Alteration in the redox state of plasma in heart-transplant patients with moderate hyperhomocysteinemia

Hyperhomocysteinemia has recently been suggested to contribute to the progression of the so-called chronic rejection or cardiac allograft vasculopathy (CAV) in heart-transplant patients in which the major determinant of the increase in homocysteine (Hcy) was the progressive decline of renal function. The exact mechanisms of tissue injury by Hcy is unknown, but some aspects of its toxicity have been related to its capacity for altering the redox state of plasma and forming protein adducts by intermediate lactone. To study the relationships between Hcy levels and variations in the redox state governed by thiols, plasma levels of Hcy, cysteine, glutathione, cysteinylglycine, and corresponding disulfides and protein-mixed disulfides were evaluated in subjects with moderate hyperhomocysteinemia represented by heart-transplant patients with (HTRF) and without (HT) renal failure, as well as patients with renal failure of different origin (RF), and compared with those of a control group (C) of normal subjects matched for age and sex. Plasma levels of Hcy and the corresponding protein mixed disulfides increased progressively in HTs, RFs, and HTRFs with respect to control. These changes were correlated with cysteine variations (as cystine and protein-mixed disulfides) but not with glutathione or cysteinylglycine that varied only as disulfides with a similar tendency. Moreover, an alteration in the plasma redox was evidenced by the decrease in thiol/disulfide ratios of cysteine, Hcy, and cysteinylglycine. In all groups, cysteine was directly correlated with Hcy but not with glutathione or cysteinylglycine, which in turn were correlated each other. Therefore levels of plasma cysteine were more linked to Hcy than to metabolism of glutathione. The clinical meaning of cysteine changes remains undefined and requires further study.     

甲状腺机能亢进患者穴位伏安特性研究

目的:观察甲状腺机能亢进(甲亢)患者与健康人大陵、神门、内关穴伏安特性的变化规律。方法:应用智能型穴位伏安特性检测仪检测56例甲亢患者与40名健康人大陵、神门、内关穴的伏安曲线,并进行比较分析。结果:甲亢患者左大陵穴的惯性面积显著大于健康人(P<0.01),甲亢患者右大陵穴的增、减程伏安面积均显著小于健康人(P<0.01)。甲亢患者左神门穴减程伏安面积和右神门穴的增程伏安面积显著小于健康人(P<0.01)。甲亢患者左内关穴减程伏安面积小于健康人(P<0.05)。结论:甲亢患者穴位的伏安特性较健康人发生变化,且对该疾病的反映主要体现在大陵穴。     

Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector TH2 subsets

1. Download high-res image (323KB)
2. Download full-size image

     

A functional 5HT2A receptor polymorphism (His452Tyr) and memory performances in Alzheimer's disease

The functional His452Tyr polymorphism in the 5HT2A receptor has been described to be associated with verbal memory in healthy adults, with worse episodic memory performances in Tyr452 (T) carriers. The aim of our study was to investigate a possible effect of this polymorphism on memory performances in Alzheimer disease (AD). We enrolled 169 patients affected by probable AD. 5HT2A genotype was determined as previously described. According to their genotype, patients were divided in T carriers (?n = 111) and non-carriers (?n = 69). We evaluated the possible effect of 5HT2A polymorphism on verbal memory tasks. A one-way MANOVA analysis did not show a positive interaction between the two groups (?p > 0.05) at the baseline and at the follow-up. Nevertheless, the analyses of the single-task effect showed lower performances for non-T carriers only in Rey's recognition task. Recent data reported poorer memory performances in healthy subjects carrying the T variant, in age-dependent manner (no differences between T vs. nT carriers were observed for age >50 years). In our AD sample, we did not find significant differences in verbal memory scores in T vs. nT carriers while a significant difference was found only in attentional task. At variance with that in healthy subjects, no correlation has been found between memory profiles of AD patients and His452Tyr polymorphism.     

