Both OEC and LIM treatment promoted an increase in epithelial hea

Both OEC and LIM treatment promoted an increase in epithelial healing, as confirmed by immunohistochemistry, which was greater in the animals that were treated with the positive control. In addition, both treatments increased cellular proliferation as measured by proliferating cell nuclear antigen and cyclooxygenase 2 expression in the gastric mucosa, vascular endothelial growth factor-mediated blood vessel formation in the margin of the ulcer, and production of gastric mucus, which fortifies the gastric protective barrier. We concluded that OEC and LIM, two common flavoring agents, promote gastric mucosal healing

without any apparent Z-DEVD-FMK purchase toxic effect, resulting in better gastric epithelial organization in the treated rats.”
“In vitro primary hepatocyte systems typically elicit drug induction and toxicity responses at concentrations much higher than corresponding in vivo or clinical plasma C-max levels, contributing to poor in vitro-in vivo correlations. This may be partly due to the absence of physiological parameters that maintain metabolic phenotype in vivo. We hypothesized that restoring hemodynamics

and media transport would improve hepatocyte architecture and metabolic function in vitro compared with nonflow cultures. Rat hepatocytes were cultured for 2 wk either in nonflow collagen gel sandwiches with 48-h media changes or under controlled hemodynamics mimicking sinusoidal circulation within a perfused Transwell device. Phenotypic, functional, and metabolic parameters were assessed at multiple selleckchem times. Hepatocytes in the devices

exhibited polarized morphology, retention of differentiation markers [E-cadherin and hepatocyte nuclear factor-4 alpha (HNF-4 alpha)], the canalicular transporter [multidrug-resistant protein-2 (Mrp-2)], and significantly higher levels of liver function compared with nonflow cultures over 2 wk (albumin similar to 4-fold and urea similar to 5-fold). Gene expression of cytochrome P450 (CYP) enzymes was significantly higher (fold increase over nonflow: CYP1A1: 53.5 +/- 10.3; CYP1A2: 64.0 +/- 15.1; Batimastat CYP2B1: 15.2 +/- 2.9; CYP2B2: 2.7 +/- 0.8; CYP3A2: 4.0 +/- 1.4) and translated to significantly higher basal enzyme activity (device vs. nonflow: CYP1A: 6.26 +/- 2.41 vs. 0.42 +/- 0.015; CYP1B: 3.47 +/- 1.66 vs. 0.4 +/- 0.09; CYP3A: 11.65 +/- 4.70 vs. 2.43 +/- 0.56) while retaining inducibility by 3-methylcholanthrene and dexamethasone (fold increase over DMSO: CYP1A = 27.33 and CYP3A = 4.94). These responses were observed at concentrations closer to plasma levels documented in vivo in rats. The retention of in vivo-like hepatocyte phenotype and metabolic function coupled with drug response at more physiological concentrations emphasizes the importance of restoring in vivo physiological transport parameters in vitro.”
“Fredriksson AG, Zajac J, Eriksson J, Dyverfeldt P, Bolger AF, Ebbers T, Carlhall CJ.

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