of the wear potential of modern implants. |
20860446 | Lower limb amputations in Trondheim, Norway. | In the city of Trondheim, Norway, diabetic lower-limb amputations accounted for one-third of all lower-limb amputations (LLAs). In an attempt to reduce this rate, a diabetic foot team was established in 1996. We present the incidence of LLA in Trondheim as measured 10 years later. |
20860447 | A randomized, controlled trial comparing local infiltration analgesia with epidural infusion for total knee arthroplasty. | There have been few studies describing wound infiltration with additional intraarticular administration of multimodal analgesia for total knee arthroplasty (TKA). In this study, we assessed the efficacy of wound bined with intraarticular regional analgesia with epidural infusion on analgesic requirements and postoperative pain after TKA. |
20860448 | 6-year follow-up of 84 patients with cartilage defects in the knee. Knee scores improved but recovery was incomplete. | The natural history of focal cartilage injury is largely unknown. In this study we investigated 6-year es in patients with arthroscopically verified, focal, full-thickness cartilage injuries of the knee. |
20860451 | A new method for liposome preparation using a membrane contactor. | In this article, we present a novel, scalable liposomal preparation technique suitable for the entrapment of pharmaceutical agents into liposomes. This new method is based on the ethanol-injection technique and uses a membrane contactor module, specifically designed for colloidal system preparation. In order to investigate the process, the influence of key parameters on liposome characteristics was studied. It has been established that vesicle-size distribution decreased with a decrease of the organic-phase pressure, an increase of the aqueous-phase flow rate, and a decrease of the phospholipid concentration. Additionally, special attention was paid on reproducibility and long-term stability of lipid vesicles, confirming the robustness of the membrane contactor-based technique. On the other hand, drug-loaded liposomes were prepared and filled with two hydrophobic drug models. High entrapment-efficiency values were successfully achieved for indomethacin (63%) and beclomethasone dipropionate (98%). Transmission electron microscopy images revealed nanometric quasispherical-shaped multilamellar vesicles (size ranging from 50 to 160 nm). |
20860450 | Effects of metal-on-metal wear on the host immune system and infection in hip arthroplasty. | Joint replacement with metal-on-metal (MOM) bearings have gained popularity in the last decades in young and active patients. However, the possible effects of MOM wear debris and its corrosion products are still the subject of debate. Alongside the potential disadvantages such as toxicity, the influences of metal particles and metal ions on infection risk are unclear. |
20860452 | Reduced dislocation rate after hip arthroplasty for femoral neck fractures when changing from posterolateral to anterolateral approach. | Recent studies have shown pared to the posterolateral approach, the anterolateral approach reduces the risk of dislocation after hip arthroplasty in patients with femoral neck fractures. We have therefore started to use the anterolateral approach on these patients and we now report the consequences of this change for the dislocation rate. |
20860454 | Assessment of distraction callus in rabbits by monitoring of the electrical impedance of bone. | Evaluation of distraction callus is important for determination of the optimal time for removal of external fixation. We attempted to determine whether there might be a relationship between the electrical impedance of bone and callus maturation, with a view to using impedance as a way of knowing when to remove a fixator. |
20860453 | Risk factors for revision due to infection after primary total hip arthroplasty. A population-based study of 80,756 primary procedures in the Danish Hip Arthroplasty Registry. | There has been a limited amount of research on risk factors for revision due to infection following total hip arthroplasty (THA), probably due to low absolute numbers of revisions. We therefore studied patient- and surgery-related risk factors for revision due to infection after primary THA in a population-based setting. |
20860457 | Pharmacogenomic strategies against microbial resistance: from bright to bleak to innovative. | The last decade saw an alarming increase in antibiotic resistance in infections, with more than 13 million deaths per year from infections. Counter strategies include hygiene, antibiotic restriction and new antibiotics such as quinupristin, linezolid, tigecycline, daptomycin and dalbavancin. Presently, pharmacogenomics with basic research is revealing new antimicrobial peptides and is applying old drugs in new ways to break resistance. New approaches with host-directed drug targeting emerge to circumvent resistance. A future systems perspective from large-scale molecular techniques and bioinformatic modeling allows pharmacogenomics to reveal new intervention angles. This includes the fight against resistance and its transmission, improved vaccines, disarmament of microbes and antibiotic options from novel molecular targets (lipids, RNA and carbohydrates). Such a system perspective is also essential for improved diagnostics and individualized medicine. However, an increase in public awareness and closer cooperation of industry and basic research are essential to turn research into powerful new drugs that will enable us to treat new arising infections in the future. |
20860463 | Influence of host genetic factors on efavirenz plasma and intracellular pharmacokinetics in HIV-1-infected patients. | Efavirenz (EFV) is characterized by interindividual pharmacokinetic variability causing inconsistent clinical responses. Previous studies have identified some possible genetic determinants of the variability in plasma concentrations. However, their impact on EFV intracellular pharmacokinetics remains mostly unexplored. |
20860464 | Effects of lipid-lowering drugs on reverse cholesterol transport gene expressions in peripheral blood mononuclear and HepG2 cells. | The ATP-binding cassette transporters, ABCA1 and ABCG1, are LXR-target genes that play an important role in reverse cholesterol transport. We examined the effects of inhibitors of the cholesterol absorption (ezetimibe) and synthesis (statins) on expression of these transporters in HepG2 cells and peripheral blood mononuclear cells (PBMCs) of individuals with primary (and nonfamilial) hypercholesterolemia (HC). |
20860465 | Host genetic variants in the IGF binding protein-3 impact on survival of patients with advanced gastric cancer treated with palliative chemotherapy. | IGF binding protein-3 (IGFBP-3) displays growth inhibitory/proapoptotic action and counteracts the IGF-1 tumor-promoting effects by downregulating its bioavailability. We investigated whether IGFBP-3 SNPs determining high IGFBP-3 circulating levels are associated with improved survival of patients with advanced gastric cancer treated with palliative chemotherapy. |
20860462 | β-blocker therapy and heart rate control during exercise testing in the general population: role of a common G-protein β-3 subunit variant. | Impaired heart rate (HR) response to exercise is associated with increased cardiovascular morbidity and mortality. We analyzed mon variants (rs5443/C825T and rs5442/G814A) in the G-protein β3 subunit (GNB3) gene modulate interindividual variation in β-blocker responses with respect to HR. |
