IDDM患者淋巴细胞内cAMP、cGMP的观察

环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)是人体细胞内生物活性物质,其含量的异常与许多疾病有关。我们对38例IDDM患者及32例正常人的淋巴细胞内环核苷酸含量作了测定,报道如下。 淋巴细胞的处理按文献[中国免疫学杂志 1988;4:423]进行。cAMP及cGMP测定按上海中医学院同位素室,~(125)I-cAMP及~(125)I-cGMP试剂盒说明书进行。     

其他

检测血浆环核苷酸的临床应用邵亚男南京医学院学报(2):25,1983 检测70例正常人血浆环磷酸腺苷(cAMP)值为28.93±5.20,环磷酸鸟苷(cGMP)为5.64±1.30(单位均为Pmole/ml),cAMP/cGMP     

心脏环磷酸腺苷和环磷酸鸟苷的受体调节及其交互作用

环磷酸腺苷 (cAMP)和环磷酸鸟苷 (cGMP)在心脏既相互依存 ,又相互拮抗 ,共同维持着心脏信号转导和功能活动的完整性 ,本文就近年来二者的受体调节和交互作用的研究进展予以综述。     

磷酸二酯酶抑制剂在哮喘治疗中的新进展

1PDE的结构与功能环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)是细胞内重要的第二信使,介导许多生理过程。高浓度的cAMP与特异性蛋白激酶结合,进一步活化这些激酶,导致各种底物磷酸化,调节细胞反应cAMP的水平由合成和降解的比例来调节。合成由腺苷环化酶和鸟苷环化酶,通过G蛋白受体耦联活化后水解ATP,GTP形成;降解则由磷酸二酯酶(PDE)负责。PDE是个蛋白酶超家族,至今已鉴定出PDE有11个家族成员[1],它们的原始序列、底物特异性、辅助因子及对抑制剂敏感性不同,其中PDE3、PDE4、PDE5、PDE7主要分布于炎症和免疫细胞中,与人类炎症反…     

磷酸二酯酶抑制剂在循环系统研究与应用进展

环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）是细胞内第二信使,对于细胞活动起着重要的调节作用。其浓度的调节主要由核苷酸环化酶的合成和磷酸二酯酶（PDEs）的水解决定。PDEs在人体内分布广泛,生理作用涉及多个研究领域。研究发现,PDEs家族至少包括11种成员,主要分布于心肌、平滑肌、血小板及血细胞、腺体等细胞内。     

Kv7通道在正常及高血压大鼠钠尿肽介导的血管舒张中的作用

<正>电压门控性钾通道Kv7家族可在血管表达,是血管张力的关键调节因素,能介导环磷酸腺苷(3',5'-cyclic adenosine monophosphate,cAMP)关联的内源性血管舒张反应——高血压的一个受损通路。但Kv7通道在非cAMP关联的血管舒张反应通路中的作用仍未明确。钠尿肽主要是通过激活环磷酸鸟苷(3',5'-cyclic guanosine monophosphate,cGMP)依赖性信号通路而具有很强的血管舒张作用。该研究探讨     

止血愈疡颗粒剂对大鼠乙酸型胃溃疡及环核苷酸的影响

自制止血愈疡颗粒剂对乙酸型胃溃疡大鼠有显著的抗溃疡作用。检测雷尼替丁组及模型组大鼠胃粘膜环磷酸腺苷／环磷酸鸟苷（cAMP／cGMP）比值分别为7．2±3．5和24．8±20．8，两组比较差异有显著性意义（P＜0．05）。表明，雷尼替丁能使大鼠胃粘膜cAMP／cGMP水平下降，提示可能cAMP／cGMP比值降低则胃酸分泌减少。止血愈疡颗粒剂表现出与雷尼替丁相同的效应。     

高血压病患者细胞钙、镁和环核苷酸含量变化

目的：探讨细胞Ca2 、Mg2 和环磷酸腺苷（cAMP）、环磷酸鸟苷（cGMP）含量及相互关系变化与高血压病的关系。方法：观察107例高血压病患者和30例正常人外周血淋巴细胞Ca2 -三磷酸腺苷酶（Ca2 -ATPase）活性、Ca2 、Mg2 、cAMP和cGMP含量变化。结果：临界高血压和高血压病各期细胞内Ca2 浓度升高、Mg2 浓度降低（P＜0．01）;高血压病各期细胞Ca2 -ATPase活性下降、cAMP和cGMP含量增高（P＜0．05～P＜0．01）。高血压病组平均动脉压与Ca2 -ATPase呈负相关、与Ca2 、cAMP和cGMP呈正相关（P＜0．05～P＜0．01）;Ca2 与Ca2 -ATPase呈负相关,与cAMP和cGMP呈正相关（P＜0．05～P＜0.01）。结论：细胞Ca2 、Mg2 转运障碍和cAMP、cGMP代谢异常可能涉及高血压病的发病机制,细胞Ca2 -ATPase活性下降、cAMP和cGMP含量升高可能部分与细胞Ca2 浓度增高、Mg2 浓度降低有关。     

磷酸二酯酶抑制剂与呼吸道疾病

磷酸二酯酶(PDE)存在于许多炎症细胞及结构细胞中,目前已发现11种.PDE抑制剂主要抑制体内环磷酸腺苷(cAMP)及环磷酸鸟苷(cGMP)水解,使细胞内cAMP及cGMP浓度增加,引起一系列生理功能,如平滑肌舒张、减轻细胞炎症及免疫反应等.PDE4特异性水解cAMP,选择性PDE4抑制剂具有广泛抗炎作用,如抑制细胞趋化,抑制中性粒细胞、嗜酸粒细胞、巨噬细胞及T细胞细胞因子及化学趋化物质释放.第二代PDE4抑制剂Cilomilast和Roflumilast已进入临床实验阶段,并已证实对支气管哮喘(简称哮喘)及慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)有效.由于胃肠道副作用,这类药物临床应用受到一定限制.PDE5可特异性水解cGMP,对缺氧性肺动脉高压和血管重塑有效.PDE3和PDE7特异性水解cAMP,PDE7参与T细胞激活.目前其他PDE抑制剂与PDE4抑制剂混合制剂正在研发中.PDE4-PDE7双重抑制剂可能对哮喘及COPD更有效.PDE3-PDE4双重抑制剂具有更强的支气管舒张作用及气道保护作用.     

环腺苷酸结合蛋白在心脏功能及相关心脏疾病中的作用研究进展

正3,5-环磷酸腺苷(cAMP)是心血管系统中细胞对于外界刺激反应的关键信号分子。它控制很多生物效应,如细胞增殖、变异和凋亡等。cAMP是ATP通过跨膜腺苷酸环化酶激活的G蛋白偶联受体~([1])。细胞内cAMP不仅由腺苷酸环化酶产生,而且由cAMP的磷酸二酯酶调控其降解,催化cAMP水解成5-AMP。磷酸二酯酶是限制cAMP合成的关键因素,并且是各种特定反应动态微小区域的关键组成部     

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.     

Effects of pinealectomy and melatonin administration on certain indices of ovarian hyperplasia and/or hypertrophy in rats with both ovaries intact or after unilateral ovariectomy

Abstract: In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham-PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross-sectional area, cross-sectional area of the granulosa layer of all the Graafian follicles and the cross-sectional areas of the corpora lutea, visible on the ovarian cross-section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham-PX, melatonin effects on these two groups may differ.