Sofosbuvir-velpatasvir en pacientes mexicanos con hepatitis C: una revisión retrospectiva

IntroductionThe sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking.MethodsA retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment.ResultsOverall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported.ConclusionTreatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.     

健脾消积颗粒对脾胃湿热型功能性消化不良患儿的临床疗效及对脑肠肽水平的影响＊

目的 探讨健脾消积颗粒治疗脾胃湿热型功能性消化不良的临床疗效及其对脑肠肽的影响。方法 按照随机数字表法将2018年2月-2019年2月我院收治的80例功能性消化不良患儿均分为对照组和观察组，对照组给予多潘立酮片治疗，观察组在对照组基础上加用健脾消积颗粒治疗，比较2组治疗效果。结果 治疗后2组主要临床症状积分均显著下降，观察组下降更为明显。观察组总有效率为95%，显著高于对照组的79.5%。观察组治疗后胃电节律异常例数明显低于对照组，治疗后2组胃动素(MTL)显著上升，神经肽Y（NPY）、神经降压素（NT）显著下降，且观察组和对照组相比，差异有统计学意义。2组治疗期间均未发生不良反应及肝肾功能异常。结论 健脾消积颗粒能够明显改善脾胃湿热型功能性消化不良患儿临床症状，改善胃动力水平，调节脑肠肽分泌水平。     

《艾滋病诊疗指南第三版(2015版)》更新解读

2015年中华医学会感染病学分会艾滋病学组发布了第三版《艾滋病诊疗指南》。新版指南强调抗病毒治疗时点前移:一旦成人确诊感染人类免疫缺陷病毒(HIV), 若无禁忌宜尽早启动抗HIV治疗。对于合并机会性感染的HIV感染者, 在感染控制、病情稳定后也应及早开始抗病毒治疗。尤其强调HIV合并结核患者在CD4阳性淋巴细胞数少于200/μL的情况下, 建议抗结核两周内即开始抗病毒治疗。在抗HIV治疗用药中, 淘汰了一些毒副作用大、依从性较差的药物, 如司他夫定、去羟肌苷、茚地那韦等, 优选抗病毒效力强、服药方便的组合, 如拉米夫定、替诺福韦、依非韦伦组合。对于HIV感染的婴幼儿, 亦主张及早抗HIV治疗。对于五岁以内的幼儿, 主张确诊后即启动抗病毒治疗。对于HIV感染的孕产妇, 建议尽快予以全程、联合抗HIV治疗, 寓防于治。     

Infección por el virus de la hepatitis C y nuevas estrategias de tratamiento

Hepatitis C is a major public health problem worldwide. This disease is caused by the hepatitis C virus, which is characterised by its genetic diversity. The infection is usually asymptomatic. However, between 60% and 80% of HCV-infected individuals will progress to chronic hepatitis, 20% to liver cirrhosis in the medium-to long-term and, each year, between 1% and 4% of these patients with cirrhosis will develop hepatocellular carcinoma (HCC). A Spanish consensus document has recently been drafted to diagnose hepatitis C in a single step, consisting of active investigation (antibodies and viremia) in a single sample, which according to the experts, would reduce the time to access treatment and avoid tracking losses. To definitively change the hepatitis C treatment paradigm, direct-acting antiviral drugs (DAAs) have been approved, whose development has been based on achieving cure rates close to 100% regardless of the genotype of the virus, ie, pangenotypes, with good tolerance and bioavailability. These drugs have constituted a real therapeutic revolution. Supplement information: This article is part of a supplement entitled «SEIMC External Quality Control Programme. Year 2016», which is sponsored by Roche, Vircell Microbiologists, Abbott Molecular and Francisco Soria Melguizo, S.A.© 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosasy Microbiología Clínica. All rights reserved.     

