Propiedades Psicométricas de la Escala de Evaluación Socioemocional Breve de Infantes y Niños (BITSEA) en una muestra de niños y niñas chilenos / Psychometric properties of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) in a sample of Chilean children

Introducción: La infancia temprana es una etapa crítica para la salud mental, por lo que es fundamental contar con herramientas eficaces para detectar tempranamente conductas infantiles relacionadas con psicopatología. Objetivo: Investigar las propiedades psicométricas de la Escala de Evaluación Socioemocional Breve de Infantes y Niños (BITSEA) en una muestra de infantes chilenos. Método: 289 padres de niños y niñas de entre 12 y 36 meses de edad completaron la BITSEA y el CBCL 1½-5. Resultados: Se encontró una confiabilidad aceptable para las puntuaciones de la subescala "problema socioemocional" (ω=0.84), y una confiabilidad baja para las puntuaciones de la subescala "competencia socioemocional" (ω=0.59). La estructura factorial fue adecuada y se observó una alta validez concurrente con otras escalas. El modelo confirmatorio mostró índices aceptables (CFI= 0.94; TLI= 0.94; SRMR= 0.07; RMSEA= 0.027). Conclusión: La BITSEA en esta muestra arrojó resultados similares a otros estudios, su aplicabilidad es prometedora para la detección temprana de problema socioemocional en la infancia temprana. Se sugiere continuar su estudio en muestra nacional representativa.

Introduction: Early childhood is a critical stage for mental health, and it is necessary to have effective tools for early detection of child behaviours related to psychopathology. Objective: to assess the psychometric properties of the Brief Infant and Toddler Social-Emotional Evaluation Scale (BITSEA) in a sample of Chilean children. Methods: 289 parents of infants and toddlers aged 12-36 months completed the BITSEA and the CBCL 1½-5. Results: Acceptable reliability was found for the "socioemotional problems" dimension (ω=0.84), and low reliability for the "socioemotional competence" subscale scores (ω=0.59). The factor structure was adequate and high concurrent validity with other scales was observed. The confirmatory model showed acceptable fit indices (CFI= 0.94; TLI= 0.94; SRMR= 0.07; RMSEA= 0.027). Conclusion: The BITSEA in this sample showed similar results to other studies, its applicability is promising for the early detection of socioemotional problems in early childhood. It is suggested to continue its study in a nationally representative sample.

Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early ß-cell damage in obesity and diabetes.

BACKGROUND AND AIMS: This is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when ß-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early ß-cell damage. MATERIALS AND METHODS: We performed a multicentric collaborative, cross-sectional, analytical, ambispective and blinded study; the RIAO from pretreated samples (PTS) of sera of 146 pediatric patients with obesity or DM and 16 healthy children, were isolated, measured by sound indirect ELISA with novel anti-hIAPP cytotoxic oligomers polyclonal antibody (MEX1). We carried out morphological and functional studied and cluster-clinical data driven analysis. RESULTS: We demonstrated by western blot, Transmission Electron Microscopy and cell viability experiments that RIAO circulate in the blood and can be measured by ELISA; are elevated in serum of childhood obesity and diabetes; are neurotoxics and works as biomarkers of early ß-cell failure. We explored the range of evidence-based medicine clusters that included the RIAO level, which allowed us to classify and stratify the obesity patients with high cardiometabolic risk. CONCLUSIONS: RIAO level increases as the number of complications rises; RIAOs > 3.35 µg/ml is a predictor of changes in the current indicators of ß-cell damage. We proposed a novel physio-pathological pathway and shows that PCD affect not only elderly patients but also children. Here we reduced the gap between basic biomedical research, clinical practice and health decision making.

Growth hormone ameliorates high glucose-induced steatosis on in vitro cultured human HepG2 hepatocytes by inhibiting de novo lipogenesis via ChREBP and FAS suppression.