Functional 5‐HT1a receptor polymorphism selectively modulates error‐specific subprocesses of performance monitoring

Our study investigates the dependence of response monitoring and error detection on genetic influences modulating the serotonergic system. This was done using the event‐related potentials (ERPs) after error (Ne/ERN) and correct trials (Nc/CRN). To induce a sufficient amount of errors, a standard flanker task was used. The subjects (N = 94) were genotyped for the functional 5‐HT1A C(−1019)G polymorphism. The results show that the 5‐HT1A C(−1019)G polymorphism specifically modulates error detection. Neurophysiological modulations on error detection were paralleled by a similar modulation of response slowing after an error, reflecting the behavioral adaptation. The 5‐HT1A −1019 CC genotype group showed a larger Ne and stronger posterror slowing than the CG and GG genotype groups. More general processes of performance monitoring, as reflected in the Nc/CRN, were not affected. The finding that error‐specific processes, but not general response monitoring processes, are modulated by the 5‐HT1A C(−1019)G polymorphism is underlined by a wavelet analysis. In summary, the results suggest a specific effect of the 5‐HT1A C(−1019)G polymorphism on error monitoring, as reflected in the Ne, and suggest a neurobiological dissociation between processes of error monitoring and general response monitoring at the level of the serotonin 1A receptor system. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin-induced diabetic rats

The aim of the present study was to investigate the effect of ginger on oxidative stress markers in the mitochondrial fractions of cerebral cortex (CC), cerebellum (CB), hippocampus (HC) and hypothalamus (HT) of diabetic rats. Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage. A marked decrease in anti-oxidant marker enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH) and increase in malondialdehyde (MDA) was observed in the diabetic rats. Decreased activities of anti-oxidant enzymes in diabetic rats were augmented on oral administration of ginger. Moreover, ginger administration depleted the MDA level, which was earlier increased in the diabetic rats. These results suggest that ginger exhibit a neuroprotective effect by accelerating brain anti-oxidant defense mechanisms and down regulating the MDA levels to the normal levels in the diabetic rats. Thus, ginger may be used as therapeutic agent in preventing complications in diabetic patients.     

Pharmacological evaluation of halogenated and non-halogenated arylpiperazin-1-yl-ethyl-benzimidazoles as D(2) and 5-HT(2A) receptor ligands

Five groups of previously synthesized and initially screened non-substituted and 4-halogenated arylpiperazin-1-yl-ethyl-benzimidazoles were estimated for their in-vitro binding affinities at the rat D(2) , 5-HT(2A) , and α(1) -adrenergic receptors. Among all these compounds, 2-methoxyphenyl and 2-chlorophenyl piperazines demonstrate the highest affinities for the tested receptors. The effects of 4-halogenation of benzimidazoles reveal that substitution with bromine may greatly increase the affinity of the compounds for the studied receptors, while the effect of substitution with chlorine is less remarkable. Most of the tested components show 5-HT(2A)/D(2) pK(i) binding ratios slightly above or less than 1, while only 4-chloro-6-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-1H-benzimidazole expresses an appropriate higher binding ratio (1.14), which was indicated for atypical neuroleptics. This compound exhibits a non-cataleptic action in rats and prevents d-amphetamine-induced hyperlocomotion in mice, which suggest its atypical antipsychotic potency.     

电针不同经穴对心肌缺血大鼠下丘脑内单胺类递质NE含量的影响

目的探讨电针不同经穴治疗心肌缺血的作用机制。方法从80只健康SD大鼠中随机选取10只作为正常对照组,其余大鼠结扎冠状动脉旋前降支复制心肌缺血模型。选取模型复制成功的大鼠随机分为模型组、"神门"组、"内关"组和"太渊"组,每组10只。除模型组外,各治疗组分别电针大鼠左侧"神门"穴、"内关"穴和"太渊"穴,每次刺激10 min,每日1次,连续3 d。采用酶联免疫吸附试验(ELISA)测定下丘脑室旁核区去甲肾上腺素(NE)的含量。结果与正常对照组比较,模型组NE含量显著降低(P0.01);与模型组比较,各电针组NE含量显著升高(P0.01或P0.05);各电针组之间比较,"神门"组NE含量显著高于"内关"组和"太渊"组(P0.05或P0.01),"内关"组NE含量显著高于"太渊"组(P0.05)。结论电针"神门""内关""太渊"穴治疗心肌缺血的机制与其促进下丘脑室旁核区单胺类递质NE的释放有关。