Novel β-Coronavirus (SARS-CoV-2): Current and future aspects of pharmacological treatments

The novel coronavirus outbreak has reported to be rapidly spreading across the countries and becomes a foremost community health alarm. At present, no vaccine or specific drug is on hand for the treatment of this infectious disease. This review investigates the drugs, which are being evaluated and found to be effective against nCOVID-19 infection. A thorough literature search was performedon the recently published research papers in between January 2020 to May 2020, through various databases like “Science Direct”, “Google Scholar”, “PubMed”,“Medline”, “Web of Science”, and “World Health Organization (WHO)”. We reviewed and documented the information related with the current and future aspects for the management and cure of COVID-19. As of 21st July 2020 a total of 14,562,550 confirmed cases of coronavirus and 607,781 deaths have been reported world-wide. The main clinical feature of COVID-19 ranges from asymptomatic disease to mild lower respiratory tract illness to severe pneumonia, acute lung injury, acute respiratory distress syndrome (ARDS), multiple organ dysfunction, and death. The drugs at present used in COVID-19 patients and ongoing clinical trials focusing on drug repurposing of various therapeutic classes of drug e.g. antiviral, anti-inflammatory and/or immunomodulatory drugs along with adjuvant/supportive care. Many drugs on clinical trials shows effective results on preliminary scale and now used currently in patients. Adjuvant/supportive care therapy are used in patients to get the best results in order to minimize the short and long-term complications. However, further studies and clinical trials are needed on large scale of population to reach any firm conclusion in terms of its efficacy and safety.     

Pharmacological evaluation and mechanistic study of compound Xishu Granule in hepatocellular carcinoma

ObjectiveIn this study, we used HepG2 human hepatocellular carcinoma cells to study the effects of Compound Xishu Granule (CXG) on cell proliferation, apoptosis, and the cell cycle in vitro. We also used a xenograft tumor model to study the anti-tumor effects of CXG and related mechanisms in vivo.MethodsThe effect of CXG on cell viability was measured using Cell Counting Kit-8 and a colony formation assay. The effect of CXG on apoptosis and the cell cycle was analyzed using flow cytometry. The in vivo anti-tumor effect of CXG was assessed by measuring the volume change in xenograft tumors after drug administration. The CXG anti-tumor mechanism was studied using western blotting assay to detect cell cycle and apoptotic associated proteins.ResultsCXG suppressed HepG2 cell proliferation in a time- and dose-dependent manner in vitro. Colony formation experiments showed that CXG administration for 24 h significantly reduced HepG2 cell formations (P < .01). Flow cytometric analysis showed that CXG treatment for 48 h promoted apoptosis and blocked HepG2 cells in the G2/M phase. Western blotting results showed that Bax was significantly up-regulated and Bcl-2 was down-regulated in graft tumor tissues and HepG2 cells after CXG administration, which increased the Bax/Bcl-2 ratio. PLK1, CDC25C, CDK1, and Cyclin B1 expression were up-regulated. CXG had a good inhibitory effect on graft tumor growth in vivo.ConclusionCXG has good anti-tumor effects in vitro and in vivo. In vitro, CXG promoted HepG2 cell apoptosis and induced G2/M phase arrest. In vivo, CXG significantly inhibited graft tumor growth. The CXG mechanism in treating hepatocellular carcinoma may be that CXG can induce abnormal apoptotic and cell cycle associated protein expression, leading to mitotic catastrophe and apoptosis.     

