Effect of fenbufen on the pharmacokinetics of sparfloxacin in rats.

The effects of fenbufen on the serum concentrations and penetration into the brain and CSF of sparfloxacin (AT-4140), a new quinolone antibacterial agent, were investigated in rats. At designated times after a bolus iv dose of sparfloxacin 10 mg/kg with or without fenbufen 20 mg/kg, arterial blood, CSF and whole brain were simultaneously collected from each rat. Sparfloxacin concentrations were assayed by HPLC. Serum concentration of sparfloxacin declined bi-exponentially with time and was not changed by coadministered fenbufen. Binding sparfloxacin to serum protein slightly decreased after the coadministration. No elevation of sparfloxacin concentrations was observed in either brain or CSF after coadministration with fenbufen except for only a few time-points. The pharmacokinetic analysis based on the physiological model indicated that fenbufen did not affect the permeability across the blood-brain or blood-CSF barrier. These results suggest that fenbufen may be unlikely to affect the pharmacokinetics, involving the entry into the central nervous system, of sparfloxacin.     

Gene expression profiling in schizophrenia and related mental disorders.

The etiology and pathophysiology of schizophrenia and related mental disorders such as bipolar disorder and major depression remain largely unclear. Recent advances in mRNA profiling techniques made it possible to perform genome-wide gene expression analysis in a hypothesis-free manner. It was thought that this large-scale data mining approach would reveal unknown molecular cascades involved in mental disorders. Contrary to this initial expectation, however, DNA microarray results in psychiatric fields have been notoriously discordant. Here the authors review the findings of DNA microarray analysis, focusing on systematic gene expression changes in schizophrenia, as well as alterations in the expression of specific genes, that have been reported and replicated. The authors also address the probable causes for the discordance among studies, possible ways to solve the problem, and their preferred approach for data interpretation.     

Wilms tumor gene immunoreactivity in primary serous carcinomas of the fallopian tube, ovary, endometrium, and peritoneum.

Wilms tumor gene (WT-1) expression has been reported in many human cancers, including most ovarian and peritoneal serous carcinomas, but has not been studied in carcinomas of the fallopian tube. In this study, the authors evaluated the immunohistochemical expression of WT-1 in serous carcinomas of the fallopian tube and compared their reactivity with that of ovarian, peritoneal, and endometrial serous carcinomas. All primary serous carcinomas of the fallopian tube (13 cases), ovaries (25 cases), and peritoneum (3 cases) were reactive with the WT-1 antibody, whereas all five primary endometrial serous carcinomas were nonreactive. WT-1 reactivity in an unknown primary serous carcinoma is therefore suggestive of an extrauterine site. The marked difference in WT-1 staining raises the possibility of genetic differences between serous carcinomas arising in the endometrium compared with those arising in the ovaries, fallopian tubes, and peritoneum.     

Study on the mass-screening of after-meal serum triglyceride concentration]

The serum triglyceride concentration (TG) tested in health checks after meals cannot properly sort out hypertriglyceridemia with reference to the upper normal limit of fasting TG (150 mg/dl) set by the Japan Arteriosclerosis Society, because TG goes up considerably after a meal. In our survey of a large number of health check examinees (free of abnormal biochemical data other than TG and diseases under medical treatment), the mean (M) of fasting TG + 2 standard deviations (SD) was close to 150 mg/dl. When the screening level was set at M + 2SD for each time span after a meal, the ratio of the screened was distributed between 19.9 and 21.8%, which was close to 23.5%, the ratio of the screened on fasting. Accordingly, the nearest round number ending with zero for the first digit is suggested to be of practical use for the screening level of after-meal TG. The average TG in females was definitely lower than that of males, though proportionately increasing with age. The ratio of the screened among females aged between 20 and 49 was 5.3% on fasting and 3.2-5.8% for after-meal time spans, and that of the screened aged in their fifties was 11.3% and 8.2-12.9% respectively.     

V gene analysis of anti-cardiolipin antibodies from (NZW x BXSB) F1 mice.

