Ghrelin, a novel growth hormone-releasing peptide isolated from human and rat stomach, is a 28 -amino acid peptide with a posttranslational acylation modification that is indispensable for stimulating growth hormone secretion by increasing intracellular Ca 2؉ concentration. It also functions in the regulation of feeding behavior, energy metabolism, and gastric acid secretion and motility. Using two different antibodies against the NH 2 -and COOH-terminal regions of ghrelin, we studied its localization in human and rat pancreas by immunohistochemistry. Ghrelin-immunoreactive cells were identified at the periphery of pancreatic islets in both species. Ghrelin co-localized exclusively with glucagon in rat islets, indicating that it is produced in ␣-cells. We identified ghrelin and des-acyl ghrelin in the rat pancreas using reverse-phase high-performance liquid chromatography combined with two radioimmunoassays. We also detected mRNA encoding ghrelin and its receptor in the rat pancreatic islets. Ghrelin increased the cytosolic free Ca 2؉ concentration in ␤-cells and stimulated insulin secretion when it was added to isolated rat pancreatic islets. These findings indicate that ghrelin may regulate islet function in an endocrine and/or paracrine manner. Diabetes 51:124 -129, 2002 G rowth-hormone secretagogues (GHSs) are small synthetic peptides and nonpeptide molecules that stimulate growth hormone (GH) release from the anterior pituitary through the GHS receptor (GHS-R) (1). GHS-R, a G protein-coupled receptor, promotes calcium release from the endoplasmic reticulum (2,3). Ghrelin, a 28 -amino acid peptide with an n-octanoylated Ser 3, was originally discovered in rat stomach as a cognate endogenous ligand for GHS-R by using an intracellular calcium influx assay on a stable cell line expressing rat GHS-R (4). The Ser 3 n-octanoylation is a unique modification necessary for ghrelin's activity. Ghrelin stimulates GH release when administered intravenously or intracerebroventricularly to rats and when applied directly to rat primary pituitary cells (4 -6). In addition, ghrelin increases food intake and body weight upon intracerebroventricular administration (7,8). Furthermore, intravenously or intracerebroventricularly administered ghrelin stimulates gastric acid secretion by activating the vagal system (9,10). These findings suggest that ghrelin is secreted in response to altered food intake or some other nutritional states and thereby plays a role in the regulation of feeding behavior, energy metabolism, and digestion. Ghrelin is produced primarily in the enteroendocrine cells of rats and humans (4,11,12). Many types of enteroendocrine cells, including insulin-and glucagonproducing cells of the pancreatic islets, develop from endodermal epithelium. Ghrelin, like insulin and glucagon, may be produced in the islets and involved in the regulation of energy metabolism.In the present study, we investigated the cellular source of ghrelin in rat and human pancreas by immunohistochemistry. Ghrelin molecules in rat pancreas we...

This work is aimed to provide a systematic design procedure to determine the process configuration, the relative position of the reactive zone, and separation sections. Instead of investigating real chemical systems, ideal chemical reaction systems with different relative volatility rankings will be studied. This provides a gradual transition as the reaction and separation properties change. The reaction considered is a reversible reaction, A + B ⇔︁ C + D, and this constitutes a quaternary system with 24 (4) possible relative volatility arrangements. These 24 systems can further be grouped into six categories according to the ranking of relative volatilities of reactants and products. The likely process configurations will be explored and design will be optimized based on the total annual cost (TAC). The results clearly indicate that the relative volatility rankings play a dominant role in the reactive distillation configuration and the TAC varies by a factor of ∼7 as we move from the most favorable case (reactants are intermediate keys) to the least favorable relative volatility ranking (products are intermediate keys). Finally, heuristics are given to correlate the relative volatility ranking to the TAC. © 2007 American Institute of Chemical Engineers AIChE J, 2007

We have found a hepatotrophic factor in plasma or sera of patients with fulminant hepatic failure and have purified human hepatocyte growth factor from plasma of these patients. In this study we developed an enzyme-linked immunosorbent assay with high specificity and sensitivity for human hepatocyte growth factor in human serum. This assay for serum human hepatocyte growth factor is a sandwich method consisting of three steps. The standard curve for human hepatocyte growth factor appeared to be linear in the range of 0.20 to 12.50 ng purified human hepatocyte growth factor/ml (2.35 to 147 pmol/L). The assay took about 4 hr. Serum human hepatocyte growth factor values in patients with fulminant hepatic failure measured by enzyme-linked immunosorbent assay showed a strong positive correlation with that by bioassay using rat hepatocytes in primary culture. The mean value of serum human hepatocyte growth factor for 30 normal subjects was 0.24 +/- 0.12 (S.D.) ng/ml; that for 23 patients with fulminant hepatic failure was 8.06 +/- 1.76 (S.E.M.) ng/ml- greater than 30 times greater than the mean value for normal subjects. Serum human hepatocyte growth factor levels in patients with acute hepatitis, chronic hepatitis and cirrhosis were found to be slightly higher than those in normal subjects, but only the increase in serum human hepatocyte growth factor of acute hepatitis patients was statistically significant. The enzyme-linked immunosorbent assay for serum human hepatocyte growth factor should prove useful for serum human hepatocyte growth factor level measurement in patients with various liver diseases.

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