足细胞和糖尿病及其肾病

肾小球足细胞损伤和丢失是肾小球硬化形成和发展的关键因素。糖尿病时足细胞可出现密度和数量减少、足突增宽、足细胞脱落等改变,且可从尿中丢失,继而导致糖尿病肾病的发生。高血糖、高血压、氧化应激及一氧化氮等可直接损伤足细胞,并抑制α3β1整合素、nephrin的表达,促进血管内皮生长因子、Ⅳ型胶原、糖基化终末产物受体、转化生长因子β等的表达而加重足细胞损伤。因而,探索足细胞损伤在糖尿病肾病发生、发展中的病理发展过程对糖尿病肾病的防治具有重要意义。     

糖尿病肾病足细胞损伤的表观遗传调控

表观遗传修饰是糖尿病肾病的重要机制之一,足细胞损伤是疾病进展的核心事件。不同表观遗传修饰方式可通过单独作用或交叉对话,改变足细胞结构和功能、促进足细胞凋亡及上皮间充质转化、影响足细胞自噬,以及参与足细胞内质网应激和线粒体功能障碍等过程,参与足细胞损伤。表观遗传是可逆的,通过治疗干预改变表观遗传修饰可能是防治糖尿病肾病的一个重要方向。     

足细胞与糖尿病肾病关系的若干研究进展

足细胞在维持肾小球滤过屏障完整性及限制血浆蛋白的滤出方面发挥重要作用,足细胞的损伤可部分解释肾小球滤过屏障结构及功能的改变的原因。在糖尿病肾病早期,足细胞损伤已出现,并可进一步导致。肾脏损伤。本文就足细胞与糖尿病肾病中若干研究进展作简要综述。     

足细胞和糖尿病及其肾病

肾小球足细胞损伤和丢失是肾小球硬化形成和发展的关键因素。糖尿病时足细胞可出现密度和数量减少、足突增宽、足细胞脱落等改变，且可从尿中丢失，继而导致糖尿病肾病的发生。高血糖、高血压、氧化应激及一氧化氮等可直接损伤足细胞，并抑制α3β1整合素、nephrin的表达，促进血管内皮生长因子、Ⅳ型胶原、糖基化终末产物受体、转化生长因子β等的表达而加重足细胞损伤。因而，探索足细胞损伤在糖尿病肾病发生、发展中的病理发展过程对糖尿病肾病的防治具有重要意义。     

足细胞能量代谢调节因子与糖尿病肾病

足细胞结构和功能异常是糖尿病肾病(DN)发生蛋白尿并不断进展的重要原因.足细胞主要通过糖酵解供能,而线粒体稳态对于足细胞正常发挥生物学功能极为重要.研究发现,糖尿病时足细胞胰岛素敏感性下降,线粒体功能障碍进而导致足细胞能量利用障碍和足细胞损伤.AMP激活的蛋白激酶(AMPK)/沉默信息调节因子1(SIRT1)/过氧化物...     

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.     

血管内皮生长因子与糖尿病肾病足细胞损伤的研究进展

肾病是糖尿病（DM）主要并发症之一。传统上糖尿病肾病（DN）研究主要集中在肾小球系膜细胞损伤机制上，足细胞损伤被认为是由日益增加的蛋白尿所引起的后期病变，而不是导致DN的原因。然而，最近人体活组织检查研究表明，DN发病过程中足细胞功能及结构上的损伤早期已出现。足细胞损伤发生发展过程中一些细胞因子的变化起着重要作用，其中血管内皮生长因子（vascular endothelial growth factor，VEGF）与足细胞损伤之间的关系最近成为研究热点,本文拟就DN时VEGF与足细胞损伤的相互关系做一综述。     

RANTES与糖尿病及其血管并发症

调节活化正常T细胞表达与分泌的趋化因子（regulated upon activation,normal T-cell espressed and secreted,RANTES）与其特异性受体结合后,可趋化炎症细胞和炎症因子到达胰腺组织,损伤胰岛β细胞功能,促进糖尿病的发生.研究发现,RANTES在糖尿病大血管及微血管内皮表面表达增加,其与黏附分子相互作用后,可激活白细胞释放多种炎症因子,诱导炎症反应及血管内皮细胞、成纤维细胞和平滑肌细胞的增殖,从而参与糖尿病大血管及微血管并发症的发生、发展.     

2型糖尿病患者尿液mindin水平与糖尿病肾病的相关性

目的探讨2型糖尿病（T2DM）患者尿液mindin的表达,分析其与糖尿病肾损伤的关系。方法选取2010年10月至2011年6月于广西医科大学第一附属医院代谢糖尿病中心及内分泌科住院的T2DM患者124例为病例组,选取同期年龄、性别匹配的健康体检者30名作为对照组。根据24h尿白蛋白定量（24h-UAE）将T2DM患者分为3组,即24h—UAE〈30mg的正常蛋白尿组60例,30mg≤24h-UAE〈300mg的微量蛋白尿组32例,24h-UAE≥300mg的大量蛋白尿组32例。应用ELISA法测定尿液mindin的水平,常规方法测定血、尿肌酐、血尿素氮、胱抑素C、空腹及餐后血糖、糖化血红蛋白（HbA1c）、C-肽等临床指标,并估算肾小球滤过率（eGFR）。组间比较采用单因素方差分析及q检验,指标间的相关分析采用Spearman相关分析及偏相关分析。结果T2DM患者尿mindin含量高于对照组f正常蛋白尿组、微量蛋白尿组、大量蛋白尿组、对照组分别为161（119～255）、332（181—445）、426（230—937）和93（51—121）ng·ml^-1·μmol^-1·L^-1,F=30．196,P〈0．05],并与24h-UAE呈正相关（r=0．453,P〈0．05）,T2DM患者各组mindin水平随24h-UAE的升高而递增;相关分析显示尿mindin与尿素氮、血肌酐、胱抑素C、血糖、24h-UAE、病程呈正相关（r=0．426、0．2336、0．383,0344、0．453、0．511,均P〈0．05）,而与eGFR呈负相关（r=-0．383,P〈0．05）;结果显示尿液mindin（OR=1．481,95％CI：1.187—1．847）、空腹血糖（OR=0．842,95％CI：0．756～0．939）、舒张压（OR=1．051,95％CI：1．003～1．101）是T2DM患者肾损伤的危险因素。结论尿液mindin可反映糖尿病肾病早期肾功能损伤并与肾功能损伤的程度相关,尿液mindin的检测对糖尿病肾病患者早期诊断、病情观察、疗效判断方面具有较好的临床应用前景。     

12/15-脂加氧酶与糖尿病微血管并发症

最近研究发现,12/15-脂加氧酶的过表达或激活可能促进了糖尿病肾病和神经病变的进展.该酶可催化花生四烯酸产生12-羟基二十碳四烯酸和15-羟基二十碳四烯酸,从而影响细胞结构、代谢和信号转导.研究发现12/15-脂加氧酶及其代谢产物可直接诱导或间接调节细胞因子导致细胞肥大、增殖和细胞外基质堆积,参与糖尿病肾病的发生.此外,该酶的过表达和激活与外周神经系统的氧化-硝化应激相关,可能参与糖尿病神经病变的发生.因此,12/15-脂加氧酶抑制剂或包含抑制剂的联合治疗可能为糖尿病微血管并发症的治疗提供新的研究方向.     

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.     

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.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.