李群辉艾滋病论文

2009年5-6月的最新研究成果。加拿大和美国研究人员6月21日发表论文称，他们发现了可能会彻底治愈艾滋病的新方法，艾滋病将有可能不再是不治之症。治愈艾滋病的关键在于找到艾滋病病毒潜伏池--艾滋病病毒在人体内的藏身之地。研究人员说，他们找到了这种潜伏池，即记忆T细胞，这是一种人体免疫细胞，尽管它是一些艾滋病病毒的藏身天堂，但也在一定程度上能限制这些病毒的活动。研究人员发现，一旦艾滋病病毒藏身到记忆T细胞中，它的命运就与记忆T细胞休戚相关:细胞活着，病毒也就活着;细胞死亡，病毒也就死亡;病毒增殖也完全依赖于细胞的分裂。因此，摧毁记忆T细胞，也就可以摧毁“躲藏”起来的艾滋病病毒。研究人员说，单使用鸡尾酒疗法等抗逆转录病毒疗法治愈不了艾滋病，是因为它对潜伏池内的艾滋病病毒鞭长莫及。于是，他们提出了结合化学疗法和抗逆转录病毒疗法来治疗艾滋病的新方法，其中，抗逆转录病毒疗法可杀灭人体内大部分艾滋病病毒，而化学疗法则专门针对“躲藏”在记忆T细胞中的艾滋病病毒，这使得艾滋病病毒在人体中再无藏身之地。这项研究的负责人、蒙特利尔大学的拉菲克-皮埃尔·瑟卡利说，这是首次研究证实，艾滋病之所以治愈不了，不是因为抗逆转录病毒疗法不起效果，而是因为有艾滋病病毒潜伏池的存在。瑟卡利说，这是初步的研究成果，希望这项成果能指导科学家消灭艾滋病病毒，他们下一步计划在动物身上进行有关试验。这项研究成果已于21日发表在英国《自然-医学》杂志上。

现在我国的很多医院，存在着一些服务质量的问题，看似是很小的事情，但是如果继续下去的话会引起巨大的医疗事故。医院不能成为一个只会赚钱，不顾老百姓生命安全的地方，如果医院变质到如此地步，那么老百姓的生面可就没有保证了，这点现在国家已经严厉查处，并且取得很大成果。可是中国医院里面的服务情况，并不是全部都会好转起来，总有极个别的医院依旧在侵害老百姓的利益，甚至侵害老百姓的生命。最近的消息是我感到很难过，因为消息里面说浙江中医院违规操作致5名患者被感染艾滋，这样的事情真的叫人觉得气愤，对于这种医院国家应该彻底的进行清理和查处了。这件事情的性质十分严重，艾滋病是一种可怕的病症，几乎没有任何的治疗方法，得病的患者会慢慢的失去生命，他们们的人生会在这一次的事件中变得黯淡无光，这些人只是普普通通的老百姓，都有自己的家庭和事业，现在他们的遭遇是很悲剧的，我觉得社会必须给予他们关心和爱护，保证他们的权益。这家医院因为使用交叉的医疗用品，根本不顾医院患者的身体健康，这才造成现在这样的悲剧发生，医院的领导和医院的工作人员，他们都有基本的医疗知识，更明白这样做的后果，但是为了自己的利益，他们什么事情都可以干出来，如果这样的人不接受最严厉的法律处罚，那么就太不公平了。国家应该通过这件事情，认真的进行总结，对于这件医疗事故的严重性，必须做出总结。同时国家相关部门要对这家医院的领导和工作人员进行逐步的审查，对于责任人必须要严惩不贷。因为医院的这种行为严重的危害到患者的生命，给社会造成的影响也是巨大的，当事责任人的行为，可以说毫无人性，如果不给严厉的惩罚，那么真是无法向社会大众交代了。

科学家发现HIV药物或能改善中年记忆力减退

科学家发现HIV药物或能改善中年记忆力减退，美国研究人员发现了记忆连接背后的关键分子机制。他们还确定了一种恢复中年小鼠大脑功能的方法，科学家发现HIV药物或能改善中年记忆力减退。

