Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain

Second generation antipsychotics (SGAs) have been linked to metabolic and bone disorders in clinical studies, but the mechanisms of these side effects remain unclear. Additionally, no studies have examined whether SGAs cause bone loss in mice. Using in vivo and in vitro modeling we examined the effects of risperidone, the most commonly prescribed SGA, on bone in C57BL6/J (B6) mice. Mice were treated with risperidone orally by food supplementation at a dose of 1.25 mg/kg daily for 5 and 8 weeks, starting at 3.5 weeks of age. Risperidone reduced trabecular BV/TV, trabecular number and percent cortical area. Trabecular histomorphometry demonstrated increased resorption parameters, with no change in osteoblast number or function. Risperidone also altered adipose tissue distribution such that white adipose tissue mass was reduced and liver had significantly higher lipid infiltration. Next, in order to tightly control risperidone exposure, we administered risperidone by chronic subcutaneous infusion with osmotic minipumps (0.5 mg/kg daily for 4 weeks) in 7 week old female B6 mice. Similar trabecular and cortical bone differences were observed compared to the orally treated groups (reduced trabecular BV/TV, and connectivity density, and reduced percent cortical area) with no change in body mass, percent body fat, glucose tolerance or insulin sensitivity. Unlike in orally treated mice, risperidone infusion reduced bone formation parameters (serum P1NP, MAR and BFR/BV). Resorption parameters were elevated, but this increase did not reach statistical significance. To determine if risperidone could directly affect bone cells, primary bone marrow cells were cultured with osteoclast or osteoblast differentiation media. Risperidone was added to culture medium in clinically relevant doses of 0, 2.5 or 25 ng/ml. The number of osteoclasts was significantly increased by addition in vitro of risperidone while osteoblast differentiation was not altered. These studies indicate that risperidone treatment can have negative skeletal consequences by direct activation of osteoclast activity and by indirect non-cell autonomous mechanisms. Our findings further support the tenet that the negative side effects of SGAs on bone mass should be considered when weighing potential risks and benefits, especially in children and adolescents who have not yet reached peak bone mass. This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism. (C) 2011 Elsevier Inc. All rights reserved.National Institute Of Arthritis And Musculoskeletal And Skin Diseases [F32AR061932, AR054604]CAPES, Brazil [0102-09-1]MMCRINational Council for Scientific and Technological Development (CNPq), Brazil [201650/2008-8]NIH [P20 RR18789, P20 RR15555, P30 RR030927

An Update on Corneal Biomechanics and Architecture in Diabetes

In the last decade, we have witnessed substantial progress in our understanding of corneal biomechanics and architecture. It is well known that diabetes is a systemic metabolic disease that causes chronic progressive damage in the main organs of the human body, including the eyeball. Although the main and most widely recognized ocular effect of diabetes is on the retina, the structure of the cornea (the outermost and transparent tissue of the eye) can also be affected by the poor glycemic control characterizing diabetes. e different corneal structures (epithelium, stroma, and endothelium) are affected by specific complications of diabetes. e development of new noninvasive diagnostic technologies has provided a better understanding of corneal tissue modifications. e objective of this review is to describe the advances in the knowledge of the corneal alterations that diabetes can induc

Structural, vibrational and electronic properties of alpha'-Ga2S3 under compression

[EN] We report a joint experimental and theoretical study of the low-pressure phase of ¿¿-Ga2S3 under compression. Theoretical ab initio calculations have been compared to X-ray diffraction and Raman scattering measurements under high pressure carried out up to 17.5 and 16.1 GPa, respectively. In addition, we report Raman scattering measurements of ¿¿-Ga2S3 at high temperature that have allowed us to study its anharmonic properties. To understand better the compression of this compound, we have evaluated the topological properties of the electron density, the electron localization function, and the electronic properties as a function of pressure. As a result, we shed light on the role of the Ga¿S bonds, the van der Waals interactions inside the channels of the crystalline structure, and the single and double lone electron pairs of the sulphur atoms in the anisotropic compression of ¿¿-Ga2S3. We found that the structural channels are responsible for the anisotropic properties of ¿¿-Ga2S3 and the A¿(6) phonon, known as the breathing mode and associated with these channels, exhibits the highest anharmonic behaviour. Finally, we report calculations of the electronic band structure of ¿¿-Ga2S3 at different pressures and find a nonlinear pressure behaviour of the direct band gap and a pressure-induced direct-to-indirect band gap crossover that is similar to the behaviour previously reported in other ordered-vacancy compounds, including ß-Ga2Se3. The importance of the single and, more specially, the double lone electron pairs of sulphur in the pressure dependence of the topmost valence band of ¿¿-Ga2S3 is stressed.The authors thank the financial support from the Spanish Research Agency (AEI) under projects MALTA Consolider Team network (RED2018-102612-T) and projects MAT2016-75586-C4-2/3-P, FIS2017-83295-P, PID2019-106383GB-42/43, and PGC2018-097520-A-100, as well as from Generalitat Valenciana under Project PROMETEO/2018/123 (EFIMAT). A. M. and P. R.-H. acknowledge computing time provided by Red Espanola de Supercomputacion (RES) and MALTA-Cluster and E. L. D. S. acknowledges Marie Sklodowska-Curie Grant No. 785789-COMEX from the European Union's Horizon 2020 research and innovation program. J. A. S. also wants to thank the Ramon y Cajal fellowship (RYC-2015-17482) for financial support. We also thank the ALBA synchrotron light source for funded experiment 2017022088 at the MSPD-BL04 beamline.Gallego-Parra, S.; Vilaplana Cerda, RI.; Gomis, O.; Lora Da Silva, E.; Otero-De-La-Roza, A.; Rodríguez-Hernández, P.; Muñoz, A.... (2021). Structural, vibrational and electronic properties of alpha'-Ga2S3 under compression. Physical Chemistry Chemical Physics. 23(11):6841-6862. https://doi.org/10.1039/d0cp06417cS68416862231