20860466 | VKORC1 polymorphisms in Brazilians: comparison with the Portuguese and Portuguese-speaking Africans and pharmacogenetic implications. | The heterogeneity of the Brazilian population renders the extrapolation of pharmacogenomic data derived from well-defined ethnic groups inappropriate. We investigated the influence of self-reported 'race/color', geographical origin and genetic ancestry on the distribution of four VKORC1 SNPs and haplotypes in Brazilians. Comparative data were obtained from two major ancestral roots of Brazilians: Portuguese and Africans from former Portuguese colonies. |
20860467 | Pharmacogenomics and active surveillance for serious adverse drug reactions in children. | Juxtaposing clinical pharmacology with human genetics, pharmacogenomics utilizes a patient's genetic information to identify genetic variants that have the potential to provide clinically relevant predictions of toxicity and efficacy. The goal is to develop personalized and genetic-based predictions of an individual's drug response and likelihood of experiencing an adverse drug reaction. The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) has implemented active adverse drug reaction surveillance to monitor and discover genetic markers related to serious adverse drug reactions in the pediatric population. Evidence-based pharmacogenomics research will inform public policy and influence drug benefit-risk decision-making. Regulatory processes and future challenges in pharmacogenomics research will be discussed. |
20860468 | Pharmacogenetics of osteoporosis-related bone fractures: moving towards the harmonization and validation of polymorphism diagnostic tools. | Osteoporosis is one of the mon skeletal chronic conditions in developed countries, hip fracture being one of its major healthcare es. There is considerable variation in the implementation of current pharmacological treatment and prevention, despite consistent mendations and guidelines. Many studies have reported conflicting findings of genetic associations with bone density and turnover that might predict fracture risk. Moreover, it is not clear whether genetic differences exist in relation to the morbidity and efficiency of the pharmacotherapy treatments. Clinical response, including beneficial and adverse events associated with osteoporosis treatments, is highly variable among individuals. In this context, the present article intends to summarize putative candidate genes and genome-wide association studies that have been related with BMD and fracture risk, and to draw the attention to the need for pharmacogenetic methodology that could be applicable in clinical translational research after an adequate validation process. This article piles analysis of important polymorphisms in osteoporosis documented previously, and it describes the simple molecular biology tools for routine genotype acquisition. Validation of methods for the easy, fast and accessible identification of SNPs is necessary for evolving pharmacogenetic diagnostic tools in order to contribute to the discovery of clinically relevant genetic variation with an impact on osteoporosis and its personalized treatment. |
20860469 | Pharmacogenomic implications of variants of monoaminergic-related genes in geriatric psychiatry. | Response to psychiatric medications in later life is highly heterogeneous plex. Monoaminergic-related polymorphisms may influence medication response and susceptibility to side effects in elderly individuals. Individuals with the lower function short (S) allele of the serotonin transporter gene (SLC6A4) insertion/deletion (indel) promoter polymorphism (5-HTTLPR) have both increased the likelihood of adverse drug events and increased the need for higher antidepressant concentrations to obtain maximum antidepressant response. By contrast, carriers of the higher expression homozygous long allele (L/L) genotype may respond at lower concentrations. The differential role of these polymorphisms appears at early stages of treatment rather than in the final antidepressant e. Research findings suggest that the rs25531 SNP may influence functional expression of the L allele. Similarly, a variable number of tandem repeats in the second intron of the serotonin transporter gene may influence the expression of SLC6A4 and the implications of these variants may be influenced by aging. Two polymorphisms, rs2242466 (-182T/C) and rs5569 (1287G/A), in the norepinephrine transporter gene (SLC6A2 or NET) have been associated with antidepressant response. Studies in dopamine-related polymorphisms have focused on associations with neuroleptic-induced movement disorders. The rs1800497 variant (Taq1A) of the dopamine receptor D2 (DRD2) gene located in a noncoding 3´ region may regulate expression of D2 receptors. The rs6280 variant (Ser9Gly) of the dopamine receptor 3 (DRD3) gene may influence the binding affinity of D3 receptors as a result of serine to glycine substitution of the receptor protein. A multicenter collaborative research effort would be an effective strategy to increase sample sizes to further investigate how gene variants impact the pharmacodynamics and pharmacokinetics of psychotropic drugs in elderly persons. |
20860470 | Pharmacogenomics instruction in US and Canadian medical schools: implications for personalized medicine. | To determine the extent of pharmacogenomics instruction at US and Canadian medical schools, characterize perceptions of curricular coverage, identify curricular resources pare responses with similar studies conducted in US pharmacy schools and British medical schools. |
20860477 | Managing invasive fungal infection in hematopoietic stem-cell transplantation. | Reduced intensity conditioning regimens and a wider range of donor sources, including cord blood, mean that more patients can be offered potentially curative allogeneic hematopoietic stem cell transplantation than ever before. Although these modalities aim to reduce procedure-related morbidity and mortality, their potential benefit may be overshadowed by a changing spectrum of problems related to the promised status of affected patients. Acute or chronic extensive graft-versus-host disease, which occasionally emerges in the late post-transplant period, and prolonged neutropenia due to delayed engraftment still carry a substantial risk of invasive fungal and other infections. As a result, advances in antifungal prophylaxis and pre-emptive treatment were widely reported at the 36th Annual Meeting of the European Group for Blood and Marrow Transplantation attended this year by approximately 3800 delegates. |