科学家们发现了记忆联系背后的一个关键分子机制。他们还发现了一种在中年小鼠中恢复这种大脑功能的方法 - 并且已经存在一种FDA批准的药物，可以实现同样的事情。

科学家确定大脑如何将记忆联系起来

研究表明，艾滋病毒药物可以对抗中年记忆丧失。

我们的大脑很少记录单个记忆——相反，它们将记忆存储成组，以便对一个重要记忆的回忆触发对其他记忆的回忆。然而，随着年龄的增长，我们的大脑逐渐失去了这种连接相关记忆的能力。

现在，加州大学洛杉矶分校（UCLA）的研究人员发现了记忆联系背后的一个关键分子机制。他们还确定了一种在中年小鼠中恢复这种大脑功能的方法 - 以及一种FDA批准的药物，可以实现同样的事情。

今天（2022年5月25日）发表在《自然》杂志上，研究结果表明了一种加强中年人类记忆的新方法，以及痴呆症的早期干预。

“我们的记忆是我们身份的重要组成部分，”加州大学洛杉矶分校大卫·格芬医学院（David Geffen School of Medicine）神经生物学和精神病学杰出教授阿尔西诺·席尔瓦（Alcino Silva）解释说。“将相关经验联系起来的能力教会了如何保持安全并在世界上成功运营。

生物学101：细胞中布满了受体。要进入细胞，分子必须锁定其匹配的受体，该受体像门把手一样工作以提供内部访问。

加州大学洛杉矶分校的研究小组专注于一种名为CCR5的基因，该基因编码CCR5受体 - HIV搭便车感染脑细胞并导致艾滋病患者记忆丧失。

席尔瓦的实验室在早期的研究中证明，CCR5表达降低了记忆回忆。

在目前的研究中，席尔瓦和他的同事们发现了小鼠连接两个不同笼子记忆的核心机制。一个微小的显微镜打开了一扇通往动物大脑的窗户，使科学家们能够观察神经元的放电并产生新的记忆。

促进CCR5基因在中年小鼠大脑中的表达会干扰记忆链接。动物们忘记了两个笼子之间的联系。

当科学家删除了动物中的CCR5基因时，小鼠能够连接正常小鼠无法连接的记忆。

席尔瓦此前曾研究过美国食品和药物管理局于2007年批准用于治疗HIV感染的药物maraviroc。他的实验室发现，马拉韦罗克还抑制了小鼠大脑中的CCR5。

“当我们将maraviroc给予老年小鼠时，该药物复制了从其DNA中遗传删除CCR5的效果，”加州大学洛杉矶分校脑研究所成员席尔瓦说。“年长的动物能够再次连接记忆。

这一发现表明，马拉韦罗可以超适应症地使用，以帮助恢复中年记忆丧失，以及逆转由HIV感染引起的认知缺陷。

“我们的下一步将是组织一项临床试验，以测试maraviroc对早期记忆丧失的影响，目标是早期干预，”席尔瓦说。“一旦我们完全了解记忆力是如何下降的，我们就有可能减缓这个过程。

这就引出了一个问题：为什么大脑需要一种干扰其连接记忆能力的基因？

“如果我们记住一切，生活将是不可能的，”席尔瓦说。“我们怀疑CCR5通过过滤掉不太重要的细节，使大脑能够连接有意义的体验。

美国研究人员发现了记忆连接背后的关键分子机制。他们还确定了一种恢复中年小鼠大脑功能的方法，以及一种美国食品药品监督管理局（FDA）批准的艾滋病药物可达到同样的效果。近日发表在《自然》杂志上的该研究成果，提出了一种加强中年人记忆的新方法，或有助于对痴呆症进行早期干预。

