肥胖患者体脂分布与肾脏损害的关系

目的:探讨肥胖患者体脂分布特点与肥胖相关性肾病(ORG)的发生及其进展中的关系。方法:对照研究30例经肾穿刺活检明确诊断的ORG患者和19例无肾脏损伤的单纯性肥胖患者,借助CT测量两组患者腹部脂肪的面积;采用B超测量肾周脂肪厚度,检测、记录胰岛素抵抗水平和肾小球滤过率以及体重指数、血脂等相关指标。并根据CT测定的内脏脂肪面积,将ORG患者分为3组,分别比较各组临床、病理和代谢异常的指标。结果:ORG患者全部(100%)表现为腹型肥胖,单纯肥胖患者中腹型肥胖仅占78·9%;前者内脏脂肪的面积约为后者的1·3倍。腹型肥胖导致ORG发生的风险是外周型肥胖患者的8·0倍。ORG空腹血糖(P<0·05)、胰岛素水平(P<0·05)和胰岛素抵抗水平(P<0·01)明显高于单纯肥胖患者。ORG总胆固醇水平高于单纯肥胖患者(P<0·05),但三酰甘油及高/低密度脂蛋白水平彼此间无明显差异。随着内脏脂肪面积的增大,ORG三组患者尿蛋白排泄量[(0·89±0·41),(1·47±0·69)和(2·25±1·23)g/24h]、局灶节段性肾小球硬化(40%,50%和100%)的比例明显增加(P<0·05,ANOVA)。与之相对应的是,肾小球滤过率、胰岛素抵抗程度亦随着内脏脂肪面积的增大而增加(P<0·05,ANOVA),脂质代谢差异不显著。C反应蛋白水平随内脏脂肪面积的增加有升高的趋势(P>0·05,ANOVA);而肾周脂肪厚度间无明显差别。结论:腹部脂肪的堆积不仅与ORG的发生,还与该病的进展密切相关。其中血流动力学异常和胰岛素抵抗可能起主要的作用。     

肥胖与高血压

肥胖和高血压均为常见病多发病，其发病率均呈上升趋势。肥胖是高血压的一个独立危险因素。肥胖与高血压共同的病理生理基础主要为胰岛素抵抗，交感神经系统（SNS）的过度激活，肾素-血管紧张素-醛固酮系统（RAAS），水钠潴留，以及leptin水平等。治疗上除行为干预外，不仅要选择合适的减肥药和降压药，同时要使用改善机体胰岛素敏感性的药物。     

肥胖相关性肾病的研究进展

随着人们饮食习惯及生活方式的改变,肥胖症发病率逐年升高,肥胖已成为世界关注的热门话题,1997年世界卫生组织(WHO)将肥胖明确为1种疾病。体重指数(BMI)是诊断肥胖的标准。BMI在24.0kg/m2~24.9kg/m2为超重,≥28为肥胖[1]。肥胖不仅是糖尿病、冠心病、高血压、睡眠呼吸暂停综合症及胰岛素抵抗(IR)的高危因素,还可能导致肾脏损害[2]。由肥胖引起的肾脏损害统称为肥胖相关性肾病(ORG)。近年来国内陆续报道关于ORG的病例后[3],临床医师对此病的认识不断提高。ORG临床表现通常隐匿起病,以蛋白尿为主,部分患者可出现镜下血尿。ORG的病理…     

肥胖相关性肾病现状

肥胖相关性肾病(ORG)以无症状蛋白尿为主要临床表现，其突出的病理改变为肾小球明显肥大，其发病机制尚未完全明确，主要以血液动力学改变、肾素-血管紧张素-醛固酮系统(RAAS)过度激活、胰岛素耐受、脂肪因子分泌异常、脂代谢紊乱及脂毒性等为主。诊断需排除其他肾脏疾病。目前缺乏特效疗法，以综合疗法为主。主要的治疗方法包括减肥手术、RAAS抑制剂、钠-葡萄糖协同转运蛋白(SGLT)2抑制剂和胰高血糖素样肽(GLP)-1受体激动剂，同时治疗各种共病，如糖尿病、高血压病、高血脂症、高尿酸血症等。     

肥胖相关性肾病患者流行病学资料及临床病理特征分析

目的:探讨中国肥胖相关性肾病(ORG)患者的临床、病理及流行病学特征. 方法:回顾性分析2002年2月至2006年11月在本研究所经肾活检确诊的90例ORG患者的临床、实验室指标和组织形态学特点.并据体重指数(BMI)将研究对象分为三组进行比较:轻度肥胖组(BMI 28.0～＜30 kg/m2)、中度肥胖组(BMI 30～＜35 kg/m2)和重度肥胖组(BMI≥ 35 kg/m2). 结果:肾活检的ORG比例为0.89%,并且在研究观察的5年间由0.62%上升至1.0%(P＜0.05).ORG患者的平均年龄为(37.5±9.26)岁,以18～44岁青年人为主,男性患者占67%.ORG患者BMI 31.2 kg/m2,100%为腹型肥胖.其中,轻度肥胖、中度肥胖和重度肥胖的患者分别占49%、37%和14%.ORG患者的平均尿蛋白为(1.48±1.2)g/24h,少量蛋白尿者(0.4～1.0 g/24h)占51.1%,大量蛋白尿者(＞3.5 g/24h)占10%,表现为典型肾病综合征者仅2例(2.22%).此外,42.2%患者有肾小球高滤过,6.67%有肾功能减退.除肾脏受累外,ORG患者同时合并多种代谢紊乱,88.1%有胰岛素抵抗,75.0%有脂代谢异常及63.1%有高血压.ORG的组织形态学特征是肾小球体积增大,70%合并局灶节段性肾小球硬化(FSGS),并以"经典型"节段硬化为主.电镜下,足突宽度增加,35.6%出现节段足突的融合.随着BMI的增加,ORG患者的蛋白尿水平(P＜0.05)、肾小球滤过功能(P＜0.05)及足突宽度(P＜0.05)显著增加. 结论:中国人群中,ORG的发病率正呈现快速上升趋势;该组患者以青年男性多见,主要表现为轻度、腹型肥胖,少量蛋白尿,代谢紊乱以及肾脏高滤过和FSGS.     