Ultrafiltration based purification strategies for surfactin produced by bacillus subtilis lb5a using cassava wastewater as substrate

BACKGROUND: Bacillus subtilis synthesizes surfactin, a powerful surface-active agent. It has interesting potential applications. However, due to its high cost of production, commercial use is impracticable. The downstream processing represents ≈60% of production costs and the culture medium ≈30%. Many reports focused, separately, on production of surfactin using by-products (reduced cost) or the purification using synthetic medium. Therefore, the aim of this work was to evaluate, for the first time, the impact of using a by-product as fermentation medium on the downstream processing based on membrane filtration. RESULTS: Membranes of PES-100-kDa efficiently retained surfactin micelles - the first step of ultrafiltration, whereas, the second step required membranes of 50-kDa to separate surfactin monomers from proteins. Ultrafiltration of crude biosurfactant was associated with fouling and/or concentration polarization resulting in lower purity than when synthetic medium was used. Further improvement in purity was achieved by partial removal of proteins prior to ultrafiltration by precipitation and extraction. The RMN and MALDI-TOFMS analyses identified 11 potential surfactin homologous composed by two amino acid sequences. CONCLUSION: Production of surfactin using cassava wastewater as a low-cost culture medium and its purification by the 2-step ultrafiltration process is feasible, nevertheless, the higher protein content of this medium as compared to the synthetic one leads to a lower purity product; further increase in purity can be achieved by applying additional purification steps prior to ultrafiltration with the subsequent increased in process cost

COL1A1 and miR-29b show lower expression levels during osteoblast differentiation of bone marrow stromal cells from Osteogenesis Imperfecta patients

Abstract\ud \ud Background\ud The majority of Osteogenesis Imperfecta (OI) cases are caused by mutations in one of the two genes, COL1A1 and COL1A2 encoding for the two chains that trimerize to form the procollagen 1 molecule. However, alterations in gene expression and microRNAs (miRNAs) are responsible for the regulation of cell fate determination and may be evolved in OI phenotype.\ud \ud \ud Methods\ud In this work, we analyzed the coding region and intron/exon boundaries of COL1A1 and COL1A2 genes by sequence analysis using an ABI PRISM 3130 automated sequencer and Big Dye Terminator Sequencing protocol. COL1A1 and miR-29b expression were also evaluated during the osteoblastic differentiation of mesenchymal stem cell (MSC) by qRT-PCR using an ABI7500 Sequence Detection System.\ud \ud \ud Results\ud We have identified eight novel mutations, where of four may be responsible for OI phenotype. COL1A1 and miR-29b showed lower expression values in OI type I and type III samples. Interestingly, one type III OI sample from a patient with Bruck Syndrome showed COL1A1 and miR-29b expressions alike those from normal samples.\ud \ud \ud Conclusions\ud Results suggest that the miR-29b mechanism directed to regulate collagen protein accumulation during mineralization is dependent upon the amount of COL1A1 mRNA. Taken together, results indicate that the lower levels observed in OI samples were not sufficient for the induction of miR-29b.Support for this work was provided by the Brazilian agencies FAPESP, CNPq,\ud and Center for Cell-based Therapy. We are also thankful to Cristiane Ayres\ud Ferreira and Adriana Aparecida Marques for their excellent technical\ud assistance

The consequences of growth hormone-releasing hormone receptor haploinsufficiency for bone quality and insulin resistance

