D-amphetamine-induced depletion of energy and dopamine in the rat striatum is attenuated by nicotinamide pretreatment

The present study examined the effects of nicotinamide on the D-amphetamine (AMPH)-induced dopamine (DA) depletion and energy metabolism change in the rat striatum. In chronic studies, co-administration of AMPH with desipramine, a drug that retards the metabolism of AMPH, (10 mg/kg, intraperitoneal [i.p.], respectively) caused a significant decrease of striatal DA content measured 7 days later. Pretreatment with nicotinamide (500 mg/kg, i.p.), the precursor molecule for the electron carrier molecule nicotinamide adenine dinucleotide (NAD), attenuated this effect of AMPH, whereas itself exerted no long-term effect on striatal DA content. In acute studies, a decrease in striatal adenosine triphospate/adenosine diphosphate (ATP/ADP) ratio was found 3 h after co-injection of AMPH and desipramine. However, nicotinamide pretreatment blocked the reduced striatal ATP/ADP ratio and resulted in a striking increase in striatal NAD content in AMPH-treated rats. Furthermore, nicotinamide was noted to increase striatal ATP/ADP ratio and NAD content in saline-treated rats. These findings suggest that nicotinamide protects against AMPH-induced DAergic neurotoxicity in the striatum of rats via energy supplement.     

α1-抗糜蛋白酶基因、早老素1基因 与阿尔茨海默病的相关分析

目的探讨中国汉族人中α１抗糜蛋白酶（ＡＡＣＴ）基因、早老素１（ＰＳ１）基因多态性与阿尔茨海默病（Ａｌｚｈｅｉｍｅｒｓｄｉｓｅａｓｅ,ＡＤ）的相关情况。方法应用ＰＣＲＲＦＬＰ方法,在１２３例患者和１４０例正常人中观察ＡＡＣＴ信号肽和ＰＳ１基因多态性的分布,进行关联分析。结果１ＡＤ患者与ＰＳ１基因等位基因１正关联,与等位基因２和基因型２／２负关联,但与１／１基因型无关;２ＡＡＣＴ信号肽基因多态性与ＡＤ无关联;３在三种ＰＳ１基因型中,ＡＡＣＴ信号肽基因多态性与ＡＤ均无关;４在ＡＡＣＴ基因ＡＡ、ＴＴ基因型中,ＰＳ１基因多态性与ＡＤ负关联,而ＴＡ型中ＰＳ１基因与ＡＤ无显著相关。结论中国人群中,ＡＤ与ＰＳ１基因２／２型负关联,而与ＡＡＣＴ信号肽基因多态性无关;ＡＡＣＴ信号肽和ＰＳ１基因多态性之间也无明显的相互影响。     

Absence of G209A and G88C mutations in the alpha-synuclein gene of Parkinson's disease in a Chinese population

A G209A mutation in the alpha-synuclein gene was recently discovered in a large Italian kindred and three unrelated Greek kindreds with autosomal dominant Parkinson's disease (PD). Subsequently, another mutation in the gene (G88C) was also identified in a German family with autosomal PD. These results indicate that the alpha-synuclein gene may have an important role in the pathogenesis of PD. This study was designed to screen the existence of both mutations of the alpha-synuclein gene among 100 Chinese patients with PD, including 80 with sporadic and 20 with familial PD. Results showed that none of our patients, both sporadic and familial PD, had either of the two mutations of this gene. We therefore conclude that although of great interest, these two mutations are not relevant for the pathogenesis of PD in a Han Chinese population.     

Diagnosis of depression by primary care physicians versus a structured diagnostic interview. Understanding discordance

In this paper, false-negative and false-positive cases of depressive illness are examined, differentiating levels of disagreement between a primary care physician's diagnosis and a standardized research diagnosis. Two stratified random samples of primary care patients in Seattle, USA (N = 373) and Groningen, The Netherlands (N = 340) were examined with the Composite International Diagnostic Interview-Primary Health Care Version (CIDI-PHC). Physician's severity ratings and diagnosis of psychological disorder were obtained. Three levels of disagreement between physician and CIDI diagnosis were distinguished: 1) complete disagreement about the presence of psychiatric symptoms (true false-negative and true false-positive patients); 2) disagreement over severity of recognized psychological illness (underestimated or overestimated); and 3) disagreement over the specific psychiatric diagnosis among those given a diagnosis (misdiagnosed or given another CIDI diagnosis). All three levels of disagreement were common. Only 27% of the false-negative cases were due to complete disagreement (true false-negatives), and 55% of the false-positives were due to complete disagreement (true false-positives). The true false-negative patients were younger, more often employed, rated their own health more favorably, visited their doctor for a somatic complaint and made fewer visits than the underestimated, misdiagnosed, and concordant positive patients. Complete disagreement in depressive diagnoses between the primary care physician and research interview is not as frequent as indicated by an undifferentiated false-negative/ false-positive analysis. Differentiating levels of disagreement does more justice to diagnostic practice in primary care and provides guidance on how to improve the diagnostic accuracy of primary care physicians.     

