CYP1A2 Downregulation by Obeticholic Acid: Usefulness as a Positive Control for the In Vitro Evaluation of Drug-Drug Interactions.

Cytochrome P450 (CYP) downregulation is a mechanism of drug-drug interaction encountered in pharmaceutical development which is difficult to evaluate in vitro because of the scarcity of evidence. A previous clinical study of obeticholic acid (OCA) with caffeine suggested that OCA may be a useful positive control to establish a method to evaluate CYP1A2 downregulation and to investigate the mechanism of its downregulation. In the present study, we investigated the ability of OCA to downregulate CYP1A2 in human hepatocytes.

Association between gene polymorphisms of connective tissue growth factor and the progression of chronic liver disease associated with hepatitis C.

Objective: Fibrogenic cytokines, such as transforming growth factor-beta 1 play a central role in the progression of liver fibrosis. Recently, functional gene polymorphisms in these cytokines have been identified, and some reports have validated the presence of associations between these polymorphisms and disease progression. Connective tissue growth factor (CTGF) is a stimulating factor for fibroblast proliferation and matrix production.

Association of TIMP-1 and TIMP-2 gene polymorphisms with progression of liver fibrosis in patients with type C chronic liver disease.

We examined the association of TIMP-1 and TIMP-2 gene polymorphisms with the progression of chronic liver disease related to the hepatitis C virus (HCV). We used PCR to analyze 188 patients with HCV-related liver disease (95 with chronic hepatitis and 93 with cirrhosis) for TIMP-1 372 T/C and TIMP-2 -418 G/C polymorphisms. Comparing chronic hepatitis and cirrhosis, there were no significant differences in TIMP-1 and TIMP-2 gene polymorphisms.

Drag current reversal in capacitively coupled arrays of small Josephson junctions.

The current-voltage characteristics of two long capacitively coupled one-dimensional arrays of small Josephson junctions were measured, where the coupling capacitance was comparable with the capacitance of the junction. The current in both arrays was simultaneously measured at various applied magnetic fields with the voltage applied to only one of the arrays. The current was induced in the unbiased array beyond the threshold voltage for the Coulomb blockade of the biased array.

Divergent synthesis and evaluation of inhibitory activities against cyclooxygenases-1 and -2 of natural withasomnines and analogues.

The divergent synthesis of natural withasomnines and analogues was achieved from 4-hydroxypyrazoles, which was prepared via alkaline hydrolysis of the Baeyer-Villiger oxidation products from 4-formylpyrazoles. Key steps of this synthesis are regioselective Claisen rearrangement of 4-allyloxypyrazoles and the Suzuki-Miyaura coupling of 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl trifluoromethanesulfonate and commercially available arylboronic acids. The Suzuki-Miyaura coupling at the final step of this strategy enabled facile access to natural withasomnines and their analogues.

The Effects of Olmesartan and Alfacalcidol on Renoprotection and klotho Gene Expression in 5/6 Nephrectomized Spontaneously Hypertensive Rats.

Recently, an angiotensin inhibitor has been shown to upregulate the klotho mRNA level in chronic renal failure. In addition, the administration of vitamin D has been reported to improve the mortality of patients with chronic renal failure. In this study, we examined the effects of an angiotensin inhibitor and/or vitamin D on the progression of chronic renal failure by using male 5/6 nephrectomized (5/6Nx) spontaneously hypertensive rats.

Functional gene polymorphisms of interleukin-10 are associated with liver disease progression in Japanese patients with hepatitis C virus infection.

Objective: The inter-individual difference in response to liver injury appears to be important in the progression of liver fibrosis. Interleukin 10 (IL-10) is an anti-inflammatory cytokine, and several functional gene polymorphisms have been found. The aim of this study was to examine the possible association of IL-10 polymorphisms with the progression of liver fibrosis in hepatitis C virus (HCV)-related chronic liver disease patients.

The genotypes of IL-1 beta and MMP-3 are associated with the prognosis of HCV-related hepatocellular carcinoma.

Background And Aim: Cytokines and matrix metalloproteinases (MMPs) are involved in tumor growth, invasion, and remote metastasis in various cancers. Recently, functional gene polymorphisms in these cytokines and MMPs have been found, and some reports have revealed an association between these polymorphisms and the prognosis of various cancers. In this study, we examined the relationship between the gene polymorphisms of interleukin 1 beta (IL-1b), IL-1 receptor antagonist (IL-1 RN), transforming growth factor beta 1 (TGF-b1), MMP-1, MMP-3, and MMP-9 and the prognosis of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).