高血压病患者血栓前状态的临床研究

目的通过观察高血压病患者血栓前状态分子标志物的变化,探讨其易并发血栓性疾病的机制,为临床早期诊治提供客观依据。方法对山东省血栓病防治工程技术研究中心与山东省交通医院2000-04~2004-05的1000例高血压病患者及100例健康对照者的血浆血栓前状态(PTS)分子标志物进行检测,包括:血管性血友病因子(vWF)、血小板α-颗粒膜蛋白-140(GMP-140)、11-去氢血栓烷B2(11-DH-TXB2)、纤维蛋白原(FIB)、抗凝血酶(AT);组织型纤溶酶原激活剂(t-PA)、纤溶酶原激活剂抑制物-1(PAI-1)的活性水平及血液流变学指标,并进行分析与评价。结果与对照组相比,高血压病患者的血浆vWF、GMP-140、11-DH-TXB2、FIB含量,PAI-1活性及血黏度均明显升高,而AT含量、t-PA活性均明显下降,差异极其显著(P<0·01)。随着血压升高,PTS标志物变化越显著(P<0·05)。结论高血压病患者存在PTS,PTS与其病情进展、血栓性疾病的发生密切相关。     

老年原发性高血压患者血栓前状态的研究

目的 探讨老年原发性高血压（EH）患者血栓前状态（PTS）分子标志物的变化及其易并发血栓性疾病的机制。方法 测定100例老年EH患者及100例老年健康对照者的血浆血管性血友病因子（vWF）、血小板α-颗粒膜蛋白-140（GMP-140）、纤维蛋白原（Fg）、凝血酶原片段1＋2（F1＋2）的含量，抗凝血酶（AT）、组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活物抑制剂-1（PAI-1）的活性及血液流变学指标，并进行了分析与评价。结果 老年EH病人血浆vWF、GMP-140、Fg、F1＋2含量、PAI-1活性、血黏度较对照组均明显升高，而AT、t-PA活性均明显下降（P〈0.01）。随着血压水平升高，PTS标志物水平变化越明显。结论 PTS与老年EH患者的病情发展及血栓性疾病的发生密切相关。     

老年高血压并发脑梗死患者凝血、抗凝、纤溶系统功能改变及意义

目的分析老年高血压并发脑梗死患者凝血、抗凝、纤溶系统分子标志物指标的变化及意义，为临床早期诊断治疗提供客观依据。方法检测100例老年高血压患者、100例老年高血压合并脑梗死患者及100例健康老年对照者血管性血友病因子抗原（vWF：Ag）、血小板α-颗粒膜蛋白-140（GMP-140）、纤维蛋白原（FIB）的含量及抗凝血酶（AT）、蛋白S（PS）、蛋白C（PC）、组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活剂抑制物-1（PAI-1）的活性，并进行分析与评价。结果与对照组相比，老年高血压患者、老年高血压合并脑梗死患者血浆vWF：Ag、GMP-140、FIB含量、PAI-1活性均明显升高，而AT、PS、PC、t-PA活性明显降低，差异具有统计学意义（P〈0．01）。结论老年高血压患者存在明显的凝血、抗凝及纤溶功能失衡，这与其病情进展及脑梗死的发生密切相关，早期防治具有重要的临床意义。     

阻塞性睡眠呼吸暂停综合征患者血栓形成前状态分子与颈动脉内膜中层厚度关系

目的： 探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血栓形成前状态(PTS)分子标志物与颈动脉内膜中层厚度关系。方法： 选择OSAHS患者56例和对照组28例,采用采用酶联免疫吸附法测定血清血小板颗粒膜蛋白-140(GMP-140)、血管性血友病因子(vWF)和抗凝血酶Ⅲ(ATⅢ)水平,采用底物发光法测定组织型纤溶酶原激活剂(t-PA)和血浆纤溶酶原激活物抑制剂1(PAI-1)水平；使用彩色多普勒超声检测颈动脉内膜中层厚度(IMT)。结果：OSAHS组血清GMP-140、vWF、Fbg、PAI-1水平高于对照组,血清ATⅢ、t-PA水平低于对照组,颈动脉内膜中层厚度高于对照组(P均＜0.05)。血清GMP-140、vWF、Fbg、PAI-1水平与IMT呈正相关(r=0.507,0.411,0.392和0.458,均P＜0.05)。血清ATⅢ、t-PA水平与IMT呈负相关(r=-0.401,-0.367,均P＜0.05)。OSAHS患者GMP-140、vWF、t-PA水平与IMT成线性回归关系。结论：OSAHS患者存在着明显的PTS,同时颈动脉内膜增厚明显。PTS是导致患者颈动脉内膜增厚的重要因素之一。     

