Analysis of the motor development in brazilian schoolchildren with corporal measures of obesity and Overweight

El objetivo de este estudio fue analizar el perfil de las características motoras de niños con sobrepeso/obesidad. Se midieron las características antropométricas y las características motoras de 284 niños sanos de 6 a 10 años, dividiéndose en tres grupos: normales, con sobrepeso y con obesidad. El instrumento utilizado es la Escala de Desarrollo Motor EDM, desarrollado por Rosa Neto en 1996. Los niños obesos mostraron una deficiencia significativa (p<0,05) en todas las estructuras motoras y en relación con su edad cronológica. Los niños con sobrepeso mostraron un retraso en el equilibrio (p<0,01), esquema corporal (p<0,02), organización espacial (p≤0,01) y organización temporal (p≤0,01). Se puede concluir que los niños con sobrepeso y obesidad tienen un retraso con respecto a sus compañeros de peso normalThe aim of this study was to analyse the profile of the motor features of children with overweight/obesity. The anthropometric and motor characteristics of 284 healthy children 6 to 10 years were measured, divided in three groups: with normal weight, with overweight and with obesity. The used instrument is the Scale of Motor Development EDM, developed by Rosa Neto in 1996. Obese children showed a significant deficiency (p<0.5) in all structures in relation to motor and chronological age. Overweight children showed a delay in equilibrium (p<0.01), body image (p<0.02), spatial organization (p<0.01) and temporal organization (p<0.01). We conclude that children with overweight and obesity are lagging behind their peers of normal weigh

First Report of Soybean (Glycine max) Disease Caused by Pseudomonas aeruginosa in Cuba

Soybean (Glycine max L.) has become one of the most widely consumed foods, however diseases caused by microorganisms can affect yields and seed quality. In March 2015, during routine survey in a soybean growing area in Pinar del Rio province, Cuba; disease symptoms were observed in some leaves. These included water-soaked necrotic spots with surrounded chlorotic halos, especially on the margins of the leaves. To identify the possible pathogens involved, leaves were disinfected with tap water, 70% ethanol and were rinsed with sterile distilled water. Small segments from diseased tissue were macerated in sterile 0.85% NaCl solution, decimal dilutions were performed and 20 µL aliquots were streaked onto King´s B medium (KB). After 24 hours of incubation at 28 oC, a fluorescent pseudomonad was isolated. Colonies were round, smooth and produced yellowish-green diffusible pigments on KB. Physiological and morphological characteristics were determined using standard microbiological techniques (Schaad et al., 200..

Population pharmacokinetic modelling of imatinib in healthy subjects receiving a single dose of 400 mg

Purpose: Imatinib is indicated for treatment of CML, GIST, etc. The population pharmacokinetics (popPK) of imatinib in patients under long-term treatment are reported in literature. Data obtained from bioequivalence trials for healthy subjects were used to evaluate the influence of demographic and pharmacogenetic factors on imatinib pharmacokinetics (PK) in a collective without concurrent drugs, organ dysfunction, inflammation etc. In addition, the differences in PK between the healthy subjects and a patient cohort was examined to identify possible disease effects. Methods: 26 volunteers were administered orally with single dose of 400 mg imatinib. 16–19 plasma samples per volunteer were collected from 0.5 up to 72 h post-dose. The popPK was built and post hoc estimates were compared with previously published PK parameters evaluated by non-compartmental analysis in the same cohort. The predictivity of the model for data collected from 40 patients with gastrointestinal stromal tumors at steady state was evaluated. Results: The popPK was best described by a two-compartment transit model with first-order elimination. No significant covariates were identified, probably due to the small cohort and the narrow range of demographic covariates; CYP3A5 phenotypes appeared to have some influence on the clearance of imatinib. Good agreement between non-compartment and popPK analyses was observed with the differences of the geometric means/ median of PK estimates below 10%. The model indicated lower clearance for patients compared to healthy volunteers (p value < 0.01). Conclusion: The two-compartment transit model adequately describes the absorption and distribution of imatinib in healthy volunteers. For patients, a lower clearance of imatinib compared to healthy volunteer was estimated by the model. The model can be applied for dose individualization based on trough concentrations assuming no significant differences in absorption between patients and healthy volunteersThis work was part of the master these of Yi-Han Chien. There was no funding for this work. P. Zubiaur’s contract with CIBERehd is fnanced by the “Infraestructura de Medicina de Precisión asociada a la Ciencia y Tecnología (IMPaCT, IMP/00009)”, Instituto de Salud Carlos III (ISCIII

PharmVar GeneFocus: CYP4F2

\ua9 2024 The Author(s). Clinical Pharmacology &amp; Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.The Pharmacogene Variation Consortium (PharmVar) serves as a global repository providing star (*) allele nomenclature for the polymorphic human CYP4F2 gene. CYP4F2 genetic variation impacts the metabolism of vitamin K, which is associated with warfarin dose requirements, and the metabolism of drugs, such as imatinib or fingolimod, and certain endogenous compounds including vitamin E and eicosanoids. This GeneFocus provides a comprehensive overview and summary of CYP4F2 genetic variation including the characterization of 14 novel star alleles, CYP4F2*4 through *17. A description of how haplotype information cataloged by PharmVar is utilized by the Pharmacogenomics Knowledgebase (PharmGKB) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) is also provided

Proteomic Profile of Peritoneal Extracellular Vesicles in cGVHD Mice Reflects a STAT1-Driven Type I IFN Signature.

