获批准的抗人类免疫缺陷病毒/获得性免疫缺陷综合征及其并发症的药物研究

 目的了解目前世界上已获得批准的抗HIV/AIDs药品与预防和治疗HIV/AIDs并发症的药品及其研发特点。方法参考美国FDA公布的数据和对一些有代表性的相关文献,对1987年以来获得批准的抗HIV/AIDs药与预防和治疗HIV/AIDs并发症的药品归纳、分析、总结和概括性介绍。结果抗HIV/AIDs药在近年来取得了较大进展,除了传统的核苷类逆转录酶抑制剂(NRTIs),蛋白酶抑制剂(PIs),非核苷类逆转录酶抑制剂(NNRTIs)和进入抑制剂(Entry inhibitors)类药物都有新的产品获得批准外,还有诸如整合酶抑制剂和复方抑制剂。但在数量上并不多,每年获得批准的产品仅有2～3种。获得批准的预防和治疗HIV/AIDs并发症的药分为抗生素、抗真菌制剂、抗病毒制剂、抗肿瘤制剂和其他5大类,但这些药多为已获得批准药品又申请用于新的适应证。结论在单种和新种类抗HIV/AIDs新药不断获得批准的基础上,单类型和多类型复方制剂逐渐增多;获得批准的抗HIV/AIDs并发症的药品以已获得批准药品用于新适应证的为多;抗HIV/AIDs及其并发症新药的数量长期处于低水平增长状态。     

抗人类免疫缺陷病毒药物及其新剂型的研究进展

 目的对目前抗人类免疫缺陷病毒(HIV)药物进行分类,并综述了抗HIV药物新剂型的研究进展。方法对近年国内外相关文献进行分析和归纳。结果抗HIV药物的不良反应和耐受性问题可通过选用合适的剂型如脂质体、透皮给药等得以改善。结论为进一步提高抗HIV药物的疗效,减缓机体对这类药物的耐受性,应深入研究一些能将该类药物有效传递到HIV病毒贮库的新剂型。     

三叶青提取物抗消化系统肿瘤作用的研究进展

三叶青提取物由中药三叶崖爬藤中提取所得,属黄酮类化合物,具有抑制肿瘤、保肝、抗炎及调节机体免疫等多种药理活性,能抑制肝癌、胃癌及结肠癌等多种消化系肿瘤细胞的增殖并促进其凋亡,而对正常细胞无明显毒副作用,其抗瘤机制包括激活胱天蛋白酶(Caspase)家族启动凋亡、引起B淋巴细胞瘤-2(Bcl-2)基因家族表达变化从而促进细胞色素C的释放等。本文对三叶青提取物抗消化系统肿瘤的作用及其机制进行了综述。     

人类免疫缺陷病毒属中医学的阴毒

从致病途径和致病特点看,人类免疫缺陷病毒属于中医学的"阴毒",艾滋病无症状期处于正邪相争阶段,人体阳气损耗尚轻,主要是阴阳平衡受到破坏,所以重在和阳,可以用阳和汤进行治疗。     

2011年某县人类免疫缺陷病毒载量抑制率下降原因分析

艾滋病（AIDS）是由人类免疫缺陷病毒（HIV）引起的一种种致命传染性疾病。血浆病毒载量（HIV1-RNA）测定是有效了解感染者和患者体内病毒复制水平、疾病发展进程以及药物治疗效果的主要手段。目前常用的HIVRNA定量测定方法有：核酸序列依赖性扩增（NASBA）技术、逆转录PCR系统技术、分枝DNA（bDNA）技术、实时荧光定量PCR扩增技术目,州医疗集团用的检测方法是分枝DNA（bDNA）技术：bDNA440。     

人类免疫缺陷病毒抗体初筛实验室的生物安全管理

为加强实验室生物安全,防止实验室交叉感染,本文试对HIV抗体初筛实验室的生物安全的若干问题进行初步探讨。1实验室要求实验室主要配置：酶标仪、洗板机、洗眼装置,离心机生物安全柜。其中,生物安全柜应放置在没有气流明显流动的地方,避免生物安全柜在工作时受外界气流影响正常的内部层流。     

