Cholesterol homeostasis and the pathophysiology of Alzheimer's disease

The past 4 years have seen a growing interest in cholesterol metabolism and its relationship to Alzheimer's disease. From the first report linking cholesterol and beta-amyloid metabolisms to the recent positive report on the use of atorvastatin (Lipitor, Pfizer Inc.), a cholesterol-lowering drug, in mild-to-moderate Alzheimer's disease, this review examines the scientific progress pertaining to etiopathology of Alzheimer's disease over the past 15 years and the central role of lipids in this field of research. The role of key proteins involved in this metabolic pathway such as apolipoprotein E, lipoprotein lipase, caveolin, hydroxy-methylglutaryl Coenzyme A reductase, low-density lipoprotein receptors, cholesterol 24-hydroxylase, acyl-coenzyme A:cholesterol acyltransferase and beta-amyloid are discussed.     

Idiopathic polypoidal choroidal vasculopathy leading to blindness

Idiopathic polypoidal choroidal vasculopathy (IPCV) has recently been recognized as a distinct cause of recurrent subretinal hemorrhages and exudates as well as multiple hemorrhagic retinal pigment epithelium detachments in the macula. IPCV is usually considered to have a good visual prognosis. We report the case of a 44-year-old woman with particularly severe bilateral macular and peripheral IPCV. The patient was followed for 13 years and had final visual acuity of counting fingers in the right eye and 20/400 in the left eye. Patients with IPCV with macular choroidal neovascularization tend to have a poor visual prognosis. This case of IPCV should alert the physician to be particularly attentive to the follow-up of these patients.     

银杏叶制剂对心绞痛患者的抗氧化和抗脂质过氧化作用

目的：探讨银杏叶制剂对心绞痛患者的抗氧化和抗脂质过氧化作用。方法：检测了７８例心绞痛患者经银杏叶制剂“天宝宁”治疗前后的血浆维生素Ｃ（Ｐ－ＶＣ）、维生素Ｅ（Ｐ－ＶＥ）、β－胡萝卜素（Ｐ－β－ＣＡＲ）、过氧化脂质（Ｐ－ＬＰＯ）以及红细胞超氧化物歧化酶（Ｅ－ＳＯＤ）、过氧化氢酶（Ｅ－ＣＡＴ）、谷胱甘肽过氧化物酶（Ｅ－ＧＳＨ－ＰＸ）、过氧化脂质（Ｅ－ＬＰＯ）值。结果：与治疗前比较,治疗后的Ｐ－ＶＣ、Ｐ－     

Susceptibility to chlordecone-carbon tetrachloride induced hepatotoxicity and lethality is both age and sex dependent.

The present paper examines the susceptibility to chlordecone (Kepone, CD) and carbon tetrachloride across different ages (35, 45, and 63-days-old) in male and female Sprague-Dawley rats using different lengths of time on a CD diet (10 ppm). The principal findings are that the hepatotoxicity and mortality associated with CD-CCl4 interaction is highly age-dependent for both sexes. There was marked hepatotoxicity occurring in both sexes as they reached 45 days-of-age and females were considerably more susceptible than males to both CD-CCl4-induced hepatotoxicity and lethality. While 63-day-old females are more susceptible to the CD-CCl4 interaction than their male counterparts, the magnitude of the sex difference is diminished from that observed in 45-day-old rats. These findings challenge the hypothesis of Mehendale (1990, Med. Hypotheses 33, 289-299) that chlordecone (CD) pretreatment eliminates the well-established sex difference in CCl4-treated rats. In contrast to the CD-CCl4 findings, the sex difference in CCl4-induced hepatotoxicity was not age-dependent and was consistent over the three ages studied. The findings that CD-CCl4 interaction is highly age-dependent (within the 3 ages tested) but that CCl4-induced hepatotoxicity is not, suggest that the CD-CCl4 interaction acts via a mechanism that does not primarily involve CCl4 potentiation.     

控制和影响神经干细胞增殖分化为神经元细胞的途径及因素

目的:探讨控制和影响神经干细胞向神经元细胞转化途径的因素。资料来源:应用计算机检索Medline和cnki数据库1990-01/2006-06期间的有关神经干细胞和增殖与分化关系的文献,检索词“NSC,proliferation,differentiation”,并限定文章语言种类为English。同时计算机检索中国生物医学文献数据库1990-01/2006-06期间的相关文献,限定文章语言种类为中文,检索词“神经干细胞、增殖、分化”。资料选择:选取关于影响神经干细胞增殖与分化特别是机制方面的相关文献,删除未进行对照的试验研究的文章,然后查余下的文献全文,进一步判断是否采用对照。纳入标准:平行对照组,即未采用影响神经干细胞增殖与分化的因素或正常对照;实验组为采用干扰神经干细胞增殖与分化的因素。排除明显不随机的试验。质量评价主要考察资料的真实性,调查设计是否严密,实施过程是否严格,统计学处理是否合理。资料提炼:共检索43篇关于神经干细胞增殖与分化分别与基因调控、生长因子、细胞因子及微环境信号等因素密切相关文章,31编符合纳入标准。排除的12篇试验中,8篇是因重复的同一研究,4篇是Meta分析研究。资料综合:神经干细胞是一种具有强大的自我更新能力和多向分化潜能的细胞,它具有分化为中枢神经系统内神经元、星形胶质细胞和少突胶质细胞的能力;其增殖与分化与基因调控、生长因子、细胞因子及微环境信号等因素密切相关,基本螺旋-环-螺旋基因、凋亡相关基因Bc1-XL、sox2等参与了神经干细胞的定向分化机制,notch信号通路、过氧化物酶体增殖分化激活受体Y信号通路也影响神经干细胞的分化方向。结论:神经干细胞的增殖与分化机制尚不十分清楚,其分化及调控机制是多因素调节和多因素相互作用的结果。     

