肠道微生态变化与非酒精性脂肪性肝病研究进展

由定植于肠道的大量固有菌群、肠道上皮细胞及肠道局部粘膜免疫系统组成了肠道微生态系统。"肝-肠轴"概念的提出为从肠道微生态角度寻找非酒精性脂肪性肝病(NAFLD)的诊疗措施提供了依据。肠道微生态失衡所致的肠道菌群过度生长、肠黏膜通透性改变、免疫功能紊乱、肠源性内毒素血症、效应细胞激活及炎症因子生成等在NAFLD发生发展中发挥了不容忽视的作用。深入研究肠道菌群与NAFLD之间的关系将为NAFLD的预防和治疗提供新靶点。     

慢性消化病患者肠黏膜屏障功能障碍与肠道微生态失衡的关系

肠黏膜屏障功能障碍（IBF）是肠道微生态改变和肠内炎性物质相互作用的后果,可造成肠壁通透性增加,导致肠道细菌或其毒性代谢产物向肠外易位.肠道菌群失调和肠道通透性增加可能是细菌移位的两个主要原因.由于肠道通透性和肠道微生态临床上都缺乏客观、准确的检测方法,既无法确定一个科学的IBF的诊断标准,也很难明确肠道微生态失衡与IBF的关系.本研究试图通过对多种慢性消化病患者肠道通透性和肠道菌群的测定,以探讨IBF与肠道微生态失衡的关系.     

饮食对非酒精性脂肪性肝病患者肠道菌群的影响

非酒精性脂肪性肝病(NAFLD)是常见的慢性肝病,肠道菌群通过"肠肝轴"与肝脏相互作用,其与NAFLD的发生和发展密切相关。近年来越来越多的研究揭示了饮食因素在肠道微生态改变和NAFLD发病中的作用。该文综述了膳食胆碱、脂肪、果糖、膳食纤维和蛋白质等饮食因素对肠道菌群的影响及其与NAFLD的关系,以期为进一步探讨饮食干预防治NAFLD提供依据。     

肠道微生态与肠易激综合征:基础与临床

肠道微生态与功能性胃肠病(FGIDs)的关系已成为目前研究热点之一。最新罗马Ⅳ标准指出FGIDs不仅仅是胃肠道疾病,脑-肠互动障碍可能贯穿肠易激综合征(IBS)发病的始终。肠道微生态失衡被认为是导致脑-肠互动障碍的重要始动因素,参与构成菌群-肠-脑轴,成为新兴研究热点。尤其是在IBS的研究中,肠道微生态失衡已被证实与IBS免疫异常和临床症状相关;使用益生菌调节IBS肠道菌群取得良好成效,其他相关菌群干预策略也在不断探索中。     

肠道微生态失衡理论的研究现状

肠道微生态包括肠道内微生物通过复杂的代谢活动影响宿主的生理、心理及病理活动,肠道微生态失衡与疾病的发生发展密切相关。本文主要从肠黏膜屏障理论、肠肝轴理论等方面,对目前肠道微生态失衡的研究做一综述,以初步分析当前肠道微生态失衡对常见肝病发生、发展的影响,为进一步对常见肝病的临床和基础研究提供理论指导。     

慢性肾功能衰竭患者肠道微生态变化及微生态制剂疗效观察

目的 :探讨慢性肾功能衰竭 (CRF)患者肠道微生态的变化及其与肾功能的关系 ,观察微生态制剂 (回春生 )治疗CRF的可行性。方法 :对CRF患者主要肠道菌群 (肠杆菌、肠球菌等需氧菌 ,双歧杆菌、类杆菌、乳杆菌等厌氧菌 )行定量培养 ,并检测肾功能 ;比较治疗前后肠道菌群、临床表现以及肾功能的变化。结果 :CRF患者普遍存在肠道微生态平衡的紊乱 ,主要体现在需氧菌群过度增殖 ,厌氧菌群明显受抑 ,且与肾功能状况明显相关 ;微生态制剂有助于改善此种失衡 ,促进临床表现与肾功能的改善。结论 :肠道微生态失衡参与了CRF的发展、恶化过程 ,微生态制剂可能为CRF的治疗提供一条新的途径。     

肠道微生态在非酒精性脂肪性肝病发病机制中的研究进展

NAFLD已成为当今发达国家和中国富裕地区慢性肝病的首要病因。近年来研究显示,肠道微生态失衡在NAFLD发病中起重要作用。肠道微生态构成和功能改变可以通过影响能量吸收和储存、产生肥胖、促进胰岛素抵抗、胆碱缺乏、干扰胆汁代谢、产生内源性乙醇等机制影响物质代谢,通过SIBO改变小肠动力及促进炎症因子吸收,这些均与NAFLD发生或从单纯脂肪性肝病进展至NASH有关。肠黏膜通透性改变、肠源性内毒素血症、肝细胞或Kupffer细胞激活及促炎因子生成在NAFLD及NASH的发生中起到核心作用。NAFLD进展到一定阶段后．又会反过来影响肠道微牛态的平衡．最终两者形成恶件循环．     

肠道微生态在放射性肠炎防治中的研究进展北大核心CSCD

放射性肠炎是放射治疗引起的肠道并发症。辐射引起肠道微生态改变、肠黏膜屏障破坏,肠道共生微生物及其代谢产物通过影响肠道黏膜屏障免疫功能在辐射损伤和辐射抗性中发挥一定作用。以肠微生态为靶点的微生态制剂和菌群移植可能为预防和治疗放射性肠炎提供新的方向。     

肠道微生态在放射性肠炎防治中的研究进展

放射性肠炎是放射治疗引起的肠道并发症。辐射引起肠道微生态改变、肠黏膜屏障破坏, 肠道共生微生物及其代谢产物通过影响肠道黏膜屏障免疫功能在辐射损伤和辐射抗性中发挥一定作用。以肠微生态为靶点的微生态制剂和菌群移植可能为预防和治疗放射性肠炎提供新的方向。     

肠道微生态改变在炎症性肠病中的作用

炎症性肠病（IBD）主要包括溃疡性结肠炎（UC）和克罗恩病（CD），其病因和发病机制尚未明确。目前认为IBD的病因为肠道微环境（肠道菌群）、宿主遗传易感性和黏膜免疫因素三者间的相互作用。近年来．随着微生态学的发展，肠道菌群与IBD发病的关系日益受到关注。本文就IBD时肠道菌群的变化、肠道微生态改变对IBD的影响以及微生态制剂对IBD的治疗作用作一综述。     

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.     

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.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.