MicroRNA-29与糖尿病及其并发症

小分子RNA(miR)是近年发现的一类广泛存在于动植物中的小分子非编码RNA,它通过抑制靶目标的转录或直接将其降解而发挥作用.miR-29是新近发现的与糖尿病及其并发症有密切关系的一类小分子RNA.研究发现,miR-29可直接参与糖尿病的基本病理生理过程,如参与胰岛素相关信号通路.同时也参与肾脏纤维化、视网膜神经元凋亡等过程,从而在糖尿病肾病、糖尿病视网膜病变等糖尿病并发症的发生中起重要作用.     

糖尿病肾病的表观遗传学机制

表观遗传学是指DNA序列不发生变化的情况下基因表达发生的可遗传的改变.大量的研究发现,表观遗传机制参与调控糖尿病肾病的肾脏纤维化、足细胞凋亡、慢性炎性反应、氧化应激等各个病理生理过程.     

糖尿病肾病的病理生理及危险因素

糖尿病肾病的病理生理及危险因素唐政综述关键词糖尿病肾病病理生理危险因素糖尿病肾病（ＤＮ）源于患者的糖代谢异常。然而，ＤＮ的确切发病机制尚不完全明了，可能有内在相互关联的多种因素参与，包括血流动力学的改变，糖代谢的异常及遗传体质因素等〔１〕。进一步明确...     

血管旁脂肪组织与糖尿病大血管病变

糖尿病大血管病变是糖尿病患者致死、致残的首要原因,其主要的病理基础为动脉粥样硬化,但其机制尚未完全阐明.血管旁脂肪组织可分泌众多脂肪细胞因子,研究发现它们不仅参与肥胖、胰岛素抵抗的病理生理过程,还可通过旁分泌和滋养血管分泌“由外至内”作用于血管壁,调节血管张力并参与动脉粥样硬化的发生、发展过程.对血管旁脂肪组织的深入研...     

糖尿病肾病及其防治

本文简述了糖尿病肾病的病理生理及病理改变,以及改善血糖控制,降低血压和饮食蛋白限制等措施对不同阶段糖尿病肾病的影响,指出早期检测和早期治疗是糖尿病肾病患者获得良好预后的关键。     

内皮素与糖尿病肾病关系的研究进展

内皮素是由21个氨基酸组成的血管活性肽,在人体许多组织和体液中广泛存在,它是目前已知作用最强且最持久的缩血管物质之一,参与多种疾病的病理生理过程。本文重点就内皮素与糖尿病肾病的关系以及干预治疗方面等研究进展作一综述。     

C肽与一氧化氮在糖尿病肾病中作用的研究进展

C肽、一氧化氮(NO)是糖尿病肾病病理演变的主要参与者,具有广泛的生物活性.本文对他们的分子结构、作用机制及其在糖尿病肾病中的病理演变过程进行综述,从细胞因子水平揭示多因素致病机制,为糖尿病肾病的防治提供新的思路.     

常用糖尿病肾病动物模型研究概述

糖尿病肾病是糖尿病进展到晚期阶段的一种微血管并发症,大约有20%~40%的糖尿病患者晚期会进展为糖尿病肾病。在全世界范围内,糖尿病肾病已经成为终末期肾脏病的主要原因。动物模型是研究糖尿病肾病发病机制和治疗方法的良好工具。目前常用的糖尿病肾病模型,都在病理生理上不同程度地模拟了人类糖尿病肾病的部分特征。但糖尿病肾病的研究并未取得可观的进展,其阻碍主要是目前尚无能够完全模拟人类糖尿病肾病所有特征的有效动物模型。本文主要从造模机制、病理生理、优缺点等方面出发,对目前常用的糖尿病肾病动物模型作一综述。     

糖尿病肾病的病理生理和病理

糖尿病肾病（ＤＮ）是糖尿病的主要长期并发症之一,其发病机理复杂,遗传易感性和长期高血糖状态导致的一些细胞因子及（或）生长因子的增多等因素可能参与其病理生理的改变。高血糖引起肾小球细胞外基质（ＥＣＭ）生成增多,降解减少及ＥＣＭ积聚导致的肾小球损伤,即为...     

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.     

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.     

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.     

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.     

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.