Human immunodeficiency virus infection and acquired immunodeficiency syndrome dementia complex: role of cells of monocyte-macrophage lineage

The entry of human immunodeficiency virus (HIV) into the central nervous system (CNS) causes both the establishment of a lifelong viral reservoir in the brain and symptoms of neurological dysfunction that have an AIDS dementia complex (ADC) clinical appearance. Neurological dysfunction in ADC patients still remains an unresolved problem. However, ADC pathogenesis may be a multistep process that starts with HIV invasion of CNS by crossing the blood-brain barrier (BBB). It progresses by developing a chronic inflammatory status that can cause dysfunction in neurons and astrocytes that result in apoptotic death. Monocytes-macrophages (M/M) may play an important role by concealing the HIV transfer across the BBB. Furthermore, HIV-infected M/M could produce and release neurotoxic factors. In this review the main mediators and cells involved in pathogenesis and development of ADC are highlighted. A better understanding of the mechanisms involved in this process may help in a successful therapeutic approach to the neuropathogenesis of HIV infection.     

Potent antiviral activity of amprenavir in primary macrophages infected by human immunodeficiency virus

Objective of the present study was then to assess the antiviral activity of the protease inhibitor amprenavir in macrophages (M/M), and to compare it with its efficacy in peripheral blood lymphocytes (PBL). M/M were obtained from blood of sero-negative healthy donors and infected with M-tropic HIV-1 strain (HIV-1(Ba-L)). The stabilized infection was assessed by monitoring the HIV-1 p24 gag antigen production in the supernatants of M/M cultures. In the setting of acute infection (treatment before HIV-1 challenge), amprenavir showed substantial activity both in M/M and PBL at similar concentrations (EC(50): 0.011 and 0.031 microM, respectively); complete inhibition of HIV-1 replication was achieved in both cell types at concentration of about 2 microM. In the setting of chronical infection (i.e. antiviral treatment several days after established infection), an antiviral effect of amprenavir was achieved in M/M, but at concentrations higher than those active in acutely infected M/M (EC(50): 0.72 microM, EC(90): 18.2 microM). The antiviral effect in chronically infected M/M was sustained for at least 2 weeks of continuous treatment. These findings suggest that amprenavir (at relatively high concentrations) has a clinically relevant antiviral effect in persistently infected reservoirs of HIV.     

医用聚乳酸类高分子材料的应用

目的:阐述医用聚乳酸类高分子材料的需求,综述聚乳酸类高分子材料在生物医学领域的应用,并对其在医学领域的应用前景进行展望。资料来源:应用计算机检索ACS美国化学学会数据库2000-01/2006-12关于医用聚乳酸类高分子材料的文章,检索词“polylactide”;利用Elsevier Science全文电子期刊数据库2000-01/2006-12进行检索,检索词“polylactide”和全文检索“Medical polymeric material”。同时利用计算机检索中国期刊全文数据库1994-01/2005-12的相关文章,限定文章语言种类为中文,检索词“聚乳酸类医用高分子材料”。资料选择:对资料进行初审,纳入标准:①关于聚乳酸类医用高分子材料的需求。②医用聚乳酸类高分子材料的合成及应用。排除标准:重复性研究。资料提炼:共收集到符合上述要求的文献100篇,排除70篇重复性研究。30篇符合纳入标准:其中6篇关于聚乳酸类医用高分子材料的需求,24篇关于医用聚乳酸类高分子材料的合成及应用。资料综合:聚乳酸是一种具有良好的生物相容性和可生物降解的聚合物,最终的降解产物是二氧化碳和水,对人体无毒、无刺激。目前,聚乳酸类材料产品在医学领域广泛用于药物控制释放载体、组织工程、骨内固定、修复、手术缝合线、人造皮肤以及三维多孔支架等。结论:医用聚乳酸类高分子材料有非常广阔的应用前景,今后研究的重点是研发高效低成本的聚乳酸制备方法,合成适应于不同医疗或其他用途的、具有优良生物相容性的聚乳酸共聚物高分子材料。     

Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN and METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage– colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU- GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G- CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.     

