Effects of ischemia-reperfusion on NMDA receptor subunits 2a and 2b level in rat hippocampus

The authors investigated the effects of ischemia and reperfusion on the N-methyl-D-aspartate receptor (NMDAR) subunits 2A and 2B concentration in rat hippocampus. At the protein level, significant increase in the amounts of NMDAR 2A and NMIDAR 2B in the rat hippocampus was observed at 1 h after reperfusion compared with control group. These results suggested that the alteration in hippocampal NMDAR2 subunit concentrations after ischemia-reperfusion might be invovlved in cognitive dysfunction and excitotoxicity.     

Two novel mutations in mitochondrial acetoacetyl-CoA thiolase deficiency

Summary We report a new patient with acetoacetyl-CoA thiolase deficiency in whom we found two new missense mutations.     

Vascular wall damage in rats induced by methidathion and ameliorating effect of vitamins E and C

We examined the effect of subacute methidathion (MD) administration on vascular wall damage and evaluated the ameliorating effects of combination of vitamins E and C against MD toxicity. The experimental groups were: rats treated with corn oil (control group), rats treated with 5 mg/kg MD (MD), and rats treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD+Vit). The groups were given MD by gavage on 5 days a week for 4 weeks at a daily dose 5 mg/kg (MD and MD+Vit) using corn oil as the vehicle. Vitamins E and C were injected at doses of 50 mg/kg intramuscularly and 20 mg/kg intraperitoneally, respectively, after the treatment with MD in the MD+Vit group. The levels of malondialdehyde (MDA) were determined in the aortic tissue. Histopathological examination was examined in the thoracic aortic tissue. MDA levels were higher in the MD group than the control group and lower in the MD+Vit group than MD group. MD administration led to irregulation, prominent breaks, and fragmentation of the elastic fibers but decrease in the irregulation and fragmantation of the elastic fibers with the combination of vitamins E and C in MD-treated rats. In conclusion, it is likely that subacute MD administration caused vascular wall damage, and that treatment with a combination of vitamins E and C after the administration of MD can reduce vascular wall damage caused by MD.     

Sulfoxidation of cysteine and mercapturic acid conjugates of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A)

The volatile anesthetic sevoflurane is degraded in anesthesia machines to the haloalkene fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE), which can cause renal and hepatic toxicity in rats. FDVE is metabolized to S-[1,1-difluoro-2-fluoromethoxy-2-(trifluoromethyl)ethyl]-L-cysteine (DFEC) and (E) and (Z)-S-[1-fluoro-2-fluoromethoxy-2-(trifluoromethyl)vinyl]-L-cysteine [(E,Z)-FFVC], which are N-acetylated to N-Ac-DFEC and (E,Z)-N-Ac-FFVC S-conjugates. Some haloalkene S-conjugates undergo sulfoxidation. This investigation tested the hypothesis that FDVE S-conjugates can also undergo sulfoxidation, by evaluating sulfoxide formation by human and rat liver and kidney microsomes and expressed P450s and flavin monooxygenases. Rat, and at lower rates human, liver microsomes oxidized (Z)-N-Ac-FFVC and N-Ac-DFEC to the corresponding sulfoxides. Much lower rates of (Z)-N-Ac-FFVC, but not N-Ac-DFEC, sulfoxidation occurred with rat and human kidney microsomes. In human liver microsomes, the P450 inhibitor 1-aminobenzotriazole completely inhibited S-oxidation, while heating to inactivate FMO decreased (Z)-N-Ac-FFVC and N-Ac-DFEC sulfoxidation only 0 and 30%, respectively. Of the various cytochrome P450s examined, P450s 3A4 and 3A5 had the highest S-oxidase activity toward (Z)-N-Ac-FFVC; P450 3A4 was the predominant enzyme forming N-Ac-DFEC-SO. The P450 3A inhibitors troleandomycin and ketoconazole inhibited >95% of (Z)-N-Ac-FFVC sulfoxidation by P450 3A4 and 3A5 and 40-100% of (Z)-N-Ac-FFVC sulfoxidation by human liver microsomes and 15-85% of N-Ac-DFEC sulfoxidation by human liver microsomes. Sulfoxidation of DFEC was also examined in human liver microsomes. Substantial amounts of sulfoxide were observed, even in the absence of NADPH or protein, while enzymatic formation was comparatively minimal. These results show that FDVE S-conjugates undergo P450-catalyzed and nonenzymatic sulfoxidation and that enzymatic sulfoxidation of (Z)-N-Ac-FFVC and N-Ac-DFEC is catalyzed predominantly by P450 3A. The extent of FDVE sulfoxidation in vivo and the toxicologic significance of FDVE sulfoxides remain unknown and merit further investigation.     

Comparison of derivative spectrophotometric and liquid chromatographic methods for the determination of rofecoxib

Two different UV spectrophotometric methods were developed for the determination of rofecoxib in bulk form and in pharmaceutical formulations. The first method, an UV spectrophotometric procedure, was based on the linear relationship between the rofecoxib concentration and the lambdamax amplitude at 279 nm. The second one, the first derivative spectrophotometry, was based on the linear relationship between the rofecoxib concentration and the first derivative amplitude at 228, 256 and 308 nm. Calibration curves were linear in the concentration range using peak to zero 1.5-35.0 microg x ml(-1). HPLC was carried out at 225 nm with a partisil 5 ODS (3) column and a mobile phase constituted of acetonitrile and water (50 :50 v/v). A linear range was found to be 0.05-35.0 microg x ml(-1). The developed methods were successfully applied for the assay of pharmaceutical dosage form. The statistics of the analytical data is also presented. The results obtained by first derivative spectrophotometry were compared with HPLC and no significant difference was found.     

Comparison of various simple insulin sensitivity and beta-cell function indices in lean hyperandrogenemic and normoandrogenemic young hirsute women

OBJECTIVE: To assess and compare various simple insulin sensitivity and beta-cell function indices in lean, hirsute, young women. DESIGN: Prospective study. SETTING: Departments of endocrinology and metabolism at a university and a state hospital. PATIENT(S): Seventy-one hirsute young women were classified as hyperandrogenemic or normoandrogenemic. MAIN OUTCOME MEASURE(S): Insulin sensitivity and beta-cell function indices derived from a single sample and an oral glucose tolerance test (OGTT). RESULT(S): Lean hyperandrogenemic hirsute women have insulin resistance and increased beta-cell function. The most sensitive indices of insulin resistance were total and 1-hour and 2-hour post-challenge insulin levels during OGTT. When a cut-off value of 3.2 or greater for homeostasis model assessment of insulin resistance (HOMA-IR) was accepted, 46% of hyperandrogenemic women and 30% of normoandrogenemic women were insulin resistant. Fasting insulin level was best correlated with the fasting insulin resistance index, HOMA-IR, and Quicky index. The HOMA-IR was best correlated with fasting insulin level and the hepatic insulin sensitivity index (ISI(HOMA)). CONCLUSION(S): Insulin levels based on OGTT are the most useful index of insulin resistance and beta-cell function index in hirsute women. The HOMA-IR may be a proposed global test for insulin resistance; it correlated well with both OGTT-derived insulin resistance and beta-cell function indices and with global insulin resistance indices derived from a single sample (such as ISI (HOMA), Quicky index, FIRI(-1), fasting Belfiore index, and glucose/insulin ratio).     

