C-C亚族趋化因子与糖尿病肾病

C—C亚族趋化因子大部分由激活的T细胞和单核细胞产生,主要包括单核细胞趋化蛋白（MCP）-1和正常T细胞活化后表达和分泌的调节蛋白（RANTES）。MCP-1和RANTES是单核／巨噬细胞的特异性趋化因子,在糖尿病肾病（DN）肾组织中表达增加。高水平的C—C趋化因子通过与其受体结合介导单核／巨噬细胞在肾组织的募集和分化,导致肾小球系膜细胞增生,细胞外基质积聚及肾小管纤维化。阻止C—C趋化因子表达将有可能为治疗DN开辟一条新的途径。     

鼻息肉组织中补体C3、C4、C1q的表达及意义

采用免疫组化SABC法检测补体C3、C4和C1q在30例鼻息肉（NP）和14例正常下鼻甲组织中的表达，对C3、C4和C1q。表达阳性细胞的类型、分布进行分析。结果显示，C3、C4和C1q。在NP组织中的阳性表达率分别为76．67％、66．67％、63．33％，在下鼻甲组织中分别为21．43％、21．43％、14．29％，两者相比，P均〈0．01；C3、C4和C1q。主要表达于NP的上皮细胞及炎性细胞中。认为补体C3、C4和C1q。在NP的发生、发展中起着重要作用。     

内皮蛋白C受体、加强蛋白C与肺部疾病的关系

内皮蛋白C受体（EPCR）是新近分离纯化的蛋白，作为蛋白C抗凝系统中新的一员，其在加强蛋白C（APC）活化和调节炎症反应方面有着重要作用。EPCR介导的活化的PC在急性肺损伤、肺纤维化和支气管哮喘等肺部炎症性疾病中具有重要意义，是未来研究的方向之一。     

Cronkhite—Canada综合征

本综合征于1955年由Cromkhite和Cana-da最先报告,故目前国际上统一称为Cronkhite-Canada syndrome(简称CCS).CCS的临床特征是患者有胃肠道多发性息肉、重度腹泻、低蛋白血症,同时伴有外胚层某些器官的发育障碍或退化提前,如毛发脱落、皮肤色素沉着和指(趾)甲萎缩等,国内学者通常称之为胃肠道息肉病-秃发-色素沉着-指甲萎缩综合征或多发性消化道息肉综合征.     

乙型肝炎病毒前C／C变异与病变进展

为探讨病毒变异与慢性乙型肝炎病变持续和加重的关系，对乙型肝炎病毒前Ｃ／Ｃ区段经聚合酶链反应后直接序列分析。１１例轻重不等的乙型肝炎病毒ｅ抗体阳性病人中均发现前Ｃ区第２８位成为终止密码；１８例乙型肝炎病毒ｅ抗原阳性病人中７例亦混合存在这一变异。Ｃ基因区变异聚集于密码８４－１０１区段，密码９７变异即有１５例。轻，中和重度病变８，６和１０例中，替代变异分别有２，６和２０个密码。中，重病人还各有１例由这一     

人血清载脂蛋白CⅠ和CⅢ的分离提纯及其单克隆抗体的制备

本文应用超速离心、凝胶过滤层析、高效液相色谱法分离纯化了人血清极低密度脂蛋白—载脂蛋白ＣⅠ和ＣⅢ。经等电聚焦电泳、十二烷基硫酸钠—聚丙烯酰胺电泳、双向免疫扩散等方法鉴定了纯度。以载脂蛋白ＣⅠ和ＣⅢ纯品免疫ＢＡＬＢ／Ｃ小鼠，应用淋巴细胞杂交瘤技术建立了４株抗人载脂蛋白ＣⅠ和２株抗人载脂蛋白ＣⅢ杂交瘤细胞。所得单克隆抗体与载脂蛋白ＡⅠ、ＡⅡ、Ｂ、ＣⅡ、Ｅ和白蛋白等无交叉反应。     

