高血压病人血浆同型半胱氨酸等活性物质浓度的变化及其意义

目的：探讨同型半胱氨酸（Hcy）、肾上腺髓质素（ADM）、降钙素基因相关肽（CGRP）与血栓素B2（TXB2）等血管活性物质与原发性高血压（EH）的关系。方法：随机选取未经治疗的EH病人42例作为研究组，按高血压分级标准分为3个亚组，对照组由20例同期健康体检的正常人组成。采受试者空腹静脉血，用荧光法定量检测Hey，以放射免疫法检测ADM、CGRP与TXB2。结果：（1）研究组血浆Hey、ADM、TXB2三者浓度明显高于对照组．而CGRP水平明显下降，有显著性差异（P均〈0.01）；（2）研究组三个亚组l级组、2级组和3级组Hcy、ADM、TXBz水平随着血压分级升高而升高，CGRP随血压分级升高而降低，组间差别有显著性（P〈0．01）；（3）研究组血浆Hcy与ADM浓度呈显著正相关（r=0．941。P〈0.01），与CGRP呈负相关（r=-0．480，P〈0．01）；其余相关性均不显著。结论：血浆同型半胱氨酸、肾上腺髓质素、降钙素基因相关肽与血栓素的含量变化与高血压病的血压升高有紧密联系。提示它们参与了高血压的发生与发展。     

细胞因子在原发性高血压中的作用探讨

目的观察原发性高血压(EH)病人血清白细胞介素-1β(IL-1β)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)浓度与高血压病的关系及厄贝沙坦对其的影响.方法用放免法检测60例高血压病病人(EH组)及28名健康体检者(对照组)血清IL-1β、IL-4、IL-6和TNF-α浓度.高血压组服用厄贝沙坦3月后重复上述检查.结果 EH组血清IL-1β、IL-4 、IL-6和TNF-α浓度高于对照组(P<0.01).采用厄贝沙坦治疗后血清IL-1β、IL-4、IL-6和TNF-α浓度显著下降(P<0.05或P<0.01).结论白细胞介素和肿瘤坏死因子与EH的发生发展有关,厄贝沙坦治疗可降低病人血清白细胞介素和肿瘤坏死因子水平.     

高血压早期肾损害肾内血流动力学异常与内皮素及降钙素基因相关肽的关系

目的:探讨原发性高血压并发早期肾损害患者肾内动脉血流动力学改变与血浆内皮素(ET-1)和降钙素基因相关肽(CGRP)水平变化的相关性.方法:根据血α1-微球蛋白及血、尿β2-微球蛋白水平将90例原发性高血压患者分为早期肾损害组(45例)和无早期肾损害组(45例),另选择健康志愿者43例为对照组.采用ELISA法对各组血浆ET-1、CGRP水平进行测定,同时用彩色超声多谱勒技术测量双侧主肾动脉(MRA)、叶段动脉(SRA)、叶间动脉(IRA)的血流收缩期峰速度(Vs)、舒张期末血流速度(Vd)、平均血流速度(Vm)、血流峰速加速时间(AT)、脉冲指数(PI)、阻力指数(RI),以上各血流参数均取左右肾动脉平均值.结果:高血压组与对照组比较,MRA、SRA、IRA的Vs、Vd、Vm显著降低(P<0.05),PI、RI明显增高(P<0.05)、AT无明显延长(P>0.05);且Vs、Vd、Vm随血压分级的增加而降低,AT随血压分级的增加而延长,PI、RI随血压分级的增加而升高.高血压早期肾损害组与无早期肾损害组比较,SRA、IRA的Vs、Vd、Vm显著降低(P<0.05),AT明显延长(P<0.05),PI和RI明显增高(P<0.05).高血压组与对照组比较,血浆ET-1水平明显增高(P<0.01),CGRP显著降低(P<0.01).高血压早期肾损害组与无早期肾损害组比较,血浆ET-1水平明显增高(P<0.001),CGRP显著降低(P<0.01).直线相关分析显示,ET-1与MRA、SRA、IRA的Vs、Vd、Vm负相关(P<0.01),与PI、RI、AT正相关(P<0.01);CGRP与MRA、SRA、IRA的PI、RI、AT负相关(P<0.01),与Vs、Vd、Vm正相关(P<0.01),均以IRA的Vd、RI相关性最好.结论:在高血压早期肾损害阶段,存在肾内血流动力学异常;而ET-1水平升高和CGRP水平下降可能是高血压早期肾损害肾内血流力学异常的原因之一.     