Congresos y Conferencias: Comunicación de Congreso - Oral - Online.Introduction: Systemic Lupus Erythematous (SLE) is a complex autoimmune disease, characterized by increased cellular death by apoptosis and defective clearance of apoptotic bodies and nuclear fragments, resulting in increased antinuclear antibody production. In this study, we have used the inducible bm12 lupus model, where an abnormal chronic graft versus host disease (cGvHD) is induced in non-autoimmune C57BL6 mice (WT) by the adoptive transfer of MHC Class II Ia-incompatible bm12 spleen cells. In the absence of CD38 in the host (CD38KO mice), we have observed a significant decrease in the severity of the disease (doi: 10.3389/fimmu.2021.713697). Objectives: Analyze the protein composition and function of EVs released by specific cell types in the peritoneal cavity of cGvHD mice, to identify predictive or diagnostic biomarkers of the disease that may help to discriminate the role of CD38 in the cGVHD lupus-like autoimmunity process. Methods: EVs were isolated by qEV size-exclusion-chromatography (SEC) from peritoneal exudates of cGVHD lupus-mice, two weeks after the adoptive transfer of bm12 cells. Protein extracts from isolated EVs were analyzed by LC-MS/MS. Protein identification was performed with ProteinScape, and MASCOT data searching using Swiss-Prot database. To quantify the protein abundance, the emPAI-based method was used. ClueGO and CluePedia apps within the Cytoscape software environment were used for functional enrichment analysis of the lists of identified proteins. Results: Data showed that peritoneal exudate EVs can be isolated by SEC in 2 distinct EV subsets, which differ in size, protein composition and functional potential. Functional enrichment analyses indicated that a significant proportion of the identified proteins were related with EVs. In cGvHD CD38KO mice, among the unique and highly abundant proteins, there were phagocytosis inductors and apoptosis inhibitors, such as CD5L and LSP1. In cGvHD WT mice were identified proteins like CD24, a GPI-anchored protein potentially involved in the apoptosis of B cells, or a number of immunoproteasome proteins, directly related with the humoral immune response, and likely linked to the STAT1-mediated increased type I IFN response observed in these mice. Conclusions: The data indicated significant differences in the protein content and abundance on the 2 EV subsets, and between EVs from cGvHD WT versus cGvHD CD38KO mice. These differences in protein content and abundance of the EVs revealed alterations in key functional networks, which might be associated with the outcome of the disease

Supporting data for the MS identification of distinct transferrin glycopeptide glycoforms and citrullinated peptides associated with inflammation or autoimmunity

This data article presents the results of all the statistical analyses applied to the relative intensities of the detected 2D-DiGE protein spots for each of the 3 performed DiGE experiments. The data reveals specific subsets of protein spots with significant differences between WT and CD38-deficient mice with either Collagen-induced arthritis (CIA), or with chronic inflammation induced by CFA, or under steady-state conditions. This article also shows the MS data analyses that allowed the identification of the protein species which serve to discriminate the different experimental groups used in this study. Moreover, the article presents MS data on the citrullinated peptides linked to specific protein species that were generated in CIA(+) or CFA-treated mice. Lastly, this data article provides MS data on the efficiency of the analyses of the transferrin (Tf) glycopeptide glycosylation pattern in spleen and serum from CIA(+) mice and normal controls. The data supplied in this work is related to the research article entitled "identification of multiple transferrin species in spleen and serum from mice with collagen-induced arthritis which may reflect changes in transferrin glycosylation associated with disease activity: the role of CD38" [1]. All mass spectrometry data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with identifiers PRIDE: PXD002644, PRIDE: PXD002643, PRIDE: PXD003183 and PRIDE: PXD003163

Cd38 deficiency ameliorates chronic graft versus Host disease murine lupus via a b-cell dependent mechanism

