Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cycloph...Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cyclophilin (Cyc) B belonging to immunophilins family with the virus subtype A V3 loop (SA-V3 loop) as well as in specifying the Cyc B segment forming the binding site for V3 synthetic copy of which, on the assumption of keeping the 3D peptide structure in the free state, may present a forwardlooking basic structure for anti-AIDS drug development. Methods: To reach the objects of view, molecular docking of the HIV-1 SA-V3 loop structure determined previously with the X-ray conformation of Cyc B was put into practice by Hex 4.5 program (http://www.loria.fr/~ritchied/ hex/) and the immunophilin stretch responsible for binding to V3 (Cyc B peptide) was identified followed by examination of its 3D structure and dynamic behavior in the unbound status. To design the Cyc B peptide, the X-ray conformation for the identical site of the native protein was involved in the calculations as a starting model to find its best energy structural variant. The search for this most preferable structure was carried out by consecutive use of the molecular mechanics and simulated annealing methods. The molecular dynamics computations were implemented for the Cyc B peptide by the GROMACS computer package (http:// www.gromacs.org/). Results: The overmolecular structure of Cyc B with V3 was built by computer modeling tools and the immunophilinderived peptide able to mask effectively the structurally invariant V3 segments embracing the functionally crucial amino acids of the HIV-1 gp120 envelope protein was constructed and analyzed. Conclusions: Starting from the joint analysis of the results derived with those of the literature, the generated peptide was suggested to offer a promising basic structure for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV’s spread.展开更多
Objectives: To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear po...Objectives: To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design: A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results: HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions: Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline.展开更多
目的研究他汀类药物体外抗人类免疫缺陷病毒I型(human immunodeficiency virus type 1,HIV-1)活性并评价匹伐他汀与其它抗HIV药物联合使用时的抗病毒活性。方法采用噻唑蓝(MTT)比色法测定他汀类药物对C8166细胞的毒性作用;合胞体计数检...目的研究他汀类药物体外抗人类免疫缺陷病毒I型(human immunodeficiency virus type 1,HIV-1)活性并评价匹伐他汀与其它抗HIV药物联合使用时的抗病毒活性。方法采用噻唑蓝(MTT)比色法测定他汀类药物对C8166细胞的毒性作用;合胞体计数检测他汀类药物对实验株HIV-1_(IIIB)诱导C8166细胞病变的抑制作用;酶联免疫吸附测定法(ELISA)测定HIV-1 p24抗原检测他汀类药物对实验株HIV-1_(IIIB)急性感染C8166细胞中病毒复制的抑制作用以及匹伐他汀与其它抗HIV药物联合用药的联合效应。结果他汀类药物中匹伐他汀具有显著体外抗HIV-1活性,匹伐他汀与核苷类逆转录酶抑制剂(替诺福韦、恩曲他滨、拉米夫定、齐多夫定)和蛋白酶抑制剂(茚地那韦和达芦那韦)联合用药时,药物间呈现协同作用;与非核苷类逆转录酶抑制剂(依曲韦林)联合用药时,药物间呈现拮抗作用;与整合酶链转移抑制剂(雷特格韦和度鲁特韦)联合用药时,药物间呈现相加作用。结论匹伐他汀除与依曲韦林联合时药物间呈现拮抗作用外,与其它抗HIV药物联用均呈现相加或协同作用。展开更多
Introduction: Human immunodeficiency virus (HIV) infection is a public health problem of concern. Anti-retroviral therapy (ART) is associated with multiple side effects. This study aimed at identifying the different h...Introduction: Human immunodeficiency virus (HIV) infection is a public health problem of concern. Anti-retroviral therapy (ART) is associated with multiple side effects. This study aimed at identifying the different hepatic manifestations of antiretroviral therapy and the responsible molecules. Patients and Methods: This was an eight months period prospective descriptive study, from January 1st to August 31st, 2015, conducted in the Department of Gastroenterology and Internal Medicine at the Brazzaville University Teaching Hospital. Study participants were treatment-na?ve HIV patients who were initiated on ART treatment during the study period. Patients with liver disease, liver cytolysis prior to initiation of therapy, and those with alternative therapy that may cause hepatotoxicity were excluded. The sample size was 110 patients. Results: The age was ranging from 25 to 70 years with a mean age of 47.5 ± 7.5 years. During the six months of follow-up, the alarming hepatic signs were observed in 26.36% of cases (n = 29) in the 3rd month of treatment. There was no observed alarming sign in the 6th month of follow-up. The cytolytic pattern was observed in 54.55% of cases (n = 60) in the 3rd month. The cholestatic pattern was observed in 6.36% of cases (n = 7) in the 3rd month. Triple therapy combination of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most used in 57.27% (n = 63) with a statistically significant p value to the occurrence of cytolytic pattern (p Conclusion: Drug induced liver toxicity occurs in a significant number of patients starting ART. The prevalence of hepatic events was high at the third month of treatment and the triple therapy of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most incriminated.展开更多
