Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem,caudate/putamen and cortex,and on dopamine D1 and D2 receptors in the caudate/putamen

Summary Rats were treated with desipramine 5mg/kg, nomifensine 10mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D₁ (³[H]SCH 23390) and D₂ (³[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither³[H]SCH 23390 nor³[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/ putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.     

Design, spectrum measurements and simulations for a 238Pu alpha-particle irradiator for bystander effect and genomic instability experiments.

Design, spectrum measurements and simulations for an alpha-particle irradiator for bystander effect and genomic instability experiments are presented. Measured alpha-particle energy spectra were used to confirm the characteristics of the source of the irradiator specified by the manufacturer of the source. The spectra were measured in vacuum with a high-resolution spectrometer and simulated with an AASI Monte Carlo code. As a next step, we simulated alpha-particle energy spectra at the target plane of the irradiator for three different source-to-target distances. In these simulations, helium was used as the medium between the source and the exit window of the irradiator; its pressure and temperature corresponded to those of the ambient air. Mean energies and full-widths at half-maximum (FWHM) were calculated for the three different helium gas tracks.     

全膝关节置换翻修术的Meta分析

目的 通过对已报道的全膝关节置换翻修术文献进行总结分析,讨探膝关节置换翻修术前后的膝关节功能、翻修的主要原因、主要并发症及不同假体的术后疗效.方法 按照以下标准收集和分析有关全膝关节置换翻修术的文献:①1990年至2002年间发表,②报告患者数大于10例,③采用通用的膝关节评分标准.一名骨科专科医生独立收集数据,一名医学统计学专家独立采用Meta统计方法分析数据.结果 共有33 篇符合条件的文献被收集.患者共1356 例,其中男429例,女611例(部分文献性别分类数据缺失),平均年龄67岁(45～49岁),加权平均随访时间57个月( 6～108 个月),加权平均术前膝关节功能总评分为49 分(15～94分),术后为84分( 58～109分),全膝关节置换翻修术前后的总评分、功能评分、活动范围等有显著性提高,差异有统计学意义(总评分t=12.507,P<0.01, 功能评分t=4.704,P<0.01,活动范围:t=5.346,P< 0.01).全膝关节置换翻修术的原因主要是假体松动(55%),其它包括聚乙烯磨损(11%)、假体不稳(10%)、感染(7%).翻修术后的主要并发症仍然为假体松动(18%),其它包括假体不稳(16% )、感染(16% )、髌骨问题( 15% )及不明原因的膝关节疼痛(13%).髌骨问题包括髌骨脱位、半脱位、髌韧带撕裂、髌股关节疼痛等.结论 可以认为膝关节置换后翻修术是一种安全有效的手术.假体松动是膝关节置换翻新的主要原因和并发症.     

Cortisol moderates the relationship between testosterone and aggression in delinquent male adolescents.

BACKGROUND: In animals, strong evidence exists for an association between testosterone and aggression. In humans, and particularly in children and adolescents, findings have been less consistent. Previous research has suggested that this may partly be due to moderating effects of other factors, e.g., hormones. This study aims to investigate the moderating effect of cortisol on the relationship between testosterone and subtypes of aggression in delinquent male adolescents. METHODS: Participants were 103 boys (mean age 13.7) referred to a delinquency diversion program. Testosterone and cortisol levels were determined from saliva samples collected during resting conditions and related to self-report scores on overt and covert aggression. RESULTS: Linear regression analyses revealed a significant interaction between cortisol and testosterone in relation to overt aggression, with a significant positive relationship between testosterone and overt aggression in subjects with low cortisol levels but not in subjects with high cortisol levels. Using the same model for covert aggression, no significant effects of testosterone, cortisol, or testosterone x cortisol interaction were found. CONCLUSIONS: These results indicate a moderating effect of cortisol on the relationship between testosterone and overt aggression in delinquent male adolescents. Implications and directions for future research are discussed.     

Parenchymal and pleural fibrosis in construction workers.

Exposure to mineral dust was studied among construction workers (N = 437) with the aid of a questionnaire and a chest X-ray examination of the lungs. The results of the questionnaire showed that 81% of the construction workers had been exposed to asbestos. Exposure had occurred in all of the occupational groups studied. Pleural plaques and/or lung fibrosis (ILO greater than or equal to 1/1) were found in 26% of the examined workers; the prevalence varied from 18 to 40% among the various occupational groups. Comparison with a representative sample of the Finnish male population from another investigation indicates that the frequency of lung fibrosis (ILO greater than or equal to 1/1) is at least two times higher among the examined construction workers than among the general population. It seems likely that exposure to asbestos dust can be considered an etiological factor for an appreciable number of the X-ray findings.     

