急性脑梗塞患者血小板内钙cAMP和TXB2含量关系的探讨

目的：为探讨急性脑梗塞急性期患者血小板内游离下，ｃＡＭＰ和ＴＸＢ２含量之间的相互关系及意义，方法：用Ｆｕｒａ－２／ＡＭ荧光技术测定了１６例急性脑梗塞患者急性期血小板内钙含量，用放射免疫分析法测定其血小板内ｃＡＭＰ和血栓素Ｂ２（ＴＸＢ２）含量。结果：患者血板小板游离Ｃａ＾２＋和ＴＸＢ２含量明显高于正常对照（Ｐ〈０．０１），而血小板内ｃＡＭＰ含量则明显低于正常对照（Ｐ〈０．０１）；血小板内游离Ｃａ＾２     

慢性肺心病急性加重期血小板内Ca^2＋cAMP和TXB2含量关系的探讨

目的：为探讨慢性肺心病急性加重期患者血小板内游离Ｃａ２＋、ｃＡＭＰ和ＴＸＢ２之间的相互关系及意义。方法：用Ｆｕｒａ－２／ＡＭ荧光技术测定了３０例慢性肺心病患者急性加重期和２５例正常对照的血小板内游离Ｃａ２＋含量，用放射免疫分析法测定其血小板内ｃＡＭＰ和ＴＸＢ２的含量。结果：患者血小板内游离Ｃａ２＋和ＴＸＢ２含量明显高于正常对照（Ｐ均＜０．０１），而血小板内ｃＡＭＰ含量则明显低于对照组（Ｐ＜０．０１），且患者中血小板内Ｃａ２＋含量和ＴＸＢ２含量均与血小板内ｃＡＭＰ含量成负相关（ｒ分别为－０．７６６和－０．５３３，Ｐ均＜０．０１），而Ｃａ２＋含量与ＴＸＢ２含量之间则呈明显的正相关性（ｒ为０．７０７，Ｐ＜０．０１）。结论：慢性肺心病急性加重期血小板处于活跃状态，可能与其内Ｃａ２＋含量升高、ＴＸＢ２生成增加、ｃＡＭＰ含量降低有关，三者相互作用来激活血小板     

肝硬化患者血浆环核苷酸、环鸟苷酸含量的变化

肝硬化患者血浆环核苷酸、环鸟苷酸含量的变化湖南医科大学附属湘雅医院邹益友，雷闽湘，钟惠菊环核苷酸（ｃＡＭＰ）及环鸟苷酸（ｃＧＭＰ）是各种动物细胞内具有重要生物效应的物质，肝硬化时，由于肝细胞变性、坏死与增殖，势必影响ｃＡＭＰ及ｃＧＭＰ的血浆含量，本文...     

冠心病患者血小板活化状态的探讨

目的：血小板表面膜蛋白颗粒（ＧＭＰ－１４０）是血小板活化状态的特异性指标。血浆ＧＭＰ－１４０的增高同样也反映了血小板的激活和释放反应,本文探讨血小板活化状态与急性心肌梗塞（ＡＭＩ）和不稳定型心绞痛（ＵＡＰ）的发病的关系,方法：对１５例ＡＭＩ和２３例ＵＡＰ患者进行血浆ＧＭＰ－１４０ｖＷＦ测定,结果：ＡＭＩ和ＵＡＰ患者血浆ＧＭＰ－１４０ｖＷＦ明显升高,发作后下降,接近正常,ＧＭＰ－１４０与血清肌酸激酶     

冠心病患者血小板活化状态的探讨

上板表面膜蛋白颗粒（ＧＭＰ－１４０）是血小板活化状态的特异性指标。血浆ＧＭＰ－１４０的增高同样也反映了血小板的激活和释放反应,对１９例急性心肌梗塞（ＡＭＩ）和２６例不稳定型心绞痛（ＵＡＰ）患者进行血浆ＧＭＰ－１４０、假血友病因子（ｖＷＦ）测定。结果显示ＡＭＩ和ＵＡＰ患者血浆ＧＭＰ－１４０、ｖＷＦ明显升高。ＧＭＰ－１４０与血清肌酸激酶及其同功酶、乳酸脱氢酶及其同功酶以及心肌梗塞和心绞痛缺血面积均呈正相关,血清ＧＭＰ－１４０是ＡＭＩ和ＵＡＰ发作时体内血小板活化的评估指标。     

