谷氨酸脱羧酶可诱导非肥胖糖尿病小鼠免疫耐受

目的 了解猪脑谷氨酸脱羧酶（ＧＡＤ）是否能预防非肥胖糖尿病（ＮＯＤ）小鼠的Ⅰ型糖尿病和影响其胰腺自身ＧＡＤ６５表达。方法 将ＧＡＤ５０μｇ与不完全弗氏佐 剂（ＦＩＡ）５０μｌ混合后给３２只４周龄ＮＯＤ雌性小鼠腹腔注射，同时１９只单独注射ＦＩＡ作为对照。每周测定体重、血糖，２０周龄时处死小鼠，观察其病理、血清Ｃ肽和ＧＡＤ抗体，并用逆转录ＰＣＲ进行胰岛ＧＡＤ６５表达半定量。结果 ２０周龄时，ＧＡＤ组小     

含弓形虫ROP1基因真核表达重组质粒DNA免疫小鼠的研究Ⅴ.IFN-γ基因真核表达重组质粒的构建及其在DNA免疫中基因佐剂的作用

目的　构建ＩＦＮ－γ基因真核表达重组质粒作为基因佐剂,观察其与ｐｃＤＮＡ３－ＲＯＰ１（ｐｃ－ＲＯＰ１） ＤＮＡ共同免疫小鼠所诱导的免疫应答。方法　将ＩＦＮ－γ基因片段定向插入真核表达载体ｐｃＤＮＡ３,双酶切鉴定,获得ｐｃＩＦＮ 重组子;碱裂解法大量制备,经肌肉注射免疫ＢＡＬＢ／ｃ小鼠,每只鼠注射ｐｃＩＦＮ、ｐｃ－ＲＯＰ１ 各１００μｇ,两周后同量加强免疫一次,以ｐｃＤＮＡ３空质粒及生理盐水组为对照。分别于免疫后第３０ 天、５０ 天、７０天共三次用ＭＴＴ法测定小鼠脾脏Ｔ淋巴细胞增殖活性及ＮＫ细胞活性;双夹心ＥＬＩＳＡ 测定血清细胞因子ＩＦＮ－γ、ＩＬ－２及酶法测定ＮＯ含量;ＥＬＩＳＡ法测定ＩｇＧ抗体滴度。结果　构建成功的作用下,该两项指标均明显提高,且ＩＦＮ－γ、ＩＬ－２ 及ＮＯ水平均较不加佐剂组显著提高（Ｐ＜ ０．０１）;而对ＩｇＧ抗体滴度无显著影响（Ｐ＞ ０．０５。结论　ＩＦＮ－γ基因佐剂具有协同ｐｃ－ＲＯＰ１ＤＮＡ免疫的作用,可增强免疫鼠细胞免疫应答,ＩＦＮ－γ、ＩＬ－２细胞因子及ＮＯ的产生     

ADA及WHO糖尿病诊断标准在中国人中检出率的变化及迁移

目的　比较美国糖尿病协会１９９７年修订的糖尿病诊断标准［ＡＤＡ（１９９７）］和世界卫生组织糖尿病诊断标准［ＷＨＯ（１９８０～１９８５）］在中国人中检出率的变化及迁移。方法　对９０６例研究对象实施７５ｇ 口服葡萄糖耐量试验（ＯＧＴＴ）。结果　ＡＤＡ（１９９７）空腹血糖（ＦＰＧ）标准较ＷＨＯ（１９８０～１９８５）标准敏感性提高１１．１５％ ,并使近１／５的糖尿病（ＤＭ）患者可免于ＯＧＴＴ而被确诊,但仍有近半数经ＷＨＯ（１９８０～１９８５）标准诊断的ＤＭ 患者被ＡＤＡ（１９９７）ＦＰＧ标准诊断为空腹血糖损害（ＩＦＧ）或正常空腹血糖者（ＮＦＧ）。结论　对用ＡＤＡ（１９９７）ＦＰＧ标准诊断为ＩＦＧ及ＮＦＧ,尤其是存在糖尿病高危因素者,有必要进行ＯＧＴＴ２小时血糖核查,以避免漏诊     