Objective Growth hormone (GH)/insulin-like growth factor (IGF) axis and insulin are key determinants of bone remodelling. Homozygous mutations in the GH-releasing hormone receptor (GHRHR) gene (GHRHR) are a frequent cause of genetic isolated GH deficiency (IGHD). Heterozygosity for GHRHR mutation causes changes in body composition and possibly an increase in insulin sensitivity, but its effects on bone quality are still unknown. The objective of this study was to assess the bone quality and metabolism and its correlation with insulin sensitivity in subjects heterozygous for a null mutation in the GHRHR. Patients and methods A cross-sectional study was performed on 76 normal subjects (68.4% females) (N/N) and 64 individuals (64.1% females) heterozygous for a mutation in the GHRHR (MUT/N). Anthropometric features, quantitative ultrasound (QUS) of the heel, bone markers [osteocalcin (OC) and CrossLaps], IGF-I, glucose and insulin were measured, and homeostasis model assessment of insulin resistance (HOMAIR) was calculated. Results There were no differences in age or height between the two groups, but weight (P = 0.007) and BMI (P = 0.001) were lower in MUT/N. There were no differences in serum levels of IGF-I, glucose, T-score or absolute values of stiffness and OC, but insulin (P = 0.01), HOMAIR (P = 0.01) and CrossLaps (P = 0.01) were lower in MUT/N. There was no correlation between OC and glucose, OC and HOMAIR in the 140 individuals as a whole or in the separate MUT/N or N/N groups. Conclusions This study suggests that one allele mutation in the GHRHR gene has a greater impact on energy metabolism than on bone quality.NIH, National Institutes of Health USA [1 R01 DK065718]FAPITEC/SE, BrazilCAPESFAEP

Diagnóstico y tratamiento de la enfermedad inflamatoria intestinal: Primer Consenso Latinoamericano de la Pan American Crohn's and Colitis Organisation

La incidencia y la prevalencia de la enfermedad inflamatoria intestinal (EII) se han incrementado en los últimos a˜nos en varios países de Latinoamérica. Existe una necesidad de concientizar a gastroenterólogos y a la población en general para poder tener un diagnóstico y tratamiento oportunos en la colitis ulcerosa crónica idiopática (CUCI) y enfermedad de Crohn (EC). Es importante que todos los médicos tengan un criterio homogéneo acerca del diagnóstico y el tratamiento de la EII en América Latina. La Pan American Crohn’s and Colitis Organisation (PANCCO) es un organismo con el propósito de incluir a todos los países del continente americano pero se enfoca de manera específica a los países latinos. Este Consenso está dividido en 2 partes para su publicación: 1) diagnóstico y tratamiento, y 2) situaciones especiales. Este es el primer Consenso latinoamericano cuyo objetivo es promover una perspectiva adaptadaa nuestros países latinos para el diagnóstico, el tratamiento y la monitorización de pacientescon CUCI y EC.© 2016 Asociaci´on Mexicana de Gastroenterolog´ıa. Publicado por Masson Doyma M´exico S.A.Este es un art´ıculo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). ABSTRACT The incidence and prevalence of inflammatory bowel disease (IBD) has increased inrecent years in several Latin American countries. There is a need to raise awareness in gastro-enterologists and the population in general, so that early diagnosis and treatment of ulcerativecolitis (UC) and Crohn’s Disease (CD) can be carried out. It is important for all physicians tohave homogeneous criteria regarding the diagnosis and treatment of IBD in Latin America. ThePan American Crohn’s and Colitis Organisation (PANCCO) is an organization that aims to includeall the countries of the Americas, but it specifically concentrates on Latin America. The presentConsensus was divided into two parts for publication: 1) Diagnosis and treatment and 2) Specialsituations.This is the first Latin American Consensus whose purpose is to promote a perspective adaptedto our Latin American countries for the diagnosis, treatment, and monitoring of patients withUC and CD.© 2016 Asociaci´on Mexicana de Gastroenterolog´ıa. Published by Masson Doyma M´exico S.A. Thisis an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Opposite-side flavour tagging of B mesons at the LHCb experiment

The calibration and performance of the oppositeside flavour tagging algorithms used for the measurements of time-dependent asymmetries at the LHCb experiment are described. The algorithms have been developed using simulated events and optimized and calibrated with B + →J/ψK +, B0 →J/ψK ∗0 and B0 →D ∗− μ + νμ decay modes with 0.37 fb−1 of data collected in pp collisions at √ s = 7 TeV during the 2011 physics run. The oppositeside tagging power is determined in the B + → J/ψK + channel to be (2.10 ± 0.08 ± 0.24) %, where the first uncertainty is statistical and the second is systematic

Measurement of the Bs0→J/ψηB_{s}^{0} \rightarrow J/\psi \eta lifetime

Using a data set corresponding to an integrated luminosity of $3 fb^{-1}$, collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of 7 and 8 TeV, the effective lifetime in the $B^0_s \rightarrow J/\psi \eta$ decay mode, $\tau_{\textrm{eff}}$, is measured to be $\tau_{\textrm{eff}} = 1.479 \pm 0.034~\textrm{(stat)} \pm 0.011 ~\textrm{(syst)}$ ps. Assuming $CP$ conservation, $\tau_{\textrm{eff}}$ corresponds to the lifetime of the light $B_s^0$ mass eigenstate. This is the first measurement of the effective lifetime in this decay mode.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-017.htm