健胃愈疡颗粒干预下大鼠胃溃疡黏膜乳癌相关肽和血小板活化因子的表达及与胃黏膜疏水性的相关性研究

目的:观察对胃溃疡复发有较好疗效的健胃愈疡颗粒对溃疡黏膜乳腺癌相关肽和血小板活化因子表达的影响,分析其可能的作用机制。方法:实验于2005-07/2006-07在湘雅医院中心实验室完成。SD大鼠110只,雌雄各半,随机抽签法分为5组,即正常对照组、假手术组、雷尼替丁组、健胃愈疡组,各20只;模型组30只。以Okabe改良法复制大鼠实验性胃溃疡,假手术组仅以生理盐水代替乙酸注入玻管内。造模后24h,雷尼替丁组、健胃愈疡组大鼠分别灌服盐酸雷尼替丁和健胃愈疡颗粒(药物组成为:柴胡、党参、白芍、延胡索、白芨、珍珠层粉、青黛、甘草,湖南湘雅制药有限公司生产)药液10mL/kg,分别相当于2.70,1.62g/kg,1次/d。假手术组、模型组灌服蒸馏水10mL/kg。10d后各组中随机取出10只大鼠剖腹取胃(处死前大鼠禁食24h),90d时将模型组20只大鼠再分为模型复发组和模型非复发组,各10只;除正常对照组、假手术组、模型非复发组大鼠腹腔内注射生理盐水外,其余各组大鼠腹腔内注射白细胞介素1,1μg/kg;在注射48h,大鼠禁食24h后,剖腹取胃。观察其对胃溃疡大鼠胃黏膜氨基己糖及磷脂含量、溃疡指数和胃黏膜血流的影响,并用RT-PCR观察乳癌相关肽乳癌相关肽和血小板活化因子表达的变化。结果:实验动物110只,全部进入结果分析。①模型组10,92d胃黏膜血流均低于正常对照组(P<0.01);健胃愈疡组同期胃黏膜血流均高于模型组(P<0.01)。②健胃愈疡组和雷尼替丁组10d溃疡指数均低于模型组(P<0.01,P<0.05);模型复发组、健胃愈疡组和雷尼替丁组92d溃疡指数均高于模型组(P<0.01);健胃愈疡组10,92d溃疡指数及复发率均低于雷尼替丁组(P<0.05,P<0.01)。③模型组10,92d氨基己糖和磷脂含量均低于正常对照组(P<0.01)。健胃愈疡组10,92d氨基己糖和磷脂含量均高于模型组和雷尼替丁组(P<0.01)。溃疡指数与氨基已糖、磷脂含量呈负相关(r=-0.957,-0.960,P<0.01)。④健胃愈疡组和雷尼替丁组10d乳癌相关肽mRNA表达较正常组和假手术组提高,血小板活化因子mRNA的表达下调(P<0.01),健胃愈疡组两指标表达变化较雷尼替丁组显著(P<0.01);模型复发组、健胃愈疡组和雷尼替丁组92d乳癌相关肽mRNA、血小板活化因子mRNA的表达同组10d比较差异无显著性意义(P>0.05);模型组乳癌相关肽mRNA、血小板活化因子mRNA的表达同组10d比较差异有显著性意义(P<0.01)。结论:健胃愈疡颗粒可提高乳癌相关肽mRNA及下调血小板活化因子mRNA的表达,影响胃黏膜氨基己糖及磷脂含量,可能是其促进溃疡愈合的机制之一。     

体外膜肺氧合技术支持治疗期间患者血乳酸浓度及其预后

目的:探讨体外膜肺氧合支持治疗患者血乳酸浓度的变化和预后。方法:于2004-12/2006-09在中国医学科学院阜外心血管病医院因脱离体外循环困难的心脏外科术后患者、扩张性心肌病和冠状动脉粥样硬化性心脏病发生心源性休克的患者共40例进行了体外膜肺氧合支持治疗,按年龄和存活预后分为4组:成人存活组、成人死亡组、儿童存活组、儿童死亡组。分析4组的治疗效果,分别抽取各组患者体外膜肺氧合建立时、体外膜肺氧合运转6h、运转中间时点、停机前6h、停机时的血乳酸浓度。结果:①体外膜肺氧合支持治疗患者40例,成人组26例,20例脱机,16例生存,10例死亡,脱机率76.9%,生存率61.5%;儿童组14例,7例脱机,5例生存,9例死亡,脱机率50.0%,生存率35.0%。②成人或儿童存活组的乳酸浓度都与死亡组有明显差别,存活组血乳酸浓度明显低于死亡组,其中建立和运转6h、中间时点的差异有显著性意义(P<0.05),其余2个时点的差异有非常显著性意义(P<0.001)。组内与建立时比较,中间时点、停止前6h、停止时差异均有显著性意义(P<0.001),血乳酸浓度逐渐降低。结论:经体外膜肺氧合支持治疗的患者,血乳酸浓度明显下降,脱机时血乳酸仍高的患者预后不良。     

gp41 sequence variability in HIV type 1 non-B subtypes infected patients undergoing enfuvirtide pressure

Enfuvirtide is the first of a new class of antiretroviral drugs that inhibits HIV entry. It is a 36 amino acid synthetic peptide that mimics the HR2 region of the HIV-1 gp41, preventing the fusion of viral and cellular membranes. Up to now, enfuvirtide was designed based on the HIV-1 B-subtype gp41, and resistance mutations to the fusion inhibitor have been investigated primarily in individuals infected with this subtype. To fill the gap, we analyzed the full length gp41 protein sequence of HIV-1 non-B strains from individuals receiving enfuvirtide-containing regimens. No primary resistance to the enfuvirtide binding domain (36-45 residues) was found. Resistance mutations were detected at follow-up visits and were comparable to those described among B-subtype HIV-1-infected patients; no sequence changes were detected in crucial HR1/HR2 gp41 sites such as the cytotoxic T lymphocyte epitope, cysteine loop, ectodomain, and 5-helix interaction and binding region.