No association between an intronic presenilin-1 gene polymorphism and schizophrenia in a Chinese population

We investigated the association between schizophrenic psychosis and an intronic polymorphism of the presenilin-1 (PS1) gene in a Chinese population. Schizophrenic and control groups had similar PS1 genotype distributions and allele frequencies, indicating that this polymorphism may not be involved in the development of schizophrenia.     

Body region prevalence of injury in alcohol- and non-alcohol-related traffic injuries

OBJECTIVE: To explore the relationship between alcohol use and body region of injury in patients injured in traffic collisions. MATERIALS AND METHODS: A prospective study of 381 patients involved in traffic collisions over the past 4 months. These patients were categorized as either using alcohol or not using alcohol on the day of the accident. Eighty of 381 patients (21%) had detectable blood alcohol concentrations. Age, sex, location of injury, helmet use, clinical diagnosis, Injury Severity Score, Glasgow Coma Scale score, and blood alcohol concentrations were collected for each patient. Blood alcohol concentrations were measured by the radioactive energy attenuation method. RESULTS: The incidence of head, face, chest, abdomen, and extremity injury in patients with alcohol use was 39%, 56%, 13%, 15%, and 55%, respectively, and 26%, 32%, 15%, 12%, and 63% in those without alcohol use, respectively. The differences in the incidence of head and facial injuries were significant between these two groups (p<0.05). Mean blood alcohol concentrations in head, face, chest, abdomen, and extremity injury were 171, 204, 215, 231, and 163 mg/dL, respectively. CONCLUSION: More injuries to the head and facial areas compared with other body parts were found in patients with alcohol use. However, alcohol level did not seem to influence the region of the body injured.     

CD2 and CD3 receptor-mediated tolerance: constraints on T cell activation

BACKGROUND: Antigen specific allograft tolerance is induced in mice by anti-CD2 plus anti-CD3epsilon monoclonal antibody (mAb) treatment. Because anti-CD2 mAb inhibits several aspects of anti-CD3epsilon driven T cell activation, we investigated what components of T cell activation are required or may be dispensed with for tolerance induction. Anti-CD3epsilon-mediated T cell activation depends on FcgammaR interactions. METHODS: To assess the role of FcgammaR-mediated T cell activation in tolerance induction, FcgammaR binding IgG or non-binding IgG3 anti-CD3epsilon mAbs were examined. RESULTS: These mAbs, administered in conjunction with anti-CD2, were equally effective in inducing tolerance. Moreover, in vivo administration of a blocking mAb directed against the FcgammaR, or the use of allograft recipients deficient in FcgammaR, had no effect on tolerance induction. Blocking IL-2 using mAb directed against IL-2 or IL-2R also did not prevent the induction of tolerance. These results suggest that complete T cell activation was not required for tolerance induction. However, substitution of a partially activating mAb, directed against the T cell receptor (TCR) beta subunit for anti-CD3epsilon, failed to synergize with anti-CD2 mAb to induce tolerance. The anti-TCRbeta mAb and anti-CD3epsilon mAb were found to differentially down modulate expression of TCR/CD3 complex subunits. In particular, anti-CD3epsilon caused transient down modulation of the TCRbeta receptor subunit and the TCRzeta signaling module, and this pattern was enhanced and prolonged by anti-CD2. Anti-TCRbeta caused persistent TCRzeta modulation but no TCRbeta modulation, and anti-CD2 did not influence this pattern. CONCLUSIONS: These results suggest that, although full T cell activation is not required for the induction of tolerance by anti-CD2 plus anti-CD3epsilon mAb, a signal transduction pathway that is associated with TCRbeta and TCRzeta expression, and, specifically, is perturbed by mAb binding of the CD3epsilon epitope, is critical.