祛瘀解毒颗粒治疗子宫内膜异位症患者卵泡液对小鼠胚胎发育的影响

目的 观察经祛瘀解毒颗粒治疗后子宫内膜异位症（endometriosis，EM）患者卵泡液对小鼠胚胎发育的影响。 方法 在常规培养液中分别加入治疗组EM患者卵泡液（祛瘀解毒颗粒）、对照组EM患者卵泡液及空白组（因输卵管因素行体外受精－胚胎移植）患者卵泡液，20只小鼠超排卵共收集189枚2 细胞鼠胚分别放入各组培养液进行培养，其中治疗组培养液70枚，对照组培养液60枚，空白组培养液59枚,观察和检测2 细胞鼠胚在体外发育至8细胞期、桑葚胚期和囊胚期的比率，及早期鼠胚优质胚胎数目和优质胚胎率。 结果 治疗组培养液有53枚鼠胚（75.71%，53/70）发育到8细胞期，48枚（68.57%，48/70）发育到桑葚胚期，45枚（64.28%，45/70）发育到囊胚期，与对照组培养液(56.67%，34/60、48.33%，29/60、35.00%，21/60)比较差异有统计学意义(P＜0.05)。治疗组有61枚优质胚胎（87.14%），对照组为44枚（73.33%），两组比较差异有统计学意义（P＜0.05）。 结论 EM患者卵泡液对早期鼠胚存在毒性作用，经祛瘀解毒颗粒治疗后EM患者卵泡液可提高早期鼠胚培养质量。     

益气复智颗粒对多发脑梗死性痴呆模型大鼠脑组织细胞凋亡的影响

目的 观察益气复智颗粒对多发脑梗死性痴呆模型大鼠脑皮质形态学、细胞凋亡的影响。方法 采用颈内动脉注射血栓的方法，复制多发梗死性痴呆大鼠模型，观察益气复智颗粒12．42g/kg分别于手术前、手术前后、手术后灌胃对实验动物脑皮质形态学、细胞凋亡的影响。结果 益气复智颗粒能使脑缺血后脑内神经细胞凋亡数目下降。结论 益气复智颗粒具有较好的保护脑神经元，阻断脑缺血致神经细胞死亡病理过程的作用。     

HPLC法测定滑膜炎颗粒中原儿茶醛的含量

目的建立滑膜炎颗粒剂中原儿茶醛的含量测定方法质量。方法采用高效液相色谱法对方中原儿茶醛进行含量测定。结果高效液相色谱法测定结果表明原儿茶醛在0．1005～1．005μg范围内呈线性关系，平均加样回收率为99．22％；RSD为0．72％。结论本法简便，重现性好、结果可靠，可作为控制滑膜炎颗粒剂的质量方法。     

Distribution of glutathione and glutathione-related enzyme systems in mitochondria and cytosol of cultured cerebellar astrocytes and granule cells

The cellular and regional distribution of glutathione (GSH) and GSH-related enzyme systems involved in cellular defense against reactive oxygen species and electrophilic xenobiotics in the nervous system has been extensively studied. However, little is known about the subcellular distribution of GSH systems in brain tissue and cultured neural cells. The present study investigates the distribution of mitochondrial and cytosolic GSH and GSH-related enzymes in cultured cerebellar astrocytes and granule cells, and compares them with levels in the adult rat cerebellum. Cytosolic GSH levels and cytosolic activities of glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in astrocytes were 57, 153, 245, and 92% higher than those found in granule cells, respectively. In contrast, granule cells contained significantly higher mitochondrial GSH levels than astrocytes. Granule cells also demonstrated comparable mitochondria/cytosolic concentrations of GSH and GR, GPX and GST activities to those observed in the cerebellar tissue, whereas ratios in astrocytes were markedly lower. Although in vitro treatments with 100 μM ethacrynic acid depleted both cytosolic and mitochondrial GSH in cultured astrocytes and granule cells in a time-dependent fashion, cellular GSH in granule cells was more resistant to the GSH-depleting agent than astrocytes. These results suggest that although GSH and GSH-related enzymes are abundant in cytosolic compartments of astrocytes, mitochondrial pools are relatively small. Since brain mitochondria are sites of significant hydrogen peroxide generation, the mitochondrial localization of GSH and its associated enzymes in neural cells provide important defenses against toxic oxygen species in the nervous system. Differences in subcellular distribution of GSH systems in individual neural cell types may provide a basis for selective cellular and/or subcellular expression of neurotoxicity.