家兔脑缺血再灌注损伤机制的研究

用家兔四动脉闭塞法建立急性完全性脑缺血后给予再灌注，观察缺血前后及再灌注后脑组织部分电解质和含水量、脑组织和血液丙二醛（ＭＤＡ）、环核昔酸（ｃＡＭＰ、ｃＧＭＰ）、血栓烷Ｂ＿２（ＴｘＢ＿２）、６－酮－前列腺素Ｆ＿（１α）（６－ｋｅｔｏ－ＰＧＦ＿（１α）含量、超氧化物歧化酶（ＳＯＤ）和谷胱苷肽过氧化物酶（ＧＳＨ－Ｐｘ）活性改变。结果：再灌注后实验组脑组织Ｃａ￣（２＋）、ＭＤＡ、ＴｘＢ＿２和ｃＡＭＰ较对照组升高（Ｐ＜０．０５），ＧＳＨ－Ｐｘ活性、６－ｋｅｔｏ－ＰＧＦ＿（１α）含量降低（Ｐ＜０．０５）；实验组血液中ｃＡＭＰ含量高于对照组（Ｐ＜０．０５）。提示脑组织Ｃａ￣（２＋）过载、氧自由基增多、ｃＡＭＰ／ｃＯＭＰ和ＰＧＩ＿２／ＴＸＡ＿２比值异常在脑缺血再灌注损伤中起着重要的作用。     

PTA1单克隆抗体诱导人血小板活化聚集和胞浆Ca^2＋水平的升高

目的：探讨血小板和Ｔ细胞活化抗原１（ＰＴＡ１）诱导人血小板活化聚集和对血小板胞浆Ｃａ２＋水平影响的机制。方法：血小板聚集与ＡＴＰ释放试验及血小板胞浆Ｃａ２＋水平测定。结果：ＰＴＡ１单克隆抗体（ＭｃＡｂ）体外可诱导人血小板活化聚集，ＥＧＴＡ与ＰＧＩ２可以完全抑制ＰＴＡ１ＭｃＡｂ诱导的血小板活化聚集，ＰＴＡ１ＭｃＡｂＦ（ａｂ′）２对ＣＤ９或ＣＤ４１诱导的血小板活化聚集无明显影响。ＰＴＡ１ＭｃＡｂ促进血小板胞浆Ｃａ２＋水平升高。结论：ＰＴＡ１ＭｃＡｂ的刺激作用与血小板膜表面Ｆｃ受体和ＣＤ４１／ＣＤ６１（ⅡｂⅢａ）复合物有关，促进血小板胞浆Ｃａ２＋水平升高为胞外Ｃａ２＋内流与胞浆内Ｃａ２＋储存释放共同作用所致。     

腰椎间盘突出症康复治疗对血小板活化的影响

目的：探讨血小板的活化在腰椎间盘突出症中的作用和康复治疗对血小板活化的影响。方法：采用双抗体夹心ＥＬＩＳＡ法测定２０例腰椎间盘突出症患者康复治疗前后和１８名正常人血浆内血小板α－颗粒膜蛋白１４０（ＧＭＰ－１４０）含量。结果：腰椎间盘突出症患者血浆ＧＭＰ－１４０水平显著高于正常对照组（Ｐ＜０．００１）,康复治疗后血浆内ＧＭＰ－１４０水平比治疗前明显降低（Ｐ＜０．００１）,但仍高于正常对照组（Ｐ＜０．０５）。结论：腰椎间盘突出症的发病与ＧＭＰ－１４０有关,康复治疗能降低或抑制血小板活化     

老年肺心病血小板,血纤溶系统活化与过氧化损伤关系探讨

本文观察４８例老年肺心病人住院治疗前后血浆ｔ－ＰＡ（纤溶酶原激活物）、ＰＡＩ（纤溶酶原激活抑制物）、ＧＭＰ－１４０（血小板α－颗粒膜蛋白），ＳＯＤ（赵氧化物歧化酶）、ＭＤＯＡ（丙二醛）的变化．结果发现肺心病急性加重期ｔ－ＰＡ值下降，而ＰＡＩ、ＧＭＰ－１４０、ＭＤＡ升高（Ｐ＜０．０１）；病情缓解期ｔ－ＰＡ回升，而ＰＡＩ、ＧＭＰ－１４０，ＭＤＡ则下降至正常对照组水平（Ｐ＜０．０５）．虽ＳＯＤ无明显玉米化，仍说明肺心病急性期有显著的血纤溶系统紊乱和血小板激活反应，形成高凝高粘滞血症及微血栓形成，加重肺循环阻力，恶化肺动脉高压和右心功能．这些与过氧化损伤相关，提示临床治疗时应予以重视．     

