日本血吸虫不同方式感染宿主的免疫病理研究

目的建立等量血吸虫尾蚴单次感染和多次感染的动物模型,比较这两种不同感染方式对家兔肝脏的损害程度。方法制作肝脏病理切片,测量单个虫卵肉芽肿的体积;放免法检测家兔血清中透明质酸(HA)、层粘连蛋白(LN);RT-PCR-ELISA半定量测定肝组织中的TGF-β1mRNA。结果单次感染组家兔急性期肉芽肿反应最明显,慢性期和晚期肉芽肿体积逐渐缩小,而多次感染组肉芽肿缩小不明显;血清中HA和LN、肝组织中的TGF-β1mRNA量,在感染各组均高于正常对照,但多次感染组升高更明显。结论等量的尾蚴,多次感染比单次感染的危害引起的肝纤维化更为严重。     

贵州都匀、从江两地牛带绦虫感染家猪的比较研究

目的通过两地牛带绦虫感染家猪,了解贵州省都匀是否存在牛带绦虫亚洲亚种。方法对都匀、从江两地绦虫病患者进行驱虫,从孕节分离虫卵感染家猪,收集囊尾蚴并观察其特征。结果两地牛带绦虫均可在家猪体内发育为囊尾蚴,感染率分别为87.5%和62.5%。囊尾蚴回收率分别为0.266%和0.028%,囊尾蚴只分布在肝脏,并以肝实质为多见。都匀囊尾蚴比从江的稍大,其外壁有小的疣状物,头节可见伸缩的顶突和两圈逗点样结构,但无明显小钩。结论①家猪可作为两地牛带绦虫的中间宿主。②形态学研究显示都匀牛带绦虫是牛带绦虫亚洲亚种,而从江牛带绦虫是传统牛带绦虫。③贵州省都匀存在牛带绦虫亚洲亚种的局部流行病区。     

亚洲带绦虫致乳猪肝纤维化实验观察

目的观察都匀亚洲带绦虫和从江牛带绦虫感染乳猪致肝纤维化的病理变化。方法用两种带绦虫孕节直接灌喂长白种乳猪,共分两组,实验组:都匀亚洲带绦虫感染乳猪2头;对照组:从江牛带绦虫感染乳猪2头。感染后40d、60d分别剖检,切取肝组织制片,HE和Cason改良三色染色,病理学观察。结果两种带绦虫感染乳猪导致肝组织不同程度的变性、坏死、炎细胞浸润及纤维组织增生。结论两种带绦虫感染乳猪均可致肝纤维化,只是纤维化的程度和表现形式不同,尤其是都匀亚洲带绦虫先形成囊尾蚴肉芽肿,继而形成肝纤维化。     

猪带绦虫囊尾蚴与亚洲带绦虫囊尾蚴蛋白双向电泳图谱分析

将2头20日龄三元杂交乳猪分别感染猪带绦虫虫卵和亚洲带绦虫虫卵,8×104个/头。感染后40 d分别收集寄生在肝脏的未成熟猪带绦虫囊尾蚴(简称猪囊尾蚴)和亚洲带绦虫囊尾蚴,制备囊尾蚴蛋白,并进行蛋白双向电泳分析,用ImageMaster 2D Plantinum 6.0软件分析差异表达蛋白。结果显示,感染后40 d肝脏寄生的未成熟猪囊尾蚴和亚洲带绦虫囊尾蚴蛋白的双向电泳凝胶上分别有(236±12)和(231±14)个蛋白斑点,差异表达2倍以上的蛋白共10个,其中猪囊尾蚴表达上调的蛋白3个,下调的蛋白7个。     

猪带绦虫虫卵感染家猪致肝纤维化相关病理分析

目的观察猪带绦虫虫卵实验感染中间宿主家猪后囊尾蚴致肝纤维化作用,并对病变程度进行定量分析。方法实验猪分成3组,将亚洲猪带绦虫虫卵以高剂量(60 000个/ml)、中剂量(40 000个/ml)和低剂量(10 000个/ml)分别灌服感染家猪,每种剂量感染2头。健康家猪2头为对照组。30 d后剖杀,取肝脏,制作病理切片,HE和Cason染色,对实验猪肝脏病变组织进行病理变化观察及胶原纤维含量分析。结果与健康对照组比较,实验组家猪肝组织发生不同程度的变性、坏死、炎细胞侵润,肝、脾指数增加(P<0.05或P<0.01);肝纤维化改变明显,胶原纤维总面积和总吸光度值增加,胶原纤维含量显著增加(P<0.05或P<0.01)。结论猪带绦虫虫卵感染家猪后以肝脏囊尾蚴寄生居多,同时发生以肉芽肿和纤维化改变为主的病理损害且较为严重。     

都匀亚洲牛带绦虫及从江牛带绦虫实验感染家畜血清酶学动态研究

目的观察都匀亚洲牛带绦虫及从江牛带绦虫实验感染猪牛的血清酶学活性的动态变化及其在肝脏损伤中的作用。方法采用都匀亚洲牛带绦虫及从江牛带绦虫孕节灌喂健康乳猪，乳牛，隔离饲养。分别于感染前、感染后25d、50d、75d抽血，检测γ谷氨酰转移酶(γ-GT)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总蛋白(TP)、前白蛋白(PA)、碱性磷酸酶(ALP)、N-乙酰-β-D氨基葡萄糖苷酶(NAG)、乳酸脱氢酶(LDH)、亮氨酸氨基肽酶(LAP)和α1抗胰蛋白酶(α1-AT)含量变化并进行分析。结果都匀亚洲牛带绦虫及从江牛带绦虫感染猪牛后，γ-GT、ALT、AST、NAG、LDH、LAP和α1-AT含量升高，感染75d与感染前相比含量呈倍数增加，而PA含量呈下降趋势。结论：都匀亚洲牛带绦虫及从江牛带绦虫感染家畜后的血清酶的活性变化，可反映宿主肝脏损伤程度。牛带绦虫囊尾蚴寄生宿主不同。其指标存在不同差异。     

