蛛网膜下腔出血后知浆t—PA、PAI—1变化的临床意义

对28例蛛网膜下腔出血（SAH）后患者的血浆组织型纤溶酶原激活物（t-PA）、纤溶酶原激活物抑制物（PAI-1）变化进行了观察,并与30例健康者进行对照。结果显示,与对照组比较,SAH后1～14天患者血浆纤溶性明显增高;其中伴发脑血管痉挛（CVS）者出血第7天、14天血浆PAI-1活性均明显高于无CVS者;出血量多者血浆t-PA、PAI-1活性较高。提示血浆t-PA、PAI-1活性在SAH后呈动态变化,二者可能均参与SAH的发生、发展、其活性测定可望成为监测SAH、CVS及出血量的有效指标。     

脑梗死患者急性期血浆PAI-1与t-PA比值的变化及临床意义

目的研究脑梗死患者急性期(发病7 d内)血浆纤溶酶原激活物抑制物-1(PAI-1)与血浆组织型纤溶酶原激活物(t-PA)比值的变化及其临床意义。方法采用酶联免疫吸附法检测67例脑梗死患者急性期血浆PAI-1t、-PA、计算PAI-1/t-PA(P/t)值,并与50名健康对照组作对照。结果脑梗死患者急性期血浆t-pA活性及PAI-1活性均升高,与正常对照组比较有统计学意义(P0.05),P/t值较正常对照组降低(P0.05)。结论脑梗死患者急性期体内纤溶活性相对亢进。在判定体内纤溶活性指标中,P/t值较t-PA、PAI-1稳定可靠。P/t值与纤溶活性呈反比关系。     

替米沙坦对高血压大鼠纤溶功能的作用机制

目的 探讨血管紧张素Ⅱ(Ang Ⅱ)促血管内皮细胞和平滑肌细胞合成与分泌纤溶酶原激活物抑制物-1(PAI-1)的受体和受体后信号转导途径以及替米沙坦对高血压大鼠纤溶参数的影响和可能机制.方法 腹主动脉部分缩窄构建高血压大鼠模型,随机分成高血压组和替米沙坦组(3 mg/kg·d)6周,另设假手术组为对照组.检测大鼠血浆与主动脉组织匀浆中Ang Ⅱ含量,血浆与主动脉孵育液中纤溶酶原激活物(t-PA)、PAI-1活性,血管内皮细胞、平滑肌细胞胞外信号调节激酶(ERK)和血管紧张素Ⅱ1型受体(AT1R)蛋白的表达.结果 ①高血压组血浆Ang Ⅱ含量、血浆PAI-1活性、血管平滑肌细胞ERK蛋白及AT1 R蛋白的表达4者之间显著正相关(r=0.89～0.96,P＜0.01～0.001).主动脉匀浆Ang Ⅱ含量、主动脉孵育液PAI-1活性、血管平滑肌细胞ERK蛋白及AT1R蛋白的表达4者之间显著正相关(r=0.86～0.96,P＜0.01～0.001).②与高血压组比较,替米沙坦能明显抑制主动脉分泌PAI-1的能力(P＜0.05),降低血浆PAI-1活性(P＜0.05),升高血浆与主动脉孵育液中t-PA活性、t-PA/PAI-1值(P均＜0.05),明显改善纤溶参数.③替米沙坦组ERK和AT1R在血管内皮细胞和平滑肌细胞的表达较高血压组明显减少(P均＜0.05).结论 替米沙坦抑制血管内皮细胞、血管平滑肌细胞ERK和AT1 R的表达,抑制Ang Ⅱ引起的PAI-1合成增加,可能是其改善纤溶功能的机制.     

脑梗塞患者血浆组织型纤溶酶原激活物及抑制物的活性变化

目的:观察脑梗塞患者不同时期血浆组织型纤溶酶原激活物(t-PA)及其抑制物(PAI-1)以及t-PA／PAI-1(T／P)值的动态变化规律及意义。方法:测定以下各组血浆t-PA、PAI-1活性:①急性脑梗塞组20例,病程第1、3、7、14、21天,②恢复期或后遗症期脑血栓患者20例;③正常对照组(健康者)20例,并进行统计学分析。结果:急性脑梗塞发病后第1天内,血浆t-PA活性明显降低(P<0.05),其后逐渐升高,第7天达到最高值,其后呈逐渐下降趋势;血浆PAI-1则相反,各测查点T／P值明显低于正常对照组,其趋势类似t-PA。结论:急性脑梗塞患者血浆纤溶活性明显下降,血浆t-PA,PAI-1含量能客观反映脑梗塞的病理过程,对治疗有指导意义。     

蛛网膜下腔出血患者ATⅢ、PAI活性变化及其与CVS关系的研究

目的动态观察蛛网膜下腔出血（SAH）患者的血液和脑脊液（CSF）中抗凝血酶Ⅲ（ATⅢ）、组织纤溶酶原激活物抑制物（PAI）活性,并探讨二者与SAH后脑血管痉挛（CVS）之间的关系。方法收集60例SAH患者3 d内及5-7 d的外周静脉血和CSF,采用发色底物法测定ATⅢ及PAI。结果CVS组SAH患者血浆和CSF中ATⅢ下降幅度、PAI升高幅度均较无CVS组明显（P〈0.05）。结论ATⅢ、PAI活性变化与CVS密切相关。     