20860474 | Anti-proliferative effect of levamisole on human myeloma cell lines in vitro. | Levamisole has been employed as an immunomodulatory agent in conjunction with 5-fluorouracil in the treatment of colon cancer relapse. At high doses, levamisole has been shown to have both anti-cancer and immunosuppressive activities. In vitro, levamisole has been shown to potentiate the anti-proliferative effect of 5-fluorouracil in several types of tumor cell lines; however, its mechanism of cytotoxic action and its molecular targets in cells remains to be elucidated. Here, the effect of levamisole on the proliferative response of the human multiple myeloma cell lines RPMI 8226 and U266B1 was studied in vitro. Treatment of both lines with varying concentrations of levamisole for 48 and 72 h in culture resulted in a significant inhibition of proliferation (unstimulated) in a dose-dependent manner, as assessed by an 3-[(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide dye assay. Furthermore, measurements of cell viability (using a trypan blue dye exclusion assay) clearly showed that the levamisole was cytotoxic. The preliminary evaluation of the mechanism of this cytotoxic effect revealed that this drug induced apoptosis in the myeloma cells, as evidenced by increases in the levels of DNA fragmentation, release of cytochrome c into the cytoplasm, and the activation of caspase-3 activity in the cells. The results of these studies strongly suggest that levamisole could be a potent anti-myeloma agent and might be considered in the treatment of multiple myeloma in the future. |
20860479 | Advances in imaging the innate and adaptive immune response to Toxoplasma gondii. | Toxoplasma gondii is an intracellular protozoan parasite that infects a wide variety of warm-blooded hosts and can have devastating effects in the developing fetus as well as the promised host. An appreciation of how this organism interacts with the host immune system is crucial to understanding the pathogenesis of this disease. The last decade has been marked by the application of various imaging techniques, such as bioluminescent imaging as well as confocal and multiphoton microscopy to study toxoplasmosis. The ability to manipulate parasites to express fluorescent/bioluminescent markers or model bined with the development of reporter mice that allow the detection of distinct immune populations have been crucial to the success of many of these studies. These approaches have permitted the visualization of parasites and immune cells in real-time and provided new insights into the nature of host-pathogen interactions. This article highlights some of the advances in imaging techniques, their strengths and weaknesses, and how these techniques have impacted our understanding of the interaction between parasites and various immune populations during toxoplasmosis. |
20860482 | Third-generation smallpox vaccines: challenges in the absence of clinical smallpox. | Smallpox, a disease caused by variola virus, is estimated to have killed hundreds of millions to billions of people before it was certified as eradicated in 1980. However, there has been renewed interest in smallpox vaccine development due in part to zoonotic poxvirus infections and the possibility of a re-emergence of smallpox, as well as the fact that first-generation smallpox vaccines are associated with relatively rare, but severe, adverse reactions in some vaccinees. An understanding of the immune mechanisms of vaccine protection and the use of suitable animal models for vaccine efficacy assessment are paramount to the development of safer and effective smallpox vaccines. This article focuses on studies aimed at understanding the immune responses elicited by vaccinia virus and the various animal models that can be used to evaluate smallpox vaccine efficacy. Harnessing this information is necessary to assess the effectiveness and potential usefulness of new-generation smallpox vaccines. |
20860480 | Type B coxsackieviruses and their interactions with the innate and adaptive immune systems. | Coxsackieviruses are important human pathogens, and their interactions with the innate and adaptive immune systems are of particular interest. Many viruses evade some aspects of the innate response, but coxsackieviruses go a step further by actively inducing, and then exploiting, some features of the host cell response. Furthermore, while most viruses encode proteins that hinder the effector functions of adaptive immunity, coxsackieviruses and their cousins demonstrate a unique capacity to pletely evade the attention of naive CD8(+) T cells. In this artcle, we discuss the above phenomena, describe the current status of research in the field, and present several testable hypotheses regarding possible links between virus infection, innate immune sensing and disease. |
20860483 | Sensing by the membrane-bound sensor kinase DcuS: exogenous versus endogenous sensing of C(4)-dicarboxylates in bacteria. | Bacteria are able to grow at the expense of mon (succinate, L-malate, fumarate and aspartate) and mon (L-tartrate and D-malate) C(4)-dicarboxylates, which ponents of central metabolism. Two types of sensors/regulators responding to the C(4)-dicarboxylates function in Escherichia coli, Bacillus, Lactobacillus and related bacteria. The first type represents membrane-integral ponent systems, while the second includes cytoplasmic LysR-type transcriptional regulators. The difference in location and substrate specificity allows the exogenous induction of metabolic genes mon C(4)-dicarboxylates, and endogenous induction by mon C(4)-dicarboxylates. The ponent sensors, DcuS and CitA, posed of an extracellular Per-Arnt-Sim (PAS) domain, two transmembrane helices, a cytoplasmic PAS and the kinase domain. The structures of the extracellular PAS domains of DcuS and CitA have been determined in the ligand-bound and the apo form. Binding of the ligand results in closing paction of the binding site, and the structural change gives rise to piston-type movement of the adjacent membrane-spanning helix-2, and signal transmission to the cytoplasmic side. For DcuS, a membrane-embedded construct has been developed that suggests (by experimentation and modeling) that plasticity of the cytoplasmic PAS domain is central to signal transduction from the membrane to the kinase. Sensor kinase DcuS of E. coli requires the C(4)-dicarboxylate transporters DctA or DcuB as co-sensors for function under aerobic and anaerobic conditions, respectively. DcuB contains a regulatory site that controls the function of DcuS and is independent from the transport region. Therefore, DcuS senses C(4)-dicarboxylates in two independent modes, responding to the effector concentration and the metabolic flux of extracellular C(4)-dicarboxylates. |
20860481 | Immune evasion by Kaposi's sarcoma-associated herpesvirus. | Persistent viral infections are often associated with serious diseases, primarily by altering functions of the host immune system. The hallmark of Kaposi's a-associated herpesvirus (KSHV) infection is the establishment of a life-long persistent infection, which leads to several clinical, epidemiological and infectious diseases, such as Kaposi's a, a plasmablastic variant of multicentric Castleman's disease, and primary effusion lymphoma. To sustain an efficient life-long persistency, KSHV dedicates a large portion of its genome to encoding immunomodulatory proteins that antagonize the immune system of its host. In this article, we highlight the strategies KSHV uses to evade, escape and survive its battle against the host's immune system. |