蛋白激酶C及抑制剂在肺癌耐药中的研究进展

耐药已成为当今肺癌化疗过程中的一大难题,其作用机制至今还不十分清楚.蛋白激酶C(protein kinase C,PKC)作为多种信号传导过程中的枢纽,不仅参与细胞信息传递、分泌、细胞分化、增殖,更重要的是参与肿瘤细胞的凋亡和分化.国内外研究表明通过抑制PKC的活性,减少其表达量可以增加细胞内药物的积聚导致胞内有效浓度的上升,从而降低肿瘤细胞耐药率.PKC抑制剂对肿瘤细胞具有明显的诱导分化、增强细胞毒性、促进细胞凋亡的作用.目前已有部分PKC抑制剂进入了临床的Ⅰ/Ⅱ期研究中,并取得了一定的疗效,通过对其作用机制的进一步深入探讨,有望在肺癌耐药的研究中取得更多的突破.     

Chronic hepatitis C genotype 1 virus: Who should wait for treatment?

Elucidation of the natural history of chronic hepatitis C(CHC)and the identification of risk factors for its progression to advanced liver disease have allowed many physicians to recommend deferral treatment(triple therapy)in favour of waiting for new drug availability for patients who are at low risk of progression to significant liver disease.Newer generation drugs are currently under development,and are expected to feature improved efficacy and safety profiles,as well as less complex and shorter duration delivery regimens,compared to the current standards of care.In addition,patients with cirrhosis and prior null responders have a low rate(around 15%)of achieving sustained virological response(SVR)with triple therapy,and physicians must also consider the decision to wait for new treatments in the future for these patients as well.Naive patients are the most likely to achieve a close to 100%SVR rate;therefore,it may be advisable to recommend that patients with mild to moderate CHC should wait for the newer therapy options.In contrast,patients with advanced fibrosis and cirrhosis will be those with the greatest need for expedited therapeutic intervention.There remains a need,however,for establishing definitive clinical management guidelines to maximize the benefit of waiting for new drugs and minimize risk of side effects and non-response to the current triple therapy.     

C5a及C5aR拮抗剂在阿尔茨海默病中的研究进展

阿尔茨海默病(AD)是一类常见的神经变性疾病〔1〕,随着年龄的增长其发病率也显著上升。AD典型的神经病理学标志包括神经元和突触的损伤,细胞外β-淀粉样蛋白沉淀(Aβ)大量聚集形成的老年斑(SP)〔2,3〕,细胞内神经纤维缠结(NFTs)神经胶质增生〔4〕,和某些补体蛋白以及这些蛋白聚合物的上     

自身免疫性肝炎患者血清补体C3和C4的临床检测意义

目的评价补体C3、C4在自身免疫性肝炎(autoimmune hepatitis,AIH)的临床检测意义。方法选取2011年5月-2013年12月于奉节县人民医院就诊的AIH患者90例,其中活动期45例,缓解期45例。采用间接免疫荧光法检测患者抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗线粒体抗体(AMA)的表达,全自动生物化学分析仪检测患者的肝功能生化指标,散射比浊法检测患者外周血中的补体C3、C4、Ig G、Ig A、Ig M的表达水平,肝脏穿刺病理组织检测判断其炎性活动水平。然后分析AIH患者C3、C4水平与炎症活动程度的关系。结果 C3、C4在AIH活动期表达水平[(0.89±0.05)g/L、(0.16±0.03)g/L]显著低于缓解期表达水平[(1.12±0.06)g/L、(0.23±0.04)g/L,P0.01];C3表达水平与AST(r=-0.248,P=0.000)、TBIL(r=-0.372,P=0.003)、DBIL(r=-0.471,P=0.012)呈负相关;C4表达水平与AIH活动期患者肝脏病理组织穿刺的HAI病理评分呈负相关(r=-0.635,P=0.000)。结论 AIH活动期患者补体C3、C4表达水平下降,可通过对其检测辅助评估肝脏炎性活动程度。     

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.