原发性高血压和心力衰竭患者血浆肾上腺髓质素和高敏C反应蛋白变化的研究

目的探讨血浆肾上腺髓质素(ADM)、高敏C反应蛋白(hs-CRP)的浓度变化,在原发性高血压(EH)、心力衰竭过程中的变化及意义。方法选取21例健康体检者(对照组)及59例老年EH患者,其中32例单纯EH(高血压组)、27例EH合并心力衰竭(心力衰竭组),用放射免疫法测定血浆ADM,用胶乳免疫增强比浊法测hs-CRP的浓度。结果高血压组患者血浆ADM及hs-CRP的浓度较对照组明显升高;心力衰竭组血浆hs-CRP、ADM浓度较对照组明显升高;在心力衰竭组和高血压组中,不同心功能分级和高血压分级的患者随心功能衰竭加重和高血压级别的升高,血浆hs-CRP及ADM的浓度均有所升高;患者血浆hs-CRP浓度及ADM浓度呈正相关。结论血浆ADM、hs-CRP合成增加是原发性高血压、心力衰竭过程中血管活性物质调节紊乱的特点,可以作为观察高血压、心力衰竭过程中心功能变化的指标。     

原发性高血压患者血浆神经肽Y的变化

目的通过观察血浆神经肽Y(NPY)在原发性高血压(EH)患者中浓度的变化,探讨血浆NPY在EH病理生理进程中的作用及在EH靶器管损害中的意义。方法选EH患者115例,以左室肥厚、脑卒中与肾功能损害为靶器官损害,其中伴有左室肥厚者21例,伴有脑卒中者13例、伴有肾功能损害者11例,为单一靶器官损害组,伴有两种或两种以上靶器官损害者19例为联合靶器官损害组,余下51例为单纯高血压而无靶器官损害组,体检健康者30例为对照组。取空腹静脉血用放射免疫方法测定NPY的血浆浓度。结果1)EH患者血浆NPY浓度高于对照组(P<0.01),不同血压级别之间血浆NPY浓度亦存在显著性差异(F=76.717,P<0.01),且随着血压级别的上升而升高。血浆NPY浓度与平均动脉压呈正相关(r=0.86,P<0.01)。2)单一靶器官损害组血浆NPY浓度高于单纯高血压而无靶器官损害组,差异有非常显著意义(P<0.01)。联合靶器官损害组血浆NPY浓度高于单纯高血压而无靶器官损害组,差异有非常显著意义,而与单一靶器官损害组相比差异无统计学意义(P>0.05)。结论血浆NPY可能与EH的病理生理进程以及EH靶器官损害的发生和发展有关,检测血浆NPY浓度可作为评价EH进程及靶器官损害程度的指标。     

老年高血压患者肾上腺髓质素与肾功能损害的关系

目的研究老年原发性高血压(EH)患者血浆肾上腺髓质素(ADM)水平的变化及其与肾功能损害的关系。方法用放射免疫法测定老年EH患者(其中高血压1级16例、2级22例、伴肾功能损害者14例)与健康对照者的血浆ADM水平,比较不同组间血浆ADM水平的差异,直线相关分析老年EH患者血浆ADM与血清肌酐(Cr)水平的关系。结果老年EH患者血浆ADM水平显著高于对照组,但1级与2级高血压组间血浆ADM水平无显著差别;老年EH伴肾功能损害组血浆ADM水平显著高于肾功能正常组;老年EH患者血浆ADM水平与血清Cr水平呈显著正相关(P<005)。结论老年EH患者血浆ADM水平显著升高,老年EH患者血浆ADM水平与血压分级无关但与肾功能损害进展有关。     

厄贝沙坦与非洛地平联用对高血压病左室肥厚的逆转作用

目的探讨厄贝沙坦、非洛地平联合用药对原发性高血压(EH)病人左室肥厚(LVH)的逆转作用.方法 EH伴LVH病人180例随机分为对照组(非洛地平每天10 mg,90例)和治疗组(厄贝沙坦每天75 mg加非洛地平每天5 mg,90例),治疗两周时若血压≥160/90 mmHg,则厄贝沙坦和非洛地平分别增加1倍,总疗程共6个月.治疗前后观察心率变化、24 h动态血压监测和彩色超声多普勒检测左室相关指标,计算左室重量指数(LVMI).结果两组治疗后均能显著降低LVMI(P＜0.01),且治疗组较对照组更为显著(P＜0.01);两组治疗前心率、24 h平均收缩压、平均舒张压比较无统计学意义(P＞0.05),治疗后24 h平均收缩压、平均舒张压较治疗前显著降低(P＜0.01),但治疗后两组间无统计学意义(P＞0.05).结论厄贝沙坦与非洛地平联用逆转EH病人LVH效果较单用非洛地平疗效更为显著.     