20860484 | The TonB energy transduction systems in Vibrio species. | Studying the organization and conservation of the TonB systems across the genus Vibrio, we can tease out trends in gene arrangement and function that lead to clues about the evolution and necessity of the proteins in multiple TonB systems. The TonB2 systems, with additional TtpC proteins, are in general more promiscuous regarding their interactions with many different TonB-dependent transporters in the outer membrane. Studies show that the TtpC protein spans the periplasmic space, suggesting that it can be the connection between the energy from the proton motive force and the outer membrane protein receptors, which the shorter TonB2 cannot provide. As an earlier system, bination of the TtpC protein and a TonB2 system must have been necessary for the function of the smaller TonB2 protein and to transduce energy in a medium that can have osmotic challenges. |
20860489 | Absent circadian rhythm of proteinuria in hospitalized patients with preeclampsia. | To study the variation of protein excretion in short-interval day-and-night collections in hospitalized preeclamptic patients on continuous bed rest. |
20860490 | A study of lipoproteins in normal and pregnancy induced hypertensive women in tertiary care hospitals of the north west frontier province-Pakistan. | To evaluate the levels of serum lipoproteins in women with pregnancy-induced hypertension pare it with the corresponding levels in pregnant women having normal blood pressure. |
20860486 | Antibiotic resistance in Chlamydiae. | There are few documented reports of antibiotic resistance in Chlamydia and no examples of natural and stable antibiotic resistance in strains collected from humans. While there are several reports of clinical isolates exhibiting resistance to antibiotics, these strains either lost their resistance phenotype in vitro, or lost viability altogether. Differences in procedures for chlamydial culture in the laboratory, low recovery rates of clinical isolates and the unknown significance of heterotypic resistance observed in culture may interfere with the recognition and interpretation of antibiotic resistance. Although antibiotic resistance has not emerged in chlamydiae pathogenic to humans, several lines of evidence suggest they are capable of expressing significant resistant phenotypes. The adept ability of chlamydiae to evolve to antibiotic resistance in vitro is demonstrated by contemporary examples of mutagenesis, bination and genetic transformation. The isolation of tetracycline-resistant Chlamydia suis strains from pigs also emphasizes their adaptive ability to acquire antibiotic resistance genes when exposed to significant selective pressure. |
20860491 | Thrombophilia mediates lowering cardiovascular risk factors in women with a history of preeclampsia. | Preeclampsia is associated with increased risk of cardiovascular disease. The aim of this pilot study was to assess whether the presence of thrombophilia results in a greater tendency to develop endothelial dysfunction and cardiovascular diseases. |
20860492 | Factors associated with patient understanding of preeclampsia. | To explore the extent to which pregnant women understand the symptoms and plications related to preeclampsia and to determine the factors that are associated with better understanding. |
20860493 | Maternal cerebral blood flow and glucose metabolism in pregnancies complicated by severe preeclampsia. | To investigate maternal cerebral blood flow and glucose metabolism in plicated by severe pared to normal pregnancies. |
20860494 | Does sulfur-hexafluoride tamponade, as an adjunct to vitrectomy and internal-limiting-membrane peeling, suffice for the treatment of retinal detachment associated with macular hole? | To evaluate the efficacy of sulfur hexafluoride tamponade, as an adjunct to vitrectomy and internal-limiting-membrane peeling, for the treatment of retinal detachment (RD) associated with macular hole (MH). |
20860485 | Leptospira as an emerging pathogen: a review of its biology, pathogenesis and host immune responses. | Leptospirosis, the most widespread zoonosis in the world, is an emerging public health problem, particularly in large urban centers of developing countries. Several pathogenic species of the genus Leptospira can cause a wide range of clinical manifestations, from a mild, flu-like illness to a severe disease form characterized by multiorgan plications leading to death. However, the mechanisms of pathogenesis of Leptospira are largely unknown. This article will address the animal models of acute and chronic leptospire infections, and the recent developments in the genetic manipulation of the bacteria, which facilitate the identification of virulence factors involved in pathogenesis and the assessment of their potential values in the control and prevention of leptospirosis. |
20860495 | Energy metabolism of leukemia cells: glycolysis versus oxidative phosphorylation. | For generation of energy, cancer cells utilize glycolysis more vigorously than oxidative phosphorylation in mitochondria (Warburg effect). We examined the energy metabolism of four leukemia cell lines by using glycolysis inhibitor, 2-deoxy-d-glucose (2-DG) and inhibitor of oxidative phosphorylation, oligomycin. NB4 was relatively sensitive to 2-DG (IC(50): 5.75 mM), consumed more glucose and produced more lactate (waste product of glycolysis) than the three other cell lines. Consequently, NB4 was considered as a "glycolytic" leukemia cell line. Dependency on glycolysis in NB4 was confirmed by the fact that glucose (+) FCS (-) medium showed more growth and survival than glucose (-) FCS (+) medium. Alternatively, THP-1, most resistant to 2-DG (IC(50): 16.14 mM), was most sensitive to oligomycin. Thus, THP-1 was recognized to be dependent on oxidative phosphorylation. In THP-1, glucose (-) FCS (+) medium showed more growth and survival than glucose (+) FCS (-) medium. The dependency of THP-1 on FCS was explained, at least partly, by fatty acid oxidation because inhibitor of fatty acid β-oxidation, etomoxir, augmented the growth suppression of THP-1 by 2-DG. We also examined the mechanisms by which THP-1 was resistant to, and NB4 was sensitive to 2-DG treatment. In THP-1, AMP kinase (AMPK), which is activated when ATP es limiting, was rapidly phosphorylated by 2-DG, and expression of Bcl-2 was augmented, which might result in resistance to 2-DG. On the other hand, AMPK phosphorylation and augmentation of Bcl-2 expression by 2-DG were not observed in NB4, which is 2-DG sensitive. These results will facilitate the future leukemia therapy targeting metabolic pathways. |
20860496 | Low-dose radiation employed in diagnostic imaging causes genetic effects in cultured cells. | Exposure to environmental, diagnostic, and occupational sources of radiation frequently involves low doses. Although these doses have no immediately noticeable impact on human health there is great interest in their long-term biological effects. |
20860497 | Dose levels from thoracic and pelvic examinations in two pediatric radiological departments in Norway - a comparison study of dose-area product and radiographic technique. | pediatric doses expressed in dose-area product (DAP) can be retrieved from only a few publications; most of which correlate DAP to patient size or large age spans. In clinical practice age is often the only available parameter describing the patient, and thus, evaluation of dose levels in pediatric radiology on the basis of DAP related to age alone would be useful in optimization work. |
20860502 | Effect of screening mammography on breast-cancer mortality in Norway. | A challenge in quantifying the effect of screening mammography on breast-cancer mortality is to provide parison groups. The use of historical control subjects does not take into account chronologic trends associated with advances in breast-cancer awareness and treatment. |
