氟中毒大鼠血清和红细胞中脂质过氧化物水平及抗氧化物质含量变化

实验用 Wistar 大鼠72只,随机分为三组,即对照组、10ppm 氟水组和30ppm 氟水组各组动物于实验后5个月及8个月分两批处理进行检查。结果表明,10ppm 氟水组大鼠于实验后8个月、30ppm 氟水组大鼠于实验后5个月及8个月其血清和红细胞中脂质过氧化物含量升高、谷胱甘肽过氧化物酶活性降低,还原型谷胱甘肽含量减少,但超氧化物歧化酶活性无明显改变。提示自由基水平的增高可能是氟病发生机制中的一个重要的中间介导环节。     

慢性氟中毒大鼠肾脏组织化学、光镜及电镜的变化

本文检查了长期饲以50ppm 含氟水而造成慢性氟中毒之大鼠肾脏,观察到肾脏碱性磷酸酶活性降低,线粒体形态结构异常,近曲小管局灶性坏死。结果提示慢性氟中毒可引起体内过量的氟蓄积于肾脏,并对其表现损害作用。     

拮氟锐抗氟毒性的研究

本文在硼抗氟毒性及其机理研究的基础上，选用硼，微量元素和中药配制成“损坏氟锐”，通过大鼠性性实验，观察了拮氟锐抗氟毒性的效果。结果表明、拮氟锐能增加尿氟含量，促进氟硼酸根离子的形成，使总排氟量增加骨氟含量降低；并对氟引起的微量元素平衡失调和碱性磷酸酶活性的高具有拮抗作用，同时，拮氟锐可拮抗氟所致的自然杀伤细胞和白细胞介素－２活性的降低。与硼比较，拮氟锐抗氟毒性的效果更明显。     

氟致大鼠肝脏脂质过氧化及硒的拮抗作用研究

通过饮水用加氟（５０ｍｇ／Ｌ）或／和加硒（０．５ｍｇ／Ｌ）的方法研究氟致大鼠肝脏脂质过氧化及硒的拮抗作用，结果表明，饮水加氟可致大鼠肝脏自由基含量，脂质过氧化物（ＬＰＯ）含量显著增加，还原型谷胱甘肽（ＧＳＨ）含量显著下降，饮水同时加硒，氟可拮抗氟致肝脏的脂质过氧化作用 ，但对氟致大鼠肝脏谷胱甘肽过氧化物酶（ＧＳＨ－ＰＸ）活性显著下降无明显的影响。     

克山病病区粮中致病因素对肝脏损伤作用的研究

本文观察了饲克山病病区粮大鼠肝脏五种酶活性和脂质过氧化物(MDA)含量的变化。结果表明,病区粮组与非病区粮组动物相比,肝脏谷胱甘肽过氧化物酶活性和T_45′-脱单碘酶活性明显下降,谷氮酰转肽酶活性和MDA含量显著增加。提示饲克山病病区粮动物伴有原发性肝脏损伤。讨论了肝脏损伤在克山病心肌坏死发生中可能起的作用。     

雄性去势大鼠肝脏生物转化酶活性及抗氧化功能的变化

在雄性大鼠去势模型上观察了大鼠肝脏生物转化酶活性及抗氧化功能的变化。结果表明，去势大鼠肝和肾上腺指数减小，肝微粒体细胞色素Ｐ４５０含量及谷胱甘肽Ｓ－转移酶活性明显降低，肝匀浆谷胱甘肽减少和丙二醛增加，这些皆呈去势时间依赖性变化。提示雄性大鼠去势后肝脏代谢能力及抗氧化功能的降低可能与雄激素水平低下有关。     