人类大脑很少记录单一的记忆，相反，它们将记忆存储成组，这样对一个重要记忆的回忆就会触发其他与时间相关的记忆。然而，随着年龄的增长，人类大脑逐渐失去了连接相关记忆的能力。

加州大学洛杉矶分校大卫格芬医学院神经生物学和精神病学教授阿尔西诺·席尔瓦领导的团队，专注于一种名为CCR5的基因，该基因与搭艾滋病毒便车感染脑细胞并导致患者记忆丧失的基因相同。席尔瓦实验室在早期的研究中证明，CCR5的表达会降低记忆回忆能力。

在当前的研究中，席尔瓦团队发现了一种潜在的核心机制，即小鼠能够将它们对两个不同笼子的记忆联系起来。研究人员以微型显微镜作为进入动物大脑的窗口，观察神经元的放电及创造的新记忆。

提高中年小鼠大脑中CCR5基因的表达会干扰记忆联系，小鼠会忘记两个笼子之间的联系。当研究人员删除小鼠体内的CCR5基因时，小鼠能将无法连接的记忆联系起来。

情景型记忆连接的实验

席尔瓦此前曾研究过FDA于2007年批准用于治疗HIV感染的药物马拉韦罗。研究发现，马拉韦罗抑制了小鼠大脑中的CCR5。当研究人员给老年小鼠服用马拉韦罗时，这种药物复制了从它们的DNA中删除CCR5的效果，年长的动物能够再次连接记忆。

该发现表明，马拉韦罗可帮助恢复中年记忆丧失，以及逆转由HIV感染引起的认知缺陷。

研究人员下一步将组织以早期干预为目标的临床试验，测试马拉韦罗对早期记忆丧失的影响。一旦完全了解记忆力是如何下降的，研究人员就有可能减缓这一过程。

艾滋病与记忆衰退，看上去是两类毫不相干的病症。《自然》杂志的一项最新研究却出人意料地将这两者联系在一起。研究发现，一种用于治疗艾滋病的药物竟有望恢复大脑的记忆功能。

要理解这个神奇的关联，我们首先要了解的是大脑记忆的方式。事实上，我们的大脑并不是独立地记忆不同的`事情，而是将相关的记忆打包来存储。例如，当你回想起你的毕业旅行时，旅行途中的风景、吃的每一顿饭、当时的天气情况——这些时间相近的相关记忆都会涌现出来。但随着年龄增长，大脑连接记忆的能力正在丧失。

大脑中记忆连接丧失的幕后机制是什么？在这项最新研究中，加州大学洛杉矶分校Alcino Silva教授领导的研究团队关注的是一种趋化因子受体：CCR5。

对于CCR5，科学家早已不陌生。早在20多年前，科学家就已经发现，HIV入侵人体细胞时靶向的就是CCR5受体。此后，针对CCR5开发的艾滋病药物已经出现并得到广泛应用。

但CCR5的生理功能还不止这些。此前，Silva教授团队已经注意到CCR5与记忆的关联。在6年前的一篇论文中，他们证明了CCR5的表达会阻止记忆的唤起，这可能也解释了艾滋病患者出现认知缺陷的原因。

图片来源：123RF

而在最新研究中，研究团队利用小鼠实验进一步发现，CCR5表达的增加阻止了记忆连接的形成。

Silva教授等人将小鼠间隔一段时间，分别放在两个不同的环境中。间隔时间不长时，小鼠在两个环境中具有相似的活跃神经元，它们能将这两个环境的记忆联系起来；但间隔12-24小时时，CCR5的表达量激增，这时小鼠活跃的神经元发生了变化，记忆连接也丢失了。

▲小鼠实验证实了CCR5受体能调控记忆连接（图片来源：参考资料[2]）

随后，他们敲除了小鼠体内的Ccr5基因，这时小鼠大脑连接记忆的能力明显提升。至此，这项研究揭示了CCR5表达在记忆连接中的关键作用。

问题来了，既然涉及同一种受体，那么靶向CCR5的抗艾滋病药物能否直接用来提升记忆连接呢？

为了检验这一点，研究团队测试了一种早已在2007年通过FDA批准上市的艾滋病药物：Maraviroc。他们让中年小鼠服用这种CCR5拮抗剂，这种药物起到了与敲除相同的效果，结果这些小鼠能够再次连接记忆。