肥胖相关性肾病患者胰岛素抵抗状态评估指标的分析

目的:以胰岛素抵抗指数(HOMA-IR)作为标准评价肥胖相关性肾病(ORG)患者胰岛素抵抗(IR)状态,并探讨血脂评估ORG患者个体IR的价值。方法:选取经临床和肾脏病理证实的ORG患者36例,健康体检的正常人266例作为对照(空腹血糖<6·1mmol/L,且BMI<25kg/m2),测定两组人群的空腹血糖、胰岛素、总胆固醇(Chol)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,计算HOMA-IR以评价ORG患者的IR状态。分析ORG人群的Chol、TG、HDL-C、LDL-C、TG/HDL-C比值与HOMA-IR的相关关系。结果:ORG患者的HOMA-IR平均值为6·32±4·11,显著高于对照组(1·98±0·89,P<0·001)。ORG的Chol、TG、TG/HDL-C比值较对照组显著升高,HDL-C显著降低(P<0·01),LDL-C升高(P<0·05)。其中以TG、TG/HDL-C比值升高更明显。Chol、TG、HDL-C、LDL-C、TG/HDL-C比值与HOMA-IR相关系数分别为0·195、0·122、-0·045、-0·019、0·143,均无统计学差异(P>0·05)。结论:HOMA-IR作为评估IR的指标同样适用于ORG患者。虽然血脂水平也被用于IR的评估,但对于ORG患者并不是理想指标。     

脂肪肾素-血管紧张素-醛固酮系统与肥胖及其相关疾病

脂肪肾素-血管紧张素-醛固酮系统(RAAS)主要存在于白色脂肪组织,表达RAAS的所有成分,具有独立调节功能.游离脂肪酸增多可使脂肪RAAS过度激活,脂肪RAAS中活性成分血管紧张素Ⅱ及醛固酮可导致脂肪细胞异常分化、脂代谢异常、胰岛素敏感性下降、炎性反应加重,从而参与肥胖及其相关疾病的发生、发展.下调过度激活的脂肪RAAS可能是治疗肥胖及其相关代谢性和炎性反应性疾病的新靶点.     

肥胖、高血压与心脏

肥胖是指身体的脂肪过多 ,可定义为超过理想体重的 2 0 % ,可是肥胖者游离脂肪酸较相同体重的瘦者为多 ,因此使用理想体重来定义肥胖可能会造成误导 ,目前主张采用体质指数 (BMI)来确定肥胖 ,即男性BMI>2 7.8kg/ m2 ,女性 BMI>2 7.3kg/ m2。尽管对肥胖者中高血压的发生情况有所争议 ,但肥胖与高血压之间的关系已较明确。1　肥胖性高血压的发病机理内分泌 ,遗传和新陈代谢机制与肥胖性高血压的发生有关 ,包括胰岛素抵抗 (IR) /高胰岛素血症 ,交感神经系统 (SNS)的过度激活 ,肾素 -血管紧张素 -醛固酮系统 (RAAS) ,水钠潴留 ,遗传机制…     

肥胖诱导胰岛素抵抗机制研究进展

<正>研究显示,肥胖尤其是腹型肥胖是胰岛素抵抗(IR)的独立危险因素,目前已证实体脂的堆积与胰岛素抵抗、2型糖尿病、代谢综合征等疾病的发病极为相关〔1〕。生理条件下,胰岛素在细胞表面结合并激活胰岛素受体,诱导胰岛素受体底物-1/2(IRS-1/2)磷酸化,磷酸化的IRS-1与蛋白质磷脂酰肌醇-3激酶(PI-3K)结合并使其激活,继而激活下游的蛋白激酶B     

过氧化物酶体增殖物激活受体γ与肥胖

过氧化物酶体增殖物激活受体 (PPAR)γ与胰岛素抵抗、脂肪细胞分化和肥胖有密切关系。PPARγ2是前脂肪细胞分化为成熟脂肪细胞以及脂肪细胞内甘油三酯蓄积的重要调节因子。PPARγ为噻唑烷二酮类 (TZD)药物的靶分子 ,长期应用TZD类药物可能会引起体重增加 ,加重代谢紊乱。近年研究显示PPARγ抑制剂可抑制肥胖和改善胰岛素抵抗。PPARγ激动剂和抑制剂与肥胖及胰岛素抵抗的关系需要进一步研究。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

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.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

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.     

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.