In (NZW x BXSB) F1 (W/B F1) male mice, systemic lupus-like disease, thrombocytopenia and coronary vascular disease with myocardial infarction occur, due to the presence of platelet-associated antibodies, anti-platelet antibodies and anti-cardiolipin antibodies (aCL). We developed monoclonal aCL and analysed the specificity of aCL. In the W/B F1 mice, there are aCL with pathogenic properties, which have an IgG isotype and reveal a cofactor-dependent binding to CL, binding activity to platelets, and lupus anti-coagulant (LA) activity. Here, we analysed the usage of VH and V kappa genes of six aCL, including two pathogenic aCL, from W/B F1 mice, in an attempt to address the question of whether or not aCL with pathogenic properties use restricted Ig V genes. Sequence analysis of VH and V kappa genes of aCL showed that the pathogenic aCL had VHJ558 and V kappa 21 or V kappa 23 genes, whereas the other aCL without pathogenic features used mainly the 7183 VH family and the random V kappa gene group. However, two pathogenic aCL showed a 86.6% homology with the IgV region, each other, indicating that they were not closely related clones. Thus, these findings suggest the possibility that usage of Ig VH genes in pathogenic aCL is not random, but that there may exist a few epitopes of antigen recognized by the pathogenic aCL.     

Effects of sex hormones on human PMN migration

It is believed that gingivitis at puberty is exaggerated by alterations of the hormonal balance. We have suggested that estradiol promotes the gingivitis at puberty while progesterone reduces it (J. Hiroshima Univ. Dent. Soc. 19: 1987). But the mechanisms of these hormones which influence gingival inflammation are not known yet. Therefore, we hypothesized that one of the possible mechanisms of sex hormones on gingival inflammation is through their action on polymorphonuclear leucocytes (PMNs) function because PMNs play an important role in periodontal disease. The purpose of this study was to investigate the effect of sex hormones on PMNs function, especially their migration in vitro. PMNs and plasma were obtained from heparinized peripheral blood of 23 healthy adults. PMNs were preincubated at 37 degrees C for 15 minutes with progesterone or 17 beta-estradiol at designated concentrations. After preincubation, PMNs migration was measured using 48-well chemotaxis micro-chamber with N-formyl-methionyl-leucyl-phenylalanine (FMLP) as chemoattractant. The levels of estradiol and progesterone in the plasma were determined using Direct Radioimmunoassay Kits and the correlation between sex hormone levels and PMNs migration was investigated. PMNs migration to 10(-6) M FMLP was enhanced significantly by progesterone at the concentrations of 200 ng/ml while it was reduced by estradiol at 0.4 ng/ml and 2.0 ng/ml. Random migration of PMNs was enhanced significantly by progesterone at 20 ng/ml while it was reduced by estradiol at 0.4 ng/ml. Significant positive correlation was found between progesterone level in plasma and the PMNs migration in vitro. Estradiol level in plasma did not have any correlation with the PMNs migration in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)     

A human seminal plasma protein blocks the motility of human spermatozoa

An inhibitor of the motility of demembranated spermatozoa has been shown to be present in human seminal plasma. This seminal plasma motility inhibitor (SPMI) was purified to apparent homogeneity and tested on intact human spermatozoa. Motility parameters of spermatozoa incubated with the sperm motility inhibitor were evaluated with the video automated Cell Soft system. SPMI decreased the percentage of motile spermatozoa in a dose-dependent manner and motility was completely blocked in the presence of 1600 units/ml. Sperm velocity and beat/cross frequency showed a similar progressive decrease as the inhibitor was augmented. However, linearity was essentially not affected. The effects of SPMI on the percentage of motile spermatozoa increased with the time of contact between the inhibitor and spermatozoa. After 120 min., the IC50 was 35% lower than that observed at five min. The presence of seminal plasma did not prevent the inhibitory effects of the seminal plasma factor on sperm motility parameters. On the contrary, a potentiating effects was observed. The data suggest that the SPMI could play a significant role in cases of infertility caused by asthenospermia.     

Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.