高血压患者阿司匹林抵抗

目的 观察高血压患者阿司匹林抵抗(AR)发生率,并探讨阿司匹林抵抗的影响因素和可能机制.方法 分别以致聚剂花生四烯酸(AA)、二磷酸腺苷(ADP)诱导,测定108名未经治疗的高血压患者服用阿司匹林前及每日服用阿司匹林100 mg,1周后的全血的血小板聚集电阻抗值.根据对阿司匹林反应分为阿司匹林抵抗:环氧化酶型阿司匹林抵抗(COX型AR);环氧化酶旁路型阿司匹林抵抗(COX-AP型AR);阿司匹林敏感(AS),同时测定服药前的血常规及血纤维蛋白原浓度.结果 高血压患者108例,总的阿司匹林抵抗发生率为55.5%,其中COX-AP型发生率为44.4%,COX型发生率为11.1%.COX-AP型和COX型AR患者服用阿司匹林后ADP诱导的的血小板聚集值均明显高于服药前[(9.0±2.7) vs (6.4±2.9)ohm,P＜0.05;(6.7±2.4) vs (5.7±2.5)ohm, P＜0.05].COX型和COX-AP型阿司匹林抵抗患者的血小板、白细胞、中性粒细胞计数明显高于阿司匹林敏感者[(215.5±20.0)/(213.5±44.3) vs (189.1±61.8)×109 (L-1), P＜0.05];[(6.20±0.5)/(6.5±1.5) vs (5.6±1.2), P＜0.05];[(3.5±0.1)/(3.8±1.6) vs (3.1±0.8)×109 L(-1), P＜0.05].结论 高血压患者存在阿司匹林抵抗,其发生机制与启动血小板聚集的途径异常有关.环氧化酶旁路的存在且功能代偿性增强是高血压患者发生阿司匹林抵抗的主要机制;环氧化酶途径异常是另一次要机制.血液中血小板、白细胞、中性粒细胞等数量增加可能对阿司匹林抵抗的发生有影响.     

高血压病患者阿司匹林抵抗与β纤维蛋白原基因启动子区-455G／A多态性的关系

目的探讨高血压患者β纤维蛋白原基因启动子区-455G／A多态性与阿司匹林抵抗的关系。方法用电阻抗法测定108例高血压患者口服阿司匹林前后ADP及花生四烯酸诱导的血小板聚集电阻抗值（ohm）,判定患者阿司匹林疗效,分为阿司匹林敏感、环氧化酶型阿司匹林抵抗,环氧化酶旁路型阿司匹林抵抗;用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法检测βFg基因启动子区-455G／A多态性,依据多态性结果分为GG基因组和GA＋AA基因组,比较不同基因组纤维蛋白原浓度以及阿司匹林抵抗发生率。结果高血压患者GG、GA、AA基因型频率分别为0．639、0．324、0．037,G、A等位基因频率分别为0．801、0．199。GA＋AA组纤维蛋白原浓度高于GG组（3．30±0．98vs2．93±0．70,p〈0．05）。环氧化酶型阿司匹林抵抗发生率GG组、GA＋AA组分别为13．04％、7．69％（Х^2=0．282,p〉0．5）;环氧化酶旁路型阿司匹林抵抗发生率GA＋AA组显著高于GG基因组（61．54％vs34．78％,Х^2=5．841,p=0．016）。结论βFg基因-455G／A启动子区携带A-455等位基因高血压患者环氧化酶旁路型阿司匹林抵抗发生率高,A-455等位基因与环氧化酶旁路型阿司匹林抵抗具有相关性。     