▲CCR5促进了与年龄相关的记忆连接衰退，而CCR5拮抗剂可以逆转这一过程（图片来源：参考资料[1]）

这项研究表明，Maraviroc的超适应症（off-label）使用能帮助重建中年小鼠丢失的记忆，以及逆转HIV感染导致的认知缺陷。

接下来，研究团队将组织临床试验，检验Maraviroc对于早期记忆丧失的干预作用：“一旦我们能彻底理解记忆力衰退的机制，我们就有可能减慢这个过程。”

对于我们的大脑来说，这个干预记忆连接的机制是否有积极意义？Silva教授也提出了他的猜想：CCR5的表达能使得大脑过滤掉不重要的细节，从而巩固更有意义的记忆。或许，这部分记忆衰退正是我们为了提升记忆所付出的代价，这正是生命演化的神奇之处吧。

舞茸β-葡聚糖对HIV（艾滋病）病人的效果

Effects of Maitake (Grifola frondosa) gulcan in HIV-infected patients

【摘要翻译】

为评估一种从舞茸中提取的β-葡聚糖MD-Fraction（舞茸D-fraction）对艾滋病（HIV）感染病人的效果，进行了长期的实验。参与实验的HIV感染者被跟踪监测CD4+ 细胞计数，病毒载量，艾滋病感染症状，继发病状况，以及健康状态。20位患者的CD4+细胞计数增加到原来的倍，8位患者降低到原来的倍。9位病人的病毒载量增加，10位降低。尽管如此，85%的受试者对于HIV引起的症状和继发病的感觉变好，这表明舞茸D-fraction对于艾滋病HIV患者具有积极的影响。

关键词： 抗HIV活性，CD4+细胞，舞茸，IL-2，MD-Fraction

注：CD4+细胞是人体免疫系统中的一种重要免疫细胞，由于艾滋病病毒攻击对象是CD4+细胞，所以其检测结果对艾滋病治疗效果的判断和对患者免疫功能的判断有重要作用。

【论文原文】

Effects of Maitake (Grifola frondosa) gulcan in HIV-infected patients

Hiroaki Nanba1)*, Noriko Kodama1), Douglas Schar 2) and Denise Turner 2)

1)Department of Microbial Chemistry, Kobe Pharmaceutical University, 4-19-1,

Motoyamakita-machi, Higashinada-ku, kobe 658-8558, Japan2)Herbal Clinical Research, 140 Columbia Road, London E2 7RG, .

The effects of MD-Fraction, a β-glucan extracted from Maitake mushroom (Grifola frondosa)， on the health status of individuals suffering from HIV infection were evaluated in a long-term trial. The HIV status of the 35 respondents who participated in the study was followed by monitoring CD4+ cell counts, viral load measure, sympotoms of HIV infection, status of secondary disease, and sense of well-being. Twenty patients reported to increase in CD4+ cell counts to times, and 8 patients reported a decrease to times. Viral load was reported to increase in 9 patients and decrease in 10 patients. However, 85% of respondents reported an increased sense of well-being with regard to various symptoms and secondary diseases caused by HIV. These results suggest that Maitake D-Fraction had a positive impact in HIV Words : anti-HIV activity; CD4+ cell; Grifola frondosa (Maitake); IL-2; MD-Fraction