Outcome for patients who relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia. Chronic Leukemia Working Party. European Bone Marrow Transplantation Group

We studied the clinical course of 130 chronic myeloid leukemia (CML) patients (89 males and 41 females) in the European Bone Marrow Transplantation Group (EBMT) registry who received transplants before January 1, 1988 and who subsequently had evidence of recurrent leukemia. All patients had received a pretransplant conditioning regimen including total body irradiation (TBI). The first evidence of relapse was cytogenetic only in 74 (57%) patients and hematologic in 56 (43%). The overall actuarial survival from relapse was 36% at 6 years, with a significantly higher proportion of survivors among female patients (53% v 30%; P < .002). In univariate analysis, the 6-year probability of survival was 52% for patients with cytogenetic relapse and 30% for patients relapsing in chronic phase (CP), while no patient who relapsed in advanced phase (AP or BC) survived more than 3.5 years from relapse (P < .0001). The actuarial survival of patients relapsing before 6 months, between 6 and 12 months, and later than 12 months after transplant was 27%, 26%, and 45%, respectively (P < .002). Among patients with cytogenetic relapse, partial or complete disappearance of Ph-positive cells occurred in 40% of untreated patients and in 42% of those treated with interferon (IFN). However, IFN therapy significantly delayed progression toward hematologic disease. Cytogenetic responses were observed in 25% of patients who received IFN for relapse into CP, while only one minor cytogenetic response was reported in patients on conventional chemotherapy. For patients presenting with cytogenetic relapse as well as for those in hematologic relapse, IFN therapy significantly improved the 2-year probability of survival. However, long-term survival for IFN-treated patients in either group was not different from long-term survival in comparable patients not receiving IFN therapy. Twenty-nine patients of this series underwent a second bone marrow transplant (BMT) and the projected survival at 4 years after the second transplant is 28%. In multivariate Cox regression analysis, four factors remained significantly associated with survival: disease phase at relapse (P < .0001), duration of time interval from BMT to relapse (P = .0001), interferon therapy at relapse (P = .0024), and patient sex (P = .0032). This retrospective study provides evidence that some patients who relapse after BMT may benefit from treatment with IFN; a second BMT may offer the chance of cure. Data from this analysis may be useful in designing future prospective trials on posttransplant CML relapse.     

Bronchial artery embolization: monitoring with somatosensory evoked potentials. Work in progress

Surgery remains the treatment of choice for massive and recurrent hemoptysis. In some instances, however, immediate surgical intervention is contraindicated. In these situations, bronchial artery embolization (BAE) has proved to be a successful definitive treatment for non-surgical candidates and a palliative therapy in patients requiring hemodynamic stabilization prior to surgery. The most serious complication of BAE is spinal cord ischemia. This relates directly to the potential anastomotic connections between the bronchial circulation and the anterior spinal artery. Somatosensory evoked potentials (SSEPs) have been used in the past to monitor spinal cord ischemia during procedures that threaten the vascularity of the spinal cord. The authors report two cases in which SSEPs were employed to monitor spinal cord ischemia during bronchial artery embolization.     

The prospects for renal xenotransplantation

Summary: Xenotransplantation of non-human organs into human recipients has long been proposed as a possible strategy to overcome the acute shortage of donor organs. However, vascular organ transplants to humans from phylogenetically disparate species such as the pig are not currently possible due to a rapid rejection process termed hyperacute rejection. This process is initiated by the binding of host pre-formed 'natural antibodies' to the donor vascular endothelium, activation of the host complement system and activation or injury of the donor endothelial cells, leading to intravascular coagulation and loss of the graft due to ischaemic necrosis within minutes to hours of engraftment. Prevention of natural antibody binding and complement activation is viewed as paramount to preventing hyperacute rejection. Even if hyperacute rejection can be prevented, further barriers to successful discordant xenografts such as delayed xenograft rejection and a donor-directed cell-mediated rejection process will still represent major obstacles. This review examines recent advances being made in the various areas of xenograft research and the potential clinical application of pig-to-human xenografts that these strategies may bring.