Prosaposin in the rat oviductal epithelial cells.

Prosaposin (PSAP) has two forms: a precursor and a secreted form. The secreted form has neurotrophic, myelinotrophic, and myotrophic properties. The precursor form is a precursor protein of saposins A-D. Although the distribution of PSAP in male reproductive organs is well known, its distribution in female reproductive organs, especially in the oviduct, is unclear. Immunoblots and immunohistochemistry of oviducts showed that oviductal tissues contain PSAP proteins, and a significant increase in PSAP was observed in the estrus-metestrus phase compared to the diestrus-proestrus phase in the ampulla. To identify PSAP trafficking in cells, double-immunostaining was performed with antibodies against PSAP in combination with sortilin, mannose 6 phosphate receptor (M6PR), or low-density lipoprotein receptor-related protein 1 (LRP1). PSAP and sortilin double-positive reactions were observed near the nuclei, as well as in the apical portion of microvillous epithelial cells, whereas these reactions were only observed near the nuclei of ciliated epithelial cells. PSAP and M6PR double-positive reactions were observed near the nuclei of microvillous and ciliated epithelial cells. PSAP and M6PR double-positive reactions were also observed in the apical portion of microvillous epithelial cells. PSAP and LRP1 double-positive reactions were observed in the plasma membrane and apical portion of both microvillous and ciliated epithelial cells. Immunoelectron staining revealed PSAP immunoreactive small vesicles with exocytotic features at the apical portion of microvillous epithelial cells. These findings suggest that PSAP is present in the oviductal epithelium and has a pivotal role during pregnancy in providing an optimal environment for gametes and/or sperm in the ampulla.

Effect of central injection of tumor-necrosis factor-like cytokine 1A and interferons on food intake in chicks.

In mammals, anorexia accompanying infection is thought to be mediated via cytokines including interleukins, interferons (IFNs), and tumor necrosis factor (TNF). However, there is a lack of related knowledge on birds. Therefore, the purpose of the present study was to determine if cytokines are associated with reduced food intake in chicks (Gallus gallus). Specifically, we evaluated the effects of TNF-like cytokine 1A (TL1A), a member of the TNF family, interferon-α (IFN-α), and interferon-γ (IFN-γ) on food intake. Additionally, the effect of lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (poly I:C) on cytokine mRNA expression in the diencephalon and spleen was also measured. Intracerebroventricular (ICV) injection of 0.05 or 0.5 µg TL1A, IFN-α, and IFN-γ had no effect on food intake. However, when 1.0 µg each of these factors was evaluated, TL1A significantly decreased food intake at 180 and 240 min after the injection, but IFN-α and IFN-γ had no effect. When chicks received intraperitoneal (IP) injections of 100 µg LPS or 400 µg poly I:C, their food intake was reduced. Diencephalic mRNA expression of TL1A was significantly decreased following IP injection of LPS or poly I:C. Additionally, diencephalic mRNA expression of IFN-γ mRNA was significantly increased by IP injection of LPS but decreased by IP injection of poly I:C. For the spleen, IP injection of LPS and poly I:C both significantly increased TL1A and IFN-γ mRNA expression. In sum, we have provided evidence that central TL1A but not IFN-α or IFN-γ are related to reduction of food intake in chicks, but the role of these cytokines for mediating anorexia associated with infections may differ from mammals.

Feeding response following central administration of mesotocin and arginine-vasotocin receptor agonists in chicks (Gallus gallus).

Mesotocin (MT) and arginine-vasotocin (AVT) are posterior pituitary derived hormones in birds and are homologous to mammalian oxytocin (OT) and vasopressin (VP), respectively. We previously reported that intracerebroventricular (ICV) injection of both MT and AVT inhibit feeding and induce wing-flapping in chicks (Gallus gallus). Because both peptides cause similar effects suggests that they might act via common receptors. However, the specific receptors of MT and AVT which mediate their anorexigenic effect have not been clarified in chicks. Thus, the purpose of the present study was to identify the receptor subtypes involved in MT- and AVT-induced anorexia and behavioral patterns by using several agonists. ICV injection of vasopressin-1 receptor agonist (V1R) (homologous to chicken AVT receptor-2 and -4 [VT2R and VT4R, respectively]), significantly decreased food intake while agonists of vasopressin-2 receptor (V2R) and OT receptor (OTR) (homologues of chicken AVT receptor-1 and MT receptor respectively) had no effect. In addition, V1R agonist induced wing-flapping although this was not affected by V2R or OTR agonists. Since VT2R has not been found in the brain of chicks, the present study suggested that VT4R might be related to the anorexigenic effect and wing-flapping induced by MT and AVT in chicks.

Early termination of immune tolerance state of hepatitis B virus infection explains liver damage.

AIM: To assess an early termination of immune tolerance state of chronic hepatitis B virus infection in Bangladesh and its clinical significance. METHODS: From a series of 167 treatment-naive chronic hepatitis B patients aged between 12 to 20 years (mean ± SD; 17.5 ± 2.8 years), percutaneous liver biopsies of 89 patients who were all hepatitis B e antigen negative at presentation were done. Of them, 81 were included in the study. They had persistently normal or raised serum alanine aminotransferase (ALT) values. A precore mutation (PCM) study was accomplished in 8 patients who were randomly selected. RESULTS: Forty-four (53.7%) patients had significant necroinflammation (HAI-NI > 7), while significant fibrosis (HAI-F ≥ 3) was seen in 15 (18.5%) patients. Serum ALT (cut off 42 U/L) was raised in 29 (35.8%) patients, while low HBV DNA load (< 10(5) copies/mL) was observed in 57 (70.4%) patients. PCM was negative in all 8 patients. CONCLUSION: This study indicates that the current concept of age-related immune tolerance state of HBV infection deserves further analyses in different population groups.

Combination therapy with antiviral drugs and hepatitis B vaccine in incidentally-detected and asymptomatic chronic hepatitis virus B carriers at Bangladesh.

Abstract Asymptomatic chronic hepatitis B virus (HBV) carriers are at risk of developing complications of liver disease, but these patients are not recommended for treatment with antiviral drugs. In fact, antiviral drugs are ineffective in these patients in the immune tolerance phase, when they have inadequate levels of host immunity. We postulated that combination therapy of an immune modulator and antiviral drugs may have potential to help these patients. Twenty-five patients with incidentally-detected asymptomatic chronic HBV were immunized with hepatitis B vaccine (10 microg of hepatitis B surface antigen) intramuscularly five times (at 0, 1, 2, 6, and 12 mo) to induce HBV-specific immunity. The patients were also treated with lamivudine (100 mg) daily for 12 mo. The combination therapy was safe for all patients with asymptomatic chronic HBV, and no increases in alanine aminotransferase or liver damage were detected in any patient. Although all of the patients were expressing HBV DNA in their serum before treatment, HBV DNA became undetectable in 16 of 25 patients, and was reduced in 9 of 25 patients at the end of the combination therapy. Combination therapy with the antiviral agent lamivudine and an immune modulator (hepatitis B vaccine) represents a potential therapeutic option for the control of HBV without liver damage in asymptomatic chronic HBV carriers.

Feeding and drinking response following central administrations of bombesin-like peptides in chicks.

Gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been isolated as homologues of bombesin. Central administration of bombesin inhibits feeding behavior in chicks (Gallus gallus) while the effects of GRP and NMB have not been reported. The purpose of the present study was to investigate whether intracerebroventricular (ICV) injection of GRP, NMB and neuromedin C (NMC, the C-terminus decapeptide of GRP) affected feeding and drinking behavior in chicks. Injection of GRP, NMC and NMB (0.2-5 nmol) decreased feeding behavior in chicks while drinking behavior was not affected. ICV injection of 5 nmol GRP and NMC decreased voluntary locomotion while NMB did not. It is therefore possible that GRP- and NMC-associated hypoactivity is related to the peptides' anorexigenic effects. GRP, NMC and NMB did not affect plasma corticosterone concentration, suggesting that hypothalamus-pituitary-adrenal axis might not be related to the anorexigenic action of these peptides. All these findings support the hypothesis that GRP, NMC and NMB function as anorexigenic factors in the brain of chicks.