内收蛋白α亚单位遗传多态性与原发性高血压

人群中约30%～50%的血压变异是由遗传因素决定的〔1〕,与原发性高血压（EH）发病相关的遗传基因可能赋予个体对EH 的易感程度.目前的遗传流行病学研究提示,内收蛋白（adducin）基因可能是 EH(尤其是盐敏感性EH)的易感基因,因此该基因多态性与EH的相关性受到广泛关注.本文就内收蛋白α亚单位（α-内收蛋白）基因多态性在其与高血压及其靶器官损害的关系以及其与利尿药物的相互作用等方面的研究进行综述.     

刺激性三磷酸鸟苷结合蛋白α亚单位基因与国人原发性高血压相关研究

目的探讨刺激性三磷酸鸟苷结合蛋白α亚单位(Gsα)基因限制性内切酶(FokI)多态性与国人原发性高血压及其左心室结构之间的关系.方法采用多聚酶链反应限制性片断长度多态性(PCR-RFLP)方法检测78例健康人(正常对照组)和142例原发性高血压患者(高血压组)Gsα基因FokI多态性,超声测定患者的左心室结构.结果①高血压组Gsα基因FokI等位基因频率与正常对照组比较有显著性差异(P＝0.018);②高血压组不同基因型患者间的左心室后壁厚度有显著性差异(P＝0.040).结论提示Gsα基因FokI多态性与国人原发性高血压及其左心室后壁厚度相关.Gsα基因可能是原发性高血压的遗传因素.     

抗高血压药物的选择

国内外几个重要的高血压治疗指南(指南)将利尿剂、β-受体阻滞剂、钙通道阻滞剂(CCB)、血管紧张素转换酶抑制剂(ACEI)、血管紧张素Ⅱ受体拮抗剂(ARB)以及α-受体阻滞剂作为一线抗高血压药物。六大类抗高血压药物的广泛应用，使高血压治疗及控制状况得到改观，大大降低了全球心血管病发生和死亡的危险。但目前如何正确选择及合理使用抗高血压药物，更大程度地使高血压患者从抗高血压药物治疗中获益，是我们今后面临的重要任务之一。     

肾素血管紧张素系统基因多态性与血管紧张素转换酶抑制剂降压疗效的个体差异

原发性高血压是多因素疾病 ,发病率高 ,成人中约 2 0 %患有此病[1] 。它是冠心病、脑卒中、左室肥厚、急性心肌梗死等心血管疾病的独立危险因素。近年来 ,不同个体对抗高血压药物的反应性差异引起人们高度重视。研究发现 ,遗传因素与个体对药物反应的差异存在着密切联系 ,学者希望能根据每个病人基因特征来选择抗高血压药物 ,提高高血压的控制率 ,最终最大限度地降低其并发症发生率和病死率。近年关于肾素血管紧张素系统 (ＲＡＳ)基因多态性与个体对血管紧张素转换酶抑制剂 (ＡＣＥＩ)类药物降压疗效差异的研究已成为抗高血压药物研究的新热…     

肿瘤坏死因子α基因G-308A多态性与高血压相关性

目的探讨肿瘤坏死因子α(TNFα)基因G-308A多态性与高血压的相关性.方法放免法检测114例高血压患者和114健康对照者血浆TNFα水平,应用聚合酶联反应-限制性片段长度多态性(PCR-RFLP)方法检测TNFα基因G-308A多态性.结果与健康对照者相比较,高血压患者血浆TNFα水平增高(P<0.01);而TNFα基因G-308A基因型和等位基因的分布,高血压患者和健康对照者相比较无显著意义(P>0.05);高血压患者基因型间血浆TNFα水平、血压值比较无统计学差异(P>0.05).结论 TNFα基因G-308A多态性与高血压无关.     

肿瘤坏死因子α基因G-308A多态性与高血压相关性

目的　探讨肿瘤坏死因子α(TNFα)基因G 30 8A多态性与高血压的相关性。方法放免法检测 114例高血压患者和 114健康对照者血浆TNFα水平 ,应用聚合酶联反应 -限制性片段长度多态性 (PCR RFLP)方法检测TNFα基因G 30 8A多态性。结果与健康对照者相比较 ,高血压患者血浆TNFα水平增高 (P <0 0 1) ;而TNFα基因G 30 8A基因型和等位基因的分布 ,高血压患者和健康对照者相比较无显著意义 (P >0 0 5 ) ;高血压患者基因型间血浆TNFα水平、血压值比较无统计学差异 (P >0 0 5 )。结论TNFα基因G 30 8A多态性与高血压无关。     

遗传基因多态性对药物疗效的影响

药物进入体内与其相关的药物转运蛋白、药物代谢酶、药物作用靶点相互作用,完成药物的效应和代谢动力学过程。编码药物代谢酶和靶点蛋白的基因称为药物相关基因,其与药物效应密切相关;如果药物相关基因缺失、单核酸多态性或基因重复等分子改变,可引起药物代谢酶、药物作用靶点和药物转运蛋白水平发生药物反应的遗传差异,导致体内药物代谢改变,影响药效。     

高血压基因多态性的相关研究及其进展

<正>随着经济的发展和生活水平的提高,高血压的患病率在我国逐年提高。尤其在中老年人群中,高血压也是其他心、脑血管疾病的主要诱因。原发性高血压的发病不仅与环境因素、生活习惯等因素密切相关,还具有明显的家族聚集性,这可能与基因的显性遗传和多基因关联遗传有关。因此,遗传因素也是原发性高血压重要的发病机制,研究高血压的基因多态性不仅可以进一步明确高血压的发病机制,还可以帮助临床上更有效的选择降压药物及指导治疗。高血压的遗传研究主要以单核苷酸多态性(SNPs)为主[1],高血压基因的SNP研究目前主要有     

肾素基因多态性与高血压

随着心脑血管病遗传因素研究的不断深人,肾素-血管紧张素系统(RAS)基因多态性与高血压的关系越来越受到人们的重视.肾素作为该系统的重要组成成分,在心脑血管病遗传学研究中备受关注,其基因多态性成为高血压、冠心病和卒中等多种疾病的候选基因.     

药物代谢酶与肝癌

研究显示,药物代谢酶基因多态性与肝癌的发生和治疗有密切关系。本文参考文献,对药物代谢酶多态性与肝癌易感性及抗肝癌药物的关系综述如下。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.