Memórias da equipe de enfermagem na primeira década da epidemia da Aids

Na década de 80 dramáticas ocorrências atingiram o país e o mundo na área da saúde com a descoberta da Síndrome da Imunodeficiência Adquirida (Aids) síndrome, causada pelo Vírus da Imunodeficiência Humana (HIV). O objetivo deste estudo foi descrever as representações sociais do HIV/Aids e as memórias sociais do cuidado de enfermagem construídas na década de 80 pela equipe de enfermagem. Optou-se por uma abordagem qualitativa, embasada na teoria de representações sociais e nos conceitos do campo da memória social. Os sujeitos do estudo foram 20 profissionais de enfermagem de serviços ambulatoriais e/ou da atenção básica, atuantes em 11 instituições públicas de saúde da cidade do Rio de Janeiro que possuem o Programa Nacional de DST/Aids. A coleta de dados foi realizada através de entrevista semiestruturada e questionário de caracterização sócio profissional. A análise dos dados deu-se em duas etapas, a primeira atraves da técnica de análise de conteúdo temática destinada a identificar nos depoimentos dos entrevistados os conteúdos discursivos relativos a década de 80. Posteriormente os trechos selecionados foram submetidos à análise lexical pelo software Alceste 4.10. Obteve-se três classes temáticas que abordaram: As percepções e as ações do cuidado de enfermagem na década de 80; Os primeiros contatos profissionais e pessoais com HIV/Aids e A mídia e a construção das representações sociais do HIV/Aids. Na primeira classe os profissionais de enfermagem relatam as memórias referentes aos cuidados prestados na década de 80, descrevendo como esse cuidado era prestado, o medo da contaminação e os profissionais que atuavam na prestação de serviços. Na classe 2 os sujeitos resgatam as primeiras vivências com as pessoas com HIV/Aids e os sentimentos experimentados neste primeiro contato. As características físicas, os aspectos emocionais, a introdução do AZT e o abandono familiar são elementos destacados. Na classe 3 são relatas as memórias referentes ao início da epidemia de HIV/Aids, com destaque para as ancoragens representacionais do surgimento do vírus, tendo especialmente o macaco como hospedeiro. Os meios de comunicação surgiram como formadores das memórias do início da epidemia, veiculando imagens, como a do cantor Cazuza, fortemente citado pelos sujeitos. Conclui-se que este estudo permitiu compreender, através das memórias e das representações, como se constituiu a atuação dos profissionais no início da epidemia, assim como a permanência de elementos simbólicos até hoje nas representações sociais do HIV/Aids.

Sequence evolution of the CCR5 chemokine receptor gene in primates

The chemokine receptor CCR5 can serve as a coreceptor for M-tropic HIV-1 infection and both M-tropic and T-tropic SIV infection. We sequenced the entire CCR5 gene from 10 nonhuman primates: Pongo pygmaeus, Hylobates leucogenys, Trachypithecus francoisi, Trachypithecus phayrei, Pygathrix nemaeus, Rhinopithecus roxellanae, Rhinopithecus bieti, Rhinopithecus avunculus, Macaca assamensis, and Macaca arctoides. When compared with CCR5 sequences from humans and other primates, our results demonstrate that:(1) nucleotide and amino acid sequences of CCR5 among primates are highly homologous, with variations slightly concentrated on the amino and carboxyl termini; and (2) site Asp13, which is critical for CD4-independent binding of SIV gp120 to Macaca mulatta CCR5, was also present in all other nonhuman primates tested here, suggesting that those nonhuman primate CCR5s might also bind SIV gp120 without the presence of CD4. The topologies of CCR5 gene trees constructed here conflict with the putative opinion that the snub-nosed langurs compose a monophyletic group, suggesting that the CCR5 gene may not be a good genetic marker for low-level phylogenetic analysis. The evolutionary rate of CCR5 was calculated, and our results suggest a slowdown in primates after they diverged from rodents. The synonymous mutation rate of CCR5 in primates is constant, about 1.1 x 10(-9) synonymous mutations per site per year. Comparisons of K-a and K-s suggest that the CCR5 genes have undergone negative or purifying selection. K-a/K-s ratios from cercopithecines and colobines are significantly different, implying that selective pressures have played different roles in the two lineages.

