Epac-Rap1与糖尿病肾病

Epac-Rap1通路是蛋白激酶A经典通路以外cAMP重要的效应通路,它在肾脏中的广泛表达,能够增强肾脏血管内皮细胞的屏障功能,影响细胞的连接、黏附和迁移,对肾脏的生理活动起到不可或缺的作用.近年研究表明,Epac-Rap1信号通路激活下游信号级联系统,通过促进细胞肥大、介导肾间质纤维化、上调炎性反应细胞因子的表达,促进糖尿病肾病的病理生理改变.相关研究为理解糖尿病肾病状态下Epac-Rap1通路的作用拓宽了视野,有助于发现分子水平治疗糖尿病肾病的新靶点.     

结缔组织生长因子在糖尿病肾病中的作用研究进展

结缔组织生长因子具有促进细胞增殖分化、血管生成、基质合成积聚等作用,在糖尿病肾病导致肾小球硬化和肾小管间质纤维化的过程中起关键性作用.通过干预结缔组织生长因子可以缓解糖尿病肾病肾脏纤维化的进展.本文对结缔组织生长因子在糖尿病肾病发生发展中的作用进行综述.     

Rho/Rho激酶信号通路与糖尿病肾病

糖尿病肾病(DN)是糖尿病重要的微血管并发症之一,其发病机制是多种因素共同作用的结果.近年来发现Rho/Rho激酶(Rho/ROCK)信号通路与多种组织重构如血管、心肌、肾纤维化等相关.高糖能够刺激肾脏细胞内Rho/ROCK信号通路的激活,后者通过调控转录因子的DNA结合活性上调多种基因的表达,从而引起各种炎性反应及肾小球纤维化,而应用此信号通路选择性抑制剂后可明显改善DN的发生和发展,从而认为Rho/ROCK信号转导通路可能在DN的发病机制中起关键作用.     

Rho/Rho激酶信号通路与糖尿病肾病

糖尿病肾病(DN)是糖尿病重要的微血管并发症之一,其发病机制是多种因素共同作用的结果.近年来发现Rho/Rho激酶(Rho/ROCK)信号通路与多种组织重构如血管、心肌、肾纤维化等相关.高糖能够刺激肾脏细胞内Rho/ROCK信号通路的激活,后者通过调控转录因子的DNA结合活性上调多种基因的表达,从而引起各种炎性反应及肾...     

色素上皮衍生因子与糖尿病肾病

色素上皮衍生因子(PEDF)是丝氨酸蛋白酶抑制剂超家族成员之一,其主要生物学作用是营养神经、神经元保护、抗氧化应激、抗炎性反应、抑制新生血管形成等.越来越多的研究显示,PEDF在糖尿病肾病中可发挥独特的保护作用,如减少肾小球细胞外基质生成、预防肾脏纤维化,并通过抑制肾脏炎性反应和氧化应激反应而抑制肾小球毛细血管内皮细胞增生、调节血管的渗透性,从而减少尿蛋白的生成.因此,PEDF有望成为糖尿病肾病的一个治疗靶点.     

Vasohibin-1与糖尿病肾病

Vasohibin-1 (VASH-1)是一种以负反馈机制调节血管生成的内皮源性分泌蛋白.它能够以负反馈作用机制抑制血管内皮生长因子的作用,参与多种抗血管生成作用.作为机体的自我防御因子,VASH-1能够维持血管内皮的完整性,从而起到抵御糖尿病微血管并发症的作用.近年研究表明,VASH-1对肾小球内皮细胞和系膜细胞具有缓解微血管损害、调节炎性反应、延缓肾间质纤维化等重要功能,对糖尿病肾病具有重要的保护作用,可能成为糖尿病肾病早期治疗的一个新靶点.     

血管紧张素Ⅱ与糖尿病肾病的关系

糖尿病时 ,由于慢性高血糖症、血流动力学改变等原因使肾脏局部的血管紧张素Ⅱ (AgⅡ )活性往往增高。活性增高的AgⅡ通过直接或间接诱导转化生长因子 β(TGF β)表达 ,刺激肾脏局部单核细胞趋化蛋白 1(MCP 1)、纤溶酶原激活物抑制剂 1(PAI 1)的表达 ,促进肾小管间质成纤维细胞的增殖、分化 ,导致大量单核巨噬细胞浸润肾小球 ,细胞外基质 (ECM)成分合成增多、降解减少。这些病理过程在肾小球、肾小管间质硬化中起重要作用。阻断或拮抗AgⅡ、TGF β的活性及下游途径有助于防止、延缓糖尿病肾病的发生、发展     

二甲双胍对糖尿病肾病的保护作用

近年的一些实验及临床观察表明,二甲双胍对糖尿病肾病有着独立于降糖作用之外的保护作用.相关机制可能包括抑制线粒体氧化呼吸链复合体Ⅰ,激活AMP活化蛋白激酶(AMPK),改善肾脏的氧化应激、炎性反应和高滤过状态,抑制晚期糖基化终末产物(AGEs)的生成,减轻肾脏脂质沉积以及肾小球硬化和间质纤维化等.对于合并肾脏并发症,估算的肾小球滤过率(eGFR)大于30 ml/(min·1.73m2)的糖尿病患者,可应用二甲双胍治疗.     

血小板衍化生长因子-BB与糖尿病肾病

血小板衍化生长因子-BB(PDGF-BB)是PDGF经典的存在形式之一,其在肾脏中的作用主要包括诱导肾脏系膜细胞增生,促进细胞外基质积聚及单核-巨噬细胞在肾组织浸润。PDGF-BB在糖尿病肾病肾脏中表达增高,高水平的PDGF-BB可引起肾小球系膜细胞增生和细胞外基质积聚,亦参与肾小管及其间质改变,从而在糖尿病肾病的发生发展中起着重要作用。PDGF-BB还能通过诱导转化生长因子-β表达协同促进糖尿病肾病肾纤维化的发展。阻止PDGF-BB表达及其信号转导将有可能是糖尿病肾病的一种治疗手段。     

巨噬细胞与糖尿病肾病

糖尿病肾病是一种慢性炎性疾病,而巨噬细胞是重要的炎性细胞,在糖尿病肾病的发生、发展中起重要作用.血液中的单核细胞在选择素、细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)、单核细胞趋化蛋白-1(MCP-1)及骨桥蛋白等细胞黏附分子或趋化因子作用下经历滚动、黏附、迁移等过程,浸润于肾组织而分化成巨噬细胞,体内持续高血糖等因素使其活化,释放转化生长因子-β(TGF-β)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1、IL-6、IL-18等细胞因子,促进肾小球系膜细胞分泌细胞外基质及成纤维细胞增殖,引起系膜细胞外基质沉淀、肾小球硬化及间质纤维化等肾损伤,从而促进糖尿病肾病的发展.调控巨噬细胞的浸润与活化可能是防治糖尿病肾病的新途径.     

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.