Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.     

High Cell-Density Culture System of Hepatocytes Entrapped in a Three-Dimensional Hollow Fiber Module with Collagen Gel

Abstract: A compact three-dimensional (3D) module is needed for hepatocyte culture in order to develop an effective hybrid artificial liver system that can retain hepa-tocellular structure and differentiated functions. We treated the 3D module with collagen gel to entrap rat hepatocytes. This method yielded a high hepatocellular density (2 times 10⁷ cells/ml) over a period of 14 days and maintained the secretion of albumin and ureogenesis at the same level as the control monolayer method. The ammonia removal remained at 43% of the Day 0 value over 8 days of perfusion. Our data show that this approach may be useful for liver support therapy in an ex-tracorporeal circuit.     

Incontinent Ileal Tube Repaired by Infolding with the Ileal Pouch Wall

In a patient who had undergone construction of a continent ileal pouch we successfully repaired an incontinent ileal tube by infolding it in an imbricated portion of the ileal pouch wall. For 2 years postoperatively the patient has been urine continent and has catheterized the pouch easily. We believe this infolding technique is useful for reconstructing the continent mechanism in patients with incompetent ileal valves.     

Magnolol inhibits leukotriene synthesis in rat basophilic leukemia-2H3 cells

We have observed an inhibitory action of magnolol on the production of leukotriene (LT) C4 and LTB4, important lipid mediators in allergy and inflammation. IgE- and A23187-stimulated production of LTC4 and LTB4 was measured by radio-immunoassay (RIA) in the absence or presence of various concentrations of magnolol in intact rat basophilic leukemia (RBL)-2H3 cells. Magnolol dose-dependently inhibited synthesis of LTC4 and LTB4. Magnolol inhibited the IgE-mediated increase of intracellular calcium ion concentration, resulting in the inhibition of cytosolic phospholipase A2 (cPLA2) and possibly 5-lipoxygenase (5-LO), both calcium ion-dependent enzymes. In cell-free studies magnolol inhibited LTC4 synthase activity. LTA4 hydrolase activity was only inhibited at the higher concentration (2.5 x 10(-5)M). These results indicate that magnolol inhibits production of LTs by inhibiting PLA2, 5-LO, LTC4 synthase and LTA4 hydrolase which are essential for LT-synthesis. Magnolol may have anti-allergic effect by blocking LT-synthesis.     

Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death

Caspase 3 is an essential death factor for the Fas-mediated cell death, and its inactivation in cells is initiated by an interaction with p21 on mitochondria or with IAP family member ILP. Survivin is also a member of IAP family and is specifically expressed during embryogenesis and in tumor cells and suppresses cell death signaling. In our current study, we demonstrated that Survivin translocation into the nucleus is dependent on Fas stimulation and cell proliferation. Survivin also interacts with the cell cycle regulator Cdk4, leading to Cdk2/Cyclin E activation and Rb phosphorylation. As a result of Survivin/Cdk4 complex formation, p21 is released from its complex with Cdk4 and interacts with mitochondrial procaspase 3 to suppress Fas-mediated cell death. Here, we propose that Survivin supports procaspase 3/p21 complex formation as a result of interaction with Cdk4 resulting in suppression of cell death signaling.     

Accuracy of direct examination and culture as compared to the anatomopathological examination for the diagnosis of chromoblastomycosis: a systematic review

BackgroundChromoblastomycosis is a skin infection caused by dematiaceous fungi that take the form of muriform cells in the tissue. It mainly manifests as verrucous plaques on the lower limbs of rural workers in tropical countries.ObjectivesThe primary objective of this review is to evaluate the accuracy of diagnostic methods for the identification of chromoblastomycosis, considering the histopathological examination as the reference test.MethodsMEDLINE, LILACS and Scielo databases were consulted using the terms “chromoblastomycosis” AND “diagnosis”. The eligibility criteria were: studies that evaluated the accuracy of tests for the diagnosis of chromoblastomycosis. Eleven studies were selected. Statistical analysis included the calculation of sensitivity and specificity of the diagnostic methods.ResultsConsidering the histopathological examination as the reference test, the culture showed a sensitivity (S) of 37.5% - 90.9% and a specificity (Sp) of 100%; while direct mycological examination showed S = 50% - 91.6% and Sp of 100% . Considering the culture as the reference test, the serology (precipitation techniques) showed S of 36% - 99%; and Sp of 80% - 100%; while the intradermal test showed S of 83.3% - 100% and Sp of 99.4% - 100%.Study limitationsThe small number of studies and very discrepant sensitivity results among them do not allow the calculation of summary measures through a meta-analysis.ConclusionsDirect mycological examination, culture, intradermal test and serology show sensitivity and specificity values ??for the diagnosis of chromoblastomycosis with no significant difference between the studies.     

Radioimmunoassay of motilin

A radioimmunoassay method of motilin was developed in our laboratory and was validated in dogs with a platinum monopolar electrode in the duodenum. We confirmed that a bolus infusion of 0.3 M tris-buffer solution or 0.1 N HCl solution in the duodenum produces a significant rise in plasma immunoreactive motilin (IRM) concentrations. This coincided with a marked increase in the percentage of spike potentials on slow waves of the duodenum, similar to phase III of interdigestive myoelectric-activity (MA). A possible relationship between plasma IRM and interdigestive MA of canine duodenum was studied. It was found that cyclic changes occurred in the fasting plasma IRM concentrations in dogs. While the peak motilin concentration was always observed in phase III, the lowest concentration of motilin was found in phase I of interdigestive MA in the duodenum. In dogs with the electrodes in the duodenum and jejunum, the peak IRM concentration did not correlate with phase III of interdigestive MA in the jejunum. A dose of synthetic porcine motilin, 0.06 g/kg/hr, which produced the plasma IRM concentration comparable to the peak fasting motilin concentration, could induce an identical phase III in the duodenum. These observations indicate that there is a relationship between cyclic changes in plasma IRM concentrations and interdigestive MA of the duodenum. It is suggested further that motilin is a hormone which may play an important role in inducing phase III of interdigestive MA in the duodenum.This work was supported by the Gastrointestinal Research Fund at The Genesee Hospital.     

Effect of synthetic chicken vasoactive intestinal peptide on pancreatic blood flow and on exocrine and endocrine secretions of the pancreas in dogs

This study was undertaken to determine the effect of synthetic chicken vasoactive intestinal peptide (VIP) on pancreatic blood flow, exocrine and endocrine secretions of the pancreas, and biliary secretion in dogs. The effect of synthetic chicken VIP on pancreatic blood flow and systemic arterial pressure was identical to that of natural chicken VIP in dogs. The present study demonstrated that synthetic chicken VIP induces significant increases in pancreatic blood flow, pancreaticobiliary secretion, and blood levels of insulin and glucose in dogs. Both the volume of pancreatic juice and blood levels of insulin were increased in consonance with the increase of pancreatic blood flow. This study suggests that the stimulatory effects of synthetic chicken VIP on exocrine and endocrine secretions of the pancreas may be related to the increased pancreatic blood flow elicited by synthetic chicken VIP.