Loss of high-affinity thrombin receptors during platelet concentrate storage impairs the reactivity of platelets to thrombin

BACKGROUND: The storage of platelet concentrates (PCs) induces a reduction in the platelet surface expression of glycoprotein (GP) Ib alpha. The location of the platelets' high-affinity binding site for thrombin has been postulated as being located on GPIb alpha. This study attempts to determine whether loss or alteration of GPIb alpha during storage of PCs is related to impairment in the reactivity of platelets to thrombin. STUDY DESIGN AND METHODS: In this study, platelet surface expression of GPIb alpha was monitored by means of flow cytometry, throughout standard storage of PCs for up to 10 days. Two thrombin- induced platelet responses, the binding of radiolabeled fibrinogen and the platelet surface expression of P-selectin, were evaluated. Thrombin- binding assays were also performed to assess the number of thrombin receptors in platelets. RESULTS: The surface expression of the GPIb/IX complex declines during storage of PCs. The thrombin-induced maximal binding of fibrinogen in platelets stored for 3, 7, and 10 days was 77 +/? 7 percent, 60 +/? 20 percent, and 34 +/? 25 percent, respectively, of that found in fresh platelets. Moreover, the concentration of thrombin needed for 50 percent of platelets to express the CD62 antigen P-selectin at the surface increased from 0.05 U per mL in fresh platelets to 0.11, 0.56, and 1.2 U per mL in platelets stored for 3, 7, and 10 days, respectively. Thrombin-binding experiments demonstrated a significant reduction in the number of high-affinity binding sites throughout storage of PCs (55 +/? 21 sites/platelet in 10-day-stored platelets vs. 73 +/? 25 in fresh platelets). A significant correlation was also observed between the number of high-affinity thrombin-binding sites and surface expression of GPIb alpha. Selective blockage of the thrombin-binding site on GPIb alpha with monoclonal antibody LJ-Ib10 also inhibited the response of fresh platelets to thrombin, up to a level equivalent to that found in 3-day-stored platelets. CONCLUSION: The loss of the GPIb alpha-located high-affinity thrombin-binding site may impair the ability of platelets to become activated by thrombin as storage time increases.     

河南省5所院校学生的亚健康状况

目的:调查河南省5所院校大学生亚健康的发生情况并分析其影响因素。方法:调查于2006-03/07在河南省5所高校完成。选择郑州大学、河南农业大学、河南财经学院、新乡医学院和安阳工学院五所不同专业院校1～4年级的大学生为对象进行亚健康调查。根据大学生"亚健康"主要表现特征,参照相关文献中关于亚健康状态的各种表现,自行设计亚健康调查表。每项问题后都有很好、稍差、明显差和很差或是没有、较少、较多和经常出现4种选项,以选择明显差、很差、较多和经常出现为亚健康标准。结果:共发放调查问卷2000份,收回有效问卷1990份。郑州大学、河南农业大学、河南财经学院、新乡医学院和安阳工学院5所大学亚健康人数分别为267,235,260,274,260人,亚健康的发生率分别为66.75%,59.34%,65.98%,68.50%,65.00%。不同专业院校大学生亚健康状态发生率与学习环境、专业特点、性别、城乡有关。亚健康的主要表现形式排在前3位的分别是长期持续疲劳,注意力难以集中,记忆力减退。在调查对象中,了解、听说过和不知晓亚健康的人数分别为441,340,1209人,占总人数的比例分别为22.16%,17.08%,60.75%。结论:大学生中相当一部分人存在亚健康状况,而社会、学习环境与心理、生活方式和人际关系等是导致大学生亚健康状况的主要因素。应正确引导大学生预防和消除亚健康状态,培养和建立新的高教教学卫生理念。     