血浆血小板α颗粒膜蛋白水平在急性心肌梗死患者发病过程中的变化

血小板α颗粒膜蛋白（ＧＭＰ１４０）是血小板活化特异性指标。我们动态监测急性心肌梗死（ＡＭＩ）患者血浆ＧＭＰ１４０水平变化，了解血小板活化对ＡＭＩ发生发展的意义。１资料与方法１．１病例：ＡＭＩ组３０例患者，诊断符合文献〔１〕的诊断标准。其中前间壁梗死６...     

Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache

Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determine whether the pain-inducing effects of sildenafil would be reflected in plasma levels of important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate (cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four women, six men) and 12 patients (12 women) suffering from migraine without aura were included in two separate double-blind, placebo-controlled, cross-over studies in which placebo or sildenafil 100 mg was administered orally. Plasma levels of CGRP, cAMP and cGMP were determined in blood from the antecubital vein. Despite the ability of sildenafil to induce headache and migraine, no significant differences in plasma levels of CGRP, cGMP and cAMP were detected after sildenafil compared with placebo. In conclusion, plasma levels of CGRP, cGMP and cAMP remain normal during sildenafil-induced headache or migraine. However, since previous studies indicate an important role of these signalling molecules, the present study questions whether cAMP and cGMP in peripheral blood can be used for monitoring pathophysiological events in headache and migraine mechanisms.     

Platelet nitric oxide metabolites in migraine

Nitric oxide (NO) is a candidate as a causative molecule in migraine. We determined nitrite, total nitrate/nitrite, and cyclic guanosine 3',5'-monophosphate (cGMP) concentrations in platelets from 30 migraine without aura (MwoA) patients and 17 migraine with aura (MwA) patients. All migraine patients were studied during their migraine attacks. The control group consisted of 28 healthy volunteers. Concentrations of platelet nitrite and total nitrate/nitrite were determined using simple and sensitive nitrate/nitrite fluorometric assay techniques. High concentrations of platelet nitrite and total nitrate/nitrite were found in patients with MwoA and MwA when compared with healthy controls. High concentrations of platelet cGMP were also found in patients with MwoA and MwA. The levels of platelet total nitrate/nitrite significantly decreased in headache-free periods after treatment with oral propranolol. These findings suggest that NO is produced in platelets during migraine attacks. It may also be related to the migrainous pain and the changes in cerebral blood flow experienced during migraine attacks. These data may provide new strategies for the treatment of migraine.     

偏头痛患者血清一氧化氮测定的临床意义

目的：研究偏头痛发作与患者血清一氧化氮（NO）和环磷酸鸟苷（cGMP)变化的关系及其临床意义。方法：用荧分光光度法和放射免疫法分别检测32列偏头痛发作期、25例间歇期和30例正常人血清中NO2和cGMP的含量。结果：偏头痛发作期患者血清中NO2和cGMP的含量明显高于间歇期和正常对照组（P＜0．01）。偏头痛间歇期患者血清中NO2和cGMP的含量仍高于正常对照组（P＜0．01）。结论：NO和cGMP的变化可能参与偏头痛的病理生理过程。     

Level of nitric oxide-dependent cGMP in patients with migraine

It is believed that nitric oxide (NO) plays a significant role in migraine attacks. This molecule is formed due to the conversion of L-arginine into L-citrulline. The target receptor for NO is ferrum in the heme group of cytoplasmic guanyl cyclase, the enzyme catalyzing cyclic guanosine monophosphate (cGMP) formation. To confirm this hypothesis, cGMP and nitrite level in the blood serum were measured in patients with migraine. The group under study included 37 subjects suffering from migraine with and without aura and 40 normal control subjects. The cGMP was measured during a migraine attack and 60 min following the administration of sumatriptan 6 mg subcutaneously. A statistically significant increase in cGMP level was observed in patients during a migraine attack compared to the controls. This level decreased after the administration of sumatriptan, but it was still higher than in the controls. No correlation was found between the increased cGMP level and pain intensification with clinical symptoms of migraine. The results suggest the participation of biochemical changes in migraine pathogenesis in the L-arginine-NO-cGMP pathway.     