脑梗死患者阿司匹林抵抗及相关基因多态性研究

目的探讨脑梗死患者阿司匹林抵抗（AR）发生率及环氧化酶-1（COX-1）基因C50T和环氧化酶-2（COX-2）基因G765C多态性与阿司匹林抵抗的相关性。方法634例首次发病的脑梗死患者,入院次13开始服用阿司匹林,服用阿司匹林治疗前和治疗7～10天后分别检N--磷酸腺苷（ADP）和花生四烯酸（AA）诱导的血小板聚集率（PAG）,并采用多聚酶链式反应结合限制性内切酶片段长度多态分析方法检测COX-1基因CSOT、COX-2基因G765C多态性。结果634例脑梗死患者中,阿司匹林抵抗（AR）者129例（20．35％）,阿司匹林半抵抗（ASR）28例（4．42％）,阿司匹林敏感（AS）477例（75．23％）。COX-1CSOT和COX-2G765C基因型及等位基因在ASR＋AR组及As组的比较差异无统计学意义（P〉0．05）;服用阿司匹林后7—10天,脑梗死患者AA诱导的血小板聚集率及ADP诱导的血小板聚集率分别下降80．00％及40．00％;无论COX-1C50T和COX-2G765C的哪种基因型均可使AA诱导血小板聚集率及ADP诱导血小板聚集率降低,但各种基因型在这些指标降低幅度的比较差异无统计学意义（P〉0．05）;COX-1基因CSOT和基因GCOX-2765C变异者AA诱导血小板聚集率在服阿司匹林前后均高于无变异者,差异有统计学意义（P〈0．05）。结论脑梗死患者阿司匹林抵抗发生率高,COX-1基因CSOT、COX-2基因G765C多态性与阿司匹林抵抗的发生无明显相关性,也不影响阿司匹林对血小板的反应性。     

冠心病患者阿司匹林抵抗的初步观察

目的初步探讨冠心病患者的阿司匹林抵抗(AR)现象及其相关因素。方法经冠脉造影确诊为冠心病患者156例,服用阿司匹林100mg/d≥1周后,分别用花生四烯酸(AA)、二磷酸腺苷(ADP)作诱导剂检测血小板聚集率(PAG)。AA诱导的PAG≥20%,同时ADP诱导的PAG≥70%者为AR;仅符合其中一项为阿司匹林半抵抗(ASR);均不符合者为阿司匹林敏感(AS)。结果156例患者中AR发生率为22.44%(35例),ASR发生率是17.95%(28例),AS发生率是59.62%(93例)。AR+ASR组中的糖尿病患者所占比例(28.57%)较AS组(9.68%)多(P<0.05);AR+ASR组患者血浆总胆固醇、低密度脂蛋白-胆固醇浓度显著高于AS组(P<0.05)。结论服用小剂量阿司匹林的冠心病患者AR+ASR发生率为40.38%;AR或ASR者血浆胆固醇浓度较高;糖尿病患者AR或ASR发生率较高。     

高血压患者阿司匹林抵抗及相关因素分析

目的探讨高血压患者阿司匹林抵抗（AR）现象及其相关因素。方法选取81例高血压病患者,服用阿司匹林100 mg/d,服用时间≥2周。分别用二磷酸腺苷（ADP）、花生四烯酸（AA）作诱导剂检测血小板聚集率（PAG）。同时满足ADP诱导的PAG≥70%、AA诱导的PAG≥20%为AR,仅满足其中一项为阿司匹林半抵抗（ASR）,均不符合者为阿司匹林敏感（AS）。结果81例高血压患者中,AR＋ASR发生率为11.1%。AR＋ASR组较AS组合并不稳定型心绞痛比例及平均血小板体积显著增加（P〈0.05）。结论不稳定型心绞痛患者更容易发生AR,平均血小板体积增大可能对AR的发生产生影响。     

阿司匹林抵抗与环氧化酶-1、环氧化酶-2及血栓烷A2受体基因多态性相关性研究

目的:探讨冠心病二级预防中的阿司匹林抵抗现象,及其与环氧化酶-1(COX1)、环氧化酶-2(COX2)、血栓烷A2受体(TBXA2R)基因多态性之间相关性。方法:选取连续服用阿司匹林100 mg大于7天的冠心病患者2 881例,选择符合阿司匹林抵抗标准的患者作为阿司匹林抵抗组(AR组),共166例;阿司匹林敏感的患者200例作为对照组。应用花生四烯酸(AA)作诱导剂测定服药后的血小板聚集功能。并采用聚合酶链反应-限制性核酸内切法(PCR-RFLP)检测COX1、COX2、TBXA2R的基因多态性。结果:阿司匹林抵抗的发生率约为5.76%(166/2 881)。三个基因共8个tag SNPs位点[COX1(rs3842788、rs4273915、rs7866582);、COX2(rs3218625);TBXA2R(rs2238630、rs2238631、rs2238633、rs3786989)]野生型、杂合子及纯合子的基因型频率在两组之间差异无统计学意义。结论:规律服药的冠心病患者阿司匹林抵抗的发生率并不高。COX1、COX2以及TBXA2R基因单核苷酸多态性与阿司匹林抵抗的发生无明显关系。     