猪苓多糖对小鼠腹腔巨噬细胞一氧化氮生成的影响及其机理

目的 探讨猪苓多糖（ＰＰＳ）的免疫调节和免疫的作用机理。方法 观察ＰＰＳ对小鼠腹腔巨噬细胞一氧化氮（ＮＯ）生成和诱导型一氧化氮合酶（ｉＮＯＳ）的影响。结果 ＰＰＳ对小鼠腹腔巨噬细胞ＮＯ生成具有明显的促进作用，呈剂量依赖依赖关系，并与干扰素－γ（ＩＦＮ－γ）具有协同促进作用。这一促进作用能被ＲＮＡ转录抑制剂放线菌素Ｄ、蛋白质合成抑制剂放线菌酮和ｉＮＯＳ抑制剂Ｌ－ＮＭＡ所抑制。结论 ＰＰＳ可能单独或与     

口服胰岛素、谷氨酸脱羧酶对NOD小鼠糖尿病发生率的影响

目的 观察雌性非肥胖糖尿病（ＮＯＤ）小鼠口服胰饥素和氨酸脱羧酶（ＧＡＤ）对糖尿病发生的影响。以及对白细胞介素４（ＩＬ－４）的血甭水平和胰腺ＩＬ－４ｍＲＮＡ转录的影响。方法 雌性ＮＯＤ小鼠分为３组：第一组给予ＰＢＳ作为对照组第二组给予胰岛素,第三组予以ＧＡＤ。ＥＬＩＳＡ法检测血清ＩＬ－４水平,Ｎｏｒｔｈｅｒｎ杂交检测胰腺Ｌ－４ｍＲＮＡ的表达。结果 胰岛素或ＧＡＤ均能抑制ＮＯＤ小鼠糖尿病的发生,ＰＢＳ     

肝损伤小鼠肝组织氧化／抗氧化平衡的变化及其与TXA2／PGI2？…

目的：探讨氧自由基（ＯＦＲ）及ＴＸＡ２－ＰＧＩ２在实验性肝损伤中的作用。方法：检测肝损伤小鼠肝组织过氧化脂质（ＬＰＯ）、超氧化物歧化酶（ＳＯＤ）含量以及血浆ＴＸＡ和ＰＧＩ２浓度。结果：与对照组比较肝损伤小鼠ＬＰＯ明显升高、ＳＯＤ明显降低，当归可逆转ＬＰＯ和ＳＯＤ的变化；肝损伤小鼠血浆ＴＸＢ２高于对照组，其浓度与肝细胞ＬＰＯ含量呈正相关（ｒ＝０．９５，Ｐ〈０．０１）。结论：ＯＦＲ与ＴＸＡ２／ＰＧＩ２     

γ-干扰素基因修饰肝细胞对感染日本血吸虫小鼠TGF-β_1及其受体的影响

目的： 探讨γ－干扰素 （ＩＦＮ－γ） 基因治疗对感染日本血吸虫小鼠转化生长因子－β１ （ＴＧＦ－β１） 及其受体的影响与抗肝纤维化作用的关系。方法： 将小鼠ＩＦＮ－γ基因重组腺病毒载体转染的肝细胞经脾移植到感染日本血吸虫尾蚴１６ ｗｋ 的小鼠, 采用ＥＬＩＳＡ、免疫组化和斑点杂交方法分析小鼠血清ＩＦＮ－γ与ＴＧＦ－β１ 表达的关系, 小鼠肝内ＩＦＮ－γ、ＴＧＦ－β１、ＴＧＦ－βＲＩＩ与Ⅰ、Ⅲ型胶原表达的关系。结果： ＩＦＮ－γ基因修饰的肝细胞经脾移植后能有效地表达, 显著地降低ＴＧＦ－β１ 、ＴＧＦ－βＲＩＩ的表达和Ⅰ、Ⅲ型胶原的含量。结论： ＩＦＮ－γ基因治疗能有效地发挥抗血吸虫病肝纤维化作用, 可能与降低ＴＧＦ－β１及其受体有关。     