脑梗死急性期并发LDVT患者凝血、抗凝及纤溶功能的变化

检测38例急性脑梗死并发下肢深静脉血栓形成（LDVT）患者与50例健康人的血管性血友病因子（vWF）、P-选择素（GMP-140）、凝血酶原片段1＋2（F1＋2）、总蛋白S（PS）水平及抗凝血酶（AT）、蛋白C（PC）、纤溶酶原（Plg）、纤溶酶原激活抑制物-1（PAI-1）活性.结果 与对照组比较,脑梗死急性期并发LDVT患者的vWF、GMP-140、F1＋2水平、PAI-1活性均明显升高,而总PS水平、AT、PC、Plg活性均明显降低,差异均有统计学意义（P＜0.01）.认为脑梗死急性期并发LDVT患者存在明显的高凝状态和较低的抗凝、纤溶活性,临床工作中应及早应用必要的抗凝药物,防止LDVT的发生.     

H型高血压患者血栓前状态分子标志物的变化

血栓前状态(PTS)是指多种因素引起的凝血、抗凝及纤溶系统平衡失调,有利于血栓形成的病理状态.近年来研究表明,通过检测血栓前状态的一些分子标志物可反映体内高凝状态或血栓形成[1].H型高血压(同型半胱氨酸≥10 μmol/L)是引发心脑血管疾病,尤其是脑卒中最重要的危险因素,但有关H型高血压患者血栓前状态的研究报道不多.我们通过检测H型高血压患者血浆血管性假性血友病因子(vWF)、血小板α颗粒膜蛋白-140(GMP-140)、纤维蛋白原(FIB)、D-二聚体(DD)、纤溶酶原激活物抑制物-1( PAI-1)和组织纤溶酶原激活物(t-PA)等指标,探讨其在H型高血压患者中的变化及其临床意义.     

血栓形成前状态分子标志物变化在不稳定性心绞痛合并糖尿病患者中的意义

目的观察不稳定性心绞痛(UAP)合并糖尿病(DM)患者体内血栓形成前状态分子标志物水平的变化及临床意义。方法随机选择2015年1月～2016年9月于海南省人民医院住院的40例UAP合并DM患者(合并症组),40例UAP患者(UAP组),40例健康对照者(对照组)。分别测定各组体内假性血友病因子(vWF)、纤溶酶原(Plg)、抗凝血酶Ⅲ(ATⅢ)、Ⅷ因子相关抗原(Ⅷ:Ag)、血小板颗粒膜蛋白-140(GMP-140),蛋白C(PC),Ⅱ因子活性(FⅡa)、组织型纤溶酶原激活物(t-PA)、组织型纤溶酶原激活物抑制剂(PAI)、D-二聚体(D-dimer)、血栓素B2(TXB2)。结果合并症组vWF,Ⅷ:Ag,GMP-140,FⅡa,PAI-1,D-Dimer,TXB2水平与UAP组以及对照组相比,明显升高(P0.05),而ATⅢ,PC,t-PA水平与UAP组以及对照组相比,明显降低(P0.05);UAP组vWF,Ⅷ:Ag,GMP-140,FⅡa,PAI-1,D-Dimer,TXB2水平与对照组相比,明显升高(P0.05),而UAP组ATⅢ,PC,t-PA水平与对照组相比,明显降低,差异具有统计学意义(P0.05)。结论 UAP合并DM患者体内存在更明显的止凝血分子标志物水平的变化,可能是影响其预后不良的重要因素。     