Increasing neopterin and decreasing endothelin-1 in plasma during insulin infusion in women

Leukocyte-derived inflammatory mediators and endothelial production of vasoconstrictive factors, such as endothelin-1, and vasodilatory and platelet anti-aggregatory factors, such as nitric oxide (NO) and prostacyclin (PGI2), may have a role in the pathogenesis of atherosclerosis. In this study we evaluated whether insulin affects the monocyte-derived inflammatory mediator neopterin and endothelin- in plasma (p), and NO and PGI2 mediators cyclic 3'-5' guanosine monophosphate (cGMP) and cyclic 3'-5' adenosine monophosphate (cAMP) in platelets. P-neopterin was measured by enzyme linked immunosorbent assay (ELISA), and p-endothelin-1, intraplatelet cAMP and cGMP were measured by radioimmunoassay (RIA) before and after euglycaemic hyperinsulinaemic clamping in 51 healthy postmenopausal women aged 53-54 years. "Placebo clamping" with NaCl infusion was performed in a subgroup of 5/51 women. During euglycaemic hyperinsulinaemic clamping, p-endothelin-1 decreased (from 3.3+/-0.2 pg/ml to 2.4+/-0.2 pg/ml; p<0.01), whereas p-neopterin (from 5.0+/-1.1 nmol/l to 6.2+/-1.4 nmol/l; p<0.001) and both intraplatelet cGMP (from 0.61+/-0.03 to 0.68+/-0.03 pmol/10(9) platelets; p<0.05) and cAMP (from 4.00+/-0.14 to 4.76+/-0.20 pmol/10(9) platelets; p<0.001) increased. Increases in cGMP (from 0.79+/-0.05 to 1.07+/-0.15 pmol/10(9) platelets; p = 0.14) and cAMP (from 4.76+/-0.15 to 5.52+/-0.36 pmol/10(9) platelets; p = 0.08) also occurred during NaCl infusion, whereas neopterin and endothelin-1 values were unchanged. In conclusion, insulin administration was associated with decreasing p-endothelin-1 levels and increasing levels of p-neopterin and intraplatelet cyclic nucleotides in accordance with vasodilatation and monocyte activation.     

Novel roles of cAMP/cGMP‐dependent signaling in platelets

Summary. Endothelial prostacyclin and nitric oxide potently inhibit platelet functions. Prostacyclin and nitric oxide actions are mediated by platelet adenylyl and guanylyl cyclases, which synthesize cyclic AMP (cAMP) and cyclic GMP (cGMP), respectively. Cyclic nucleotides stimulate cAMP‐dependent protein kinase (protein kinase A [PKA]I and PKAII) and cGMP‐dependent protein kinase (protein kinase G [PKG]I) to phosphorylate a broad panel of substrate proteins. Substrate phosphorylation results in the inactivation of small G‐proteins of the Ras and Rho families, inhibition of the release of Ca²⁺ from intracellular stores, and modulation of actin cytoskeleton dynamics. Thus, PKA/PKG substrates translate prostacyclin and nitric oxide signals into a block of platelet adhesion, granule release, and aggregation. cAMP and cGMP are degraded by phosphodiesterases, which might restrict signaling to specific subcellular compartments. An emerging principle of cyclic nucleotide signaling in platelets is the high degree of interconnection between activating and cAMP/cGMP‐dependent inhibitory signaling pathways at all levels, including cAMP/cGMP synthesis and breakdown, and PKA/PKG‐mediated substrate phosphorylation. Furthermore, defects in cAMP/cGMP pathways might contribute to platelet hyperreactivity in cardiovascular disease. This article focuses on recent insights into the regulation of the cAMP/cGMP signaling network and on new targets of PKA and PKG in platelets.     