20860503 | A large-scale, consortium-based genomewide association study of asthma. | Susceptibility to asthma is influenced by genes and environment; implicated genes may indicate pathways for therapeutic intervention. Genetic risk factors may be useful in identifying subtypes of asthma and determining whether intermediate phenotypes, such as elevation of the total serum IgE level, are causally linked to disease. |
20860506 | A randomized trial of a telephone care-management strategy. | Studies have shown that telephone interventions designed to promote patients' self-management skills and improve munication can increase patients' satisfaction and their use of preventive services. The effect of such a strategy on health care costs remains controversial. |
20860505 | A randomized study of endobronchial valves for advanced emphysema. | Endobronchial valves that allow air to escape from a pulmonary lobe but not enter it can induce a reduction in lobar volume that may thereby improve lung function and exercise tolerance in patients with pulmonary hyperinflation related to advanced emphysema. |
20860504 | Fondaparinux for the treatment of superficial-vein thrombosis in the legs. | The efficacy and safety of anticoagulant treatment for patients with acute, symptomatic superficial-vein thrombosis in the legs, but without itant deep-vein thrombosis or symptomatic pulmonary embolism at presentation, have not been established. |
20860522 | Comparison of flanged and unflanged acetabular cup design. An experimental study using ceramic and cadaveric acetabuli. | Adequate depth of cement penetration and cement mantle thickness is important for the durability of cemented cups. A flanged cup, as opposed to unflanged, has been suggested to give a more uniform cement mantle and superior cement pressurization, thus improving the depth of cement penetration. This hypothesis was tested experimentally. |
20860524 | Review of carbon nanotubes toxicity and exposure--appraisal of human health risk assessment based on open literature. | Carbon nanotubes (CNTs) possess many unique electronic and mechanical properties and are thus interesting for numerous novel industrial and biomedical applications. As the level of production and use of these materials increases, so too does the potential risk to human health. This study aims to investigate the feasibility and challenges associated with conducting a human health risk assessment for carbon nanotubes based on the open literature, utilising an approach similar to that of a classical regulatory risk assessment. Results indicate that the main risks for humans arise from chronic occupational inhalation, especially during activities involving high CNT release and uncontrolled exposure. It is not yet possible to draw definitive conclusions with regards the potential risk for long, straight multi-walled carbon nanotubes to pose a similar risk as asbestos by inducing mesothelioma. The genotoxic potential of CNTs is currently inconclusive and could be either primary or secondary. Possible systemic effects of CNTs would be either dependent on absorption and distribution of CNTs to sensitive organs or could be induced through the release of inflammatory mediators. In conclusion, gaps in the data set in relation to both exposure and hazard do not allow any definite conclusions suitable for regulatory decision-making. In order to enable a full human health risk assessment, future work should focus on the generation of reliable occupational, environmental and consumer exposure data. Data on toxicokinetics and studies investigating effects of chronic exposure under conditions relevant for human exposure should also be prioritised. |
20860523 | Effect of appetizer administration on plasma leptin level in human volunteers. | The present study aimed at evaluating the effect of appetizer administration on plasma leptin levels of human volunteers. The ginger-based appetizers, namely ginger munch, fruit munch, jeera munch and appetizer drink, developed in the Defence Food Research Laboratory were used for 45 volunteers. Leptin was analyzed using the BioSource enzyme-amplified sensitivity immunoassay kit. The fasting plasma leptin level for men and women ranged between 0.5 and 19.5 ng/ml and between 2 and 36 ng/ml, respectively. The decreased (6-16%) plasma leptin levels after consumption of appetizers indicated their appetizing effect. |
20860525 | Use of uncertainty factors by the SCOEL in their derivation of health-based occupational exposure limits. | The aim of this study was to investigate how the Scientific Committee on Occupational Exposure Limits (SCOEL) of the European Commission uses uncertainty factors when proposing health-based indicative occupational exposure limit values (IOELVs). In total, 75 IOELVs in 62 summary documents published from 1991 to 2003 were analyzed. For 31 of the IOELVs, no explicit uncertainty factor (EUF) was stated. For these, we calculated an implicit safety margin (ISM) as the ratio between the point of departure (POD, derived from the NOAEL or LOAEL of the critical effect) and the proposed IOELV. We further analysed whether date of mendation, type of critical effect, nature of POD or amount of available data influenced the magnitude of the EUFs and ISMs. The ISMs varied little (range 1-5), while the EUFs showed more variability (range 1-50). The EUFs remained unaffected over time and the ISMs decreased slightly. Significant differences in the magnitude of the EUFs, but not ISMs, were found between critical effects, however, contrary to expected the average EUFs and ISMs for irritation were similar to those for more severe systemic effects. The nature of the POD affected the ISMs and EUFs only slightly and less than expected. Both EUFs and ISMs showed a weak but significant negative correlation with the amount of available toxicological data, measured as the number of relevant publications in PubMed, whereas SCOEL statements on data sufficiency had no influence. Overall, the most striking difference was that between EUFs and ISMs, the former being on average 2.1 times higher. |
20860526 | Ecology of sexual dimorphism and clinal variation of coloration in a damselfly. | Sexual selection, more so than natural selection, is posited as the major cause of sex differences. Here I show ecological correlations between solar radiation levels and sexual dimorphism in body color of a Hawaiian damselfly. Megalagrion calliphya exhibits sexual monomorphism at high elevations, where both sexes are red in color; sexual dimorphism at low elevations, where females are green; and female‐limited dimorphism at midelevations, where both red and green females exist. Within a midelevation population, red females are also more prevalent during high daily levels of solar radiation. I found that red pigmentation is correlated with superior antioxidant ability that may protect from UV damage and confer a benefit to damselflies in exposed habitats, including males, which defend exposed mating habitats at all elevations, and females, which are in shaded habitats except at high elevation. This study characterizes the ecology of sexual dimorphism and provides a new, ecological hypothesis for the evolution of female‐limited dimorphism. |
