Effects of intravenously administered synthetic kassinin on splanchnic circulation and exocrine pancreatic secretion were examined in six anesthetized dogs. Kassinin caused dose-related increases in the blood flow in superior mesenteric artery and portal vein, and produced an initial increase followed by a decrease in pancreatic blood flow, but did not affect the exocrine pancreatic secretion. This study demonstrates that kassinin affects splanchnic blood flow in dogs, and suggests that kassinin or a kassinin-like substance functions as a neuropeptide controlling the splanchnic circulation in mammalian species.

Animals↗

PubMedDate not supplied

Effects of synthetic human pancreastatin on pancreatic secretion and blood flow in rats and dogs.

Effects of synthetic human pancreastatin-52 and human pancreastatin-29 on pancreatic secretion and blood flow were examined in rats and dogs. Synthetic human pancreastatin-52 and human pancreastatin-29 were equally potent in suppressing the release of amylase stimulated by cholecystokinin in rats in vivo. However, neither human pancreastatin-52 nor human pancreastatin-29 altered basal and cholecystokinin-stimulated amylase release from isolated dispersed rat pancreatic acini. In studies in dogs, human pancreastatin-29 suppressed releases of amylase and protein stimulated by cholecystokinin, but did not alter pancreatic blood flow. These results suggest that the inhibitory effects of pancreastatin on pancreatic secretion do not involve a direct action on pancreatic acinar cells nor alteration of pancreatic blood flow. Pancreastatin probably is important in regulating exocrine pancreatic secretions as well as endocrine pancreatic secretions.

Amylases↗

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A newly developed three-layer agarose microcapsule for a promising biohybrid artificial pancreas: rat to mouse xenotransplantation.

We examined the effectiveness of an improved version of a three-layer agarose microcapsule in islet xenotransplantation. The microcapsule is composed of a mixture of 5% agarose and 5% polystyrene sulfonic acid. The other two outer layers are polybrene and carboxymethyl cellulose. The agarose/polystyrene sulfonic acid membrane is for the purpose of immunoisolation, suppression of complement activity and reinforcement of the microcapsule. The polybrene layer suppresses the polystyrene sulfonic acid leakage by forming a polyionic complex at the surface of the agarose/polystyrene sulfonic acid membrane. The outermost layer, a carboxymethyl cellulose coating, improves the biocompatibility of the microcapsule. In vitro static incubation study showed that the insulin secretion from rat islets in microcapsules in response to 16.7 mM glucose stimulation was more than four times higher than that on 3.3 mM glucose stimulation (n = 8). In an in vivo study, 500 rat islets in microcapsules were xenogenically implanted in the abdominal cavity of mice with streptozotocin-induced diabetes. The graft survival times ranged from 2 to 5 mo, the average being 75 days (n = 5). Our results demonstrate that the improved version of the three-layer agarose microcapsule can effectively prolong the xenograft survival time without employing immunosuppressants, suggesting that this microcapsule could provide a promising biohybrid artificial pancreas for future clinical applications.

Animals↗

PubMedDate not supplied

Application of a novel B cell line MIN6 to a mesh-reinforced polyvinyl alcohol hydrogel tube and three-layer agarose microcapsules: an in vitro study.

This study examines the function of a novel B cell line (MIN6) enclosed in hybrid bioartificial pancreas with mesh-reinforced polyvinyl alcohol hydrogel tube (MRPT) or with improved, three-layer agarose microcapsules. MIN6 was established from insulinomas obtained by targeted expression of the simian virus 40 T-antigen gene in transgenic mice. MIN6 retains the ability to secrete insulin in response to physiological glucose concentrations. The MRPT and the three-layer agarose microcapsules, which were developed to act as an artificial pancreas, were readily permeated by insulin, glucose, and other nutrients. Both can immunoisolate enclosed MIN6 cells from the recipient's humoral and cellular immunosystems, which causes a xenogeneic rejection response. MIN6 cells (5.0 x 10(6) or 1.5 x 10(6)) were enclosed in MRPT or in a hundred three-layer microcapsules and subjected to an in vitro perifusion study or a static incubation study to observe the insulin release from each bioartificial pancreas in response to glucose stimulation. In vitro study revealed that the insulin secretion in response to 16.7 mM glucose stimulation was twice that with 3.3 mM glucose stimulation with both MRPT and the three-layer agarose microcapsules. The present study demonstrates that MIN6 effectively functions as a bioreactor for the hybrid bioartificial pancreas. The application of MIN6 cells to the hybrid bioartificial pancreas may offer a solution to the current serious dearth of organs.

Animals↗

PubMedDate not supplied

Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells.

We have examined the relationship between the expression and activation of the IL-6 receptor and the possible involvement of IL-6 in the resistance of radiation-induced apoptosis in pancreatic cancer cells. Levels of IL-6 in the incubation media measured with ELISA were 1900 pg/ml in CFPAC-1, 54 pg/ml in HPAC and less than 0.2 pg/ml in MIAPaCa-2 and AsPC-1. Western blot demonstrated gp80 protein (IL-6 receptor a subunit) in all pancreatic cancer cell lines except in AsPC-1. When immunoprecipitation was performed, the bands indicating phosphorylated gp130 (IL-6Rbeta) were observed in CFPAC-1 and HPAC, however, no band was found in MIAPaCa-2 or in AsPC-1 cells. RT-PCR and Western blot demonstrated that mRNA and protein expression for Bcl-2 and Bcl-XL was substantially increased by the IL-6 treatment in CEPAC-1 cells, but not in AsPC-1 cells. Neither exogenous IL-6 nor neutralizing anti-IL-6 mAb affected the proliferation of CFPAC-1 and AsPC-1 cells. However, the IL-6 treatment significantly attenuated the susceptibility to radiation in CFPAC-1 cells but not in AsPC-1 cells, and the neutralizing anti-IL-6 mAb significantly increased the radiosensitivity of CFPAC-1 cells. The results indicated that IL-6 might be produced in a paracrine and/or autocrine fashion in pancreatic cancer cells. In-6 inhibits radiation-induced apoptosis and enhances the survival of the cells through a functional receptor system, which is associated with the up-regulation of anti-apoptotic Bcl-2 family proteins, especially Bcl-XL.

