Quantitative analyses of schizophrenia-associated metabolites in serum: serum D-lactate levels are negatively correlated with gamma-glutamylcysteine in medicated schizophrenia patients.

The serum levels of several metabolites are significantly altered in schizophrenia patients. In this study, we performed a targeted analysis of 34 candidate metabolites in schizophrenia patients (n = 25) and compared them with those in age- and gender-matched healthy subjects (n = 27). Orthogonal partial least square-discriminant analysis revealed that complete separation between controls and patients was achieved based on these metabolites. We found that the levels of γ-glutamylcysteine (γ-GluCys), linoleic acid, arachidonic acid, D-serine, 3-hydroxybutyrate, glutathione (GSH), 5-hydroxytryptamine, threonine, and tyrosine were significantly lower, while D-lactate, tryptophan, kynurenine, and glutamate levels were significantly higher in schizophrenia patients compared to controls. Using receiver operating characteristics (ROC) curve analysis, the sensitivity, specificity, and the area under curve of γ-GluCys, a precursor of GSH, and D-lactate, a terminal metabolite of methylglyoxal, were 88.00%, 81.48%, and 0.8874, and 88.00%, 77.78%, and 0.8415, respectively. In addition, serum levels of D-lactate were negatively correlated with γ-GluCys levels in patients, but not in controls. The present results suggest that oxidative stress-induced damage may be involved in the pathogenesis of schizophrenia.

Marked increase in the histamine content of neointima after stent implantation of pig coronary artery and growth-promoting effects of histamine in cultured smooth muscle cells.

After coronary stent implantation, the unfavorable in-stent restenosis often occurs by the formation of neointima due to the proliferation of smooth muscle cells. Platelet-derived growth factor (PDGF) and other peptide growth factors contribute to this process, but little is known about the role of non-peptide factors in this process. In the present study, the role of histamine, a non-peptide factor, in the formation of neointima was investigated using a pig coronary model of in-stent restenosis and a culture system of coronary smooth muscle cells. A Palmaz-Schatz stent was implanted in the left anterior descending coronary artery of male pigs. At 1, 2 and 4 weeks after stenting, the histamine content of neointima was determined to be 326 +/- 82, 1427 +/- 280 and 440 +/- 69 pmol/mg protein, respectively, by HPLC fluorometry. In contrast, the histamine content of arterial media from the untreated control arteries was only 15.3 +/- 1.6 pmol/mg protein. These results demonstrate that the histamine content of neointima is about 20 to 90-fold that of the normal media. In vitro, histamine by itself did not stimulate the proliferation of cultured smooth muscle cells, but potentiated the PDGF-stimulated proliferation of the cultured cells via a mechanism independent of H1 and H2 histamine receptors. Thus, histamine may be an important non-peptide factor in the pathogenesis of in-stent restenosis.

Association between chromogranin b gene polymorphisms and schizophrenia in the Japanese population.

BACKGROUND: We found in previous work a significant association between schizophrenia and D20S95 on chromosome 20p12.3. In this study, we analyzed 10 microsatellite markers and found an association of schizophrenia with D20S882 and D20S905 that flank D20S95. The chromogranin B gene (CHGB) is 30 kb from D20S905. The chromogranin B (secretogranin I) belongs to a series of acidic secretory proteins that are widely expressed in endocrine and neuronal cells, and its cerebrospinal fluid levels have been reported to decrease in patients with chronic schizophrenia. METHODS: We screened for polymorphisms in CHGB with polymerase chain reaction direct sequencing methods in 24 Japanese schizophrenic patients and identified a total of 22 polymorphisms. Allelic and genotypic distributions of detected polymorphisms were compared between unrelated Japanese schizophrenic patients (n = 192) and healthy control subjects (n = 192). RESULTS: Statistically significant differences in the allelic distributions were found between schizophrenic patients and control subjects for 1058C/G (A353G) (corrected p = 7.7 x 10(-5)) and 1104A/G (E368E) (corrected p = 8.1 x 10(-6)). The 1058C/G and 1104A/G alleles were in almost complete linkage disequilibrium and were in linkage disequilibrium with D20S95. CONCLUSIONS: Results suggest that the CHGB variations are involved in the susceptibility to schizophrenia in our study population.

[A study of the relationship between community networking and confidentiality].