20860521 | Cytochrome P450 regulation: the interplay between its heme and apoprotein moieties in synthesis, assembly, repair, and disposal. | Heme is vital to our aerobic universe. Heme cellular content is finely tuned through an exquisite control of synthesis and degradation. Heme deficiency is deleterious to cells, whereas excess heme is toxic. Most of the cellular heme serves as the prosthetic moiety of functionally diverse hemoproteins, including cytochromes P450 (P450s). In the liver, P450s are its major consumers, with >50% of hepatic mitted to their synthesis. Prosthetic heme is the sine qua non of P450 catalytic biotransformation of both endo- and xenobiotics. This well-recognized functional role notwithstanding, heme also regulates P450 protein synthesis, assembly, repair, and disposal. These less well-appreciated aspects are reviewed herein. |
20860527 | Synthesis and characterisation of two novel proton transfer compounds and their inhibition studies on carbonic anhydrase isoenzymes. | Two novel proton pounds were prepared between 2,4-dichloro-5-sulphamoylbenzoic acid (lasamide) (Hsba) and ethylenediamine (en), namely ethane-1,2-diaminium 2,4-dichloro-5-sulphamoylbenzoate (1), and also between Hsba and 2-amino-3-methylpyridine (2-amino-3-picoline) (amp), namely 2-amino-3-methylpyridinium 2,4-dichloro-5-sulphamoylbenzoate (2). All these were characterised by elemental, spectral (IR and UV-vis), thermal analyses, and single crystal X-ray diffraction studies. Compounds 1 and 2 crystallised in the P-1 and P21/c space groups, respectively. Intermolecular non-covalent interactions, such as ion pairing, hydrogen bonding, and π-π stacking were observed for these pounds. The free ligands Hsba, en and amp, the products 1 and 2, and acetazolamide (AAZ) as the pound, were also evaluated for their in vitro inhibitor effects on the human carbonic anhydrase isoenzymes (hCA I and hCA II) purified from erythrocyte cells by affinity chromatography for their hydratase and esterase activities. The half maximal inhibitory concentration (IC(50)) values for products 1 and 2 with respect to hydratase activity are 0.15 and 0.32 μM for hCA I and 0.06 and 0.15 μM for hCA II, respectively. The IC(50) values of the same inhibitors for esterase activity are 0.13 and 0.8 μM for hCA I and 0.14 and 0.1 μM for hCA II, respectively. In relation to esterase activities, the inhibition equilibrium constants (Ki) were also determined and found to be 0.137 and 0.99 μM on hCA I and 0.157 and 0.075 μM on hCA II for 1 and 2, respectively. parison of the inhibition studies of the newly pounds 1 and 2 to the pounds Hsba and amp and also to AAZ indicated that 1 and 2 have an effective inhibitory activity on hCA I and II, and might be used as potential inhibitors. |
20860528 | Managing pain in the workplace: a focus group study of challenges, strategies and what matters most to workers with low back pain. | Most working adults with low back pain (LBP) continue to work despite pain, but few studies have assessed self-management strategies in this at-work population. The purpose of this study was to identify workplace challenges and self-management strategies reported by workers remaining at work despite recurrent or persistent LBP, to be used as a framework for the development of a workplace group intervention to prevent back disability. |
20860529 | Efficacy and safety of ritonavir dose reduction based on the tipranavir inhibitory quotient in HIV-infected patients on salvage antiretroviral therapy with tipranavir/ritonavir. | Ritonavir-related adverse events have been reported in patients taking tipranavir/ritonavir at the licensed dosage of 500/200 mg twice daily (bid). The aim of this open-label, prospective, single-arm pilot study was to evaluate the efficacy and safety of a ritonavir dose reduction to 100 mg bid guided by the tipranavir virtual inhibitory quotient (vIQ) in HIV-infected patients receiving tipranavir/ritonavir 500/200 mg bid whose viral load was <50 copies/ml and whose tipranavir vIQ was >60. Viral load, blood chemistry, and tipranavir and ritonavir trough concentrations (C(trough)) in plasma were determined at baseline and up to 48 weeks. If the tipranavir vIQ fell to <40, the ritonavir dose was increased to 200 mg bid. The primary endpoint was the percentage of treatment failure after 48 weeks. Eleven patients were enrolled. At baseline, the median (IQR) CD4+ T-cell count and vIQ were 380 (231-520) cells/mm(3) and 233.4 (73.8-584.8), respectively. Ten patients (90.9%) maintained a viral load <50 copies/ml at week 48. Geometric mean (95% confidence interval) tipranavir C(trough) decreased from 24.7 (12.9-47.5) mg/l at baseline to 13.6 (7.1-26.2) mg/l at week 48 (p = 0.194), but the ritonavir dose had to be raised in only one patient. Median triglycerides and ALT concentrations decreased from 177.2 (132.9-292.4) mg/dl and 59 (23-128) IU/l at baseline to 158.0 (131.0-186.0) mg/dl and 28 (20-71) IU/l at week 48 (p = 0.047, p = 0.041), respectively. As a conclusion, ritonavir-dose reduction to 100 mg bid as a treatment-simplification strategy guided by the tipranavir vIQ in patients receiving salvage therapy with tipranavir/ritonavir 500/200 mg bid seems to be safe enough to be tested in adequately powered clinical trials. |
20860530 | Functional polymorphism of the MMP-1 promoter (-1607 1G/2G) in potentially malignant and malignant head and neck lesions in an Indian population. | Matrix metalloproteinases (MMP) are a family of zinc-dependent proteases that degrade the ponent of the extracellular matrix. Our study explores the association of the MMP1 gene promoter (-1607 1G/2G) polymorphisms in oral submucous fibrosis (OSMF) and head and neck squamous cell carcinoma (HNSCC) in an Indian population. The MMP1 single-nucleotide polymorphism (SNP) was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 412 patients with OSMF, 422 with HNSCC and 426 controls. Our results showed that the frequency of 1G/2G or 2G/2G promoter genotypes having the 2G allele is associated with higher enzymatic activity and significantly increases in OSMF (p<0.001) and HNSCC cases (p<0.00). In this study, results concluded that SNPs in the MMP1 promoter region may be associated with susceptibility to OSMF as well as HNSCC in an Indian population and addiction habits such as areca nut chewing and alcohol abuse may enhance the expression of the 2G allele of MMP1 genes in OSMF and HNSCC cases. |
20860531 | Interferon-γ and IL-5 production correlate directly in HIV patients co-infected with mycobacterium tuberculosis with or without immune restoration disease. | IL-5 and interferon-γ responses were investigated in mitogen-stimulated whole-blood cultures from HIV patients with and without Mycobacterium tuberculosis disease, to determine whether an imbalance of Th1/Th2 cytokines contributes to susceptibility to M. tuberculosis disease or to immune restoration disease (IRD) associated with M. tuberculosis after starting antiretroviral therapy (ART). Interferon-γ levels were constant on ART, whilst IL-5 levels generally rose over time. We suggest that increased IL-5 production reflects a recovery of CD4(+) T cell function and that a Th1/Th2 imbalance is not associated with increased susceptibility to M. tuberculosis disease or IRD associated with M. tuberculosis upon starting ART. |
