Low bone mass in microscopic colitis

<p>Abstract</p> <p>Background</p> <p>Microscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis.</p> <p>Aims</p> <p>The aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis.</p> <p>Methods</p> <p>Fourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively) were measured using immunoassays.</p> <p>Results</p> <p>Low bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm²; p < 0.01). Bone mineral density at the non-dominant radius was decreased in microscopic colitis patients (0.565 ± 0.093 vs. 0.667 ± 0.072 g/cm²; p < 0.05) but unaffected in Crohn's disease patients (0.672 ± 0.056 g/cm²). Mean beta-crosslaps concentration was higher in microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p < 0.05). A negative correlation between beta-crosslaps concentration and the femoral and radius t-scores was evident in microscopic colitis patients.</p> <p>Conclusions</p> <p>Low bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.</p

Free Energy Simulations of a GTPase: GTP and GDP Binding to Archaeal Initiation Factor 2

International audienceArchaeal initiation factor 2 (aIF2) is a protein involved in the initiation of protein biosynthesis. In its GTP-bound, "ON" conformation, aIF2 binds an initiator tRNA and carries it to the ribosome. In its GDP-bound, "OFF" conformation, it dissociates from tRNA. To understand the specific binding of GTP and GDP and its dependence on the ON or OFF conformational state of aIF2, molecular dynamics free energy simulations (MDFE) are a tool of choice. However, the validity of the computed free energies depends on the simulation model, including the force field and the boundary conditions, and on the extent of conformational sampling in the simulations. aIF2 and other GTPases present specific difficulties; in particular, the nucleotide ligand coordinates a divalent Mg(2+) ion, which can polarize the electronic distribution of its environment. Thus, a force field with an explicit treatment of electronic polarizability could be necessary, rather than a simpler, fixed charge force field. Here, we begin by comparing a fixed charge force field to quantum chemical calculations and experiment for Mg(2+):phosphate binding in solution, with the force field giving large errors. Next, we consider GTP and GDP bound to aIF2 and we compare two fixed charge force fields to the recent, polarizable, AMOEBA force field, extended here in a simple, approximate manner to include GTP. We focus on a quantity that approximates the free energy to change GTP into GDP. Despite the errors seen for Mg(2+):phosphate binding in solution, we observe a substantial cancellation of errors when we compare the free energy change in the protein to that in solution, or when we compare the protein ON and OFF states. Finally, we have used the fixed charge force field to perform MDFE simulations and alchemically transform GTP into GDP in the protein and in solution. With a total of about 200 ns of molecular dynamics, we obtain good convergence and a reasonable statistical uncertainty, comparable to the force field uncertainty, and somewhat lower than the predicted GTP/GDP binding free energy differences. The sign and magnitudes of the differences can thus be interpreted at a semiquantitative level, and are found to be consistent with the experimental binding preferences of ON- and OFF-aIF2

Albumin and mammalian cell culture: implications for biotechnology applications

Albumin has a long historical involvement in design of media for the successful culture of mammalian cells, in both the research and commercial fields. The potential application of albumins, bovine or human serum albumin, for cell culture is a by-product of the physico-chemical, biochemical and cell-specific properties of the molecule. In this review an analysis of these features of albumin leads to a consideration of the extracellular and intracellular actions of the molecule, and importantly the role of its interactions with numerous ligands or bioactive factors that influence the growth of cells in culture: these include hormones, growth factors, lipids, amino acids, metal ions, reactive oxygen and nitrogen species to name a few. The interaction of albumin with the cell in relation to these co-factors has a potential impact on metabolic and biosynthetic activity, cell proliferation and survival. Application of this knowledge to improve the performance in manufacturing biotechnology and in the emerging uses of cell culture for tissue engineering and stem cell derived therapies is an important prospect

Liver architecture, cell function, and disease.

The liver is an organ consisting of the largest reticulo-endothelial cell network in the body and playing an important role in host defense against invading microorganisms. The organ is comprised of parenchymal cells and many different types of non-parenchymal cells, all of which play a significant role. Even biliary epithelial cells are not only the target in autoimmune liver diseases but also have central role in orchestrating several immune cells involved in both innate and acquired immunity. Tissue damage caused by various agents results in inflammation, necrosis, fibrosis, and, eventually, distortion of normal hepatic architecture, cirrhosis, and functional deterioration

Development of Fluorinated 1-.Methyl-4-Phenyl-1 ,2,3,6-. Tetrahydropyridine Analogs with Potent Nigrostriatal Toxicity for Potential Use in Positron Emission Tomography Studies1

ABSTRACT The discovery of 1-methyl-4-phenyl-

Comparison of the effects of 1,25 dihydroxyvitamin D and 25 hydroxyvitamin D on bone pathology and disease activity in Crohn's disease patients

Background: Vitamin D is essential for osteopenia therapy in Crohn's disease (CD). The active form of vitamin-D (aVD) is the 1.25(OH)2D. There are no data available whether aVD or plain vitamin-D (pVD) has any advantage in managing osteoporosis in CD or has tiny effect oil the activity of the disease itself. Our work is a prospective study to compare the effects of aVD and pVD oil bone metabolism and the clinical course of CD. Methods: In all. 37 inactive CD patients were involved in the Study and divided into 2 age-, gender-. and t-score-matched groups. Group A was treated with aVD while group B received pVD. Osteocalcin, beta-CrossLaps, osteoprotegerin, and receptor activator clear factor kappa-B ligand concentrations were estimated at the start of file Study and at 6 weeks and 3 and 12 months. The activity of CD was also measured clinically and by laboratory parameters. Results: At week 6 the Crohn's Disease Activity Index (CDAI) scores and concentration of C-reactive protein decreased (69.44 +/- 58.6 versus 57.0 +/- 54.89 and 15.8 +/- 23.57 mmol/L versus 7.81 +/- 3.91 mmol/L. respectively, P < 0.05) parallel with markers of bone turnover (beta-CrossLaps: 0.46 +/- 0.21 ng/mL versus 0.40 +/- 0.25 ng/mL, and osteocalcin: 32.29 +/- 15.3 ng/mL versus 29.98 +/- 14.14 ng/mL. P < 0.05), however, osteoprotegerin concentration (marker of osteoblast activity) increased (3.96 +/- 2.1 pg/mL versus 4.58 +/- 2.19 pg/mL) in group A, but did not change in group B. Osteocalcin and beta-CrossLaps concentrations changed more significantly by the 3rd month: however. these changes disappeared by the 12th month. Conclusions: According to our study, aVD has it more prominent short-term beneficial effect on bone metabolism and disease activity in CD compared with pVD