Legal and ethical conflicts arise in building a community network for mental health workers with confidentiality. Another ethical problem is encountered by involving mental health volunteers who are not obliged to be confidential. The authors made a questionnaire from the following six points of view: 1) the current attitudes of mental health professionals and workers toward confidentiality, 2) the degree of disclosure of individual information, 3) the relation between collaboration with family and confidentiality, 4) the range of extended confidence, 5) the extent of sharing individual information with volunteers, 6) the guidelines of confidentiality. The questionnaire was delivered to the following objects: 1,471 mental health professionals, 3,400 mentally disabled people and 3,400 of their family members. The returned questionnaires were analyzed and led to the following conclusions. The authors also conducted a bibliographical investigation on this subject. 1) Attitudes toward confidentiality varied among mental health professionals and also among mental health facilities. This created difficulties and confusion among them. 2) Transmission of individual information to the caregiving family members is important to help the mentally disabled, however, mental health professionals varied in the extent to which they informed them. 3) Mental health professionals in the same institute were regarded as an extent of extended confidence by 67.5% of the mentally disabled and 80.5% of family members. The caregiving family members were also regarded as such by 58.4% of the mentally disabled and 69.5% of family members. 4) The methods of transmission of individual information within a facility and/or with other facilities varied among mental health professionals. 5) A contract of confidentiality with volunteers was made only by 8.1% of mental health professionals. However, 34.1% of the mentally disabled and 24.0% of family members refused to transmit individual information to such volunteers. 6) Disclosure of individual information to the mentally disabled or their representatives is inevitable for them to authorize transmission of their individual information to others. Authorization of transmission of their individual information without knowing the content of such records is not valid authorization. 7) It is necessary to establish guidelines on confidentiality, according to 42.1% of the mentally disabled and 44.2% of their family members.

Production of hydrogen peroxide in situ in cardiac myocytes during hypoxia-reoxygenation as assessed with cerium.

Free radicals have been implicated in myocardial reperfusion injury. Hydrogen peroxide (H(2)O(2)) is one possible source of reactive oxygen intermediates. We studied the formation and toxicity of H(2)O(2) in isolated myocytes during hypoxia-reoxygenation with the use of cerium. This method involves formation of an electron-dense precipitate when H(2)O(2) reacts with cerium chloride (CeCl(3)). Single myocytes were obtained from rat hearts by collagenase digestion. Isolated myocytes were reoxygenated for 15 min after 30 min of hypoxia. The cells were treated with digitonin to increase the permeability of the plasma membrane, and CeCl(3) was added to detect intracellular H(2)O(2) on electron microscopy. In the nonhypoxia control group, the ultrastructure of cells was well preserved, and no dense deposits were found in myocytes. In the hypoxia-reoxygenation group, precipitates, i.e., Ce-H(2)O(2) reaction products, were found inside and along swollen mitochondria, and cell viability was reduced to 72.3% of control. These results indicate that endogenous H(2)O(2) is generated by mitochondria and that its release into the cytosol may lead to myocyte death under pathological situations such as hypoxia-reoxygenation.

Mechanisms of restenosis after coronary intervention: difference between plain old balloon angioplasty and stenting.

BACKGROUND: Restenosis after coronary intervention remains an unsolved and important clinical problem. We histologically examined the mechanism of restenosis after both balloon injury and stenting. METHODS: Coronary arteries of swine were subjected to balloon injury and stenting. Next, just after stenting or at 7, 14, or 28 days, the animals were sacrificed for the evaluation by morphometric analysis, histological observation, and immunostaining. RESULTS: The neointimal area peaked at 14 days in the balloon injury group (BG) and increased linearly up to 28 days in the stent group (SG). At 28 days, the total vascular area in the BG was reduced to 78% of the control values. In the SG, the total vascular area remained enlarged. According to the phenotypic analysis, the vascular smooth muscle cells (VSMCs) in the neointimal area at 28 days were the contractile type in the BG and the synthetic type in the SG. Proliferating cell nuclear antigen (PCNA) and macrophage-positive cells were not observed in neointima in the BG at 28 days, whereas they were observed around the stent struts in the SG. In addition, numerous inflammatory cells, such as neutrophils and eosinophils, were also present in the SG. CONCLUSIONS: Restenosis after balloon injury consisted of arterial remodeling and neointimal hyperplasia, whereas that after stenting consisted mostly of neointimal hyperplasia. The neointimal area in the SG lasted longer than that in the BG. Continuous inflammation may be an important factor in the restenosis of stenting.

Comparison of the morphological changes of restenosis after the implantation of various types of stents in a swine model.

BACKGROUND: Stent design causes the differences of restenosis rate, but the morphological differences after the various types of stent implantation have not been clarified. DESIGN: Seven types of stents were implanted in pig coronary arteries to clarify how the mechanism of restenosis differs with coil stents and tube stents. METHODS: The left anterior descending coronary arteries (LADs) of pigs were injured using coronary angioplasty balloons (diameter: 3.0 mm; length: 20 mm; balloon/artery ratio: 1 : 2). Fourteen days after the injury, four types of coil stents (Cordis, Wiktor, GR-I, and GR-II) and three types of tube stents (Palmaz-Schatz, gfx, and Multilink) were implanted, and the LADs were extracted 28 days after the implantation. RESULTS: The proliferated neointima was eccentric in the coil stents and concentric in the tube stents. Although there was no significant difference in the area of neointima, the area of the lumen was significantly larger in the tube stents than in the coil stents ( < 0.01) because of the larger area of stent. Cells positive for anti-proliferating cell nuclear antigen antibody were mainly observed around the stent struts, and most of these cells were also positive for either anti-macrophage or anti-smooth muscle actin antibodies. CONCLUSIONS: Compared to the coil stents, the tube stents induce less negative remodelling including stent recoil, resulting in a wider luminal area. In order to prevent restenosis, it is crucial to implant a stent that will cause less negative remodelling.