冠心病患者阿司匹林抵抗相关因素分析

目的:探讨冠心病患者阿司匹林抵抗(AR)的发生率,并对其临床相关因素进行分析。方法:选择264例正规服用阿司匹林(75～100mg/d)超过1个月的冠心病患者,分别用胶原(COL)和二磷酸腺苷(ADP)作为诱导剂测定其静脉血中血小板聚集功能,根据结果分为AR组、阿司匹林半抵抗(ASR)组和阿司匹林敏感(AS)组,分析各组间的临床特征,找出可能与AR有关的因素。结果:所有入选者中AR发生率为8.71%(23/264),ASR发生率为18.56%(49/264),AR+ASR总发生率27.27%。AR组、ASR组中,女性和伴糖尿病者及外周血小板计数较AS组高(P<0.05)。结论:冠心病患者AR+ASR的总发生率为27.27%,其发生可能与性别、伴糖尿病以及外周血小板数目有关。     

缺血性脑卒中患者环氧化酶-1、-2基因多态性与阿司匹林抵抗的关系

目的探讨环氧化酶(COX)的基因多态性与阿司匹林抵抗(AR)的关系。方法选取缺血性脑卒中(IS)患者300例,依据血小板聚集率分为阿司匹林敏感组(AS组,180例)、阿司匹林半抵抗组(ASR组,84例)和AR组(36例);比较3组一般临床资料,采用光比浊法检测血小板聚集率。应用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)技术检测COX基因多态性,并比较两组基因型和等位基因分布差异。结果 AR组与ASR组COX-1上A-842/C50T有统计学差异(P<0.05),而COX-2-765G>C(rs20417)无统计学差异(P>0.05)。结论 COX-1上的T等位基因是其突变基因,C/T和TT突变会增加AR的风险,而COX-2-765G>C的基因突变与AR无相关性。     

冠脉粥样硬化患者AR中医证型分布及活血胶囊对血瘀型AR的干预作用

目的明确阿司匹林抵抗与冠状动脉粥样硬化患者中医证型的关系以及中药活血胶囊对阿司匹林抵抗血瘀型患者的影响,为有效降低阿司匹林抵抗发生率提供预测和治疗新思路。方法对冠状动脉粥样硬化需服用阿司匹林的310例患者通过专家商讨确定其所属中医证型,随访两年;并在临床研究前后测定血小板聚集率。将发生阿司匹林抵抗血瘀型的37例患者随机分成三组,空白对照组(13例)、活血胶囊治疗组(12例)、活血胶囊联合阿司匹林组(12例)。用以研究活血胶囊改善阿司匹林抵抗的作用。结果心血瘀阻型发生阿司匹林抵抗(28.5%)明显高于寒凝心脉型(10.0%)、痰浊内阻型(16.7%)、心气虚弱型(15.9%)、心肾阴虚型(15.0%)和心肾阳虚型(20.0%),经χ2检验差异有统计学意义(P<0.05)。心血瘀阻型患者服用活血胶囊3个月可降低血小板聚集率,但与空白组比较差异无统计学意义;而活血胶囊联合阿司匹林治疗明显降低血小板聚集率,与空白组比较差异有统计学意义(P<0.05)。结论心血瘀阻型患者更易发生阿司匹林抵抗;活血化瘀方药活血胶囊具有降低血小板聚集的作用,联合应用阿司匹林能够明显降低阿司匹林抵抗的发生。     

心脑血管疾病患者阿司匹林抵抗的临床与实验研究

目的探讨心脑血管疾病患者阿司匹林抵抗(aspirin resistance,AR)的发生率、可能影响因素及其对预后的影响。方法采用光学法测定157例服用阿司匹林的心脑血管疾病患者的血小板聚集率,其中高血压76例、脑梗死56例、冠心病25例,将AR和阿司匹林半抵抗患者作为非阿司匹林敏感(aspirin sensitive,AS)组(59例),其余患者作为AS组(98例),并同时检测肝、肾功能、血脂、血糖等生化指标,分析该患者群中AR的发生、相关危险因素及预后。结果非AS组冠心病患者较AS组明显增多(P0.05)。糖尿病、高脂血症与AR发生相关(OR=4.438,OR=2.943,P0.01)。非AS组脑梗死和心肌梗死再发率明显高于AS组(15.05% vs 3.06%,P0.05;18.64% vs 7.14%,P0.01)。结论 AR对预后影响大,可使心脑血管事件再发风险显著升高,应及时调整药物剂量或者联合应用其他抗血小板药物。     

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.     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.