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

The role of thymic tolerance in CNS autoimmune disease

The contributions of the peripheral adaptive and innate immune systems to CNS autoimmunity have been extensively studied. However, the role of thymic selection in these conditions is much less well understood. The thymus is the primary lymphoid organ for the generation of T cells; thymic mechanisms ensure that cells with an overt autoreactive specificity are eliminated before they emigrate to the periphery and control the generation of thymic regulatory T cells. Evidence from animal studies demonstrates that thymic T cell selection is important for establishing tolerance to autoantigens. However, there is a considerable knowledge gap regarding the role of thymic selection in autoimmune conditions of the human CNS. In this Review, we critically examine the current body of experimental evidence for the contribution of thymic tolerance to CNS autoimmune diseases. An understanding of why dysfunction of either thymic or peripheral tolerance mechanisms rarely leads to CNS inflammation is currently lacking. We examine the potential of de novo T cell formation and thymic selection as novel therapeutic avenues and highlight areas for future study that are likely to make these targets the focus of future treatments

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

Phenotypic correlation of characteristics in the gilt performance test with an average number of live-born piglets through all achieved births, during the reproductive exploitation

ABSTRACT Reproductive efficacy of sows dictates the level of profitability of the production itself, and the moment of testing and selection of gilts for breeding (as the parents of a future generation), represents a very important moment. Given the fact that the selection of gilts for breeding is partly based on the weight-gain in the test, in this study we examined the influence of a daily weight-gain of gilts in the test of the manifestation of important reproductive characteristics - the size of the litter of the first and the other parities, as well as the percentage of sows that gave birth in relation to previous breeding process. Data of the 11637 tested gilts that completed the performance test have been used for the test. The studied characteristics were: the weight-gain at the end of the test, the number of live-born piglets, the number of stillborn piglets and the number of grown-weaned piglets in the first litter and the total number of live-born piglets, the total number of stillborn piglets and the total number of grown-weaned piglets. The results obtained in this study showed the effect of weight-gain in the reproductive efficacy test in the number of the live-born piglets in the first and from the 2nd to the 9th parity, as well as the percentage of the sows included in the next breeding process. By including all selected independent variables that showed the adequate statistical significance in correlation with the dependent variable, the determination coefficient rises to a value of 0.098 which represents 9.80% of the influence on the dependent variable, that can be explained by the independent variable, which leads to the conclusion that the binding strength between the variable "average live" and all the independent variables: “the number of litters”, the MLD depth” and “the back-fat thickness”, is very weak, which is not a rare case in multiple regression.</jats:p