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.     

Prolonged CD4+ lymphocytopenia and thrombocytopenia in a chimpanzee persistently infected with human immunodeficiency virus type 1.

The immunologic and virologic status of a chimpanzee inoculated with multiple isolates of the human immunodeficiency virus type 1 (HIV-1) were assessed over 57 months to determine whether prolonged thrombocytopenia and CD4+ lymphocytopenia observed in the animal might be associated with long-term HIV infection. Although the chimpanzee showed no signs of disease, it lost both CD4+ (as low as 134 cells/microliter) and CD8+ lymphocytes approximately 30 months after initial infection, followed by thrombocytopenia that has persisted for greater than 2 years. Lymphopenia and thrombocytopenia were preceded by or coincided with the appearance of antibodies cross-reactive with histone H2B and decreased levels of complement component C4; an eightfold decrease in HIV-specific antibody titers; the inability of CD8+ lymphocytes to suppress virus replication; impaired proliferative responses to T cell mitogens; and the isolation of cell-free HIV from plasma. These data suggest that, given sufficient time, HIV-infected chimpanzees may develop disease.     

Rectal transmission of human immunodeficiency virus type 1 to chimpanzees

Inoculation of chimpanzees with human immunodeficiency virus type 1 (HIV-1) has been used as a model system to define mechanisms of pathogenesis and to test protective efficacy of candidate HIV-1 vaccines. In most of these studies, the animals were inoculated intravenously. However, because HIV-1 is transmitted primarily across mucosal surfaces, future evaluations of vaccines should employ mucosal routes for administering infectious virus to immunized animals. To develop a model of rectal transmission of HIV-1, chimpanzees were exposed without trauma to 4 different HIV-1 strains at doses ranging from 200 to 10,000 TCIDs. Infection, characterized by seroconversion and repeated isolation of virus from lymphocytes, was established in 1 of 5 animals. This animal was sequentially inoculated with a subtype B and then an E strain and was infected with both strains. The results show that rectal exposure of adult chimpanzees to cell-free HIV-1 was not an efficient mode of transmission in this cohort.     

Implementing a screening and diagnosis program for dementia in primary care

BACKGROUND: Primary care physicians are positioned to provide early recognition and treatment of dementia. We evaluated the feasibility and utility of a comprehensive screening and diagnosis program for dementia in primary care. METHODS: We screened individuals aged 65 and older attending 7 urban and racially diverse primary care practices in Indianapolis. Dementia was diagnosed according to International Classification of Diseases (ICD)-10 criteria by an expert panel using the results of neuropsychologic testing and information collected from patients, caregivers, and medical records. RESULTS: Among 3,340 patients screened, 434 scored positive but only 227 would agree to a formal diagnostic assessment. Among those who completed the diagnostic assessment, 47% were diagnosed with dementia, 33% had cognitive impairment—no dementia (CIND), and 20% were considered to have no cognitive deficit. The overall estimated prevalence of dementia was 6.0% (95% confidence interval (CI) 5.5% to 6.6%) and the overall estimate of the program cost was $128 per patient screened for dementia and $3,983 per patient diagnosed with dementia. Only 19% of patients with confirmed dementia diagnosis had documentation of dementia in their medical record. CONCLUSIONS: Dementia is common and undiagnosed in primary care. Screening instruments alone have insufficient specificity to establish a valid diagnosis of dementia when used in a comprehensive screening program; these results may not be generalized to older adults presenting with cognitive complaints. Multiple health system and patient-level factors present barriers to this formal assessment and thus render the current standard of care for dementia diagnosis impractical in primary care settings. Supported by grant R01 HS10884-01 from the Agency for Healthcare Research and Quality.     

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。