Increased nitrosative and oxidative stress in platelets of migraine patients

The molecular mechanisms of migraine have not been fully clarified yet. Increased nitrosative and oxidative stress may be associated with migraine attacks. Platelets may play an important role in migraine patients and they can reflect the lability of tissues to nitrosative/oxidative stress. In the present study, we aimed to determine the levels of nitrosative and oxidative stress markers in platelets of migraine patients during headache-free and attack periods. A total of 56 subjects (22 migraine without aura, 14 migraine with aura, and 20 age- and sex-matched healthy controls) were included in the study and nitric oxide (NO) metabolites, malondialdehyde (MDA), and thiol (SH) groups were measured in platelets. During migraine attacks, platelet levels of nitrate, nitrite and MDA were significantly higher in migraineurs than these in control subjects (p = 0.042, p = 0.005 and p = 0.042, respectively). By contrast, during headache-free period, no statistically significant differences were found in the platelet levels of nitrate, nitrite and MDA between migraineurs and controls (p > 0.05), although the marginal increases were detected in migraineurs. These results suggest that increased biomarkers of nitrosative and oxidative stress in platelets may be important in migraine patients, especially during attacks; increase of NO metabolites in platelets during attacks supports the opinion that NO may play a modulatory role in biological processes particularly by vasodilatation in migraine attacks. Therefore, MDA and NO metabolites may serve as useful markers to show the increased vulnerability to nitrosative and oxidative stress in migraine patients.     

Complicated migraine studied by phosphorus magnetic resonance spectroscopy

The brain and skeletal muscle of eight adult patients with migraine with prolonged auras or migraine strokes leaving a permanent hemianopic defect were studied by phosphorus magnetic resonance spectroscopy. Biochemical assays performed on muscle biopsy and platelets had revealed abnormal mitochondrial enzyme activities. Brain magnetic resonance spectroscopy showed an abnormally low phosphocreatine to inorganic phosphate ratio in all patients, apparently due to decreased phosphocreatine and increased inorganic phosphate contents. Muscle phosphorus magnetic resonance spectroscopy showed low recovery from exercise in seven patients. Three patients had an increased phosphocreatine/inorganic phosphate ratio at rest, and the exercise transfer characteristics were abnormal in four patients for relatively low levels of exercise. The mitochondrial metabolic defects present in platelets and muscle of complicated migraine patients are therefore also expressed in the brain.     

Platelet Gamma-Aminobutyric Acid Levels in Migraine and Tension-Type Headache

Gamma-aminobutyric acid (GABA) levels in platelets were measured in 19 patients with migraine (7 males and 12 females, average age: 36.5 years) and 27 patients with chronic tension-type headache (TH; 9 males and 18 females, average age: 48.9 years). Twenty-one normal healthy volunteers composed the control group (11 males and 10 females, average age 34.9 years). The GABA levels in platelets were determined using high performance liquid chromatography with fluorescent detection (HPLC-FC). The GABA levels in platelets were 30.8 +/- 11.7 pmol/10(9) platelets (mean +/- S.D.) in the patients with migraine, 43.1 +/- 11.8 pmol/10(9) platelets in the patients with TH and 34.7 +/- 8.1 pmol/10(9) platelets in the healthy controls. The platelet GABA levels in the patients with TH were significantly higher than in the migraine patients and the healthy controls (p less than 0.05). The possible role of GABA in headache is discussed. We consider that TH may be a state of neuronal hyperexcitability similar to migraine and that GABA in the platelets of patients during TH attacks may be elevated to counterbalance it. Alternatively, we suggest that the rise of GABA levels in platelets is related to emotional factors, such as depression, in the TH patients. Further studies must be undertaken concerning the relationship between platelet GABA levels and headache.     

Platelet levels of dopamine are increased in migraine and cluster headache

OBJECTIVE: To measure plasma and platelet levels of dopamine in patients with migraine with aura, migraine without aura, and cluster headache. BACKGROUND: Clinical, genetic, and pharmacological evidences suggest that an abnormality of dopaminergic system plays a role in migraine pathogenesis. Direct evidence of an abnormal metabolism of dopamine in migraine, however, is lacking. METHODS: Plasma and platelet levels of dopamine were measured in patients with migraine with aura or migraine without aura during headache-free periods and in patients with cluster headache during the remission and active periods, as compared with healthy control subjects, using a multichannel electrochemical high-performance liquid chromatography system. RESULTS: Plasma levels of dopamine were not detectable with our methodology. Platelet levels of dopamine were higher in both types of migraine (migraine without aura = .20 +/- .17 ng/10(8) platelets; migraine with aura = .16 +/- .19 ng/10(8) platelets) than in control subjects (.10 +/- .11 ng/10(8) platelets), although in migraine with aura patients the difference was not significant. Patients with cluster headache showed the highest levels of platelet dopamine (.34 +/- .36 ng/10(8) platelets). CONCLUSIONS: Our results support the hypothesis that the dopaminergic system is impaired in migraine and cluster headache and suggest that high platelet levels of dopamine may represent an abnormal biochemical phenotypic trait of these primary headaches.