Genetic polymorphisms and heart failure.

Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism. Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system. Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study gene-gene interactions and gene-environment interactions.     

我省医学临床教学基地建设的现状与思考

对我省医学临床教学基地评审结果进行分析，就大部分基地教学意识不强、教学设施不完善、教学条件有待改善、师资队伍素质水平不高等问题进行了阐述，并针对存在的问题提出建议和思考，从建章立制规范管理、加强建设、提供保障、重视培训、提高素质、强化管理、创新机制等方面进行探索，希望能使我省医学临床教学基地质量得以提高、完善，为我省培养一流的医学专业人才奠定基础．     

蝌蚪提取液诱导人早幼粒白血病细胞分化的实验研究

目的 :探讨蝌蝌提取液 (T871)对白血病细胞的诱导分化作用。方法 :利用细胞生长曲线、形态学观察、细胞免疫化学及原位mRNA杂交和完整细胞原位斑点印迹技术 ,观察了T871诱导HL 60细胞分化的作用和分化过程中癌基因c myc、c myb表达的变化。结果 :T871能抑制HL 60细胞的增殖 ,形态学表现为类似单核 /巨噬细胞 ,同时T871还能使HL 60细胞的NBT还原能力、ANAE活性显著增强 ,同时伴有癌基因c myc、c mybmRNA表达的下调。结论 :T871能诱导HL 60细胞向单核 /巨噬细胞方向分化 ,c myc、c myb癌基因可能参与了此过程     

Alteration of Elastin, Collagen and their Cross-links in Abdominal Aortic Aneurysms

OBJECTIVES: although the mechanism of arterial dilation and aneurysm development has not been clarified, the degradation of elastin and collagen plays undoubtedly a critical role. We evaluated the elastin and collagen content through the detection of their cross-links in aneurysmal and non-aneurysmal abdominal aortic walls. MATERIALS AND METHODS: in 26 human abdominal aortic aneurysm specimens obtained during surgery and in 24 autopsy control samples of non-aneurysmal abdominal aorta the tissue content of elastin and collagen cross-links were measured by HPLC. Collagen was also detected by evaluating two characteristic amino acids, 4-hydroxyproline (4-hypro) with a colorimetric method and 5-hydroxylysine (5-hylys) by gas chromatography. RESULTS: significantly fewer elastin cross-links were found in aneurysm samples compared to controls (desmosines and isodesmosines: 90% reduction; p<0.01). The opposite was true for pyridinoline collagen cross-links (350% increase) and deoxypyridinolines (100% increase, p=0.01). Tissue content of 5-hylys, 4-hypro and total amino acids were reduced significantly by 50% in aneurysmal samples. CONCLUSIONS: beside confirming decreased elastin content in aneurysmal walls, these results show a concurrent increase of collagen cross-links. Since total collagen markers were decreased (decreased 4-hypro and 5-hylys) it is reasonable to suggest that in aneurysmal aortic walls old collagen accumulates cross-links while new collagen biosynthesis is somehow defective.     

Brachial Plexus Nerve Block Exhibits Prolonged Duration in the Elderly

Background: Upper limb trauma occurs frequently in elderly patients for whom peripheral nerve blocks are often preferred for anesthesia. The characteristics of such regional blocks have, however, never been described in an elderly population. Therefore, the authors assessed prospectively the onset and duration of upper extremity peripheral nerve block (the mid-humeral block) in elderly and young patients undergoing emergency upper extremity surgery.

Methods: Consecutive patients aged > 70 yr or < 70 yr received a mid-humeral block with a small volume of ropivacaine, 0.75%. Five milliliters was injected onto each of the musculocutaneous, radial, ulnar, and median nerves. Time to complete sensory and motor block and durations of complete sensory and motor block were assessed. Results are shown as median and its 95% confidence interval.

Results: Median ages were 77 yr (95% CI, 72-81 yr) and 39 yr (95% CI, 27-46 yr) in the two groups. Both groups had similar times to complete sensory blockade. The elderly group had longer durations of complete sensory (390 min [range, 280-435 min]vs. 150 min [range, 105-160 min];P < 0.05) and motor (357 min [range, 270-475 min]vs. 150 min [range, 90-210 min];P < 0.05) blockade. Duration of complete sensory block was significantly correlated with age ([rho] = 0.56;P < 0.05).     

Interleukin-3 dependent c-myc protein expression during the cell cycle of murine mast cells.

Aim of the study was to evaluate the relationship between the mitogenic stimulus interleukin-3 to normal murine mast cells and the cell cycle dependent expression of the nuclear c-myc protein. In order to do that on a cell by cell basis, we measured the nuclear c-myc protein simultaneously by flow cytometry, via specific monoclonal antibodies, and the DNA content via the intercalating dye propidium iodide. When cells were deprived from interleukin-3 (IL-3), proliferation was inhibited and the majority of cells arrested in early G1 (G1A, characterized by low c-myc content). Readdition of IL-3 resulted in a slow transition of cells from G1A to late G1 (G1B, at higher c-myc content) before DNA synthesis started. G1A cells with low c-myc content do not undertake DNA synthesis. Using a stathmokinetic methodology we confirmed that the G1A cells are early postmitotic G1 phase cells. The low content of c-myc within these cells appears a direct consequence of reduced c-myc levels during mitosis. Cumulatively, the data suggest that c-myc protein levels of murine mast cells fall at mitosis and that these levels must rise before cells can traverse the G1 phase. Our data are compatible with a model in which c-myc protein content of G1 phase cells has to reach a critical threshold before the cells can move further into the cell cycle.     

运动训练对雄性大鼠垂体─性腺轴功能的影响

本研究通过使用自己制造的大鼠流动水游泳池，对雄性大鼠进行了６周递增负荷的游泳训练，以此来探讨运动训练对大鼠垂体－性腺轴功能的影响，结果显示：与安静对照大鼠相比，训练大鼠的一般状态较差，血清睾酮水平显著降低（Ｐ＜０．０５），血清睾酮／皮质酮比值平均降低了３０％以上；而血清ＬＨ和ＦＳＨ水平未见明显变化。通过对大鼠睾丸组织ＬＨ／ＣＧ受体的测定，显示运动训练虽未引起其最大结合量的改变，却能使其解离常数显著升高（Ｐ＜０．０５）。提示此种训练可能通过降低睾丸ＬＨ／ＣＧ受体对垂体分泌ＬＨ的亲和力，从而影响睾酮的合成。