Effect of Obstructive Jaundice and Nitric Oxide on the Profiles of Intestinal Bacterial Flora in Wild and iNOS−/− Mice

We previously reported that the plasma level of endotoxin and colonic expression of IgA in the mouse increased with obstructive jaundice induced by bile duct ligation (BDL). To elucidate the mechanism of the BDL-induced increase, we analyzed the effect of BDL on intestinal flora in wild type and inducible nitric oxide synthase (iNOS)-deficient mice (iNOS−/−) using the terminal restriction fragment length polymorphism analysis (T-RFLP) and 16S rDNA clone libraries. The amounts of bacterial DNA detected in fecal samples from both animal groups pretreated with antibiotics were extremely low as compared with untreated groups. We found that the profiles of enteric bacteria changed markedly after BDL. The bacterial composition is significantly different between not only wild type and iNOS−/− mice but also those before and after BDL, respectively. Among enteric bacteria examined, Lactobacillus murinus was found to increase markedly after BDL in rectum of both animal groups. However, Escherichia coli markedly increased after BDL in the iNOS−/− mice. These findings suggest that profiles of enteric flora change markedly in animals during obstructive jaundice by some mechanism that is affected by bile constituents and iNOS-derived NO

Fasting Differentially Modulates the Immunological System: Its Mechanism and Sex Difference

The immunological properties and hormonal metabolism in rodents are affected by physical and psychological stress more strongly in males than in females. To elucidate the mechanism and physiological significance of the sex difference in the susceptibility of animal to stresses, changes in the immunological system in plasma and intestine and hormonal status in plasma were compared among 8-week-old male and female ICR mice before and after fasting. During the fasting of animals, the expression of immunoglobulin A in intestinal mucosa, and cortisol, interleukin-10 and interferon-γ in plasma increased. These changes occurred more apparently in males than in females. Under identical conditions, the plasma levels of testosterone decreased markedly with concomitant occurrence of apoptosis in the testis, while the plasma levels of estradiol decreased calmly, and no appreciable apoptosis occurred in the ovary. These results indicate that testosterone enhances the stress-induced modulation of the immune system by some mechanism that was antagonized by estradiol

alpha-lipoic acid suppresses 6-hydroxydoparnine-induced ROS generation and apoptosis through the stimulation of glutathione synthesis but not by the expression of heme oxygenase-1

We previously reported that the generation of reactive oxygen species (ROS) is the initial event in cell death induced by 6-hydroxydopamine (6-OHDA), an experimental model of Parkinsonism. Since recent studies suggested the important role of antioxidant activity of alpha-lipoic acid (LA) in the suppression of apoptosis of various types, we studied the effect on 6-OHDA-induced apoptosis of PC12 cells. Biochemical analysis revealed that LA suppressed the 6-OHDA-induced ROS generation, increase of caspase-like activity and chromatin condensation. The suppression of 6-OHDA-induced apoptosis by LA required pre-incubation of PC12 cells with LA for 12-24 h. LA increased the intracellular levels of heme oxygenase-1 (HO-1) and glutathione (GSH) and stimulated the expression of GSH synthesis-related genes such as cystine/glutamate antiporter and gamma-glutamylcysteine synthetase (gamma-GCS). However, Sn-mesoporphyrin IX, an inhibitor of HO-1, did not attenuate the LA-induced suppression of apoptosis. In contrast, buthionine sulfoximine, an inhibitor of gamma-GCS, attenuated the LA-induced suppression of ROS generation and chromatin condensation. in addition, a transcription factor Nrf2, which regulates the expression of antioxidant enzymes such as gamma-GCS, translocated to the nucleus by LA. These results suggested that LA suppressed the 6-OHDA induced-apoptosis by the increase in cellular glutathione through stimulation of the GSH synthesis system but not by the expression of HO-1.</p

Gallbladder adenocarcinoma with human chorionic gonadotropin: a case report and review of literature

<p>Abstract</p> <p>Background</p> <p>The case of adenocarcinoma with human chorionic gonadtropin (HCG), primary in the male gallbladder, is extremely rare. A Medline search has shown only a few similar cases reported.</p> <p>Methods</p> <p>We herein describe a case of primary gallbladder adenocarcinoma associated by ectopic HCG positive tumor cells in a 79-year-old male.</p> <p>Results</p> <p>Pathological examination showed a mixture of moderately and poorly differentiated adenocarcinoma with ectopic HCG and placental alkaline phosphatase (PlAP) in tumor cells, though the increase of serum or urinary HCG secretion was not confirmed. The literatures were also reviewed.</p> <p>Conclusions</p> <p>A case of gallbladder cancer with ectopic HCG production is quite rare in the literature, though many similar cases in other site, especially in GI tract, are reported. Embryological consideration suggests the increased frequency of similar cases more than being thought now.</p

The Role of gp91phox and the Effect of Tranexamic Acid Administration on Hair Color in Mice

We observed that on long-term breeding, gp91phox-knockout (gp91phox&#8722;/&#8722;) mice developed white hair. Here, we investigate the origin of this hitherto unexplained phenomenon. Moreover, we investigated the effect of tranexamic acid administration on the hair color in gp91phox&#8722;/&#8722; mice. We administered tranexamic acid (about 12 mg/kg/day) orally to 9-week-old C57BL/6j (control) and gp91phox&#8722;/&#8722; mice, thrice a week for 12 months. Compared to control mice, gp91phox&#8722;/&#8722; mice showed more white hair. However, the concentrations of reactive oxygen species and the levels of interleukin (IL)-1&#946; and transforming growth factor (TGF)-&#946; in the skin were lower than those in the control group. Furthermore, increase in white hair was observed in the control mice upon administration of the IL-1&#946; antagonist. On the other hand, administration of tranexamic acid led to brown colored hair on gp91phox&#8722;/&#8722; mice. Although tranexamic acid treatment did not alter the expression levels of melanocortin receptor 1 and agouti signaling protein on hair follicles, it increased the expression of mahogunin ring finger protein 1 (MGRN1) and collagen XVII. These results suggested that retention of black hair requires the gp91phox/ROS/IL-1&#946;/TGF-&#946; pathway and that elevated levels of MGRN1 and collagen XVII lead to brown hair in gp91phox&#8722;/&#8722; mice