中医药干预人类免疫缺陷病毒耐药的机遇和挑战

艾滋病严重威胁着人类的健康,虽然高效抗逆转录病毒疗法(highly active anti-retroviral therapy,HAART)的使用使艾滋病的病情进展得到了明显遏制,但是逐年增加的人类免疫缺陷病毒(HIV)耐药问题凸显,影响HAART临床效果甚至导致治疗失败。本文通过对HIV生物学特性、HIV耐药原因、发生率、易发人群、突变位点等研究回顾,从疗程长而可供更换药物缺少、对所有服药者耐药监测和检测仍以更换药物为结局的不可行性、中药干预其他耐药的经验及临床试验中药干预HIV耐药显示出较好的苗头,提出目前国情下是中药干预HIV耐药的大好时机,同时也提出了诸多困难和挑战。希望通过中医药干预能最大限度减少和延缓耐药性的产生,解决我国目前艾滋病防治亟待解决的重大问题。     

浅谈人类免疫缺陷病毒/获得性免疫缺陷综合征发热的基本病机

发热是艾滋病常见的症状之一。通过对新疆、广东、河南三地区78例人类免疫缺陷病毒/获得性免疫缺陷综合征(HIV/AIDS)发热患者的临床流行病学调查,结合在艾滋病高发区救治的临床体会,认为脾气虚损为HIV/AIDS发热的基本病机。     

埃及药用植物中抗人类免疫缺陷病毒药物的研究

对来自埃及的97种药用植物的天然植物及其甲醇提取物和水提取物的抑制逆转录 (RT)酶和抑制HIV 1诱导的细胞病理作用 (CPE)进行体外评价。余甘子Phyllanthu semblica L .果实的甲醇提取物显示出很强的抑制HIV-1的RT作用 ,其 50%抑制浓度 (IC₅₀)值为 9μg·mL^-1。对甲醇提取物通过生物活性导向分级分离 (bioactivi ty guidedfractionation)得到抑制性有效物质PutranjivainA (PA) ,其IC₅₀ 值为 3.9μm。巴豆Crotontiglium种子的水提物和甲醇提取物可以显著的抑制传染性和HIV 1诱导的MT 4细胞的CPE ,它们的IC₅₀ 值分别为 0.0 25μg·mL^-1和 2.0μg·mL^-1,且均低于产生细胞毒性的浓度 (选择性指数分别为 34.4和50.0)。通过生物活性导向分级分离 ,从甲醇提取物中分离得到 8种佛波醇酯 ,对它们抑制HIV-1诱导的MT-4细胞的CPE的活性进行评价。发现 12O 十四 (烷 )酰佛波醇-13-乙酸酯 (TPA)既是HIV-1诱导的CPE的抑制剂 (IC₁₀₀值为 0.4 8ng·mL^-1) ,又是PKC的活化剂。另证明 ,12O-乙酰佛波醇-13-癸酸酯 (APD)有抗HIV-1的作用 (IC₁₀₀ 值为 7.6ng·mL^-1) ,但没有PKC的活化作用。     

氟尿嘧啶体外抗艾滋病毒作用

从分子生物学角度看,在肿瘤和获得性免疫缺陷综合征（艾滋病）的发生中,RNA逆转录病毒扮演了十分重要的角色.艾滋病毒HIV-1,HIV-2和人类T细胞白血病病毒HTLV-Ⅰ,HTLV-Ⅱ在病毒传播途径,T细胞嗜性,合胞体形成,依赖Mg2＋的逆转录酶,P24核心蛋白质作用于转录或转录后的病毒编码蛋白等方面有很多相似处.所以,作用于肿瘤的有效药物,如作用机制属于上述的任一环节,则同样也能作用于艾滋病,且有效.笔者在进行一种配合物体外抗艾滋病毒研究中,发现氟尿嘧啶具有较强的体外抗艾滋病毒活性.     