氧化应激对糖尿病肾病时细胞、细胞外基质及血管通透性的影响机制

目的:糖尿病肾病及其引起的终末期肾病近年来在全球的发病情况逐年提高,该病预后差、治疗费用高,成为世界范围内严重危害人类健康的公共卫生问题。糖尿病肾病发病机制错综复杂,氧化应激被认为是重要的共同的机制之一。本文探讨氧化应激对糖尿病肾病的影响。资料来源:应用计算机检索MEDLINE,CBM,CNKI数据库及手工检索1997-01/2006-11期间的相关文献。包括临床研究(不限研究对象的年龄、性别、种族。)和基础研究,不限体内或体外研究。中文检索词包括“氧化应激”,“活性氧类”,“糖尿病肾病”和“发病机制”;英文检索词有“diabetic nephropathies”,“oxidative stress”,“reactive oxygen species”,“PKC”和“TGF-β”。资料选择:共收集到相关文献991篇,阅读全部文章的文题和大部分文章的摘要。选择文献所述内容与糖尿病肾病时氧化应激作用相关的文献。排除重复性研究和Meta分析类文章。资料提炼:共得到符合纳入条件的文献142篇,排除849篇。选择其中30篇进行分析,其中英文25篇,中文5篇,英文有1篇为手工检索的增刊。资料综合:糖尿病肾病的发病机制错综复杂,肾脏的结构和功能变化包括高滤过、肾脏和肾小球的肥大、细胞外基质的堆积、肾小球基底膜的增厚和肾小球滤过屏障功能的异常。这些变化是多因素共同作用的结果,在众多发病机制中,氧化应激被认为是共同机制之一。在正常情况下,活性氧的产生和抗活性氧水平二者处于平衡状态,当活性氧蓄积过多就会攻击机体,即氧化应激。氧化应激的产生主要是活性氧类产生过多和清除减少以及糖尿病肾病患者体内氧化应激水平增加导致的。氧化应激对糖尿病肾病的影响包括活性氧类可以增加细胞膜的通透性;使肾细胞内的谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶等抗氧化酶发生糖化或氧化,肾组织抗氧化能力降低,细胞内关键酶和转运蛋白Na-K-ATP酶失活等。结论:氧化应激作用可以增加细胞膜的通透性,使肾组织抗氧化能力降低,是糖尿病肾病的重要发病机制之一。     

ID2-VEGF-related Pathways in the Pathogenesis of Kaposi's Sarcoma: A Link Disrupted by Rapamycin

The Id-proteins are a family of four related proteins implicated in the control of differentiation and cell-cycle progression. Down-regulation of Id-gene expression is essential for the differentiation of several cell types. In addition, deregulated Id2 activity inhibits the Rb tumor suppressor pathway and promotes the expression of vascular endothelial growth factor (VEGF). Several members of VEGF family could be involved in Kaposi's sarcoma (KS) development and progression. Lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) is the first marker of lymphatic endothelial competence during development in the mature vasculature, and is also expressed on KS spindle cells. Rapamycin (RAPA), an immunosuppressive drug, has been shown to reverse KS growth and to reduce tumor angiogenesis. We evaluate, in transplantation-associated KS and in cultured KS-cells the RAPA effect on Id2 and on de novo lymphangiogenesis. Markers of lymphatic-endothelial-cells (VEGFR-3, LYVE-1) and Id2, expressed at low levels within the normal skin, were up-regulated in KS and returned to normal levels after RAPA introduction. The association between Id2 and lymphangiogenesis is suggested by co-localization of Id2, VEGFR-3 and LYVE-1. RAPA inhibition on Id2 expression was confirmed in vitro in KS-cells, both in basal conditions and upon stimulation with VEGF. In conclusion, our data would suggest a novel molecular mechanism for the antineoplastic effects of RAPA in posttransplant KS.     

Choosing event‐driven and daily HIV pre‐exposure prophylaxis – data from two European PrEP demonstration projects among men who have sex with men

IntroductionDaily and event‐driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event‐driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence.MethodsWe analysed pooled data from two prospective cohort studies among MSM: Be‐PrEP‐ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three‐monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018.Results and discussionWe included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94).ConclusionsA quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered.     

Clinical features of chromosome 22q11.2 microdeletion syndrome in 208 Chilean patients

Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines.