OBJECTIVETo investigate the therapeutic effects of peptide YY against hepatic fibrosis in rats and explore the possible mechanism.

METHODRat models of hepatic fibrosis were established with a subcutaneous injection of carbon tetrachloride and randomized into normal control group, model group, peptide YY (PYY)-treated group, octreotide-treated group, and interferon gamma-treated group. Serum levels of the hepatic function indices and hepatic fibrotic index were detected, and the hepatic fibrosis grade was assessed using HE staining. The expression of transforming growth factor beta1 (TGFbeta1) were determined with immunohistochemical staining method.

RESULTSThe rats in PYY-treated group showed significantly different serum levels of TBIL, HA and LN from the rats in the model group (P<0.05). PYY significantly reduced hepatic fibrosis scores and lowered TGFbeta1 expression as compared with the model group.

CONCLUSIONSPYY can down-regulate TGFbeta1 expression to inhibit the development of hepatic fibrosis with comparable efficacy with interferon gamma and octreotide.

Animals ; Carbon Tetrachloride ; Immunohistochemistry ; Liver Cirrhosis, Experimental ; chemically induced ; drug therapy ; metabolism ; Male ; Peptide YY ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; biosynthesis

Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS.
Adolescent ; Area Under Curve ; Biopsy ; Body Mass Index ; Body Weight ; Child ; Cholecystokinin/*blood ; Ghrelin ; Humans ; Insulin/*blood/metabolism ; Male ; Obesity ; Peptide Hormones/*blood/metabolism ; Peptide YY/*blood ; Prader-Willi Syndrome/*blood ; Time Factors

Neuropeptide Y (NPY) receptors are present in cardiac membranes. However, its physiological roles in the heart are not clear. The aim of this study was to define the direct effects of pancreatic polypeptide (PP) on atrial dynamics and atrial natriuretic peptide (ANP) release in perfused beating atria. Pancreatic polypeptides, a NPY Y4 receptor agonist, decreased atrial contractility but was not dose-dependent. The ANP release was stimulated by PP in a dose-dependent manner. GR 23118, a NPY Y4 receptor agonist, also increased the ANP release and the potency was greater than PP. In contrast, peptide YY (3-36) (PYY), an NPY Y2 receptor agonist, suppressed the release of ANP with positive inotropy. NPY, an agonist for Y1, 2, 5 receptor, did not cause any significant changes. The pretreatment of NPY (18-36), an antagonist for NPY Y3 receptor, markedly attenuated the stimulation of ANP release by PP but did not affect the suppression of ANP release by PYY. BIIE0246, an antagonist for NPY Y2 receptor, attenuated the suppression of ANP release by PYY. The responsiveness of atrial contractility to PP or PYY was not affected by either of the antagonists. These results suggest that NPY Y4 and Y2 receptor differently regulate the release of atrial ANP.
Animals ; Arginine/analogs & derivatives/pharmacology ; Atrial Natriuretic Factor/*metabolism ; Benzazepines/pharmacology ; Gene Expression Regulation ; Pancreatic Polypeptide/pharmacology ; Peptide YY/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Neuropeptide Y/agonists/antagonists & inhibitors/*metabolism

OBJECTIVETo investigate the effects of peptide YY (PYY) on subcutaneous transplantation tumor of human hepatoma in nude mice and preliminarily explore the mechanisms.

METHODSHepG2 human hepatic carcinoma cells were injected into nude mice subcutaneously, and the resultant tumor were taken and prepared into small tissue blocks. The tissue blocks were implanted subcutaneously into nude mice to establish mouse models bearing human hepatoma. Thirty-two such mouse models were assigned equally into 4 groups to receive subcutaneous PYY injection at a high or low dose, intraperitoneal injection of floxuridine (positive control group), or subcutaneous normal saline injection (negative control group). The general condition of the tumor-bearing mice and the growth of the tumors were observed.

RESULTSCompared with the negative control group, the high- and low-dose PYY groups showed reduced gross tumor volume, lowered serum AFP, tumor weight, and cAMP content in the tumor tissue (P<0.05).

CONCLUSIONPYY can inhibit the growth of subcutaneous hepatoma in nude mice, which might be associated with the reduction of cAMP content in the tumors following PYY treatment.

Animals ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Cell Line, Tumor ; Cyclic AMP ; metabolism ; Humans ; Liver Neoplasms, Experimental ; drug therapy ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Peptide YY ; therapeutic use ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

PURPOSE: Postinfectiously irritable bowel syndrome (PI-IBS) develops in 3-30% of individuals with bacterial gastroenteritis. Recent studies demonstrated increases in inflammatory components in gut mucosa of PI-IBS patients even after complete resolution of infection. We aimed to investigate histological changes in colon and rectum of PI-IBS subjects after long term period of infection. MATERIALS AND METHODS: We recruited PI-IBS subjects who had been diagnosed IBS after complete resolution of enteritis caused by shigellosis outbreak 3 years earlier. We compared unmatched four groups, PI-IBS (n = 4), non PI-IBS (n = 7), D-IBS (n = 7, diarrhea predominant type) and healthy controls (n = 10). All of them underwent colonoscopic biopsy at three areas, including descending colon (DC), sigmoid colon (SC) and rectum, which were assessed for 5-hydroxytryptamine (5-HT)/peptide YY (PYY)-containing enterochromaffin (EC) cell, intraepithelial (IEL) and lamina propria T lymphocyte (CD3), CD8 lymphocytes, mast cells and CD68/calprotectin+ macrophages. RESULTS: All subjects had no structural or gross abnormalities at colonoscopy. In PI-IBS, 5-HT containing EC cells, PYY containing EC cells, IELs, CD3 lymphocytes, CD8 lymphocytes, mast cells, and CD68 + macrophages were increased compared to control (p < 0.05). In D-IBS, PYY containing EC cells, IELs, and CD3 lymphocytes were increased compared to control (p < 0.05). In PI-IBS, 5-HT containing EC cells tended to increase and PYY containing EC cells, CD8 lymphocytes, mast cells, and CD68+ macrophages were increased compared to non PI-IBS (p < 0.05). Calprotectin + marcrophages were decreased in PI-IBS, non PI-IBS and IBS compared to control. CONCLUSION: The immunoendocrine cells were sporadically increased in PI-IBS, non PI-IBS and D-IBS compared with control. Our findings in a very small number of patients suggest that mucosal inflammation may play a role in long-term PI-IBS, and that other sub-groups of IBS and larger scale studies are needed to confirm this observation.
Adult ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; CD8-Positive T-Lymphocytes/cytology ; Case-Control Studies ; Colon, Descending/pathology ; Colon, Sigmoid/pathology ; Colonoscopy ; Dysentery, Bacillary/*complications ; Enterochromaffin Cells/cytology ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa/*pathology ; Irritable Bowel Syndrome/metabolism/*pathology ; Macrophages/cytology ; Male ; Mast Cells/cytology ; Peptide YY/metabolism ; Rectum/pathology ; Serotonin/metabolism