单核细胞趋化蛋白-1与糖尿病肾病

糖尿病肾病(DN)是终末肾功能衰竭的主要原因,主要的病理改变是肾小球肥大、细胞外基质积聚以及肾小球硬化.多种机制参与了DN的发生、发展,其中肾脏被炎性反应细胞如单核/巨噬细胞浸润是DN的标志之一.单核细胞趋化蛋白-1(MCP-1)是一种对单核细胞具有特异趋化功能的细胞因子,参与单核/巨噬细胞的浸润,在DN的发生、发展中起重要作用.     

糖尿病肾病患者血清MMP-2水平检测及临床意义

目的 探讨血清基质金属蛋白酶-2(MMP-2)在糖尿病肾病(DN)发生、发展中的作用.方法 将60例2型糖尿病患者分为单纯组(单纯糖尿病)、非肾衰组(DN不伴慢性肾衰竭)、肾衰组(DN伴慢性肾衰竭)各20例,另选20例健康者作为对照组,采用ELISA法测定四组血清MMP-2水平.结果 三个糖尿病组MMP-2水平均较对照组降低,非肾衰组较肾衰组升高.结论 DN血清MMP-2水平下降与DN的发生及发展有关,MMP-2可能参与DN细胞外基质纤维化.     

糖尿病肾病患者体内细胞间黏附分子-1含量测定

近期研究提示，可溶性细胞间黏附分子一1(sICAM一1)在糖尿病肾病(DN)中的表达量增加，是DN免疫反应和炎性反应的物质基础之一。在糖尿病微血管病变中起一定作用。我们检测2型DN患者体内sICAM-1含量，旨在探讨sICAM是否可作为反映DN病变程度的指标。     

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.     

2型糖尿病患者血清hs-CRP、TNF-α和Hcy水平及与糖尿病肾病的关系

目的 探讨2型糖尿病(T2DM)患者血清超敏C反应蛋白(hs-CRP)、TNF-α和同型半胱氨酸(Hcy)的变化及与糖尿病肾病(DN)的关系.方法 将80例T2DM患者分为单纯糖尿病组25例、早期DN组29例、临床DN组26例,另选择25例健康体检者作为对照组,分别采用免疫散射比浊法检测血清hs-CRP水平,放射免疫法测定TNF-α水平,化学分光法检测Hcy水平.比较四组血清hs-CRP、TNF-α和Hcy水平与DN的关系.结果 DN患者血清hs-CRP、TNF-α和Hcy水平均明显高于正常对照组(P均＜0.05).结论 hs-CRP、TNF-α和Hcy在DN的发生、发展中起重要作用,其水平与DN的程度呈一致性,三者可作为DN病情的监测指标.     

活性氧簇及抗氧化治疗与糖尿病肾病

糖尿病肾病(DN)是最严重的糖尿病并发症之一.目前,越来越多的证据证明了活性氧簇(ROS)在DN的发生和发展中扮演着重要的角色.本文简述了DN中ROS调节的信号通路,包括高糖介导ROS产生的机制、ROS活化信号转导通路、ROS与糖尿病肾脏基质的重构;抗氧化治疗对DN作用的评价以及ROS在DN发病机制中有争议的观点等几个问题.糖尿病患者体内存在的多种代谢紊乱都会导致氧化应激、ROS增加,使一些信号通路如丝裂原活化蛋白激酶(MAPK)通路活化增加而导致DN的发生和发展.这为抗氧化治疗是否能成为预防和治疗DN的新策略提供了一定依据.     

肿瘤坏死因子-α与糖尿病肾病

肿瘤坏死因子(TNF)-α是重要的炎性反应因子,越来越多的证据显示其参与糖尿病肾病(DN)的发生.TNF-α通过多种机制引起DN肾脏损伤,包括损伤肾小球通透屏障,改变肾脏局部血流动力学,促进系膜细胞增殖及系膜外基质沉积,正调节免疫炎性反应,诱导细胞凋亡等.目前针对其活性的调节已成为临床治疗DN的一个新策略,研究较广泛的...     

PDGF与糖尿病肾病

血小板源性生长因子(PDGF)主要通过自分泌、旁分泌及内分泌作用参与糖尿病肾病(DN)的发生、发展.PDGF-BB在糖尿病肾脏局部高表达,与转化生长因子协同促进肾小球系膜细胞增生及细胞外基质的合成,导致糖尿病肾小球硬化的发生,而应用阻止PDGF-BB表达的方法则可有效防止DN的发生.     

叶酸、维生素B12与高同型半胱氨酸血症及2型糖尿病肾病的相关性

糖尿病肾病(DN)是糖尿病(DM)的慢性微血管并发症,是DM 病人致死、致残率较高的原因之一.近年来大量基础性研究已解释高同型半胱氨酸(HCY)血症在DN发病过程中的生物学作用及血浆HCY水平与肾功能损害状况的平行性,且流行病学研究也证实了两者之间的相关性,可见高血糖作为DN发生发展的关键因素,而高HCY血症则是重要的加重危险因素之一[1～3].     

早期糖尿病肾病患者144例外周血白细胞检测及临床意义的关系

糖尿病肾病(DN)是糖尿病的主要远期并发症,也是导致终末期肾病的主要原因之一,其发生机制目前尚未完全阐明.近年来,在对一些炎症因子与微循环关系的研究中发现,炎症反应在DN发生、发展中发挥了重要作用[1],但炎症与早期DN的研究报道较少.白细胞是机体防御系统的重要组成部分,是炎症反应的标志.本文通过对2型糖尿病(T2DM)患者及早期DN患者进行外周血白细胞计数(WBC)观察,以进一步探讨炎症与DN的关系.     

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.