Acquired immune deficiency syndrome (AIDS) is caused by HIV infection, which attacks helper T cells (CD4+ cells) and decreases the body’s immunity. In 1991, we studied the effect of a Grifola frondosa . Gray (Maitake) extract, named MD-Fraction on HIV, which is believed to be a cause of AIDS. Sulfated MD-Fraction was found to prevent HIV from killing helper T (CD4+) cells: almost 100% of CD4+ cells survived challenge by HIV at concentrations of sulfated MD-Fraction of around 1 pg/ml, and the results were presented in an abstract paper at the 8th International AIDS conference in Amsterdam in July 1992. National Institute of Health and National Cancer Institute in . also confirmed the anti-HIV activity of the sulfated form of MD-Fraction. NCI doctors have recognized that the sulfated MD-Fraction is the most effective among all anti-HIV polysaccharides known to date and is as powerful as the drug azidothymidine (AZT). However, the sulfated MD-Fraction has the strong side-effect of toxicity to cells in vivo. On the other hand, we have reported that a β1,6-glucan having a β 1,3-branched chain (named MD-Fraction) can enhance immunocompent cell activities (Hishida et al., 1988; Nanba et al., 1987; Nanba et al., 1993).In this paper, we report that Maitake appears to work on several levels in HIV conditions, by (a) direct inhibition of the human immunodeficiency virus (HIV), (b) stimulation of the body’s own natural defense system against HIV, and (c) making the body less vulnerable to opportunistic disease.

Materials and Methods：

Preparation of Maitake tablets  Tablets containing 250 mg of dried Maitake powder(φ200 μm) and 5 mg of vitamin C were prepared with a tabloid of MD-Fraction  Dried Maitake powder (500 g) was autclaved with 3,000 ml of distilled water at 120℃ for 60 min, and the water-soluble layer obtained was saturated with the same volume of ethanol at 4℃ for 12 h. After removal of floating material, this ethanol solution was saturated to 80% with ethanol and stored at 4℃ for 10 h. The pellet obtained by centrifugation at 5,000×g for 20 min was suspended in a small volume of distilled water and protein was removed by passage through a DEAE-cellulofine column (4×80cm). Finally 1 g of purified MD-Fraction was of virions  The HIV genome is known to have nine genes, three expressing structural protein and six expressing regulating protein. Anti-HIV-Env antibody was produced in blood from 10 wk to 12 yr after HIV infection. The coagulation test of antigen was performed with HIV-Env antibody collected from blood. Viral loads were counted in 50-μl portions of patients’ of interleukin-2 (IL-2)  Production of IL-2 in blood was detected with IL-2 ELISA Kit Intertest-2X (Genzyme Co. .)Counting of CD4+ cells and CD8+ cells  CD4+ cells were counted by flow cytometric analysis after treatment of 10 μl of blood with CD4+- monoclonal antibody (Cytovax Biotechologies Inc.) The count of CD8+ cells was obtained by subtracting the CD4+ cell count from the total count of T cells determined by flow cytometric of Maitake  A supply of Maitake was given to each HIV carrier at a dose level of 6 g of tablets or 20mg of purified MD-Fraction together with 4 g of tablets per day for 360d.

Results：The main focus in monitoring the progress of HIV disease is CD4+ cells (helper T cells). The normal range of CD4+ cell count is 500-1,200 cells/10μl of blood. A level of 200-500 cells indicates that some damage has occured. Below 200 cells, the individual is highly susceptible to secondary diseases. An elevated viral load indicates an increased risk of damage to CD4+ cells. The significance of these activities in regard to HIV infection relates to the immune system. Both IL-2 and interferon are activated by the immune system response to infection by viral disease. After administration of Maitake tablets for 12 mo to 35 respondents (24 in England and 11 in .), 20 responders reported an increase in CD4+ cell counts and 8 reported a decrease , as shown in Table 1. Nine respondents reported an increase in viral load, 10 reported a decrease and 2 patients reported static, Typical individual results were as follows.