Structure analysis of CCR5 from human and primates

It is well known that the chemokine receptor CCR5 plays very important roles in HIV-1 virus infection. A three-dimensional molecular model of human CCR5 was generated by SYBYL, a distance geometry-based homologous modeling package, using the corresponding transmembrane domain of bacteriorhodopsin as the template. On the basis of human CCR5 model, we also built 18 3D molecular models of CCR5 in primates from Pongo pygmaeus, Pygathrix nemaeus, Macaca assameniss, Trachy-pithecus phayrei, T. francoisi, M. arotoides, Rhinopithecus roxellance, R, bieti, R. avunculus, Hylobates leucogenys, Pan troglodytes, Gorilla gorilla, Cercopithecus aethiops 1, C. aethiops 2, Papio hamadryas M. mulatta, M. fascicularis and M. nemestrina. Structural analyses and statistics results suggested that the main-chains of the primate CCR5 were similar to that of the human CCR5 and that the fit-RMS deviation values of these primate CCR5 were less than 0.1 Angstrom. Moreover, the structures of these CCR5 proteins, except those of the African green monkey 1 (C.aet1), do not have a remarkable difference. It is proved that the 14th residue is possibly very important in the inhibition infections by M-tropic HIV-1, and it is also demonstrated that the 13th residue of human CCR5 was changed from asparagine into aspartic acid in all these primates. It means that the primate CCR5 no longer depend on CD4 for efficient entry, but human CCR5 may have evolved subsequently due to the use of CD4 as a receptor, allowing the high-affinity chemokine receptor-binding site of HIV to be sequestered from host immune surveillance. (C) 2000 Elsevier Science B.V. All rights reserved.

Structural analysis of human CCR2b and primate CCR2b by molecular modeling and molecular dynamics simulation

CCR2b, a chemokine receptor for MCP-1, -2, -3, -4, plays an important role in a variety of diseases involving infection, inflammation, and/or injury, as well as being a coreceptor for HIV-1 infection. Two models of human CCR2b (hCCR2b) were generated by h

AIDS 免疫治疗相关腺病毒载体的构建

艾滋病（AIDS）是人类免疫缺陷病毒（HIV）感染后引起的一种严重危害人类健 康的致死性传染病。抗HIV 药物挽救和延长了很多HIV 感染者的生命，提高了其生活 质量，但是仍然不能治愈AIDS 和预防传播。最终有效控制HIV 传播和感染的方法可能 仍将依赖于HIV 疫苗的应用。HIV 感染对感染者以及社会造成的灾难性后果使得发展 一个有效的艾滋病疫苗变得尤为紧迫和重要。 负载HIV-1 抗原的DC 回输到HIV-1 感染者体内可以诱导产生较强的抗HIV-1 细 胞免疫反应，这种免疫反应理论上和临床试验都表明治疗AIDS 有效，而且对HARRT 治疗能够产生很好的协同作用。我们拟用感染了重组腺病毒的DC，回输到HIV-1 感染 者体内，期望可以较好地控制病毒复制和阻止感染。为此，本研究我们制备了重组腺病 毒vAd-gp140、vAd-tat 和vAd-gp140-tat，为后续研究奠定基础。 结构蛋白Env 是激发抗体反应的抗原，由于Env 全长有较大细胞毒性，本文采用 了截短的gp140 分子，删除了gp41 的胞内段，降低了gp140 蛋白的细胞毒性。同时保 留了gp41 的跨膜区，表达的蛋白可被正确地锚定在细胞表面，提高蛋白的免疫原性。 将gp140 分子克隆到复制缺陷型的腺病毒载体中，用Wester Blotting 方法检测到gp140 在293 细胞中的表达。 有效的抗 HIV-1 的疫苗应该能够同时激发针对多种亚型病毒株的细胞和体液免疫 反应。早期病毒蛋白激发的CTL 应答在控制病毒载量上更为有效，而且Tat 蛋白的重 要免疫抗原表位和功能区域在不同HIV-1 病毒株之间是高度保守的。Tat 蛋白的多种生 物学功能使得它成为较强的免疫原、共抗原和佐剂，激发T 细胞抗原表位的Th1 型反 应和CTL 反应，扩大体内T 细胞识别的抗原表位谱，提高T 细胞特异性免疫反应。本 文扩增了HIV-1ⅢB 的tat 基因，克隆到复制缺陷性的腺病毒中，构建了重组腺病毒 vAd-tat，并在293 细胞中表达了分子量大小为15kDa 的蛋白。早期蛋白和结构蛋白的联合免疫能够全面地控制病毒复制，在动物实验中一定程度 上保护了猴子。我们将已得到表达的gp140 和tat 基因进行融合表达。利用融合PCR 技 术，扩增gp140 和tat 的融合基因，构建携有HIV-1 gp140-tat 融合基因的重组腺病毒 vAd-gp140-tat。gp140-tat 在293 细胞中的融合表达还需要进一步验证。 下一步的工作是将构建好的重组腺病毒感染DC，检测外源基因在DC 中的表达水 平，对DC 表面分子表型的影响以及对DC 功能的影响。