目的对23个四氢-咪唑-苯二氮酮(TIBO)类抗艾滋病药物分子进行定量构效关系(QSAR)研究。方法采用本实验室新近提出的三维全息原子场作用矢量(3D-HoVAIF)表征TIBO类抗艾滋病药物分子结构。然后运用偏最小二乘回归(partial least square re...目的对23个四氢-咪唑-苯二氮酮(TIBO)类抗艾滋病药物分子进行定量构效关系(QSAR)研究。方法采用本实验室新近提出的三维全息原子场作用矢量(3D-HoVAIF)表征TIBO类抗艾滋病药物分子结构。然后运用偏最小二乘回归(partial least square regression,PLS)建立3D-HoVAIF描述符与TIBO类抗艾滋病药物活性之间的QSAR模型。结果用此方法建模的复相关系数(R2cum)、交互校验复相关系数(Q2cum)和模型的标准偏差(SD)分别为R2cum=0.824,Q2cum=0.778与SD=0.56,均优于文献值。结论3D-HoVAIF能较好表征TIBO类抗艾滋病药物分子结构信息,因而能建立具有良好稳定性和预测能力的QSAR模型。展开更多
文摘Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cyclophilin (Cyc) B belonging to immunophilins family with the virus subtype A V3 loop (SA-V3 loop) as well as in specifying the Cyc B segment forming the binding site for V3 synthetic copy of which, on the assumption of keeping the 3D peptide structure in the free state, may present a forwardlooking basic structure for anti-AIDS drug development. Methods: To reach the objects of view, molecular docking of the HIV-1 SA-V3 loop structure determined previously with the X-ray conformation of Cyc B was put into practice by Hex 4.5 program (http://www.loria.fr/~ritchied/ hex/) and the immunophilin stretch responsible for binding to V3 (Cyc B peptide) was identified followed by examination of its 3D structure and dynamic behavior in the unbound status. To design the Cyc B peptide, the X-ray conformation for the identical site of the native protein was involved in the calculations as a starting model to find its best energy structural variant. The search for this most preferable structure was carried out by consecutive use of the molecular mechanics and simulated annealing methods. The molecular dynamics computations were implemented for the Cyc B peptide by the GROMACS computer package (http:// www.gromacs.org/). Results: The overmolecular structure of Cyc B with V3 was built by computer modeling tools and the immunophilinderived peptide able to mask effectively the structurally invariant V3 segments embracing the functionally crucial amino acids of the HIV-1 gp120 envelope protein was constructed and analyzed. Conclusions: Starting from the joint analysis of the results derived with those of the literature, the generated peptide was suggested to offer a promising basic structure for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV’s spread.
文摘Objectives: To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design: A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results: HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions: Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline.
文摘Introduction: Human immunodeficiency virus (HIV) infection is a public health problem of concern. Anti-retroviral therapy (ART) is associated with multiple side effects. This study aimed at identifying the different hepatic manifestations of antiretroviral therapy and the responsible molecules. Patients and Methods: This was an eight months period prospective descriptive study, from January 1st to August 31st, 2015, conducted in the Department of Gastroenterology and Internal Medicine at the Brazzaville University Teaching Hospital. Study participants were treatment-na?ve HIV patients who were initiated on ART treatment during the study period. Patients with liver disease, liver cytolysis prior to initiation of therapy, and those with alternative therapy that may cause hepatotoxicity were excluded. The sample size was 110 patients. Results: The age was ranging from 25 to 70 years with a mean age of 47.5 ± 7.5 years. During the six months of follow-up, the alarming hepatic signs were observed in 26.36% of cases (n = 29) in the 3rd month of treatment. There was no observed alarming sign in the 6th month of follow-up. The cytolytic pattern was observed in 54.55% of cases (n = 60) in the 3rd month. The cholestatic pattern was observed in 6.36% of cases (n = 7) in the 3rd month. Triple therapy combination of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most used in 57.27% (n = 63) with a statistically significant p value to the occurrence of cytolytic pattern (p Conclusion: Drug induced liver toxicity occurs in a significant number of patients starting ART. The prevalence of hepatic events was high at the third month of treatment and the triple therapy of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most incriminated.
文摘目的对23个四氢-咪唑-苯二氮酮(TIBO)类抗艾滋病药物分子进行定量构效关系(QSAR)研究。方法采用本实验室新近提出的三维全息原子场作用矢量(3D-HoVAIF)表征TIBO类抗艾滋病药物分子结构。然后运用偏最小二乘回归(partial least square regression,PLS)建立3D-HoVAIF描述符与TIBO类抗艾滋病药物活性之间的QSAR模型。结果用此方法建模的复相关系数(R2cum)、交互校验复相关系数(Q2cum)和模型的标准偏差(SD)分别为R2cum=0.824,Q2cum=0.778与SD=0.56,均优于文献值。结论3D-HoVAIF能较好表征TIBO类抗艾滋病药物分子结构信息,因而能建立具有良好稳定性和预测能力的QSAR模型。
