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抗病毒治疗不仅将HIV感染从一个致死性疾病转变为一种可以治疗的慢性疾病,同时减少了HIV在人群间的传播,近年来“治疗即是预防”的观念已被人们所认可。随着研究的深入,人们发现HIV暴露前预防(PrEP)能有效减少HIV在高危人群间的传播。临床试验显示PrEP是安全的,可以有效预防HIV感染。目前,欧美国家及WHO指南均推荐对男男性行为者、感染HIV高风险的异性性行为者、HIV单阳伴侣中的HIV阴性者以及静脉吸毒者等高危人群进行PrEP。推荐使用的药物和方法是每日口服替诺福韦和恩曲他滨合剂,部分人群也可使用替诺福韦。PrEP应结合其他预防措施如安全套使用、静脉吸毒的处理以及抗病毒治疗来进一步降低HIV感染的风险。目前,PrEP面临的主要挑战是伦理学、药物可及性、服药依从性以及使用率等问题,应该针对高危人群大力推行PrEP,让更多的人群受益减少HIV感染。 相似文献
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Fangfang Jin Qiyue Hu Hongbo Fei Hejun Lv Shenglan Wang Bin Gui Junzhen Zhang Wangyang Tu Yun Zhang Lei Zhang Hong Wan Limin Zhang Bin Hu Fanglong Yang Chang Bai Feng He Lianshan Zhang Weikang Tao 《ACS medicinal chemistry letters》2021,12(2):195
In this study, a series of novel hydroxyamidine derivatives were identified as potent and selective IDO1 inhibitors by structure-based drug design. Among them, compounds 13–15 and 18 exhibited favorable enzymatic and cellular activities. Compound 18 showed improved bioavailability in mouse, rat, and dog (F% = 44%, 58.8%, 102.1%, respectively). With reasonable in vivo pharmacokinetic properties, compound 18 was further evaluated in a transgenic MC38 xenograft mouse model. The combination of compound 18 with PD-1 monoclonal antibody showed a synergistic antitumor effect. These data indicated that compound 18 as a potential cancer immunotherapy agent should warrant further investigation. 相似文献
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目的探讨和研究氯吡格雷联合溶栓治疗急性心肌梗死的临床疗效。方法选取2012年1月—2013年5月之间该院收治的50例急性心肌梗死患者作为研究对象,根据入院编号进行随机分组,分为观察组和对照组,各25例,对照组单纯采用重组人组织型纤溶酶原激酶衍生物进行溶栓治疗,观察组患者则在溶栓治疗基础上加用氯吡格雷联合治疗,对比两组患者的疗效及心肌酶谱变化。结果观察组患者总有效率92.0%,显著高于对照组患者的76.0%,差异有统计学意义(P<0.05);治疗前两组患者的肌酸激酶、肌酸激酶同工酶对比差异无统计学意义,治疗后观察组显著低于对照组,差异有统计学意义(P<0.05)。结论氯吡格雷联合溶栓治疗急性心肌梗死的疗效确切,相较于单纯溶栓治疗更具优势,能够有效降低心肌酶水平,提高疗效,值得在临床上推广和应用。 相似文献
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Pavlak M Stojković R Radacić-Aumiler M Kasnar-Samprec J Jercić J Vlahović K Zinić B Radacić M 《Journal of cancer research and clinical oncology》2005,131(12):829-836
Purpose: The purpose of this study was to investigate in vivo antitumor activity of newly synthesized N-sulfonylpyrimidine derivatives 1-(p-toluenesulfonyl)cytosine (4H), 1-(p-toluenesulfonyl)cytosine hydrochloride (4H×HCl) and zinc(II) complex of 1-(p-toluenesulfonyl)cytosine (4K). Materials and methods: In order to do that we have used mouse anaplastic mammary carcinoma (AMCa). Tumor cells (106) in a volume of 0.02 ml were transplanted into the thigh of the right hind leg of CBA mice. All compounds were dissolved
in distilled water immediately before injecting to animals. Results: Antitumor effect of these compounds depends on drug doses and time interval between tumor transplantation and drug application.
Further the efficacy of these compounds depends on number of drug injections, i. e. whether drug was given in single or in
multiple doses. Multiple doses of 400 mg/kg of 1-(p-toluenesulfonyl)cytosine (4H) showed good antitumor effect when applied on day 1, 3, 5, 7 and 9 after tumor transplantation.
Still good but slightly lower antitumor effect was also achieved when that compound was given in a single dose (1,200 mg/kg)
on day 1 after tumor transplantation. The longest period of tumor growth time was obtained after application of 1-(p-toluenesulfonyl)cytosine hydrochloride (4H×HCl) given as a single dose (300 mg/kg) on day 1 or on day 6 after tumor implantation.
However, antitumor effect of zinc(II) complex of 1-(p-toluenesulfonyl)cytosine (4K) was very strong when 300 mg/kg was given on day 1 or day 6, while this effect was slightly
lower when drug (200 mg/kg/inj) was given on day 1, 3, 5, 7 and 9 or on day 6, 8, 10, 12 and 14. Conclusion: In this work it has been found that N-1-sulfonylcytosine derivatives have strong antitumor activity against mouse mammary carcinoma which is a good reason for
further research of these compounds both in experimental and preclinical studies. 相似文献
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Quinocetone (QCT) is a new feeding antibacterial agent in the QdNOs family. The mechanism of its adrenal toxicity is far from clear. This study was conducted to estimate the adrenal cell damage induced by QCT and its bidesoxy-quinocetone (B-QCT) metabolite and to further investigate their mechanisms. Following doses of QCT increasing from 5 to 50 μM, cell apoptosis and necrosis, mitochondrial dysfunction and redox imbalance were observed in porcine adrenocortical cells. The mRNA levels of the six components of intermediary enzymes and the adrenal renin-angiotensin-aldosterone system (RAAS) displayed a dysregulation induced by QCT, indicating that QCT might influence aldosterone secretion not only through the upstream of the production but also through the downstream of the adrenal RAAS pathway. In contrast, B-QCT had few toxic effects on the cell apoptosis, mitochondrial dysfunction and redox imbalance. Moreover, LCMS-IT-TOF analysis showed that no desoxy metabolites of QCT were found in either cell lysate or supernatant samples. In conclusion, we reported on the cytotoxicity in porcine adrenocortical cells exposed to QCT via oxidative stress, which raised awareness that its toxic effects resulted from N→O groups, and its toxic mechanism might involve the interference of the steroid hormone biosynthesis pathway. 相似文献
70.
Design,Synthesis, Biological Evaluation and Binding Mode Modeling of Benzimidazole Derivatives Targeting the Cannabinoid Receptor Type 1 下载免费PDF全文