一种预防或治疗艾滋病的药物及其制备方法和应用

提供一种药用有效成分酒花查尔酮(xanthahumol)用于预防和治疗艾滋病。具体地，利用植物啤酒花(Humulus lupulus)为原料，通过酒精提取和溶剂处理，硅胶柱层析以氯仿/乙酸乙酯混合溶剂洗脱，结晶得到酒花查尔酮(xanthahumol)纯品。实验证明该化合物具有显著的体外抗HIV-1活性，可用于制备预防和治疗艾滋病的药物。

黄芩甙锌配合物药物用途

本发明公开了配合物黄芩甙锌在制备预防和治疗艾滋病的药物中的应用，其结构式见图1，分子式为ZnC23O13H20(1-3.5)H2O。黄芩甙与黄芩甙锌均能抑制HIV-1感染细胞与正常细胞间的融合，但黄芩甙锌的细胞毒性低于黄芩甙，对HIV-1的治疗指数(TI)高于黄芩甙，其治疗效果比黄芩甙好。

一种抗人免疫缺陷病毒Ⅰ型p24蛋白的单克隆抗体及其应用

一种抗人免疫缺陷病毒I型(HIV-1)p24蛋白的单克隆抗体及其应用，属生物技术领域。单克隆抗体的免疫原为HIV-1B亚型p24基因工程重组蛋白；是由免疫小鼠的脾细胞与骨髓瘤细胞融合产生的杂交瘤p3JB9、p5F1和p6F4细胞系分泌产生；属于免疫球蛋白IgG1型；与猴免疫缺陷病毒SIVAGM、猴逆转录D型病毒SRV交叉反应；与CCR5 嗜性病毒株HIVAda-M和耐药株HIV74V反应；p5F1和p6F4能与临床分离株HIVKM018反应，而 p3JB9不能与临床分离株HIVKM018反应。单克隆抗体可以与其它单克隆抗体或多克隆抗体组合，或可作放射性同位素、酶、荧光素化合物、化学发光化合物或胶体金属离子的标记，用于制备定性或定量检测各种体液、培养上清或细胞、组织中p24抗原的试剂。具有制备方法简单，效价高；单克隆抗体特异性强，灵敏度高。

治疗艾滋病的药物组合物,其制备方法及其用途

本发明提供一种治疗艾滋病的药物组合物，其中含有治疗艾滋病有效量的式(I)化合物联苯环辛二烯类木脂素(+)-戈米辛 K3[(+)-gomisin K3]及可药用载体和/或赋形剂。该药物组合物通过抑制逆转录酶和蛋白酶活性的作用机制，从而达到抑制HIV-1病毒的增殖。本发明同时给出了该药物组合物的制备方法，及其在制备逆转录酶抑制剂药物和在制备抗艾滋病药物中的应用。

光动力疗法抑制人免疫缺陷病毒复制的实验研究

通过对人免疫缺陷病毒复制过程的抑制作用研究，探索光动力疗法(PDT)在艾滋病防治中的潜在价值。使 用不同稀释浓度的光敏剂血卟啉单甲醚(HMME)和亚甲蓝(MB)分别与人免疫缺陷病毒HIV一1Ⅲs或宿主细胞 MT4，C8166或H9／HIV-IⅢB孵育2 h。以波长630 nm能量密度0．3 J／cm2的半导体激光进行照射。继续孵育若干 小时后，用噻唑蓝(MTT)比色法检测细胞存活率或合胞体计数，同时收集培养上清液用ELISA法检测HIV-I p24 抗原。结果表明，光动力疗法能显著抑制人免疫缺陷病毒诱导的细胞一细胞融合(HMME-PDT抑制率64．68％， MB-PDT抑制率61．56％)和病毒一细胞融合(HMME—PDT抑制率85％，Mt}PDT抑制率73．64％)，并对游离病毒 有很强的杀伤作用，最高可达到100％。光动力疗法不能抑制慢性感染期和急性感染2 h后病毒的复制过程。可 见光动力疗法对游离病毒和病毒感染诱导的膜融合有显著抑制作用，有可能为艾滋病的防治提供一种新的方法。

