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[The establishment of a human pancreatic mixed ductal-endocrine carcinoma cell line].

OBJECTIVE: Establishment of a human pancreatic mixed ductal-endocrine carcinoma cell line. METHODS: A specimen of this type of cancer was obtained from a male patient at the head of pancreas. The tumor tissue was minced into pieces and inoculated subcutaneously in nude mice. With two successive subcutaneous implants, a piece of tumor tissue taken from the 2(nd) implanted neoplasm of a nude mouse was minced into minute tissue masses and inoculated in a media containing 10% fetal bovine serum. RESULTS: Currently, it has been passed to the 55(th) passage. Cells of this cell line (PC-EN) kept simultaneously the morphologic patterns of a pancreatic ductal and endocrine tumor which were verified by histochemistry and immunohistochemistry assays. Some of the PC-EN cells showed presence of neuroendocrine granules by electron microscopy. The growth rate of this cell line was relatively low. Kakryotype analysis showed two cell populations with its major mode of chromosomes numbers as 48 in one, and 56 in the other. Study on K-ras gene demonstrated that PC-EN harbored a mutated codon 12. Several gastrointestinal hormones and CEA were detected in PC-EN cells and in the supra-cultured medium using radioimmunoassay. CONCLUSIONS: The cellular and molecular biologic characteristics of PC-EN cells illustrated that this cell line preserved the morphology of a pancreatic ductal and endocrine tumor and possessed a special growth property, chromosome karyotype, and mutation of Ki-ras gene, but also showed a biologic exocrine and endocrine functions of the pancreas. The establishment of PC-EN cell line will provide a useful model in vitro for further investigating the cellular and molecular biology of exocrine and endocrine tumors of the pancreas.

Aneuploidy↗

Aorta response to secretin in intact and diabetic rats.

The influence of secretin (10(-10) - 10(-8) M), a gastrointestinal hormone, on the relaxing response of rat thoracic aorta rings preconstricted by 40 mM KCl was studied by measuring changes in isometric tension in intact and diabetic animals. Initial contraction of aorta rings was markedly decreased in diabetic state. Secretin administered at two higher doses (10(-9), 10(-8) M) caused significant relaxation. In diabetes, relaxing effect was observed at all three doses of the peptide. These data indicate that secretin relaxes thoracic aorta rings and state of diabetes markedly amplifies the relaxant response to this peptide.

Animals↗

Protein synthesis in human gastric mucosa: effects of pentagastrin, secretin, and 13-nle-motilin.

This study in man (n = 35) deals with the effects of in vivo administration of pentagastrin, synthetic secretin, and 13-norleucine-motilin (13-nle-motillin), respectively, on the in vitro incorporation of 14C-leucine into gastric mucosal protein. From the results presented it may be concluded that pentagastrin has a trophic influence on gastric mucosa in man, too, while protein synthesis in human duodenal mucosa remains unaltered. As the incorporatin of 14C-leucine into gastric mucosal protein is inhibited both by secretion and 13-nle-motiln, it may be hypothesised that secretin and motilin act as functional antagonists of gastrin in the regulation of human gastric mucosal protein synthesis.

Adult↗

13-norleucine motilin versus pentagastrin: contrasting and competitive effects on gastrointestinal myoelectrical activity in the conscious dog.

In conscious fasted dogs, with chronically-implanted electrodes in stomach and small intestine, typical aborally-propagated interdigestive myoelectric complexes were induced by the infusion of 13-nor-leucine motilin (13-Nle-M); whereas when the normal interdigestive activity was abolished by the infusion of pentagastrin, the resulting 'postprandial' pattern of activity was not significantly modified by the administration of 13-Nle-M. Results from this study provide further evidence that Motilin as well as Gastrin may be involved in the control of gastrointestinal motility in dogs.

Animals↗

Reconstruction after total gastrectomy.

After total gastrectomy it is necessary to realize the reconstruction of the upper part digestive tract. It is necessary to choose the reconstruction method, which provides good life quality, and extensive physiologic regulation of gastrointestinal hormones after total gastrectomy. There is no ideal reconstruction method. Nowadays there are about 70 kinds of reconstruction methods. It is very important to preserve the duodenal passage. Also the production of reservoir is important. The conclusions of studies are not homogeneous. The patients can benefit from the reconstruction preserving duodenal passage and formed by pouch. (Fig. 1, Ref. 23.).

Animals↗

Gastroduodenal motor response to natural motilin and synthetic position 13-substituted motilin analogues: a comparative in vitro study.