在H型高血压患者中检测血栓前状态分子标志物的意义

目的 观察H型高血压患者血栓前状态分子标志物中的血管性假性血友病因子(vWF)、血小板α-颗粒膜蛋白-140(GMP-140)、组织型纤溶酶原激活物抑制物(PAI-1)以及纤维蛋白原(FIB)的变化,分析其临床意义.方法 连续选取120例H型高血压患者为观察组,以同期住院的60例同型半胱氨酸(Hcy)正常的原发性高血压患者为对照组,30例体检健康者为空白对照组.检测3组入选者血浆vWF、GMP-140、PAI-1、FIB,并予以比较、分析.结果 从观察组到对照组、空白对照组,受试者血浆vWF 、GMP-140、PAI-1、FIB依次降低,两两比较差异有统计学意义(P＜0.01).结论 H型高血压患者可能具有更高的血栓形成风险.     

阻塞性睡眠呼吸暂停综合征患者血栓形成前状态分子与颈动脉内膜中层厚度的关系

目的:探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血栓形成前状态(PTS)分子标志物与颈动脉内膜中层厚度的关系。方法:选择OSAHS患者56例和健康体检者28例为对照组,采用酶联免疫吸附法测定血清血小板颗粒膜蛋白-140(GMP-140)、血管性血友病因子(v WF)和抗凝血酶(AT)水平,采用底物发光法测定组织型纤溶酶原激活剂(t-PA)和血浆纤溶酶原激活物抑制剂1(PAI-1)水平;使用彩色多普勒超声检测颈动脉内膜中层厚度(IMT)。结果:OSAHS组血清GMP-140、v WF、Fbg、PAI-1水平高于对照组,血清AT、t-PA水平低于对照组,颈动脉内膜中层厚度高于对照组(P均0.05)。血清GMP-140、v WF、Fbg、PAI-1水平与IMT呈正相关(r=0.507,0.411,0.392和0.458,均P0.05)。血清AT、t-PA水平与IMT呈负相关(r=-0.401,-0.367,均P0.05)。OSAHS患者GMP-140、v WF、t-PA水平与IMT成线性回归关系。结论:OSAHS患者存在着明显的PTS,同时颈动脉内膜增厚明显,PTS是导致患者颈动脉内膜增厚的重要因素之一。     

瑞舒伐他汀对血脂正常阻塞性睡眠呼吸暂停综合征合并高血压患者血栓前状态的影响

目的 研究瑞舒伐他汀对血脂正常的阻塞性睡眠呼吸暂停综合征（OSAS）合并高血压患者血栓前状态的影响.方法 血脂正常的OSAS合并高血压患者75例,随机分成瑞舒伐他汀组40例,常规治疗组35例,另选取25名门诊健康体检者作为对照组.检测一氧化氮（NO）、内皮素（ET-1）及血管性假性血友病因子（vWF）、血小板颗粒膜蛋白（GMP-140）、组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活物抑制剂-1（PAI-1）的水平变化.结果 ①治疗前两组OSAS合并高血压患者NO、t-PA低于健康对照组,差异有统计学意义（P＜0.05）;ET-1、vWF、GMP-140、PAI-1水平均高于健康对照组,差异有统计学意义（P＜0.01）.②治疗后瑞舒伐他汀组及常规治疗组NO、t-PA水平均较治疗前升高,瑞舒伐他汀组NO、t-PA高于常规治疗组,差异有统计学意义（P＜0.05）.③治疗后瑞舒伐他汀组及常规治疗组ET-1及vWF、GMP-140、PAI-1均较治疗前降低,瑞舒伐他汀组ET-1、vWF,GMP-140低于常规治疗组,差异有统计学意义（P＜0.01）.结论 对于血脂正常的OSAS合并高血压患者,瑞舒伐他汀可通过提高血浆NO、t-PA浓度和降低ET-1、vWF、GMP-140、PAI-1浓度等非调脂机制改善血栓前状态.     

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.     

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.     

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.