氯沙坦对高血压病患者单核细胞趋化蛋白-1的影响

目的 观察氯沙坦对高血压病患者血浆中单核细胞趋化蛋白-1(MCP-1) 水平及血管内皮功能的影响.方法 100例高血压患者随机分为氯沙坦(50 mg/d)组和氨氯地平(5 mg/d)组,疗程12周.分别于治疗前后检测血浆MCP1、一氧化氮(NO)、血管假性血友病因子(vWF)浓度.选取45名健康体检者作为对照组,监测指标同上.结果 与对照组相比,高血压病患者血浆中MCP-1和vWF浓度均明显升高(P<0.01),NO浓度明显下降(P<0.01);氯沙坦组和氨氯地平组治疗12周后血压均明显下降(P<0.01),两组间血压下降程度无统计学意义(P>0.05);两组患者MCP-1、vWF水平均显著降低(P<0.01),NO水平显著升高(P<0.01);氯沙坦组较氨氯地平组降低MCP-1、vWF和升高NO的作用更显著(P<0.01).结论 相对于氨氯地平来说,氯沙坦能更显著降低高血压患者MCP1,改善血管内皮功能,这种作用独立于其降压作用之外.     

雄性自发性高血压大鼠代谢综合征相关指标及药物干预的研究

目的:探讨早期雄性自发性高血压大鼠(SHR)血清尿酸(UA)和血脂代谢异常在高血压靶器官损害进程中的作用,并观察厄贝沙坦(irbesartan)对血尿酸和血脂代谢的影响。方法:对象为15周龄雄性SHR20只和正常雄性同龄WistarKyoto(WKY)大鼠10只。将SHR随机分为两组:厄贝沙坦治疗组(按厄贝沙坦50mg/kg.d从饮水给药);SHR阳性对照组。后者与WKY正常对照组喂以等量蒸馏水代替。实验于三个月后停药,测体重和血压,检测血清UA、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)值。结果:实验三个月后,与WKY组比较,SHR组UA水平显著增高(P<0.05),血压和TG水平显著增高(P<0.01);与SHR组比较,厄贝沙坦组血压和TG水平显著降低(P<0.01),UA水平显著降低(P<0.05)。结论:高血压病早期已经存在着高尿酸血症和血脂异常等代谢异常的临床征象,厄贝沙坦既具有降低TG又具有降低UA的作用,可能有抗动脉粥样硬化和肾保护作用。     

厄贝沙坦和依那普利对高血压患者血管紧张素及醛固酮的影响

目的:探讨厄贝沙坦和依那普利对原发性高血压(EH)的降压疗效及对血浆血管紧张素Ⅱ(ATⅡ)、醛固酮(ALD)的影响。方法:检测轻中、度EH患者55例、正常对照者20例的血浆ATⅡ、ALD水平。55例EH患者中27例接受厄贝沙坦治疗,28例接受依那普利治疗,疗程12周。治疗4、12周时复测ATⅡ、ALD。结果:厄贝沙坦组治疗4周时ATⅡ水平升高(P<0.01),12周时其水平无明显改变。依那普利组ATⅡ水平下降(P<0.01),12周时其水平较4周时增高(P<0.05),但亦显著低于治疗前(P<0.01)。ALD水平在两组中4周后均显著下降(P<0.01),12周后其水平较4周时增高(P<0.05),但仍比治疗前显著下降(P<0.05)。两组降压效果相似,厄贝沙坦组药物不良反应较少。结论:厄贝沙坦和依那普利降压效果相似,厄贝沙坦使血浆ATⅡ水平升高,依那普利使ATⅡ水平下降。两组均可能不能完全抑制醛固酮的生成。     

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.     

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.     

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.