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1.
Materials (Basel) ; 15(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36079242

RESUMO

LaBaCo2-xMoxO5+δ (LBCMx, x = 0-0.08) cathodes synthesized by a sol-gel method were evaluated for intermediate-temperature solid oxide fuel cells. The limit of the solid solubility of Mo in LBCMx was lower than 0.08. As the content of Mo increased gradually from 0 to 0.06, the thermal expansion coefficient decreased from 20.87 × 10-6 K-1 to 18.47 × 10-6 K-1. The introduction of Mo could increase the conductivity of LBCMx, which varied from 464 S cm-1 to 621 S cm-1 at 800 °C. The polarization resistance of the optimal cathode LBCM0.04 in air at 800 °C was 0.036 Ω cm2, reduced by a factor of 1.67 when compared with the undoped Mo cathode. The corresponding maximum power density of a single cell based on a YSZ electrolyte improved from 165 mW cm-2 to 248 mW cm-2 at 800 °C.

3.
BMC Gastroenterol ; 21(1): 2, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407159

RESUMO

BACKGROUND: Portal hypertension (PH) is the main cause of complications and death in liver cirrhosis. The effect of oral administration of octreotide (OCT), a drug that reduces PH by the constriction of mesenteric arteries, is limited by a remarkable intestinal first-pass elimination. METHODS: The bile duct ligation (BDL) was used in rats to induce liver cirrhosis with PH to examine the kinetics and molecular factors such as P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and cytochrome P450 3A4 (CYP3A4) influencing the intestinal OCT absorption via in situ and in vitro experiments on jejunal segments, transportation experiments on Caco-2 cells and experiments using intestinal microsomes and recombinant human CYP3A4. Moreover, RT-PCR, western blot, and immunohistochemistry were performed. RESULTS: Both in situ and in vitro experiments in jejunal segments showed that intestinal OCT absorption in both control and PH rats was largely controlled by P-gp and, to a lesser extent, by MRP2. OCT transport mediated by P-gp and MRP2 was demonstrated on Caco-2 cells. The results of RT-PCR, western blot, and immunohistochemistry suggested that impaired OCT absorption in PH was in part due to the jejunal upregulation of these two transporters. The use of intestinal microsomes and recombinant human CYP3A4 revealed that CYP3A4 metabolized OCT, and its upregulation in PH likely contributed to impaired drug absorption. CONCLUSIONS: Inhibition of P-gp, MRP2, and CYP3A4 might represent a valid option for decreasing intestinal first-pass effects on orally administered OCT, thereby increasing its bioavailability to alleviate PH in patients with cirrhosis.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Hipertensão Portal , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Células CACO-2 , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Humanos , Absorção Intestinal , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Octreotida , Ratos
4.
Exp Ther Med ; 12(6): 3716-3722, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28105103

RESUMO

The aim of the present study was to increase the intestinal transport of octreotide (OCT) by targeting the first-pass impact to identify a potential method for decreasing portal vein pressure (PVP) using oral OCT. Thus, the bioavailability of intestinally absorbed OCT was evaluated in normal rats and rats with portal hypertension (PH) that had been administered P-glycoprotein/multidrug resistance-associated protein 2/cytochrome P450 3A4 (P-gp/MRP2/CYP3A4) inhibitors. The mRNA and protein expression levels of P-gp, MRP2 and CYP3A4 were evaluated in normal and PH rats with or without OCT and the inhibitors using RT-PCR, western blot and immunohistochemical analyses. The potential effects of the inhibitor administration on PVP were also examined. The results suggest that P-gp, MRP2 and CYP3A4 play important roles in prohibiting the enteral absorption of OCT, particularly under a PH environment. Moreover, inhibitors of P-gp, MRP2 and CYP3A4 decrease the first-pass effects of OCT and effectively reduce PVP under PH conditions. Therefore, the present results suggest P-gp, MRP2 and CYP3A4 are key factors in the intestinal absorption of OCT. The inhibition of P-gp, MRP2 and CYP3A4 can markedly decrease the first-pass effects of OCT, and their use may facilitate the use of orally administered OCT.

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