20860532 | Incidence of HIV type 1 infection, antiretroviral drug resistance, and molecular characterization in newly diagnosed individuals in Argentina: A Global Fund Project. | An HIV incidence estimation was performed among men who have sex with men (MSM), drug users (DUs), sex workers (SWs), and pregnant women (PW) from Argentina. Volunteers older than 18 years old without a previous HIV-positive diagnosis were included. HIV-positive samples were analyzed by the Serological Testing Algorithm for Recent HIV Seroconversion (STARHS) to estimate incidence. By partial RT-PCR and sequencing of the HIV pol gene, an HIV subtype and resistance profile were determined. A total of 12,192 volunteers were recruited from October 2006 to September 2008. A higher HIV prevalence was detected among trans SWs (33.9%, 38/112), male SWs (10.8%, 12/111), and MSM 10.4% (161/1549). HIV incidence estimates by STARHS was also higher on trans SWs (11.31 per 100 person-years), male SWs (6.06 per 100 person-years), and MSM (6.36 per 100 person-years). Antiretroviral primary resistant mutations were detected in 8.4% of the study group, with a higher frequency in female DUs (33.3%). Phylogenetic analysis showed that 124 (57.9%) samples were subtype B, 84 (39.3%) intersubtype BF binants, 5 (2.3%) subtype C, and 1 (0.5%) subtype F in the pol region. Subtype B was monly found in MSM and male SWs whereas the intersubtype BF binant was more prevalent in female DUs, female SWs, and PW. Given the high HIV prevalence and incidence found in most of these groups, monitoring the continuing spread of the HIV epidemic is essential for determining public health priorities, assessing the impact of interventions, and estimating current and future health care needs. |
20860534 | HIV-1 drug resistance transmission networks in southwest Switzerland. | To determine viral subtypes and resistance mutations to antiretroviral treatment (ART) in untreated HIV-1 acutely infected subjects from Southwest Switzerland. Clinical samples were obtained from the HIV primary infection cohort from Lausanne. Briefly, pol gene was amplified by nested PCR and sequenced to generate a 1 kb sequence spanning protease and reverse transcriptase key protein regions. Nucleotide sequences were used to assess viral genotype and ART resistance mutations. Blood specimens and medical information were obtained from 30 patients. Main viral subtypes corresponded to clade B, CRF02_AG, and F1. Resistant mutations to PIs consisted of L10V and accessory mutations 16E and 60E present in all F1 clades. The NNRTI major resistant mutation 103N was detected in all F1 viruses and in other 2 clades. Additionally, we identified F1 sequences from other 6 HIV infected and untreated individuals from Southwest Switzerland, harboring nucleotide motifs and resistance mutations to ART as observed in the F1 strains from the cohort. These data reveal a high transmission rate (16.6%) for NNRTI resistant mutation 103N in a cohort of HIV acute infection. Three of the 5 resistant strains were F1 clades closely related to other F1 isolates from HIV-1 infection untreated patients ing from Southwest Switzerland. Overall, we provide strong evidence towards an HIV-1 resistant transmission network in Southwest Switzerland. These findings have relevant implications for the local molecular mapping of HIV-1 and future ART surveillance studies in the region. |
20860533 | Oral mucoceles and ranulas may be part of initial manifestations of HIV infection. | It is well documented and generally accepted that enlargement of parotid salivary glands, as part of HIV-related salivary gland diseases (HIV-SGD), may be the initial symptoms/manifestations of the HIV infection. Oral mucoceles and ranulas are also frequently described as oral manifestations, in association with HIV infection. However, little is known about these latter lesions as being the initial symptoms indicative of an HIV infection. This prospective study has investigated the possibility that oral mucoceles in general, and ranulas in particular, could be the initial symptoms of an underlying and undiagnosed HIV infection. A total of 50 patients including cases of oral mucoceles and ranulas were consulted in a tertiary referral hospital set up. Nineteen (63%) out of 30 HIV-positive patients presenting with oral mucoceles/ranulas, did not know their HIV status at the first consultation. Oral mucoceles/ranulas were for these patients, the only motives for visiting the health facility, and they were also the only clinical identifiable features (symptoms). Oral mucoceles and ranulas should, in the context of HIV-salivary gland diseases, be considered as initial symptoms and early manifestations of HIV infection. Routine HIV testing in all patients with oral mucoceles and ranulas is, according to this study, justified and should be mended. |
20860536 | The pivotal role of VEGF in adipose-derived-stem-cell-mediated regeneration. | Several lines of evidence suggest that VEGF is a key regulator of the paracrine effects of adipose-derived stem cells (ASCs), but the mechanism of action remains to be identified. |
20860537 | Doubling of water intake increases daytime blood pressure and reduces vertigo in healthy subjects. | We studied the effect of increased water intake on ambulatory blood pressure (BP) in healthy individuals. Blood pressure was recorded after 2 weeks of either regular (RWI) or extra water intake (EWI, an additional 30 ml water/kg body weight per day) in 20 healthy subjects (10 males, 10 females). The extra water intake (RWI: 1.7 ± 0.59 l, EWI: 3.7 ± 0.84 l, respectively, p < 0.0001, i.e., an increase of 2 liters) induced an increase in mean arterial daytime BP from 89.0 ± 5.5 mmHg during RWI to 91.4 ± 6.4 mmHg during the EWI phase (p = 0.005), while night-time BP was unchanged by the intervention. The visual-analogue-scale (VAS, maximum score of 10) score corresponding to the statement "I often experience vertigo" was 3.1 ± 2.6 during RWI and decreased to 2.1 ± 2. 1 during EWI phase (p = 0.008). In conclusion,two liters of extra water intake for 2 weeks significantly increased daytime blood pressure and reduced a sense of vertigo in healthy individuals. |
20860539 | Novel technologies to detect atelectotrauma in the injured lung. | Cyclical recruitment and derecruitment of lung parenchyma (R/D) remains a serious problem in ALI/ARDS patients, defined as atelectotrauma. Detection of cyclical R/D to titrate the optimal respiratory settings is of high clinical importance. Image-based technologies that are capable of detecting changes of lung ventilation within a respiratory cycle include puted tomography (dCT), synchrotron puted tomography (SRCT), and electrical impedance tomography (EIT). Time-dependent intra-arterial oxygen tension monitoring represents an alternative approach to detect cyclical R/D, as cyclical R/D can result in oscillations of PaO₂ within a respiratory cycle. Continuous, ultrafast, on-line in vivo measurement of PaO₂ can be provided by an indwelling PaO₂ probe. In addition, monitoring of fast changes in SaO₂ by pulse oximetry technology at the bedside could also be used to detect those fast changes in oxygenation. |