Clinical importance of erythrocyte malondialdehyde levels as a marker for cognitive deterioration in patients with dementia of Alzheimer type: a repeated study in 5-year interval

OBJECTIVES: The aim of the present study was to determine the effects of aging and dementia of the Alzheimer type (DAT) on lipid peroxidation and antioxidant enzyme activities. DESIGN AND METHODS: Twenty-six patients with DAT were included in the present study. Group I: 26 patients diagnosed as DAT and studied 5 yr ago. Group II: This group consisted of the same patients as Group I at the present time. Activities of CuZn superoxide dismutase (CuZn SOD) and glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) concentrations of these 26 subjects were measured and mini mental state examination (MMSE), brief psychiatric rating scale (BPRS), Hamilton depression rating scale (HDRS) were applied. RESULTS: The results revealed that 26 dementia patients had worsened cognitive symptoms and significantly increased CuZn SOD and MDA levels and decreased GSH-Px levels after 5 yr. Significant correlation was found between age and CuZn SOD (r: +0.406, p: 0.034), and between MMSE and MDA (r: -0.411, p: 0.032). CONCLUSIONS: We can conclude that MDA, CuZn SOD, and GSH-Px were significantly affected in the patients with Alzheimer disease. The most striking finding of this study is the significant correlation between MMSE and MDA in patients with DAT.     

蛇胆汁中牛磺胆酸含量测定方法的比较研究

目的：比较分析了３种测定蛇胆汁中主要成分牛磺胆酸含量的方法,制定科学合理统一的质量标准。方法：用薄层层析－磷钼酸比色法、薄层扫描法及高效液相色谱法对蛇胆汁中主要成分牛磺胆酸进行测定,并将结果进行比较分析。结果：薄层层析－磷钼酸比色法、薄层扫描法及高效液相色谱法的含量测定结果有一定差异,平均回收率分别为９７．４８％,９８．５１％和１００．３４％,ＲＳＤ分别为４．６％,４．３％和１．５％。结论：高效液     

急性心肌梗塞并室性心律失常130例

１　临床资料　１９９６～１９９８发病后１２ｈ就诊的住院ＡＭＩ患者１３０（男７６,女５４）例,年龄（５４．２±１５）岁．室性心律失常统计以ＡＭＩ后９６ｈ内为限．前壁心肌梗塞２８例,下壁心肌梗塞２８例,前间壁心肌梗塞１９例,高侧壁心肌梗塞１７例,后壁心肌梗塞２０例,广泛性心肌梗塞１８例．入院时首先描记第１份１２导联心电图,入院后依病情随时描记心电图变化情况,并持续心电监护９６ｈ,室性心律失常以出现频发室性早搏（３次／ｍｉｎ）,室性早搏在Ⅱ级以上（ＬＤＷＮＷＶ）级,成对室速,室性心动过速为观察对象．１…     

Ochratoxin A reduces NMDA receptor subunits 2A and 2B concentrations in rat hippocampus: partial protective effect of melatonin

Ochratoxin A (OTA) is a mycotoxin produced by several fungi. Many foods can be contaminated by OTA, which is consequently found in the blood of humans and animals. It is known that OTA accumulates in the brain. The aim of this study was to investigate the effects of OTA on the brain. For this purpose, the effect of OTA on N-methyl-D-aspartate (NMDA) receptor subunits 2A (NR2A) and 2B (NR2B) in the hippocampus and the protective effect of melatonin were investigated. Three groups of eight rats were used: controls, OTA-treated rats (OTA dose 289 microg/kg per day) and OTA+melatonin-treated rats (melatonin dose 10 mg/kg per day). After four weeks of treatment, electrophoretic examinations were performed using SDS-polyacrylamide gel electrophoresis and Western blotting of hippocampal homogenates of the different groups. The concentrations of NR2A and NR2B in the OTA group were significantly lower than in the control group. The concentration of NR2B was significantly increased when melatonin was co-administered with OTA compared with OTA only. There was also a significant increase in NR2A levels when melatonin was co-administered with OTA. As a result, subchronic administration of OTA reduced hippocampal NMDA receptor subunits 2A and 2B concentrations in rats. It was thought that this alteration might affect cognitive functions because hippocampal NMDA receptors are involved in the memory and learning processes. Melatonin exhibited a partially protective effect on NR2A and NR2B against OTA.