IFN-γ对亚洲牛带绦虫囊尾蚴病小鼠肝肉芽肿的影响

采用免疫组织化学技术链酶亲和素?鄄生物素化过氧化物酶复合物技术观察感染小鼠不同时期肝内γ干扰素（IFN-γ）水平，以及细胞外基质纤维连接蛋白（FN）、层连蛋白（LN）、Ⅲ型前胶原（PCⅢ）水平及分布，并以FN、LN及PCⅢ作为判断IFN-γ对肝纤维化抑制作用的动态变化指标。结果表明，都匀亚洲牛带绦虫感染小鼠肝内IFN-γ含量与肝纤维化程度呈反比（P<0.01），注射IFN-γ后囊尾蚴肉芽肿面积明显减少，囊尾蚴肉芽肿减少（P值均<0.01）。     

都匀亚洲带绦虫与从江牛带绦虫实验感染牛和猪的比较研究

目的比较贵州省都匀亚洲带绦虫与从江牛带绦虫在牛和猪体内的发育情况。方法用都匀带绦虫孕节和从江带绦虫孕节分别灌喂5～33d龄健康乳牛2头和3头、17～23d龄健康乳猪各2头。于感染后25～85d分别剖检、观察牛和猪体内囊尾蚴的分布、大小、形态及成熟情况。结果在感染都匀带绦虫62、85d的2头乳牛肝脏中共检获28个囊尾蚴,其大小为1.16～1.91mm×1.03～1.50mm。在感染都匀带绦虫50、62d的2头乳猪肝脏中共检获67个囊尾蚴,大小为1.28～2.84mm×1.26～2.57mm。两组囊尾蚴仅分布在肝脏且形态特征相同,活体观察成熟囊尾蚴均可见到头节上有4个吸盘和伸缩活动的顶突。压片染色镜检,31%的囊尾蚴顶突略凸,69%的顶突略凹,56%的顶突周围有两圈退化的小钩。在感染从江带绦虫25、35、67d的3头乳牛体内共检获2745个囊尾蚴,为全身分布,大小为0.86～6.52mm×0.66～4.39mm。在感染从江带绦虫50、67d的2头乳猪体内共检获106个囊尾蚴,仅分布于肝脏,其大小为1.08～2.86mm×0.96～2.68mm。从江带绦虫在牛和猪体内的囊尾蚴,活体观察及压片染色镜检,囊尾蚴原头节均未发现顶突和小钩。结论都匀带绦虫为亚洲带绦虫,在牛和猪体内囊尾蚴仅分布于肝脏,其囊尾蚴常具有退化小钩;从江带绦虫为传统牛带绦虫,在牛体内囊尾蚴呈全身分布,在猪体     

转化生长因子β1和结缔组织生长因子在肝纤维化中的表达

目的:观察肝纤维化不同阶段转化生长因子β1 (TGF-β1)和结缔组织生长因子(CTGF)在肝组织内表达的相关性．方法:41例行肝组织活检慢性病毒性肝炎患者,免疫组织化学检测TGF-β1和CTGF,并用多媒体彩色图像分析仪对上述二指标进行图像分析定量．结果:按肝纤维化分组,除S1,S2期无统计学差别意义外,TGF-β1和CTGF均随纤维化分期加重而表达增加(F=49．56,23．01,P<0．05)．按炎症活动度分组G1,G2,G3,G4组间TGF-β1两两比较无显著性差异．G1,G2,G3组CTGF两两比较无显著性差异,而G4组则有统计学意义．肝组织中TGF-β1,与CTGF呈正相关(r=0．855, P<0．05)．TGF-B1和CTGF与血清PCⅢ,LN, HA,ⅣC均呈正相关(TGF-β1:r=0．744,0．815, 0．756,0．741,P<0．05;r=0．663,0．690,0．686, 0．640．P<0．05)．结论:肝脏TGF-β1和CTGF表达水平与肝组织纤维化程度密切相关,在早期肝硬化阶段CTGF表达更可靠．     

慢性肝病患者血清转化生长因子β_1水平与肝纤维化的关系

目的 探讨血清转化生长因子β_1(TGF-β_1)水平与肝纤维化的关系及在肝纤维化中的诊断价值。方法对139例肝病患者血清采用ELISA法检测TGF-β_1水平,并同时采用放射免疫法检测血清HA、LN、Ⅳ-C等肝纤维化血清学指标。结果 随着病情加重、肝纤维化程度加深,血清TGF-β_1逐渐升高,以肝硬变组最明显;血清TGF-β_1水平与血清HA、LN、Ⅳ-C均呈明显的正相关,且与Ⅳ_C相关更密切。结论 血清TGF-β_1与肝纤维化有密切联系,其血清水平可反映肝纤维化的程度,可作为诊断肝纤维化的一项可靠的新的血清学指标。     

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.