Trabajo presentado en el II Congreso investigación PTS, celebrado en Granada (España) del 09 al 11 de febrero de 2022.Absence of mouse cell surface receptor CD38 in Cd38-/- mice suggests that this receptor acts as positive regulator of inflammatory and autoimmune responses. Here we report that in the setting of a chronic graft versus host disease (cGVHD) lupus model induced by the transfer of B6.C-H2bm12/KhEg (bm12) spleen cells into co-isogenic Cd38-/- B6 mice causes milder lupus-like autoimmunity with lower levels of anti-ssDNA autoantibodies than the transfer of bm12 spleen cells into WT B6 mice. I In addition, significantly lower percentages of Tfh cells, as well as GC B cells, plasma cells and T-bet+CD11chi B cells are observed in Cd38-/- mice than in WT mice, while the expansion of Treg cells, and Tfr cells is normal, suggesting that the ability of Cd38-/- B cells to respond to allogeneic help from bm12 CD4+ T cells is greatly diminished. The frequencies of T-bet+CD11chi B cells, which are considered the precursors of the autoantibody secreting cells, correlate with anti-ssDNA autoantibody serum levels, with IL-27, and sCD40L. Proteomics profiling of spleens from WT cGVHD mice reflects a STAT1-driven type I IFN-signature, which is absent in Cd38-/- cGVHD mice. Kidney, spleen and liver inflammation was mild and resolved faster in Cd38-/- cGVHD mice than in WT cGVHD mice. We conclude that in B cells CD38 functions as a modulator receptor that controls autoimmune responses

Modulation of hypothalamic AMPK phosphorylation by olanzapine controls energy balance and body weight

[Background]: Second-generation antipsychotics (SGAs) are a mainstay therapy for schizophrenia. SGA-treated patients present higher risk for weight gain, dyslipidemia and hyperglycemia. Herein, we evaluated the effects of olanzapine (OLA), widely prescribed SGA, in mice focusing on changes in body weight and energy balance. We further explored OLA effects in protein tyrosine phosphatase-1B deficient (PTP1B-KO) mice, a preclinical model of leptin hypersensitivity protected against obesity.[Methods]: Wild-type (WT) and PTP1B-KO mice were fed an OLA-supplemented diet (5 mg/kg/day, 7 months) or treated with OLA via intraperitoneal (i.p.) injection or by oral gavage (10 mg/kg/day, 8 weeks). Readouts of the crosstalk between hypothalamus and brown or subcutaneous white adipose tissue (BAT and iWAT, respectively) were assessed. The effects of intrahypothalamic administration of OLA with adenoviruses expressing constitutive active AMPKα1 in mice were also analyzed.[Results]: Both WT and PTP1B-KO mice receiving OLA-supplemented diet presented hyperphagia, but weight gain was enhanced only in WT mice. Unexpectedly, all mice receiving OLA via i.p. lost weight without changes in food intake, but with increased energy expenditure (EE). In these mice, reduced hypothalamic AMPK phosphorylation concurred with elevations in UCP-1 and temperature in BAT. These effects were also found by intrahypothalamic OLA injection and were abolished by constitutive activation of AMPK in the hypothalamus. Additionally, OLA i.p. treatment was associated with enhanced Tyrosine Hydroxylase (TH)-positive innervation and less sympathetic neuron-associated macrophages in iWAT. Both central and i.p. OLA injections increased UCP-1 and TH in iWAT, an effect also prevented by hypothalamic AMPK activation. By contrast, in mice fed an OLA-supplemented diet, BAT thermogenesis was only enhanced in those lacking PTP1B. Our results shed light for the first time that a threshold of OLA levels reaching the hypothalamus is required to activate the hypothalamus BAT/iWAT axis and, therefore, avoid weight gain.[Conclusion]: Our results have unraveled an unexpected metabolic rewiring controlled by hypothalamic AMPK that avoids weight gain in male mice treated i.p. with OLA by activating BAT thermogenesis and iWAT browning and a potential benefit of PTP1B inhibition against OLA-induced weight gain upon oral treatment.This work was funded by grants PID-2021-122766OB-100 (to AMV) and PID2019-104399RB-I00 (to GS) funded by Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación /10.13039/501100011033 and “ERDF A way of making Europe” by the European Union. We also acknowledge grants H2020 Marie Sklodowska-Curie ITN-TREATMENT (Grant Agreement 721236, European Commission), S2017/BMD-3684 (Comunidad de Madrid, Spain), Fundación Ramón Areces (Spain) and CIBERdem (ISCIII, Spain) to AMV. JWE was funded by the Swedish Diabetes Foundation and the Novo Nordisk Foundation (NNF20OC0063864). VF was a recipient of a contract from ITN-TREATMENT and is currently a PhD fellow from the Portuguese Foundation for Science and Technology (FCT, Portugal)/ERDF (2020.08388.BD). CF was awarded with Sara Borrell contract (CD19/00078, ISCIII, Spain)

The second-generation antipsychotic drug aripiprazole modulates the serotonergic system in pancreatic islets and induces beta cell dysfunction in female mice

