47 research outputs found
Effect of melatonin on the severity of l-arginine-induced experimental acute pancreatitis in rats
AIM: To determine the effect of melatonin pre- and post-treatment on the severity
of L-arginine (L-Arg) -induced experimental pancreatitis in rats. METHODS: Male
Wistar rats (25) were divided into five groups. Those in group A received two
injections of 3.2g/kg body weight L-Arg i.p. at an interval of 1h. In group MA,
the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to
L-Arg administration. In group AM, the rats received the same dose of melatonin
1h after L-Arg was given. In group M, a single dose of melatonin was administered
as described previously. In group C the control animals received physiological
saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg
injection. RESULTS: L-Arg administration caused severe necrotizing pancreatitis
confirmed by the significant elevations in the serum amylase level, the
pancreatic weight/body weight ratio (pw/bw), the pancreatic IL-6 content and the
myeloperoxidase activity, relative to the control values. Elevation of the serum
amylase level was significantly reduced in rats given melatonin following L-Arg
compared to rats injected with L-Arg only. The activities of the pancreatic
antioxidant enzymes (Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT))
were significantly increased 24 h after pancreatitis induction. Melatonin given
in advance of L-Arg significantly reduced the pancreatic CAT activity relative to
that in the rats treated with L-Arg alone. In the liver, L-Arg significantly
increased the lipid peroxidation level, and the glutathione peroxidase and
Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the
control rats. Melatonin pre-treatment prevented these changes. CONCLUSION:
Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced
changes during acute pancreatitis, and may therefore be helpful in the supportive
therapy of patients with acute necrotizing pancreatitis
Effect of Intraduodenal Bile and Na-Taurodeoxycholate on Exocrine Pancreatic Secretion and on Plasma Levels of Secretin, Pancreatic Polypeptide, and Gastrin in Man
The effect of intraduodenally administered cattle bile (CB) and Na-taurodeoxycholate (TDC) on basal pancreatic secretion and plasma levels of secretin, pancreatic polypeptide (PP), and gastrin were investigated on two separate days in 10 fasting volunteers. Doses of 2-6 g CB and 20&600 mg TDC were given intraduodenally at 65-min intervals. Volume, bicarbonate, lipase, trypsin, amylase, and bilirubin were measured in 10-min fractions of duodenal juice, and GI peptides determined by radioimmunoassay. CB and TDC enhanced significantly and dose-dependently volume, bicarbonate and enzyme secretion, and plasma secretin and PP levels. In contrast, plasma gastrin showed only a marginal increase. We conclude that the hydrokinetic effect of intraduodenal CB and TDC is at least partially mediated by secretin. Gastrin could be ruled out as a mediator of the ecbolic effect, whereas other GI peptides, primarily CCK, and/or neural mechanisms must be considered possible mediators. Both pathways may also play a role in the PP release
Islet Formation during the Neonatal Development in Mice
The islet of Langerhans is a unique micro-organ within the exocrine pancreas, which is composed of insulin-secreting beta-cells, glucagon-secreting alpha-cells, somatostatin-secreting delta-cells, pancreatic polypeptide-secreting PP cells and ghrelin-secreting epsilon-cells. Islets also contain non-endocrine cell types such as endothelial cells. However, the mechanism(s) of islet formation is poorly understood due to technical difficulties in capturing this dynamic event in situ. We have developed a method to monitor beta-cell proliferation and islet formation in the intact pancreas using transgenic mice in which the beta-cells are specifically tagged with a fluorescent protein. Endocrine cells proliferate contiguously, forming branched cord-like structures in both embryos and neonates. Our study has revealed long stretches of interconnected islets located along large blood vessels in the neonatal pancreas. Alpha-cells span the elongated islet-like structures, which we hypothesize represent sites of fission and facilitate the eventual formation of discrete islets. We propose that islet formation occurs by a process of fission following contiguous endocrine cell proliferation, rather than by local aggregation or fusion of isolated beta-cells and islets. Mathematical modeling of the fission process in the neonatal islet formation is also presented
Bioinformatic identification of proteins with tissue-specific expression for biomarker discovery
<p>Abstract</p> <p>Background</p> <p>There is an important need for the identification of novel serological biomarkers for the early detection of cancer. Current biomarkers suffer from a lack of tissue specificity, rendering them vulnerable to non-disease-specific increases. The present study details a strategy to rapidly identify tissue-specific proteins using bioinformatics.</p> <p>Methods</p> <p>Previous studies have focused on either gene or protein expression databases for the identification of candidates. We developed a strategy that mines six publicly available gene and protein databases for tissue-specific proteins, selects proteins likely to enter the circulation, and integrates proteomic datasets enriched for the cancer secretome to prioritize candidates for further verification and validation studies.</p> <p>Results</p> <p>Using colon, lung, pancreatic and prostate cancer as case examples, we identified 48 candidate tissue-specific biomarkers, of which 14 have been previously studied as biomarkers of cancer or benign disease. Twenty-six candidate biomarkers for these four cancer types are proposed.</p> <p>Conclusions</p> <p>We present a novel strategy using bioinformatics to identify tissue-specific proteins that are potential cancer serum biomarkers. Investigation of the 26 candidates in disease states of the organs is warranted.</p