2-甲酰(乙酰)取代喹啉缩氨基硫脲的合成

缩氨基硫脲类化合物有抗肿瘤、抗病毒和抗菌等多种药理活性。Barret等首次报道了乙二醛二缩氨基硫脲(Ⅰ)的抗疟活性。Klayman等研究了缩     

Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium

Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.     

Left ventricular dysfunction in Klinefelter syndrome is associated to insulin resistance, abdominal adiposity and hypogonadism

Objective Epidemiological data suggest there is an increased risk of dying from heart disease among patients with Klinefelter syndrome (KS). Due to high prevalence of hypogonadism and metabolic syndrome, we speculated that patients with KS may have subclinical changes in the left ventricular function. Therefore, the aim was to assess left ventricular long axis function by tissue Doppler echocardiography in patients with KS and relate these findings to the metabolic status and testosterone levels. Design Cross-sectional study. Out-patient clinic. Patients We investigated 25 unselected patients with KS, recruited from endocrine and fertility clinics. Twenty-five age-matched males served as controls. Measurements Left ventricular systolic long axis function (velocities and strain rate) assessed by tissue Doppler echocardiography related to free testosterone, fasting values of plasma glucose, insulin, homeostasis model assessment (HOMA)-index, cholesterol and triglycerides in addition to dual energy X-ray absorptiometry (DEXA) scan derived assessment of truncal body fat. Results The long axis function was significantly reduced in patients with KS (peak systolic velocities 4·4 ± 1·3 vs. 5·3 ± 1·0 cm/s, P < 0·01 and strain rate –1·3 ± 0·3 vs.–1·6 ± 0·3 s⁻¹, P < 0·01). However, the ventricular dysfunction was mainly attributed KS patients with metabolic syndrome. The peak systolic velocities were significantly correlated to truncal body fat (r = –0·72, P < 0·01) and free testosterone (r = 0·63, P < 0·01), but uncorrelated to plasma glucose, insulin and HOMA-index. Conclusion Systolic long axis function is decreased in patients with KS and metabolic syndrome. The decrease in myocardial systolic function was significantly related to truncal body fat and hypogonadism, but not correlated to insulin sensitivity.     

Childhood Diabetes in the Nordic Countries: A Comparison of Quality Registries

Background:In 2008 a Nordic collaboration was established between the quality registries in Denmark, Iceland, Norway, and Sweden to improve quality of care for children with diabetes. This study aimed to describe those registries and confirm that the registry variables are comparable. Selected variables were used to demonstrate outcome measurements.Methods:The organization of the registries and methodology are described. Cross-sectional data for patients between birth and 14.9 years with type 1 diabetes mellitus in 2009 (n = 6523) from 89 centers were analyzed. Variables were age, gender, and diabetic ketoacidosis at onset, together with age, gender, HbA1c, insulin regimen, and severe hypoglycemia at follow-up in 2009.Results:All 4 registries use a standardized registration at the onset of diabetes and at follow-up, conducted at the local pediatric diabetes centers. Methods for measuring HbA1c varied as did methods of registration for factors such as hypoglycemia. No differences were found between the outcomes of the clinical variables at onset. Significant variations were found at follow-up for mean HbA1c, the proportion of children with HbA1c < 57 mmol/mol (NGSP/DCCT 7.4%), (range 15-31%), the proportion with insulin pumps (range 34-55%), and the numbers with severe hypoglycemia (range 5.6-8.3/100 patient years).Conclusions:In this large unselected population from 4 Nordic countries, a high proportion did not reach their treatment target, indicating a need to improve the quality of pediatric diabetes care. International collaboration is needed to develop and harmonize quality indicators and offers possibilities to study large geographic populations, identify problems, and share knowledge.     

Identification of Candida species in the clinical laboratory: a review of conventional,commercial, and molecular techniques

In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so‐called non‐albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time‐consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species.     

国内六大行政区域六城市中老年人群膝关节骨性关节炎患病危险因素比较

目的：了解中国不同地区间中老年人群膝关节骨性关节炎患病危险因素。方法：调查时间为2005—07／08。①从中国六大行政区（西北，华北，华东。中南，东北，西南）选出六城市（西安，石家庄，上海。广州，哈尔滨市，成都），用分层多阶段整群抽样方法，抽取6218名40岁及以上具有正式户口常住男女人群进行膝关节骨性关节炎的流行病学问卷调查（包括一般情况、现病史、既往史、体格检查、X射线片检查情况和疾病诊断6个方面，共计94个问题141个变量指标），并对其中4808名有症状者进行X射线平片膝正侧位投照。②膝关节骨性关节炎诊断标准为临床症状阳性加X射线Kellgren ＆ Lawrence分级二级及以上者。③计算患病率，并采用Epilnf06．0和SPSS 10．0软件对其中83个变量进行多因素非条件Logistfc回归分析，表示疾病与暴露因素之间联系强度的指标用比值比（OR），若OR〉1，说明疾病发生危险性增加，与暴露因素呈正关联；若OR〈1，说明疾病发生危险性减少，与暴露因素呈负关联。 结果：①六城市膝关节骨性关节炎总患病率为15．6％，其中西安7．7％，石家庄11．2％，上海9．8％。广州30．5％，哈尔滨16．9％，成都17．5％，各城市患病率比较差异显著（P〈0．01）。②Logistic回归分析膝关节骨性关节炎在大部分城市有共同的危险因素如年龄大（OR=1．032—1．181），使用蹲坑排便年限长（OR=1．021-1．077），体质量高（OR=1．048—1．073），和开始饮酒年龄大（OR=1．008～1．028）；而从事专职体育运动（OR=1．651，西安），骨质疏松病史（OR=3．311，石家庄），吸烟（OR=2．654，石家庄），类风湿关节炎病史（OR=4．964，上海），文化程度高（OR=2．593，上海），女性（OR=2．510，广州），姐妹骨关节炎史（OR=13．251，哈尔滨），母亲骨关节炎史（OR=5．683，成都）等危险因素分别在不同地区出现． 结论：年龄大、使用蹲坑排便年限长、体质量高和开始饮酒年龄大是中国六地区膝关节骨性关节炎患病的共同危险因素，同时，不同地区主要危险因素又有一定差异。     