Apoptosis↗

PubMedDate not supplied

Effects of short physical exercise on the concentrations of alpha 1-microglobulin and beta 2-microglobulin in human plasma.

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Adult↗

PubMedDate not supplied

Metabolism of cholecystokinin-33 in vivo: effect of L-364,718, a CCK receptor antagonist.

Metabolism of cholecystokinin (CCK) and the effect of L-364,718, a specific CCK-A receptor antagonist, on the metabolism of CCK were examined in dogs. In conscious dogs, 45 min intravenous infusion of synthetic human CCK-33 (100 pmol/Kg/hr) caused an integrated CCK response over 90 min of 675 +/- 51 pmol-90 min/L, and the plasma CCK levels declined promptly with a t1/2 of 2.2 +/- 0.3 min after cessation. Organ extraction of CCK-33 by the kidney, mesenteric organs, and liver was examined in anesthetized dogs. From the gradients of the plasma levels between afferent and efferent vessels for each organ after bolus injection of CCK-33 (50 pmol/Kg), renal extraction ratio was 0.30 +/- 0.04, and mesenteric extraction ratio was 0.19 +/- 0.04. Hepatic extraction was not detected. T1/2 and extraction ratios were not affected by the preinjection of L-364,718 (20 nmol/Kg). The results indicate in dogs that exogenously administered CCK-33 is degraded by the mesenteric organs as well as the kidney but not by the liver, and that receptor-mediated mechanisms are not involved in these degradation pathways of CCK.

Anesthesia↗

PubMedDate not supplied

Mechanism of apoptosis induced by cisplatin and VP-16 in PANC-1 cells.

Cisplatin and VP-16 were used to study the induction of apoptosis in Panc-1 cells. Cisplatin and VP-16 inhibited the growth of Panc-1 cells. After 2 hours exposure to cisplatin or VP-16, attached and detached cells were subjected to TUNEL staining to calculate the ratio of apoptosis. In detached cells TUNEL positive ratios increased in a time- and dose-dependent manner. In Western blotting, Bax expression was obviously up-regulated, but Bcl-2 remained almost constant. The results suggested that in Panc-1 cells cisplatin and VP-16 induced apoptotic cell death which was mediated through the interaction of Bax expression in the presence of mutated p53.

Antineoplastic Agents↗

PubMedDate not supplied

Intracellular Ca2+ response of pancreatic acini in cerulein-induced acute pancreatitis in rats.

BACKGROUND/AIMS: To approach the mechanism of impaired signal transduction in cerulein-induced pancreatitis, in vitro acinar cell responses including the intracellular Ca2+ dynamics were evaluated. METHODOLOGY: Rats were infused with 10 micrograms/kg/h of cerulein for 4 hours, and the pancreas was dispersed. A binding study for 125I-CCK, intracellular Ca2+ measurement, and an amylase secretion analysis were performed in dispersed pancreatic acini. RESULTS: The binding study for 125I-CCK revealed that the CCK-binding capacity (Bmax) was decreased, although the binding affinities (Kd high and Kd low) were not altered. An in vitro amylase secretion analysis evoked higher basal secretion but little response. In the control acini, the in vitro application of a physiological dose of CCK (10 pM) evoked intracellular Ca2+ oscillations, and a higher dose of CCK (100 pM, 1 nM) evoked a large transient rise in the intracellular Ca2+ concentration. In cerulein-treated acini, 10 pM CCK evoked no intracellular Ca2+ release, and 100 pM CCK evoked only oscillated Ca2+ concentrations. A higher dose (1 nM) of CCK evoked a transient rise, but the peak Ca2+ level was significantly lower than that in the control (p < 0.05). CONCLUSIONS: These data suggest that both CCK receptors and intracellular Ca2+ mobilizations are similarly desensitized. The attenuation of amylase secretion is partly due to impaired signal transduction, including impaired intracellular Ca2+ release.

Amylases↗

PubMedDate not supplied

An exogenous cdk inhibitor, butyrolactone-I, induces apoptosis with increased Bax/Bcl-2 ratio in p53-mutated pancreatic cancer cells.

We investigated the effects of an exogenous cdk inhibitor, butyrolactone-I, on cell growth inhibition, apoptosis induction, and the regulation of apoptosis in pancreatic cancer cells with mutated p53. Cell growth was dose-dependently inhibited by Butyrolactone-I in PANC-1 and AsPC-1 cells. Phosphorylation of pRb and Cyclin A expression were significantly inhibited in Butyrolactone-I-treated cells. Apoptotic cell death was detected by both Hoechst staining and TUNEL assay. In butyrolactone-I-treated PANC-1 cells, expression of p53 protein was unchanged, but Bax expression was slightly upregulated and Bcl-2 expression was predominantly down-regulated. Bax/Bcl-2 ratio reached 9.6-fold increase compared to the control at the maximum. The time course of changes in Bax/Bcl-2 ratio was similar to that in the TUNEL-positive ratio. These data, suggest that dynamic changes of the Bax/Bcl-2 ratio might be important in determining point of apoptosis induction in pancreatic cancer cells with p53 mutation.

4-Butyrolactone↗