γ-干扰素基因修饰肝细胞对感染日本血吸虫小鼠TGF-β_1及其受体的影响

目的： 探讨γ－干扰素 （ＩＦＮ－γ） 基因治疗对感染日本血吸虫小鼠转化生长因子－β１ （ＴＧＦ－β１） 及其受体的影响与抗肝纤维化作用的关系。方法： 将小鼠ＩＦＮ－γ基因重组腺病毒载体转染的肝细胞经脾移植到感染日本血吸虫尾蚴１６ ｗｋ 的小鼠, 采用ＥＬＩＳＡ、免疫组化和斑点杂交方法分析小鼠血清ＩＦＮ－γ与ＴＧＦ－β１ 表达的关系, 小鼠肝内ＩＦＮ－γ、ＴＧＦ－β１、ＴＧＦ－βＲＩＩ与Ⅰ、Ⅲ型胶原表达的关系。结果： ＩＦＮ－γ基因修饰的肝细胞经脾移植后能有效地表达, 显著地降低ＴＧＦ－β１ 、ＴＧＦ－βＲＩＩ的表达和Ⅰ、Ⅲ型胶原的含量。结论： ＩＦＮ－γ基因治疗能有效地发挥抗血吸虫病肝纤维化作用, 可能与降低ＴＧＦ－β１及其受体有关。     

GAD预防NOD鼠胰岛炎的机理研究

目的研究本室自制猪脑ＧＡＤ是否能保护ＮＯＤ鼠胰岛β细胞免遭破坏及其意义。方法在４周龄ＮＯＤ鼠注射ＧＡＤ，对照组注射等量牛血清白蛋白（ＢＳＡ），分别于１９周龄、２５周龄和４７周龄处死，胰腺组织常规制成石蜡切片，ＡＢＣ免疫组化染胰岛β细胞并光镜下计数。结果同周龄ＧＡＤ组发生胰岛炎程度和胰岛炎评分均明显低于ＢＳＡ组：同周龄ＧＡＤ组胰岛β细胞计数明显高于ＢＳＡ组，均有显著性差异（Ｐ＜０．００１）；胰岛炎分值与胰岛β细胞阳性率存在密切负相关（Ｐ＜０．００１）。结论本室自制猪脑ＧＡＤ能减轻ＮＯＤ雌鼠胰岛炎的发生和保护胰岛β细胞免遭破坏的作用。     

人类高血压与内皮功能

１８６５年生理学家Ｈｉｓ首先提出内皮（Ｅｎｄｏｔｈｅｌｉ－ｕｍ）这一概念,其研究历史可概况如下：１９７６年Ｖａｎｅ发现内皮细胞合成并分泌前列腺素Ｉ２（ＰＧＩ２）,１９８０年Ｆｕｒｃｈｇｏｔｅ首先提出内皮依赖性舒张因子（Ｅｎｄｏｔｈｅｌｉ－ｕｍｄｅｒｉｖｅｄｒｅｌａｘｉｎｇｆａｃｔｏｒ;ＥＤＲＦ）的概念。１９８７年Ｐａｌｍｅｒ和Ｌｇａｒｒｏ提出ＥＤＲＦ为一氧化氮（ＮＯ）样物质,并发现左旋精氨酸（Ｌ－Ａｒｇｉｎｉｎｅ;Ｌ－Ａｒｇ）为ＮＯ前体。１９９３年证明ＮＯ的舒张作用由环鸟苷酸（ｃＧＭＰ）介导完成…     

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.     

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.     

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.     

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.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.