[Aims/hypothesis]: Second-generation antipsychotic (SGA) drugs have been associated with the development of type 2 diabetes and the metabolic syndrome in patients with schizophrenia. In this study, we aimed to investigate the effects of two different SGA drugs, olanzapine and aripiprazole, on metabolic state and islet function and plasticity. [Methods]: We analysed the functional adaptation of beta cells in 12-week-old B6;129 female mice fed an olanzapine- or aripiprazole-supplemented diet (5.5–6.0 mg kg−1 day−1) for 6 months. Glucose and insulin tolerance tests, in vivo glucose-stimulated insulin secretion and indirect calorimetry were performed at the end of the study. The effects of SGAs on beta cell plasticity and islet serotonin levels were assessed by transcriptomic analysis and immunofluorescence. Insulin secretion was assessed by static incubations and Ca2+ fluxes by imaging techniques. [Results]: Treatment of female mice with olanzapine or aripiprazole for 6 months induced weight gain (p<0.01 and p<0.05, respectively), glucose intolerance (p<0.01) and impaired insulin secretion (p<0.05) vs mice fed a control chow diet. Aripiprazole, but not olanzapine, induced serotonin production in beta cells vs controls, likely by increasing tryptophan hydroxylase 1 (TPH1) expression, and inhibited Ca2+ flux. Of note, aripiprazole increased beta cell size (p<0.05) and mass (p<0.01) vs mice fed a control chow diet, along with activation of mechanistic target of rapamycin complex 1 (mTORC1)/S6 signalling, without preventing beta cell dysfunction. [Conclusions/interpretation]: Both SGAs induced weight gain and beta cell dysfunction, leading to glucose intolerance; however, aripiprazole had a more potent effect in terms of metabolic alterations, which was likely a result of its ability to modulate the serotonergic system. The deleterious metabolic effects of SGAs on islet function should be considered while treating patients as these drugs may increase the risk for development of the metabolic syndrome and diabetes.This work was funded by H2020 Marie Sklodowska-Curie ITN-TREATMENT (Grant Agreement 721236, European Commission). We also acknowledge grants RTI2018-094052-B-100/ AEI/10.13039/501100011033 (Ministerio de Ciencia e Innovación y Fondo Europeo de Desarrollo Regional [FEDER]) and S2017/BMD-3684 (Comunidad de Madrid, Spain), and grants from Fundación Ramón Areces (Spain) and CIBERDEM (ISCIII, Spain)

Evaluación densitométrica del tratamiento con hormonas sustitutivas y alendronato en la osteoporosis experimental en ratas

El tratamiento de la osteoporosis (OP) es preventivo pues solo se dispone de fármacos antirresortivos, tales como los bifosfonatos, careciéndose de verdaderas drogas osteoformadoras. Las medidas preventivas están dirigidas a alcanzar mayor masa ósea durante el crecimiento, evitar pérdidas en OP ya establecidas y disminuir el riesgo de fracturas cuando la masa ósea esté disminuida. El alendronato, como otros bisfosfonatos, inhibe la actividad de osteoclastos y por ende la resorción ósea. Como los estrógenos y progesterona son importantes para mantener el hueso, se los prescribe como terapia de reemplazo hormonal en mujeres posmenopáusicas. Se realizaron ensayos de 8 meses de duración con 48 ratas hembras cepa Wistar, de 4 meses de edad, conformándose un lote ovariectomizado (OV, n= 36) y otro testigo (n=12) con cirugía simulada (maniobra quirúrgica sin ovariectomía). A los 3 meses, los OV fueron separados en 3 lotes de 12 ratas cada uno (OV sin tratamiento, OV tratados con alendronato y OV con hormonas). El objetivo fue evaluar la terapia con alendronato (en dosis semanales de 0,27 mg/animal, durante 5 meses, vía oral) en forma comparativa a la de estrógeno-progesterona(durante 5 meses vía SC en dosis mensuales de 250 ug de benzoato de estradioly 6,25 mg de caproato de hidroxiprogesterona). Las evaluaciones de concentración mineral ósea (CMO) y densidad mineral ósea (DMO) se efectuaron por densitometría dual de rayos X (DXA), realizada mediante un software especial para pequeños animales. El tratamiento hormonal produjo efectos benéficos significativos en DMO y CMO de las regiones espinal lumbosacra (p&lt;0,001) y coxofemoral (p&lt;0,0001) respecto a OV sin tratamiento. El alendronato solo obtuvo diferencias significativas en CMO de región coxofemoral. Se concluye que en el modelo experimental de OP, la respuesta al tratamiento con estrógeno-progesterona fue más eficiente que la obtenida con alendronato, al lograr mantener DMO y CMO similares a las de los testigos