Grafting assay distinguishes promotion sensitive from promotion resistant JB6 cells

The JB6 mouse epidermal cell system has been used extensively as an in vitro transformation model for the study of tumor promotion. The standard JB6 cell assay for promotion of transformation is carried out in soft agar or other anchorage independent conditions. The present study was directed to the development of an in vivo model to distinguish the promotion resistant (P-) and promotion sensitive (P+) progression phenotypes. Results indicate that the grafting assay distinguishes P- and P+ cells in vivo with P+ but not P- cells forming tumors within 7-9 weeks. Expression of dominant negative mutant jun TAM67 blocks both anchorage independent transformation response and graft bed tumor formation by P+ cells, suggesting that the requirement for AP-1 activation in transformation now applies in vivo. Expression of mutated p53 produced a gain of P+ phenotype in P- cells in vitro, but not in vivo. Histochemical and Northern blot analysis for expression of various keratinocyte markers revealed no evidence for expression, suggesting a loss of keratinocyte markers following establishment in culture. In summary, the skin-grafting assay described in this study appears to be a valid in vivo assay for distinguishing the preneoplastic progression phenotypes represented by JB6 P- and P+ cells.      

Hypoglycaemia and elevated urine ethylmalonic acid in a child homozygous for the short-chain acyl-CoA dehydrogenase 625G > A gene variation

The aim of this case report is to call attention to short-chain acyl-CoA dehydrogenase (SCAD) deficiency as a possible contributory factor to hypoglycaemia in childhood. We report on a previously healthy 14 mo-old Danish boy who presented with hypoglycaemia and metabolic acidosis after a few days of upper airway infection. After two days on a normal diet, he recovered clinically and biochemically. A thorough biochemical examination did not reveal the cause of the hypoglycaemia. However, the excretion of ethylmalonic acid in two morning urine samples was moderately increased, and hence the SCAD gene was screened for mutations. We found the child homozygous for the G > A SCAD gene variation at position 625. Conclusion: In this patient, reduced function of the SCAD protein is reflected in the excretion of ethylmalonic acid, a marker of intracellular accumulation of butyryl-CoA and the cytotoxic butyric acid. Furthermore, gluconeogenesis might be compromised owing to lack of reducing equivalents from the oxidation of short-chain fatty acids in the fasting or stressed state, thus contributing to the predisposition for fasting hypoglycaemia.     

北京崇文区中老年原发性骨质疏松症的发生及其影响因素：分层多阶段整群抽样调查

目的:了解北京市崇文区中老年人原发性骨质疏松症患病情况及其影响因素。方法:①调查对象:选择1998-06/09居住在北京市崇文区具有正式户口的常住男女人群,按照分层多阶段整群抽样方法抽取年龄在40～85岁中老年人为调查对象。②实验方法和评估指标:骨密度测量采用双能X线骨密度测定仪测量308名中老年人腰椎(L2～L4)前后位及股骨上端的骨股颈、三角区(Ward's)和大粗隆的骨密度;问卷调查分为一般情况、月经和生育史、药物应用史、饮食习惯和体格检查情况。结果:308名中老年人接受调查,其中男140名,女168名。年龄40～85岁,平均(60.80±10.12)岁。①各年龄段不同性别中老年人腰椎和股骨上端骨密度测量结果:大粗隆、骨股颈和三角区骨密度无论男女均随着年龄的增长有下降趋势。②各年龄段不同性别中老年人原发性骨质疏松症患病率情况:腰椎、大粗隆和三角区部位的患病率女性高于男性,股骨颈部位的患病率男性高于女性。男性以股骨颈原发性骨质疏松症检出率最高,女性以三角区检出率最高。原发性骨质疏松症患病率随着年龄的增加有增高的趋势。③Ward's三角区骨密度单因素分析:年龄、绝经后年限、生育次数与Ward's三角区骨密度呈负相关(P<0.05);居住环境采光条件、每周蛋类摄入量、身高和体质量与Ward's三角区骨密度呈正相关(P<0.05)。男性和女性、服用钙剂组和未服用钙剂组、服用避孕药物组和未服用避孕药物组、受背痛困扰组和未受背痛困扰之间差异有显著性(P<0.05)。④Ward's三角区骨密度多因素分析:年龄、体质量、绝经年限(女性)是引起骨密度降低的3个重要因素。结论:对于男性人群腰椎骨密度正常,但有明显骨质增生者应参考股骨上端骨密度方能作出正确评价。绝经后高龄妇女、低体质量的人群是原发性骨质疏松的高危人群。