A Screening Strategy for Selection of Anti-HSV-1 and Anti-HIV Extracts from Algae

In order to find new sources of antiviral agents with different mechanisms of action, extracts of 49 algae were assayed for antiherpes simplex virus (HSV) and anti-human immunodeficiency virus (HIV) activities. Twenty-five aqueous extracts showed anti-HSV activity, four of which were found to be most potent inhibitors with a selective index more than 1000. Eight samples of the aqueous extracts were identified as having activity against HIV replication. The result suggests that the extracts from algae are a promising source of antiviral agents which may act on different stages in virus replication cycle.     

Antiinflammatory Activity of Holmskioldia sanguinea Extracts

A carrageenin-induced oedema model was investigated to compare and elucidate the antiinflammatory effects of three fractions (CHCl₃, n -BuOH and H₂O) from the aerial parts of Holmskioldia sanguinea . The H₂O (20 and 40 mg) and n -BuOH (200 mg) fractions were found to be effective compared with standard hydrocortisone. The effective dose and lethal dose (LD₅₀) value indicated that the extract was non-toxic.     

Antioxidant Activity of Moringa oleifera Tissue Extracts

Moringa oleifera is an important source of antioxidants, tools in nutritional biochemistry that could be beneficial for human health; the leaves and flowers are used by the population with great nutritional importance. This work investigates the antioxidant activity of M. oleifera ethanolic (E1) and saline (E2) extracts from flowers (a), inflorescence rachis (b), seeds (c), leaf tissue (d), leaf rachis (e) and fundamental tissues of stem (f). The radical scavenging capacity (RSC) of extracts was determined using dot‐blots on thin layer chromatography stained with a 0.4 mm 1,1‐diphenyl‐2‐picrylhydrazyl radical (DPPH) solution; spectrophotometric assays were recorded (515 nm). Antioxidant components were detected in all E1 and E2 from a, b and d. The best RSC was obtained with E1d; the antioxidants present in E2 reacted very slowly with DPPH. The chromatogram revealed by diphenylborinate‐2‐ethylamine methanolic solution showed that the ethanolic extract from the flowers, inflorescence rachis, fundamental tissue of stem and leaf tissue contained at least three flavonoids; the saline extract from the flowers and leaf tissue revealed at least two flavonoids. In conclusion, M. oleifera ethanolic and saline extracts contain antioxidants that support the use of the plant tissues as food sources. Copyright © 2012 John Wiley & Sons, Ltd.     

四角蛤蜊提取物抗氧化活性研究

目的对四角蛤蜊抗氧化活性进行评价研究。方法采用水提醇沉的工艺路线分别得到四角蛤蜊总提液(MV)、醇沉沉淀(MP)及醇沉上清液(MS)。采用背部皮下注射D-半乳糖建立小鼠衰老模型,评价MV、MP及MS对模型小鼠肝脏与血清中SOD、MDA、GSH-PX、CAT各项指标的影响。以不同极性溶剂对MS萃取,得到石油醚、乙酸乙酯、正丁醇与水部位,评价各部位清除DPPH自由基、清除超氧自由基、螯合和还原铁的能力。结果给予MV、MP、MS的小鼠肝组织SOD、GSH-PX、CAT显著升高(P0.05),MDA显著降低(P0.05),血清的SOD、GSH-PX显著升高(P0.05),MDA显著降低(P0.05)。MS萃取水部位对DPPH自由基清除、超氧自由基清除和还原能力最强;MS萃取乙酸乙酯部位螯合能力最强。结论四角蛤蜊具有较好的抗氧化活性,其活性较强部位是MS萃取水部位。     

Antiviral Activity of Aloe Extracts against Cytomegalovirus

Substances extracted from the leaves of aloe plants have been reported to have antiviral effects against enveloped viruses in in vitro test systems. In the present studies, we have assessed the antiviral activity of partially purified extracts prepared from the gel portion of leaves of Aloe barbadensis Miller against human cytomegalovirus (CMV) by plaque inhibition tests (PIT), flow cytometry and morphometry assays. Six test extracts of gel filet portions of aloe leaves were prepared; i.e. R1 from immature leaves harvested in the early summer, S1 from mature leaves harvested in the autumn, F1 from S1 after freezing at −20°C, and R2, S2 and F2 which were ethanol treated extracts of R1, S1 and F1, respectively. When test aloe extracts were added at various concentrations during the course of infection with CMV, R1, S1 and F2 at concentrations of 10⁻¹ inhibited plaque formation. The addition of S1 to the medium between 12 and 36 h after initiation of CMV infection, a time of high DNA synthesis, caused the most effective plaque inhibition. Flow cytometric and morphometric analyses revealed no significant differences in aloe extract treated, CMV infected cells compared with non-aloe treated CMV infected control cells. The results suggest that a major mechanism of inhibition of CMV infection by aloe extracts is through interference with DNA synthesis.     