复方丹参滴丸对不稳定型心绞痛患者血小板活化及纤溶活性的影响

目的　探讨复方丹参滴丸对不稳定型心绞痛 (UA)患者血小板活化状态和纤溶活性的影响。方法　 40例 UA患者随机分为常规治疗组 (2 0例 )和复方丹参滴丸组 (2 0例 )。疗程 4周。治疗前后测定血浆中血小板 α-颗粒膜蛋白 (GMP-14 0 )、组织型纤溶酶原激活剂 (t-PA)及其抑制物 (PAI-1)水平。结果　两组 UA患者治疗后 GMP-14 0含量、PAI-1活性均明显降低 (P<0 .0 5 ;P<0 .0 1) ,t-PA活性显箸升高 (P<0 .0 5 ;P<0 .0 1)。复方丹参滴丸组降低 GMP-14 0和升高 t-PA的幅度高于常规治疗组 (P<0 .0 5 )。结论　复方丹参滴丸能有效抑制血小板活化、改善纤溶活性     

辛伐他汀对冠心病患者纤溶参数的影响

目的了解冠心病患者纤溶参数的变化,并观察辛伐他汀对冠心病患者纤溶参数的影响。方法测定87例正常对照者和108例冠心病患者血浆组织型纤溶酶原激活物(t-PA)活性和纤溶酶原激活物抑制物-(1PAI-1)活性,随后108例冠心病患者被随机分成常规治疗组和常规治疗+辛伐他汀40mg每日一次(辛伐他汀组)。治疗14d后复测t-PA活性和PAI-1活性。结果与正常对照组相比较,冠心病患者纤溶参数异常,t-PA活性下降,PAI-1活性上升(P<0.01)。常规治疗组治疗后纤溶参数无显著变化(P>0.05)。辛伐他汀组纤溶参数明显改善,表现为t-PA活性上升,PAI-1活性下降(P<0.01)。结论冠心病患者纤溶参数明显异常,辛伐他汀能改善冠心病患者纤溶参数。     

永久心脏起搏术后GPⅡb/Ⅲa、tPA、PAI-1的变化

目的:探讨永久心脏起搏术后对血小板膜糖蛋白Ⅱb/Ⅲa(GPⅡb/Ⅲa),纤溶酶原激活剂(tPA),纤溶酶原激活剂抑制剂-1(PAI-1)的影响。方法:对41例置入永久心脏起搏器患者,测定其术前当天、术后1、7 d 的GPⅡb/Ⅲa、tPA、PAI-1。结果:血小板GPⅡb/Ⅲa在术后1 d及术后7 d均较术前明显降低(P<0．05)。 tPA与术前比较差异无统计学意义(P>0．05),PAI-1术后7 d较术前升高(P<0．05)。结论:心脏起搏降低了血小板活性,升高了PAI-1水平,提示纤溶系统的失衡可能与心脏起搏患者静脉血栓的形成有关。     

介入封堵术对成人先天性心脏病患者血浆t-PA和PAI-1水平的影响

目的评价介入封堵术对成人先天性心脏病(CHD)患者血浆组织型纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制物-1(PAI-1)水平的影响.方法采用酶联免疫吸附法检测70例CHD患者及30例健康人(正常对照组)血浆t-PA、PAI-1水平.所有CHD患者分别于介入封堵术前头天,术后24 h,1、3、6、12个月检测血浆t-PA、PAI-1水平.结果介入封堵术前,CHD患者血浆t-PA、PAI-1水平比正常对照组明显增高(P＜0.01).介入封堵术后1个月,CHD组血浆PAI-1水平开始逐渐下降,术后6个月恢复正常水平;血浆t-PA水平在术后1个月升高,术后3个月始下降,术后6个月恢复正常水平.结论介入封堵术可通过改变血浆t-PA、PAI-1水平而改善成人CHD患者的内源性纤溶功能.     

复方丹参滴丸对冠心病患者纤溶系统t-PA、PAI-1含量与活性的调控

目的观察复方丹参滴丸对冠心病患者内源性纤溶活性及血管内皮功能的影响，探讨其作用机制。方法冠心病患者78例，随机分为对照组和复方丹参滴丸组。对照组采用常规治疗；复方丹参滴丸组在常规治疗基础上加用复方丹参滴丸每次10粒，每日3次。两组用药时间均为4周。比较治疗前后血浆组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活剂抑制因子-1（PAI-1）活性及浓度。结果复方丹参滴丸治疗4周后，患者血浆PAI-1活性及浓度下降（P〈0．05），t—PA活性及浓度含量升高（P〈0．05），与治疗前比较差异有统计学意义；常规治疗组治疗前后t-PA和PAI-1活性差异无统计学意义。结论复方丹参滴丸可有效地调控改善冠心病患者内源性纤溶活性及血管内皮功能。     

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.