Patient A  The initial CD4+ count of 90 cells rose as high as 460 cells (average CD4+ count: 355) in the study period, but viral load was undetected throughout. Previous symptoms were Kaposi’s sarcoma, pneumocystis carinii pneumonia, and allergic conjunctivitis, all of which resolved and remained controlled during study period. The patient consistently reported feeling very well and energy levels much B  The initial CD4+ count of 400 cells rose to 620 cells after the treatment. The viral load of 15,200 copies/ml in CD4+ cells decreased to 5,000 copies/ml. IL-2 production was also increased times by Maitake treatment. Previous symptoms were Kaposi’s sarcoma, verrucae, anal warts, anal herpes, diarrhea, chest infections, and fatigue. Following the study period, when the patient received 6 g of Maitake tablets together with 20mg of MD-Fraction per day, Kaposi’s sarcoma became static, verrucae and anal warts were resolved, and other symptoms became C  The initial CD4+ count of 510 cells showed little change at 500 cells after the study, but the viral load of 60,000 copies/ml in CD4+ cell decreased to 1,000 copies/ml. The patient had day and night sweats, bouts of colds, mucous membrane irritation and fatigue as previous symptoms, but after the course of Maitake all symptoms were resolved. In particular, a direct effect on the sweats was D  The initial CD4+ count of 425 rose to 680 counts (average ) during the study. The viral load of 20,000 copies/ml increased to 93,000 copies/ml, but skin, oral, and gastric Candida, catarrh, irritable bowel, and aching muscles as previous symptoms were all improved by E  The initial CD4+ count of 17 cells decreased to 7 cells during the study, while the viral load of 55,000 copies/ml increased to 62,000 copies/ml. AIDS, oral Candida, and wasting disease as previous symptoms persisted despite the treatment with Maitake. The CD4+ cell counts and HIV viral loads of other patients who received Maitake for 1 yr are shown in Tables 2 and 3. It is known that long infection period of HIV makes seriously symptoms and secondary disease. Therefore, as shown in Tables 4 and 5, we examined that these symptoms and diseases were improved by Maitake treatment. Symptoms depends on HIV infection, such as weight loss, hair loss, night sweat, fever, dry cough and leg pain, were improved by Maitake almost in 50% of patients (as Table 4), also secondary diseases, such as toxoplasmosis, cryptococcosis, herps, kaposi’s sarcoma and mycopathy, were cured in 40-50% of patients. Table 6 indicates that the percentage of patients reporting changes in symptoms and sense of well-being following treatment.

Discussion ：The MD-Fraction exhibited an enhancing effect on CD4+ cells, the target cells of HIV, upon oral administration in animals (Hishida et al., 1988). Even though it was a non-controlled trial, this clinical study indicated that MD-Fraction and Maitake powder were effective in patients with breast cancer, lung cancer, or liver cancer. These human tests suggest that the active ingredients of Maitake have significant healing and preventative potential in HIV-responders by stimulating the immune system. The present study indicates that when MD-Fraction and Maitake enhanced the activities of immuno-competent cells such as macrophages, cytotoxic T cells (CD8+) or helper T cell (CD4+), the HIV in CD4+ cells was directly killed or its multiplication was suppressed. However, even if these cellular activities were increased by MD-Fraction, HIV in CD4+ cells of AIDS patients did not decrease. All of the results shown here indicate that there is evidence to support a more structured investigation in to the potential benefits of Maitake and MD-Fraction in the treatment of HIV infection. The results also indicate that this trial study needs to be done on a larger scales, as many questions remain unanswered.

Literature cited：Hishida I., Nanba H. And Kuroda H. 1988. Anti-tumor activity exhibited by oral administered extract from fruit body of Grifola frondosa (Maitake). Chem. Pharm. Bull. 36: H., Hamaguchi A. and Kuroda H. 1987. The chemical structure of an anti-tumorpolysaccharide in fruit bodies of Grifola frondosa (Maitake). Chem. Pharm. Bull. 35:  H. and George S. R. 1993. Effects of Maitake (Grifola frondosa) for HIV-positive or fibroid tumor patients. 113th Congr. Pharmaceutical Society of Japan, Osaka, Japan, March 29-31, . Anti-tumor activity of orally administered D-Fraction from Maitake mushroom Grifola frondosa. J Naturopath. Med. 4: 10-15.