Thiazoline Peptides and a Tris-Phenethyl Urea from Didemnum molle with Anti-HIV Activity

As part of our screening for anti-HIV agents from marine invertebrates, the MeOH extract of Didemnum molle was tested and showed moderate in vitro anti-HIV activity. Bioassay-guided fractionation of a large-scale extract allowed the identification of two new cyclopeptides, mollamides E and F (1 and 2), and one new tris-phenethyl urea, molleurea A (3). The absolute configurations were established using the advanced Marfey's method. The three compounds were evaluated for anti-HIV activity in both an HIV integrase inhibition assay and a cytoprotective cell-based assay. Compound 2 was active in both assays with IC(50) values of 39 and 78 μM, respectively. Compound 3 was active only in the cytoprotective cell-based assay, with an IC(50) value of 60 μM.     

11种昆虫提取物的抑菌活性研究

目的:寻找新的抑菌类化合物及开展昆虫天然产物化学的研究,通过药理实验找出昆虫的有效抑菌活性部位。方法:采用溶剂两段提取法提取昆虫虫体,用二氯甲烷溶剂浸渍2次,再用70%甲醇浸渍2次获得昆虫提取物。并采用了药敏试验法给药物定性和浓度梯度稀释法测出药物的最低抑菌浓度(minimum inhibitory concentration,MIC)值。结果:在11种昆虫中,只有蝉蜕和蝼蛄2种昆虫的昆虫提取物(分别为蝉蜕正丁醇部、蝼蛄乙酸乙酯、蝉蜕乙酸乙酯和蝉蜕水部位),对金黄色葡菌球菌和结核杆菌有较明显的抑菌活性,其中蝉蜕乙酸乙酯对金黄色葡萄球菌的抑菌作用极强。结论:该研究将为抗生素新药先导化合物的发现和拓展昆虫化学研究方向提供新的思路。     

贵州产天冬醇提液体外氧自由基清除作用的研究

目的:研究贵州产天冬醇提液体外清除羟自由基(·OH)与超氧阴离子自由基(02-)的作用.方法:选取贵州产天冬为研究对象,采用乙醇回流提取法提取其醇提液;采用连苯三酚法在碱性溶液中自氧化反应产生超氧阴离子自由基(02-),采用邻二氮菲-Fe(Ⅱ)/H202体系产生羟自由基(·0H),研究天冬醇提液体外清除自由基的作用;结果:贵州产天冬醇提液对02-具有显著的清除及抑制作用(P＜0.05),而且随着药物浓度的增加,其清除及抑制作用也随之增加;贵州产天冬醇提液对·OH也有一定的清除作用(P＜0.05),其清除率为(35.1±0.16)％.结论:贵州产天冬醇提液对02-具有显著的清除及抑制作用,对·OH也有一定的清除作用.     

金莲花不同花部提取物的抗炎活性

目的:研究金莲花花萼、花冠、花蕊群、子房、花柄5个花部提取物的抗炎活性,探讨抗炎活性与其总黄酮含量的相关性。方法:通过LPS诱导的RAW264.7细胞体外炎症模型,采用Griess试剂法测定细胞的NO释放量,考察不同花部提取物的抗炎活性;采用硝酸铝比色法测定各花部提取物的总黄酮含量。结果:金莲花各花部提取物均能抑制LPS诱导的RAW264.7细胞分泌NO,抑制率顺序为子房和花蕊群花萼和花柄花冠;各花部提取物的总黄酮含量顺序为花柄花萼花冠子房花蕊群。结论:金莲花各花部提取物均有抗炎作用,且抗炎活性的强弱与其总黄酮含量不成正比。