Could proteinuria evaluation be helpful in predicting renal progression in apolipoprotein E-deficient (E-/-) mice with chronic renal failure?

Sir, We read with interest the recent article by Buzello et al. [1]on renal changes in apo E^-/- mice after subtotal nephrectomy.They compared renal lesion development in male wild-type C57BL/6mice with that of genetically modified male apo E^-/- mice aftereither sham operation, unilateral nephrectomy or subtotal nephrectomy(SNX) by removal of 75% of the cortex in one kidney and removalof the contralateral kidney. They found     

拉萨地区冠心病与幽门螺杆菌感染相关性研究

目的探讨西藏拉萨地区幽门螺杆菌（Helicobacter pyloric，Hp）感染与冠心病及多种危险因素的关系。为该地区冠心病的防治提供依据。方法分为冠心病组46例和非冠心病组51例，应用检测血抗HpIgG及-C-尿素呼气试验方法检测Hp感染情况，并分别测定各组血脂、血糖、餐后2h血糖、C反应蛋白、纤维蛋白原、白细胞总数。结果冠心病组患者血清抗HpIgG阳性率为50．0％（23／46），明显高于非冠心病组的23．5％（12／51），P〈0．05；冠心病患者Hp现症感染率为54．3％（25／46），明显高于非冠心病组的31．3％（27／51），P〈0．05；冠心病组Hp感染患者血脂、空腹及餐后2h血糖、C反应蛋白、纤维蛋白原较非感染患者明显升高（P〈0．05）。结论Hp感染与冠心病相关，可能是拉萨地区冠心病发病的独立危险因素。     

Comparative mouse skin tumorigenicity and induction of Ha-ras mutations by bay region diol epoxides of 5-methylchrysene and 5,6- dimethylchrysene

We compared the tumor-initiating activities toward mouse skin of two structurally related polycyclic aromatic hydrocarbon diol epoxides: racemic anti-1,2,3,4-tetrahydro-5,6-dimethylchrysene-1,2-diol-3,4- epoxide (5,6-diMeCDE) and racemic anti-1,2,3,4-tetrahydro-5- methylchrysene-1,2-diol-3,4-epoxide (5-MeCDE). Tumors induced by these diol epoxides were analysed for mutations in the Ha-ras gene. 5,6- diMeCDE is derived from the non-planar parent compound 5,6- dimethylchrysene, and reacts to approximately equal extents with dA and dG in DNA, whereas 5-MeCDE is derived from a nearly planar parent compound, 5-methylchrysene, and reacts mainly with dG in DNA. 5,6- diMeCDE, at initiating doses of 33, 100 or 400 nmol per mouse, induced 1.2, 2.2 and 6.2 skin tumors per mouse, respectively. It was significantly less tumorigenic than 5-MeCDE which induced 3.1, 7.5 and 9.1 skin tumors per mouse at the same doses. Tumors induced by 5,6- diMeCDE had a large number of CAA-->CTA mutations in codon 61 of the Ha- ras gene: 50, 55 and 75% of the tumors analysed had this mutation at the 33, 100 and 400 nmol doses. No mutations were found in codons 12 and 13 in the tumors induced by 5,6-diMeCDE. In contrast, CAA-->CTA mutations in codon 61 were rarely seen in tumors induced by 5-MeCDE. At the highest dose of 5-MeCDE, 20% of the tumors analysed had mutations at G of codons 12 and 13. The results of this comparative study support the hypothesis that mutations in the Ha-ras gene in mouse skin tumors induced by PAH diol epoxides occur as a result of their direct reaction with the gene. However, pathways other than the commonly observed Ha- ras codon 61 mutations are clearly important in mouse skin tumorigenesis by these diol epoxides.      

Possible role of CYP2B6 genetic polymorphisms in ifosfamide‐induced encephalopathy: report of three cases

Ifosfamide (IFA) is a potent alkylating antitumoral agent, but its use is limited by neurological side effects. IFA is a racemic mixture of two enantiomeric forms, R‐IFA and S‐IFA with a stereoselective metabolism by CYP3A4 and CYP2B6, leading either to bioactive or to toxic pathways. In three consecutive cases of pediatric patients who exhibited IFA‐induced encephalopathy (IIE), genotyping of clinically relevant single‐nucleotide polymorphisms associated with decreased CYP3A4 and CYP2B6 activities was performed. Genetic investigations revealed the presence of CYP2B6 rs4803419 (C>T) in one patient while the two others carried the CYP2B6*6 allelic variant. All patients carried CYP3A4 wild‐type genotype (CYP3A4*1/*1). Because CYP2B6‐deficient alleles may be responsible for an increased conversion of S‐IFA into neurotoxic metabolites, screening for CYP2B6 polymorphisms may help to avoid IIE and improve clinical outcomes.     

Psychological distress among Ugandan adolescents living with HIV: Examining stressors and the buffering role of general and religious coping strategies

HIV infection increases the risk of psychological distress among adolescents living with HIV (ALHIV), which, in turn, increases risky behaviours such as medication non-adherence, substance use, and sexual risk-taking. The majority of studies on psychological distress among ALHIV have been conducted in high-income countries; data on the prevalence and correlates of psychological distress among ALHIV in sub-Saharan Africa (SSA) are scarce, yet over two-thirds of the global population of ALHIV resides in SSA. The purpose of this study was to identify the contextually relevant correlates of psychological distress among Ugandan ALHIV. Utilizing the stress and coping framework, we explored the risk and protective factors for psychological distress in cross-sectional sample of 464 ALHIV (aged 12–19; 53% female) at a large HIV treatment centre in Kampala, Uganda. The stressors associated with psychological distress included daily hassles, major negative life events, HIV-related quality of life, and stigma. Protective factors included psychosocial resources such as religious coping, satisfaction with social support, and general coping style and behaviours. Social support and optimism were significantly associated with psychological distress. Findings underscore the need for mental health services for ALHIV in Uganda and other resource-limited settings.     

Sexual and reproductive health: Progress and outstanding needs

We examine progress towards the 1994 International Conference on Population and Development (ICPD) commitment to provide universal access to sexual and reproductive health (SRH) services by 2014, with an emphasis on changes for those living in poor and emerging economies. Accomplishments include a 45% decline in the maternal mortality ratio (MMR) between 1990 and 2013; 11.5% decline in global unmet need for modern contraception; ~21% increase in skilled birth attendance; and declines in both the case fatality rate and rate of abortion. Yet aggregate gains mask stark inequalities, with low coverage of services for the poorest women. Demographic and Health Surveys and Multiple Indicator Cluster Surveys from 80 developing countries highlight persistent disparities in skilled birth attendance by household wealth: in 70 of 80 countries (88%), ≥80% of women in the highest quintile were attended by a skilled provider at last birth; in only 23 of the same countries (29%) was this the case for women in the lowest wealth quintile. While there have been notable declines in HIV incidence and prevalence, women affected by HIV are too often bereft of other SRH services, including family planning. Achieving universal access to SRH will require substantially greater investment in comprehensive and integrated services that reach the poor.