Absence of association between an intercellular adhesion molecule 1 gene E469K polymorphism and Alzheimer's disease in Finnish patients

Increased expression of intercellular adhesion molecule 1 (ICAM1), a protein known to contribute to inflammatory responses, has been detected in the brain tissue of patients with Alzheimer's disease (AD) and animals modelled to mimic AD or Parkinson's disease (PD). ICAM1 may, thus, be implicated in the pathogenesis of these disorders. Our purpose was to investigate whether genetic variants of the ICAM1 gene have a role in causing susceptibility to AD and/or PD. We genotyped the E469K polymorphism of ICAM1 in 196 AD, 52 PD and 202 control patients of Finnish origin. The distributions of the genotype and allele frequencies of the polymorphism did not differ significantly between the AD, PD or the control patients. We therefore conclude that the E469K polymorphism of ICAM1 is not a risk factor for AD or PD.     

Brain oscillatory responses to an auditory-verbal working memory task in mild cognitive impairment and Alzheimer's disease.

We report preliminary findings on EEG oscillatory correlates of working memory in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Event-related desynchronization (ERD) and synchronization (ERS) of the 1-20 Hz EEG frequencies were studied using wavelet transforms in elderly controls, MCI patients and mild probable AD patients performing an auditory-verbal Sternberg memory task. Behaviourally, the AD patients made more errors than the controls and the MCI group. Statistically significant differences during the encoding of the memory set were found between the controls and the MCI group, such that the latter group showed ERD in the approximately 10-20 Hz frequencies. The findings may reflect different, compensatory encoding strategies in MCI. During retrieval, the most obvious differences were observed between the controls and the AD group: the ERD in the approximately 7-17 Hz frequencies was absent in the AD group particularly in anterior and left temporal electrode locations. This finding might indicate that AD is associated with deficient lexical-semantic processing during the retrieval phase in working memory tasks. Future studies with larger patient groups are needed to establish the diagnostic value of ERD/ERS patterns in MCI and AD.     

Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase (BCHE) gene interactions with the apolipoprotein E epsilon4 allele as risk factors in Alzheimer's disease and in Parkinson's disease with coexisting Alzheimer pathology

Alzheimer's disease (AD) and Parkinson's disease (PD) are genetically heterogeneous. Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase (BCHE) genes may modify the risk of these disorders. We investigated whether common polymorphisms present in these genes operate as risk factors for AD and PD in Finnish subjects, independently or in concert with the apolipoprotein E ε4 allele (APOE ε4). Eighty late onset sporadic AD patients, 53 PD patients (34 of whom had concomitant AD pathology), and 67 control subjects were genotyped for the insertion (I)/deletion (D) polymorphism of DCP1 and the K variant of BCHE. In logistic regression analysis, the DCP1 *I allele in combination with APOE ε4 significantly increased the risk of AD (OR 30.0, 95% CI 7.3-123.7), compared to subjects carrying neither of the alleles. Similar analysis showed that the risk of AD was significantly increased in subjects carrying both the BCHE wild type (*WT/*WT) genotype and ε4 (OR 9.9, 95% CI 2.9-33.8), compared to those without this BCHE genotype and ε4. Further, the risk of PD with AD pathology was significantly increased for carriers of DCP1 *I and ε4 (OR 8.0, 95% CI 2.1-31.1). We thus conclude that, in Finns, interaction between DCP1 *I and ε4 increases the risk of AD as well as of PD with coexisting Alzheimer pathology, which underlines the importance of the DCP1 I/D polymorphism in the development of Alzheimer neuropathology, whereas the wild type BCHE genotype in combination with ε4 had a combined effect with regard to the risk of AD.


Keywords: Alzheimer's disease; Parkinson's disease; dipeptidyl carboxypeptidase 1; butyrylcholinesterase     

Epidermal SH-protease inhibitor in human neoplasms and their metastases

The presence of the human epidermal SH-protease inhibitor in human tumours of different types was examined using double radial immunodiffusion against specific antisera to the inhibitor. The immunoreactive protein was found to be present in all the tumours with criteria of epidermoid carcinoma identifiable microscopically. Most small cell anaplastic, fusiform, and polygonal bronchial carcinomas were also found to contain immunoreactive protein. If the primary tumour contained the inhibitor, all metastases examined were also found to contain it. The identity of the inhibitors in epidermoid carcinomas and in epidermis was confirmed by immunoelectrophoretic and gel chromatographic methods. The results suggest that the epidermal SH-protease inhibitor is a property closely associated with squamo-epithelial tissue differentation, which also appears in neoplastic squamous epithelium.     

Localization of the human SH-protease inhibitor in the epidermis. Immunofluorescent studies.

Human epidermis contains a low molecular weight SH-protease inhibitor (Human Epidermal Inhibitor = HEI), whose epidermal localization was performed with the indirect immunofluorescence method. The fluorescence was most intensive in the cytoplasms of epidermal cells, often occurring perinuclearly. The fluorescent material in the frozen sections was often finely granular and occasionally extended outside the cytoplasm, while the fluorescence in fixed sections was more uniform, but weaker. Stratum basale generally stained poorly or not at all, as did also stratum lucidum. Stratum corneum stained fairly intensively throughout. In addition to fixation, the outcome of staining was also affected by the thickness of the epidermis, particularly stratum corneum. The significance of this inhibitor for the differentiation of epidermal cells and the keratinization of epidermis has therefore been discussed, and the authors assume it to be of considerable significance in these processes.