Motor effects of graded concentrations of pure natural porcine motilin (13-Met-M) and synthetic motilin analogues - the methionine in position 13 substituted with either norleucine (13-Nle-M) or leucine (13-Leu-M) - on the rabbit, guinea-pig, rat, and human gastrointestinal smooth muscle were examined in vitro. Congruent species specificity of the motor activity of the motilins under study could be demonstrated in that muscle strips from rabbit and man were highly sensitive, whereas guinea-pig and rat preparations proved refractory to the polypeptides. In rabbit duodenal muscle and fundic muscle of the human stomach, graded concentrations of 13-Met-M, 13-Nle-M, and 13-Leu-M, respectively, produced graded increases in the contractile responses. The concentration-response curves were superimposable. Calculated maximal contractile responses (CMR's) and polypeptide doses for one-half maximal responses (D50 values) were not significantly different between the three motilins. Moreover, pharmacological analysis revealed that the motor effects of 13-Met-M, 13-Nle-M, and 13-Leu-M are uniformly not mediated via nervous pathways: neither blockage of axonal conduction by tetrodotoxin nor anticholinergic action by atropine exerted any detectable influence. Viewing the data presented, one may conclude that in man and rabbit, 1) natural porcine motilin and its synthetic position 13-substituted analogues, 13-Nle-M and 13-Leu-M, are of equal efficacy for gastroduodenal motor activity, and 2) position 13 of the amino acid sequence of motilin (22-residue chain) is not pertinent to the active site of the molecule.

Acetylcholine↗

[Changes in indicators of external and internal secretion of the pancreas during treatment of chronic pancreatitis of alcoholic etiology with somatostatin analogs].

AIM: To study somatostatin (SS) content in patients with chronic pancreatitis (CP) and effects of sandostatin (a synthetic analogue of SS) on endo- and exocrine pancreatic functions in CP patients. MATERIAL AND METHODS: SS plasma levels were measured by radioimmunoassay in basal conditions in 32 CP patients. Sandostatin treatment was given to 20 patients with CP of alcohol etiology (twice a day subcutaneously for 5 days). In the course of the treatment the following indices were measured: serum trypsin, amilase, lipase, alpha 2-macroglobulin, general antitryptic activity, blood immunoreactive insulin in basal conditions and after intravenous injection of glucose. RESULTS: SS levels in peripheral blood were elevated in patients with complicated alcoholic CP. Sandostatin in CP used for 5 days had no significant impact on insulin secretion, levels of pancreatic enzymes, inhibiting system of blood. 90% patients with alcoholic CP experienced relief of pain which may relate to suppression of stimulated secretion of gastrointestinal hormones as well as to a favourable action of sandostatin on stabilization of membranes of acinar cells. CONCLUSION: Sandostatin administration in CP patients is justified and is especially recommended in the complicated course.

Adult↗

[Nutrition and health--ideal body weight for the obese unrealistic; health benefit by moderate sustained weight loss].

The aim of achieving a normal or ideal body weight in the treatment of obesity is an obsolete goal. It stems from the time that obesity was not yet seen as a chronic incurable disease. A more realistic treatment goal is to reduce the body weight by 10-15% over a prolonged period of time. This moderate weight loss will result in a decreased risk for and incidence of obesity-associated diseases. Weight reduction and maintenance is countered by a decrease in resting-energy expenditure and in thermogenesis by food intake, a decreased energy expenditure through physical exercise, a reduced fat oxidation, a relative leptin deficiency and an excess of the gastrointestinal hormone ghrelin. Just as with hypertension and diabetes, the only option is life-long management with the normalisation of abnormal values within a given range.

Energy Intake↗

[The somatostatin analog SMA (201-995) as adjuvant treatment in patients with external fistulae of the digestive system].

Six patients with gastrointestinal fistulae treated with a potent inhibitor of gastrointestinal hormones, the somatostatin analogue SMS 201-995 are reported. All patients had severe intraabdominal diseases and underwent a mean of 3.5 surgery procedures during their hospital stay. When the patients were analyzed individually a mean reduction of 42.5% (P < 0.050 of basal fistulae output was observed after treatment. In three patients the fistulae closed after seven and ten days of treatment with the analogue; the other three patients died after a protracted hospital stay which included multiple admissions to the Intensive Care Unit. When the output of all fistulae treated where analyzed together it showed a tendency to decrease, but it didn't reach statistical significance.

Adult↗