Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans

Bile acids are synthesized from cholesterol in the liver and subjected to multiple metabolic biotransformations in hepatocytes, including oxidation by cytochromes P450 (CYPs) and conjugation with taurine, glycine, glucuronic acid, and sulfate. Mice and rats can hydroxylate chenodeoxycholic acid (CDCA) at the 6β-position to form α-muricholic acid (MCA) and ursodeoxycholic acid (UDCA) to form β-MCA. However, MCA is not formed in humans to any appreciable degree and the mechanism for this species difference is not known. Comparison of several Cyp-null mouse lines revealed that α-MCA and β-MCA were not detected in the liver samples from Cyp2c-cluster null (Cyp2c-null) mice. Global bile acid analysis further revealed the absence of MCAs and their conjugated derivatives, and high concentrations of CDCA and UDCA in Cyp2c-null mouse cecum and feces. Analysis of recombinant CYPs revealed that α-MCA and β-MCA were produced by oxidation of CDCA and UDCA by Cyp2c70, respectively. CYP2C9-humanized mice have similar bile acid metabolites as the Cyp2c-null mice, indicating that human CYP2C9 does not oxidize CDCA and UDCA, thus explaining the species differences in production of MCA. Because humans do not produce MCA, they lack tauro-β-MCA, a farnesoid X receptor antagonist in mouse that modulates obesity, insulin resistance, and hepatosteatosis

Acute Low Back Pain with Radiculopathy: A Double-Blind, Randomized, Placebo-Controlled Study

Abstract Objective: The aim of this study was to investigate the clinical effects of low-level laser therapy (LLLT) in patients with acute low back pain (LBP) with radiculopathy. Background Data: Acute LBP with radiculopathy is associated with pain and disability and the important pathogenic role of inflammation. LLLT has shown significant antiinflammatory effects in many studies. Materials and Methods: A randomized, double-blind, placebo-controlled trial was performed on 546 patients. Group A (182 patients) was treated with nimesulide 200 mg=day and additionally with active LLLT; group B (182 patients) was treated only with nimesulide; and group C (182 patients) was treated with nimesulide and placebo LLLT. LLLT was applied behind the involved spine segment using a stationary skin-contact method. Patients were treated 5 times weekly, for a total of 15 treatments, with the following parameters: wavelength 904 nm; frequency 5000 Hz; 100-mW average diode power; power density of 20 mW=cm 2 and dose of 3 J=cm 2 ; treatment time 150 sec at whole doses of 12 J=cm 2 . The outcomes were pain intensity measured with a visual analog scale (VAS); lumbar movement, with a modified Schober test; pain disability, with Oswestry disability score; and quality of life, with a 12-item short-form health survey questionnaire (SF-12). Subjects were evaluated before and after treatment. Statistical analyses were done with SPSS 11.5. Results: Statistically significant differences were found in all outcomes measured ( p < 0.001), but were larger in group A than in B ( p < 0.0005) and C ( p < 0.0005). The results in group C were better than in group B ( p < 0.0005). Conclusions: The results of this study show better improvement in acute LBP treated with LLLT used as additional therapy

Models, strategies, and methods for effective teaching

Models, strategies, and methods for affective teaching has been written to respond to the challenges to teacher education presented by national and state legislation and the frustration expressed by teacher education graduates who found it difficult to transfer what was studied on campus to the reality of modern schools and classrooms. this book was written to help you whether you are a teacher education student pr practicing professional.XV, 480 p.:ill.; 24 cm