Cutaneous nociception: Role of keratinocytes

Recent years have brought an enhanced understanding of keratinocyte contribution to cutaneous nociception. While intra‐epidermal nerve endings were classically considered as the exclusive transducers of cutaneous noxious stimuli, it has now been demonstrated that epidermal keratinocytes can initiate nociceptive responses, like Merkel cells do for the innocuous mechanotransduction. In the light of recent in vivo findings, this article outlines this paradigm shift that points to a not yet considered population of sensory epidermal cells.     

Fundamentals about onset and progressive disease character of type 2 diabetes mellitus

ResearchGate is a world wide web for scientists and researchers to share papers, ask and answer questions, and find collaborators. As one of the more than 15 million members, the author uploads research output and reads and responds to some of the questions raised, which are related to type 2 diabetes. In that way, he noticed a serious gap of knowledge of this disease among medical professionals over recent decades. The main aim of the current study is to remedy this situation through providing a comprehensive review on recent developments in biochemistry and molecular biology, which can be helpful for the scientific understanding of the molecular nature of type 2 diabetes. To fill up the shortcomings in the curricula of medical education, and to familiarize the medical community with a new concept of the onset of type 2 diabetes, items are discussed like: Insulin resistance, glucose effectiveness, insulin sensitivity, cell membranes, membrane flexibility, unsaturation index (UI; number of carbon-carbon double bonds per 100 acyl chains of membrane phospholipids), slow-down principle, effects of temperature acclimation on phospholipid membrane composition, free fatty acids, energy transport, onset of type 2 diabetes, metformin, and exercise. Based on the reviewed data, a new model is presented with proposed steps in the development of type 2 diabetes, a disease arising as a result of a hypothetical hereditary anomaly, which causes hyperthermia in and around the mitochondria. Hyperthermia is counterbalanced by the slow-down principle, which lowers the amount of carbon-carbon double bonds of membrane phospholipid acyl chains. The accompanying reduction in the UI lowers membrane flexibility, promotes a redistribution of the lateral pressure in cell membranes, and thereby reduces the glucose transporter protein pore diameter of the transmembrane glucose transport channel of all Class I GLUT proteins. These events will set up a reduction in transmembrane glucose transport. So, a new blood glucose regulation system, effective in type 2 diabetes and its prediabetic phase, is based on variations in the acyl composition of phospholipids and operates independent of changes in insulin and glucose concentration. UI assessment is currently arising as a promising analytical technology for a membrane flexibility analysis. An increase in mitochondrial heat production plays a pivotal role in the existence of this regulation system.     

NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine

6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT15¹3 and NUDT15¹2 genotypes were at a 10–15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT15¹3 and NUDT15¹2, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients.     

△LuxS的表型分析及其在GBS毒力调控机制研究中的应用

目的采用LuxS缺失突变株模型对B型链球菌中数量感应相关分子LuxS的功能及与其相关的自诱导因子-2数量感应通路进行研究，以探索其毒力调控机制。方法采用RT-PCR法、菌落印迹分析、生长曲线测定、cAMP因子测定等方法对该缺失突变菌株的表型特性进行了研究。最后应用哈氏弧菌作为报告菌株，通过生物发光测定法分析了突变株对B型链球菌诱导报告菌株中的生物发光活性的影响。结果发现此缺失突变可导致B型链球菌中scpB基因表达的上调；与野生株相比，突变株的生物发光诱导活性比野生株降低了大约两倍。结论本研究结果证实了LuxS在GBS中AI-2数量感应通路中的重要性，并为GBS中毒力调控机制的进一步研究提供了新的线索。     

三磷酸腺苷结合盒运转体A1与颈动脉粥样硬化斑块的关系

目的 探讨三磷酸腺苷结合盒运转体A1(ATP binding cassette transporter A1,ABCA1)在人颈动脉粥样硬化斑块中的表达变化及作用机制.方法 收集24例人颈动脉粥样硬化斑块标本和10例肠系膜动脉标本(对照组),采用RT-PCR测定ABCA1 mRNA和视黄酸X受体α(RXRα)mRNA表达水平,并采用Western Blot检测ABCA1及RXRα的蛋白表达水平.24例人颈动脉粥样硬化斑块标本按病理分级,比较病理组织为Ⅲ级和Ⅰ级动脉粥样硬化组织间ABCA1 mRNA、RXRαmRNA表达水平及蛋白表达水平.结果 颈动脉粥样硬化斑块组的ABCA1 mRNA(0.79±0.04)和RXRα mRNA(0.73±0.04)表达与对照组相比上调,差异有统计学意义(P＜0.05);ABCA1 mRNA与RXRα mRNA增加水平相关(P＜0.05);颈动脉粥样硬化斑块的ABCA1蛋白表达(0.22±0.03)下调水平与对照组(0.53±0.03)相比差异有统计学意义(P＜0.05);Ⅲ级和Ⅰ级动脉硬化斑块ABCA1mRNA、RXRα mRNA及蛋白表达水平差异有统计学意义(P＜0.05).结论 ABCA1及RXRα蛋白表达水平下调可能是进展性动脉粥样硬化损害的关键因素.     