硼、硒、氟宁、维生素C对氟中毒动物生化指标的影响

通过给大白鼠饮用高氟水,导致骨软化型氟中毒动物模型,同时分别给予四硼酸钠、亚硒酸钠、蛇纹石、维生素C,观察动物血中钙、磷含量及碱性磷酸酶活性,骨中胶原、钙及氟水平和尿氟含量的变化。 实验结果显示:硼能降低血清ALP活性;氟宁能增加骨中胶原及钙含量;硒能提高血钙浓度加速尿氟排泄;维生素C亦能增加血钙、骨胶原和尿氟含量。这些药物对氟的生化改变的影响,对防治氟中毒将起重要作用。     

腺苷酸激活蛋白激酶与肥胖大鼠肝脏脂质沉积的关系

目的探讨肥胖大鼠肝脏组织腺苷酸激活蛋白激酶(AMPK)的表达及其对肝脏脂质沉积的影响。方法选用18只刚断乳的SPF级SD雄性大鼠,随机挑选6只普通饲料喂养为正常组,另一组12只高脂饲料喂养,12 w后成功建立肥胖模型大鼠6只。分别检测体重、Lee指数、内脏脂肪、肝湿重等指标。通过油红O染色和检测肝脏甘油三酯(TG)、总胆固醇(TC)含量评估两组大鼠肝脏脂质沉积的情况。采用Western印迹检测大鼠肝脏磷酸化(p)-AMPK/AMPK、p-ACC/ACC水平。结果与正常组大鼠相比,肥胖组大鼠体重与Lee指数、附睾脂肪、肾周脂肪量、肝湿重、肝脏内TG与TC含量均显著升高,油红O染色结果显示肥胖组肝脏脂质沉积较正常组明显增多。Western印迹结果显示,与正常组大鼠比较,肥胖组大鼠肝脏p-AMPK/AMPK和p-ACC/ACC表达明显降低。两组大鼠肝脏组织中p-AMPK、p-ACC表达水平与肝脏TG、TC呈负相关。结论高脂饮食诱导食源性肥胖大鼠可降低AMPK的活性,从而导致肝脏组织TG、TC合成增加,脂质在肝脏组织中沉积增加。     

肝细胞刺激再生因子对大鼠实验性肝损伤的疗效及作用机制的研究

本文研究了肝细胞刺激再生因子(HSS)对大鼠实验性肝损伤的疗效及作用机制。研究结果显示HSS能明显促进肝脏的修复,而肝细胞沉淀物无此作用,同时还测定了巨噬细胞酸性磷酸酶活性。结果显示在HSS组其活性明显上升。应用HSS治疗肝衰竭的机理可能是被激活的巨噬细胞清除体内内毒素。     

皮质酮对大鼠脂肪代谢的影响

目的 观察压力应激激素皮质酮（CORT）对大鼠血脂、肝脏脂肪浓度以及肝脏脂肪代谢的影响。方法24只SD大鼠随机分为三组,各8只。对照组背部注射玉米油,CORT25mg／kg组将25mg／kgCORT加入玉米油后注射,CORT100mg／kg组将100mg／kgCORT加入玉米油后注射,1次／d,共4d。检测各组血清总胆固醇（Tc）、甘油三酯（TG）、磷脂（PL）、高密度脂蛋白（HDL-c）和肝脏TC、TG、PL含量,并测定肝脏脂肪酸合成酶（FAS）、磷脂酸磷酸酶（PAP）、葡萄糖6磷酸脱氢酶（G6PDH）、苹果酸酶（ME）活性,以及FAS、G6PDH、ME脂肪酶的mRNA。结果与对照组相比,CORT25mg／kg组及100ms／ks组大鼠体质量增加明显减缓（P均〈0．05）,血清TC、TG、PL、HDL-c水平均显著升高（P均〈0．05）,大鼠肝脏,TC及TG含量明显增加（P均〈0．05）,肝脏磷脂有下降趋势,肝脏脂肪酶FAS、PAP、G6PDH、ME活性明显增加（P均〈0．05）,FAS、G6PDH、MEmRNA表达量也明显上升（P均〈0．05）。结论CORT能显著促进大鼠肝脏脂肪的合成,提高血脂浓度。     

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.     

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.     

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.     

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.     

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.