云南楚雄丙型肝炎基因型分布的特点

目的了解楚雄地区丙型肝炎病毒基因型分布的地域特点。方法统计楚雄州医院2013年12月～2016年2月诊治的146例HCV-RNA阳性患者丙型肝炎基因分型相关资料。从PUBMED、CNKI查阅周边地区丙肝基因型资料作为对比。结果楚雄地区丙肝基因型:1型32例(21.92%),2型4例(2.74%),3型99例(67.81%),6型11例(7.53%),无4、5型。亚型:1a型1例(0.68%),1b型31例(21.23%),2a型4例(2.74%),3a型20例(13.70%),3b型78例(53.42%),3i型1例(0.68%),6a型1例(0.68%),6u型1例(0.68%),6v型2例(1.37%),6n型7例(4.79%)。结论楚雄地区的丙型肝炎基因型特点:基因型以3型及1型为主。亚型:以3b为主,其次为1b、3a。少见基因型3i、6a、6n、6u、6v也有分布。无4、5型。其分布与邻国、邻省不同,与云南省内3b为主的大趋势一致,但与各地州市也有区别。其分布特点与各自的传播路线、范围、入体途径、强度相关;不可避免受全球流行的大背景所影响。随着交通条件改善,楚雄在毒品运输中的地位由集散地或节点下降为过境通道,性传播渐取代毒品传播成为HCV传播的主要途径,并以此桥接普通人群,也因此形成其独特的基因分布。     

Voriconazole and the liver

Voriconazole is an azole useful for the prophylaxis and the treatment of aspergillosis and other fungal infections in immunosuppressed subjects, as those found in aplasia after aggressive polychemotherapy treatments, after hematopoietic stem cell, liver or lung transplantation. Its administration in therapeutic doses lead to extremely varied serum levels from patient to patient and even to the same patient. The explanations are varied: nonlinearpharmacokinetics, certain patient-related factors, including genetic polymorphisms in the cytochrome P450 2C19 gene, the kidney and liver function, simultaneous administration with other drugs metabolised by the same cytochrome. It is recommended to maintain the serum concentrations of voriconazole between 1.5 and 4 μg/m L. At lower values its efficacy decreases and at higher values the risk of neurological toxicity increases. Even at these concentrations it is not excluded the possible appearance of a variety of toxic effects, including on the liver, manifested by cholestasis, hepatocytolisis, or their combination. It is recommended to monitor the clinical and laboratory evolution of all patients treated with voriconazole, and of the serum levels of the drug of those who belong to risk groups, even if there is still no consensus on this issue, given the lack of correlation between the serum level and the occurrence of adverse effects in many patients.     

Inefficient and abortive classical complement pathway activation by the calcium inositol hexakisphosphate component of the Echinococcus granulosus laminated layer

Persistent extracellular tissue-dwelling pathogens face the challenge of antibody-dependent activation of the classical complement pathway (CCP). A prime example of this situation is the larva of the cestode Echinococcus granulosus sensu lato, causing cystic echinococcosis. This tissue-dwelling, bladder-like larva is bounded by a cellular layer protected by the outermost acellular “laminated layer” (LL), to which host antibodies bind. The LL is made up of a mucin meshwork and interspersed nano-deposits of calcium inositol hexakisphosphate (calcium InsP₆). We previously reported that calcium InsP₆ bound C1q, apparently initiating CCP activation. The present work dissects CCP activation on the LL. Most of the C1 binding activity in the LL corresponded to calcium InsP₆, and this binding was enhanced by partial proteolysis of the mucin meshwork. The remaining C1 binding activity was attributable to host antibodies, which included CCP-activating IgG isotypes. Calcium InsP₆ made only a weak contribution to early CCP activation on the LL, suggesting inefficient C1 complex activation as reported for other polyanions. CCP activation on calcium InsP₆ gave rise to a dominant population of C3b deposited onto calcium InsP₆ itself that appeared to be quickly inactivated. Apparently as a result of inefficient initiation plus C3b inactivation, calcium InsP₆ made no net contribution to C5 activation. We propose that the LL protects the underlying parasite cells from CCP activation through the combined effects of inefficient permeation of C1 through the mucins and C1 retention on calcium InsP₆. This mechanism does not result in C5 activation, which is known to drive parasite-damaging inflammation.     

Hepatitis C infection and psychiatric burden in two imprisoned cohorts: Young offenders and opioid-maintained prisoners

Prisoners constitute a considerable gap in the hepatitis C virus (HCV) tested population. The present study examined HCV prevalence in imprisoned opioid-maintained patients (OMT-P) and adolescents and young adults (AYA, 14–26 years). In addition, HCV testing and treatment provision, knowledge of HCV status and psychiatric comorbidity were assessed. Data collection took place in six Austrian prisons. Participants were N = 133 for OMT-P (78% male, mean age 35.7 years) and N = 71 for AYA (100% male, mean age 19.8 years). Analysis of HCV serology was conducted. Psychiatric comorbidity and addiction severity were assessed applying standardized questionnaires and interviews. Antibodies were detected in 74.4% of OMT-P, and in 45.0% HCV infection was confirmed. Only one AYA was infected with HCV. None of the participants was receiving treatment for HCV. Eleven percent of OMT-P (50.7% of AYA) did not know their HCV status, and 14.3% of OMT-P (36.6% of AYA) had not been tested in prison. Among OMT-P, lifetime IDU [OR = 330.33, CI = 25.91–4433.20] and age at first IDU [OR = 0.90, CI = 0.82–0.98] significantly predicted HCV status. In both samples, a high prevalence of affective disorders was observed. Despite the high prevalence of HCV among opioid-dependent detainees, the unique opportunities for comprehensive testing and treatment of HCV are substantially underutilized. This is in stark contrast to the UN Basic Principles for the Treatment of Prisoners.