用生物发光法定量测定绿脓杆菌对聚苯乙烯的粘附

本文用生物发光技术建立了定量测定绿脓杆菌(PA)对聚苯乙烯表面粘附的研究方法,同时观察了影响 PA 粘附的某些因素,比较了12株 PA 菌株对聚苯乙烯的粘附率。结果表明:在生物发光(BL)反应体系中,在萤虫素/萤虫素酶浓度给定的条件下,发光强度与 PA 释放的 ATP 量呈剂量依赖关系;在 PA 粘附体系中,其与聚苯乙烯表面的粘附随菌量的增加和粘附时间的延长而增加并受其缓冲液 pH 和菌龄的影响;不同 PA 菌株在同一条件下对聚苯乙烯的粘附率具有很大差别。     

Comparison between a swim-up and a Percoll gradient technique for the separation of human spermatozoa

Two methods of separating human sperm were compared using twenty-two semen samples. The sperm were separated by a swim-up technique or by self-migration on a Percoll gradient followed by medium change. After separation, the sperm obtained were assessed for progressive motility, ATP content, energy charge index ([ATP + 0.5 ADP]/[ATP + ADP + AMP]) and morphology. In general, and especially for semen samples containing less than 20 X 10(6) sperm/ml, separation by Percoll gradient selected sperm that were superior to those separated by the swim-up technique. The relatively high energy charge index (greater than 0.8) showed that the sperm tolerated the separation conditions well. It is suggested that self-migration on a Percoll gradient should prove useful for obtaining sperm of high quality.     

The participation of adenosine receptors in the adenosine 5''-triphosphate-induced relaxation in the isolated rabbit corpus cavernosum penis

AIM: To investigate the participation of adenosine receptors in the adenosine 5'-triphosphate (ATP)-induced relaxation in the corpus cavernosum penis (CCP) of rabbits. METHODS: The ATP-induced relaxation was assessed on the noradrenaline precontracted CCP of rabbits in the presence and absence of 8-(3-chlorostyryl)caffeine (CSC); an adenosine A(2A) receptor antagonist; alloxazine and MRS1754; adenosine A(2B) receptor antagonists; and ARL67156, an inhibitor of ecto-nucleoside triphosphate diphosphohydrolases. RESULTS: Adenosine and ATP relaxed the noradrenaline precontracted CCP of rabbits in a concentration-dependent manner. The adenosine- and ATP-induced relaxations were suppressed by alloxazine and MRS1754, but not by 8-(3-chlorostyryl)caffeine. ARL67156 potentiated the ATP-induced relaxation but not the adenosine-induced one. MRS1754 suppressed the ATP-induced relaxation potentiated by ARL67156. CONCLUSIONS: The above results suggest that, in the CCP of rabbits, the adenosine receptor mediating adenosine-induced relaxation is of the A(2B) receptor and the ATP directly causes relaxation through the A(2B) receptor on the CCP.     

3种钾通道在哮喘豚鼠气道高反应中的作用

目的：探讨钙激活钾通道（KCa）、延迟整流型钾通道（Kdr）和ATP敏感型钾通道（KATP）在哮喘豚鼠气道高反应中的作用。 方法： 采用离体气管环张力实验，观察加入特异性钾通道阻断剂后，与不加阻断剂相比气管环对组胺反应的量效曲线的差异。 结果： （１）加入KCa阻断剂TEA后，对照组气管环对组胺的反应变化不显著，而哮喘组气管环对10-4mol/L、10-3mol/L组胺的收缩反应均显著低于不加TEA的气管环(P<0.01)，量效曲线明显下移；（2）加入Kdr阻断剂4-AP后，对照组气管环对10-3mol/L组胺的最大收缩反应明显下降(P<0.05)，组胺的量效曲线下移，哮喘组气管环对10-4mol/L、10-3mol/L组胺的收缩反应均低于不加4-AP的气管环(P<0.01)，且下降程度较对照组大（P<0.05），量效曲线明显下移；（3）加入KATP阻断剂glibenclamide后，对照组和哮喘组气管环对组胺的量效曲线与不加glibenclamide的气管环相比变化均无明显差异。 结论： 在豚鼠哮喘模型中，KCa和Kdr活性的降低在气道高反应的发生中起介导作用，KATP作用不明显。     

Reassessment of the accuracy of traditional sperm characteristics and adenosine triphosphate (ATP) in estimating the fertilizing potential of human semen in vivo

Receiver operating characteristic curves and accuracy parameters were computed for traditional sperm characteristics (concentration, motility, morphology) and the number of peroxidase negative cells, and the concentration of adenosine triphosphate (ATP) in semen from populations of fertile and infertile men, and men who achieved a pregnancy after varicocele treatment. The percentage and concentration per millilitre of spermatozoa with rapid linear progressive motility, and the ATP concentration, provided the best discrimination between fertile and treated fertile from infertile men. The misclassification rate was higher for sperm morphology, total progressive motility and viability, whereas sperm concentration and the total sperm count per ejaculate had the worst discriminating power. The number of peroxidase negative cells per 100 spermatozoa was highly specific in identifying men who achieved pregnancy after varicocele treatment. The lower limit of normality of sperm characteristics was remarkably different between fertile men and men achieving pregnancy after treatment or during infertility work-up.