恒河猴TRIM5α的组织分布及不同刺激促进PBMC中TRIM5α转录水平的上调

TRIM5α(tripartite motif protein 5-alpha)蛋白是恒河猴体内一种非常重要的限制因子,能抑制人免疫缺陷病毒(HIV-1,human immunodeficiency virus type 1)、马感染性贫血病毒(EIAV, equine infectious anemia virus)和猫免疫缺陷病毒(FIV, feline immunodeficiencyvirus)等逆转录病毒的复制.恒河猴TRIM5α的组织分布以及在受到外界刺激时TRIM5α mRNA表达量的变化研究还未见报道.本研究从中国恒河猴的各组织中提取总RNA,以β-actin基因作为内参照,通过半定量RT-PCR检测各组织中TRIMSα mRNA的表达.选择HIV-GFP-VSVG假病毒感染外周血单核细胞(peripheral blood mononuclear cell,PBMC),非特异性刺激剂--佛波脂(Phorbol myfismte acetate,PMA)+离子霉素(ionomycin,Ion)及CD28抗体+CD49d抗体分别共刺激恒河猴PBMC,研究不同刺激对恒河猴TRIM5α mRNA表达水平的影响.结果表明:TRIM5α mRNA表达于所研究的恒河猴21种组织中,免疫系统和泌尿生殖系统组织中表达量最高,而神经系统组织,如大脑、脊髓中表达较少,其他组织中未见明显的表达差异;HIV-GFP-VSVG感染和用PMA+Ion、CD28抗体+CD49d抗体分别共刺激PBMC能促进PBMC中TRIM5α mRNA的转录水平的上调.

Chemical Constituents from Fruit Hulls of Garcinia mangostana ( Cuttiferae

从山竺(Garcinia mangostana)果壳中分离得到6个化合物,通过MS,1D 1NMR以及与文献对照鉴定它们为4个(口山)酮类化合物:α-mangostin(1),β-mangostin(2),γ-mangostin(3),5,9-dihydroxy-8-methoxy-2,2-dimethyl-7-(3-methylbut-2-enyl)-2H,6H-pyrano-[3,2-b]-xanthen-6-one(4),以及表儿茶素(epicatechin,5)和一个双苄类化合物egonol(6).其中化合物5和化合物6为首次从该植物中分离得到.对化合物1～5进行抗HIV-1 RT活性筛选结果表明,化合物2和化合物5在浓度200 μg/ml的条件下,其对HIV-1 RT抑制率分别为41.97%和47.72%;同一实验结果显示化合物1,3和4没有抑制HIV-1 RT作用.

New rotenoids from roots of Mirabilis jalapa

Four new rotenoids named mirabijalone A-D-1) (1-4), together with 9-O-methyl-4-hydroxyboeravinone B (5), boeravinone C (6) and F (7), and 1,2,3,4-tetrahydro-1-methylisoquinoline-7,8-diol (8), were isolated from the roots of Mirabilis jalapa. The structures of these compounds were determined on the basis of their HR-EI-MS, IR, UV, H-1- and C-13-NMR (DEPT). and 2D NMR (HMQC, HMBC, NOESY) data. Among them, 1,2,3,4-tetrahydro-1-methylisoquinoline-7,8-diol (8) showed a 48% inhibition against HIV-1 reverse transcriptase at 210 mug/ml.

4-Benzyl-5-ethyl-2-(2-furylcarbonylmethylsulfanyl) pyrimidin-6(1H)-one

The title compound, C19H18N2O3S, shows favourable activity against HIV-1. The phenyl ring is twisted with respect to the pyrimidine ring by 61.56 (9)degrees. Intermolecular N-H center dot center dot center dot O and C-H center dot center dot center dot O

Chemical Constituents from the Leaves and Stems of Schisandra lancifolia

A new nortriterpenoid, 20-hydroxymicrandilactone D (1) and a novel lignan glycoside, lancilignanside A (2) were isolated from leaves and stems of Schisandra lancifolia, together with three known nortriterpenoids (3-5) and nine known phenolics (6-14). The structures of new compounds 1 and 2 were determined by detailed analysis of their 1D and 2D NMR spectra, and chemical evidences. In addition, compounds 1-2, 6-7, and 9-11 showed anti-human immunodeficiency virus (HIV)-1 activities with 50% effective concentration (EC50) in the range of 3.0-99.0 mu g/ml. Compound 12 was not bioactive in this assay with EC50 more than 200 mu g/ml.