20860540 | Low-molecular-weight heparins do not modify obliterative airway disease in rat tracheal allografts. | Immunosuppressive and antiproliferative effects of heparin may be beneficial in the field of solid organ transplantation. The aim of this study was to examine the effect of low-molecular-weight heparin pounds on the development of obliterative airway disease (OAD) in the rat tracheal transplant model. Allogenic heterotopic tracheal transplantations were performed from Brown-Norway into Lewis rats. Recipients were treated either with nadroparin, enoxaparin, parnaparin, or vehicle from day 0 until harvesting at day 7 or 21. Graft rejection was morphometrically assessed to determine the extent of luminal obliteration end epithelial necrosis. All tracheal grafts harvested at day 7 demonstrated nearly equivalent degree of luminal obstruction regardless of treatment regimen. Likewise, at day 21 the extent of airway narrowing and the degree of inflammatory cell infiltration were similar among the groups. Moreover, loss of airway epithelium was not prevented by LMWH treatments. Finally, intragraft mRNA expression for transforming growth factor-β1 and platelet-derived growth factor-A, interleukin-2, interferon-γ, and monocyte chemoattractant protein-1 did not differ between the groups. In contrast with findings in other animal models, treatment with LMWH preparations did not modify the development of OAD in rat tracheal allografts. |
20860538 | Deficiency of matrix metalloproteinase-13 increases inflammation after acute lung injury. | Human and animal studies of acute lung injury (ALI) have shown that matrix metalloproteinases (MMPs) play an important role in disease pathogenesis, but despite being detected during ALI, the function of the collagenase MMP-13 in ALI is unknown. To evaluate this role of MMP-13, mice deficient in MMP-13 (KO) were examined after hyperoxic lung injury, pared to wild-type (WT) mice. There was no survival difference between KO and WT mice. There was also no difference in fibrosis between WT and KO mice, as determined by hydroxyproline content and collagen expression by real-time polymerase chain reaction (PCR). Within the bronchoalveolar lavage (BAL), the KO mice exhibited a significant increase in inflammatory cells, pared to the WT mice (5.51 × 10(5) versus 2.35 × 10(5) cells/mL; P = .001). Increased levels of the chemokine monocyte chemoattractant protein 1 (MCP-1) were observed in the lungs of the KO mice, confirmed via immunohistochemistry. In a subsequent in vitro experiment, MMP-13 was shown to cleave MCP-1. In ALI in the MMP-13 KO mice, MCP-1 could therefore remain active and potentially attract macrophages to the BAL. This study suggests a direct role for MMP-13 in modifying the inflammatory response in the lung after ALI. |
20860541 | Growth differentiation factor 15 in different stages of heart failure: potential screening implications. | Identification of individuals in the early stage of heart failure (HF) may allow earlier initiation of disease-modifying treatment. We evaluated concentrations of the growth differentiation factor (GDF)-15 at different stages and its potential screening value in 208 subjects. Plasma GDF-15 was measured by using an enzyme-linked immunosorbent assay. GDF-15 was positively correlated with the stages of HF (r=0.804, p<0.001). In distinguishing patients with stage B HF, the area under the curve was 0.873 (p<0.001). These findings indicate that GDF-15 concentration was elevated with the progressing stages of HF and might have potential screening implications for stage B HF. |
20860542 | Low-level laser therapy with a pulsed infrared laser accelerates second-degree burn healing in rat: a clinical and microbiologic study. | This study was carried out to investigate the influence of pulsed-wave low-level laser therapy (LLLT) on the healing of a deep second-degree burn model in rat. |
20860543 | Inflammation and immune response in acute aortic dissection. | The aim of our study was to evaluate the lymphocyte subpopulations and the cytokines in the peripheral blood of patients with type-A Stanford acute aortic dissection (AAD group) and to determine whether inflammatory cells are present at the site of aortic dissection. |
20860544 | Severe laryngeal dysplasia in a 20-year-old nonsmoker treated with CO2 laser excision: a case report and review of the literature. | We present the unusual case of a 20-year-old female nonsmoker with severe laryngeal dysplasia managed with endoscopic CO(2) laser resection with frozen-section analysis. We use her case as a platform for discussion of the current evidence surrounding laryngeal dysplasia, particularly etiology and the use of lasers in management. |
20860545 | Investigation of coronal leakage of root fillings after smear-layer removal with EDTA or Nd:YAG lasing through capillary-flow porometry. | This study investigates the effects of Nd:YAG laser bined with different irrigation protocols on the marginal seal of root fillings. |
20860547 | Current and new cytomegalovirus antivirals and novel animal model strategies. | Cytomegalovirus (CMV) is a significant health problem among immunosuppressed individuals. In particular, transplant and AIDS patients and the developing fetus in utero are highly susceptible to CMV. In these vulnerable populations, infection leads to life threatening end organ viral disease or in surviving newborn babies to deafness or to mental retardation. Currently, the most effective way to control CMV infection, given the lack of an effective vaccine, is by antiviral therapy. However, available antivirals suffer plications associated with prolonged use, such as drug toxicity as well as the emergence of resistant strains of virus. Additionally, since CMV has plex immune evasion strategies, to avoid innate and adaptive immune responses, there is a need for new antiviral development. Any antiviral should be tested in a controlled animal model but species specificity of HCMV precludes the direct study of the virus in an animal model. Consequently, animal CMV in their respective animal host are used to study intervention strategies. In this review, both current and new antiviral strategies are discussed as are the various animal models and strategies to improve existing antiviral animal models by humanizing animal CMV. |
20860548 | Drugs acting on mast cells functions: a cell biological perspective. | Mast cells are bone marrow derived cells capable of secreting many active molecules: mediators stored in specific granules, such as histamine and heparin; small molecules produced immediately upon stimulation, such as lipid derivatives and nitric oxide; and many constitutively secreted, pleiotropic cytokines. Thanks to these secretion products and perhaps direct cell-cell interactions, mast cells play roles in inflammation and tissue repair, angiogenesis and fibrosis. Mast cells themselves respond to many mediators of their own, giving rise to autocrine loops. Successful anti-allergic therapies have typically targeted the receptors for mast cell secretory products, particularly those for histamine. Among agents directly affecting mast cells, disodium chromoglycate and glucocorticoids are known since some time, while new pharmacological approaches may stem from the recognition of an interference with mast cell growth and differentiation by cyclosporine A, monoclonal antibodies, interferons, and JAK3 inhibitors. The action of agents that affect mast cell differentiation and function is considered here from a cell and tissue biological perspective as a premise to the application of these agents to the clinics, therefore special attention has been paid to references pertaining to humans. |