OBJECTIVE: Growth hormone (GH) deficiency has been associated with increased steatosis but the molecular mechanism has not been fully elucidated. We investigated the effect of GH on lipid accumulation of HepG2 cells cultured on an in vitro steatosis model and examined the potential involvement of insulin-like growth factor 1 (IGF-1) as well as lipogenic and lipolytic molecules. METHODS: Control and steatosis conditions were induced by culturing HepG2 cells with 5.5 or 25 mmol/l glucose for 24 h, respectively. Afterward, cells were exposed to 0, 5, 10 or 20 ng/ml GH for another 24 h. Lipid content was quantified as well as mRNA and protein levels of IGF-1, carbohydrate responsive element-binding protein (ChREBP), sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyltransferase 1A (CPT1A), and peroxisome proliferator-activated receptor alpha (PPAR-alpha) by qPCR and western blot, respectively. Data were analyzed by one-way ANOVA and the Games-Howell post-hoc test. RESULTS: In the steatosis model, HepG2 hepatocytes showed a significant 2-fold increase in lipid amount as compared to control cells. IGF-1 mRNA and protein levels were significantly increased in control cells exposed to 10 ng/ml GH, whereas high glucose abolished this effect. High glucose also significantly increased both mRNA and protein of ChREBP and FAS without having effect on SREBP1c, CPT1A and PPAR-alpha. However, GH inhibited ChREBP and FAS production, even in HepG2 hepatocytes cultured under steatosis conditions. CONCLUSIONS: Growth hormone ameliorates high glucose-induced steatosis in HepG2 cells by suppressing de novo lipogenesis via ChREBP and FAS down-regulation.

Education with a multimedia web platform improves knowledge and HbA1c of Mexican patients with type 2 diabetes. Open clinical trial. / La educación con una plataforma multimedia en web mejora los conocimientos y la HbA1c de pacientes mexicanos con diabetes tipo 2. Ensayo clínico abierto.

INTRODUCTION: The patient with diabetes mellitus type requires to receive education about the disease aimed at improving knowledge and skills for their control. The objective of this study is to evaluate the efficacy of nutritional therapy and education through a multimedia site on the level of knowledge and metabolic control in patients with type 2 diabetes. PATIENTS AND METHODS: Open-label clinical trial of 12 months of follow-up in 161 patients with type 2 diabetes. A total of 101 patients were assigned to the intervention group with nutrition therapy (TN) + Nutriluv (multimedia site in diabetes), 80 patients to the TN control group. The glycosylated hemoglobin (HbA1c), glucose, cholesterol, triglycerides, LDL and HDL cholesterol were measured at the beginning and end. Weight, waist circumference, percentage of fat, systolic blood pressure and diastolic blood pressure were recorded. The level of knowledge was measured with the Diabetes Knowledge Questionnaire (DKQ24). RESULTS: The knowledge in diabetes improved in the group with TN+Nutriluv compared with the TN group (P<0.05). HbA1c, HDL, diastolic blood pressure and waist circumference, improved in the group with TN+Nutriluv (P<0.05). In the group with TN, cholesterol HDL, diastolic blood pressure, waist circumference and the fat percentage was increased (P<0.05). They had a higher risk of having an HbA1c>7% who had more years of diagnosis of diabetes. CONCLUSIONS: The use of a multimedia site with education in diabetes, improves knowledge, HbA1c, and other indicators of cardiovascular risk in diabetes type 2 patients.

Metodología para la elaboración de la Guía de práctica clínica / Methodology for the development of the Clinical guideline for the diagnosis and treatment of precocious puberty

Resumen Introducción: La Sociedad Mexicana de Endocrinología Pediátrica presenta recomendaciones para el diagnóstico y el tratamiento de la pubertad precoz (PP), condición definida como el desarrollo de caracteres sexuales por incremento en la secreción hipofisiaria de gonadotropinas antes de los 8 años en las niñas y de los 9 años en los niños. Métodos: Se realizaron tres revisiones sistemáticas de ensayos clínicos controlados sobre intervenciones para el tratamiento de la PP, pruebas diagnósticas y estudios observacionales sobre efectos a largo plazo de la PP. La evaluación de la calidad de los estudios y la extracción de datos se realizó por pares. La evidencia se graduó con el sistema de la Scottish Intercollegiate Guidelines Network (SIGN) y del Oxford Centre for Evidence-Based Medicine (OCEBM) para las recomendaciones sobre la intervención y el diagnóstico, respectivamente. Las recomendaciones generadas se sometieron a un consenso por el método Delphi y fueron validadas por otros 143 endocrinólogos pediatras certificados mediante un cuestionario en línea. Resultados: Mediante consenso se generaron 12 recomendaciones para el diagnóstico de PP, siete sobre diagnóstico de causas secundarias de PP, ocho sobre intervenciones para inhibición de la pubertad, cinco sobre otras intervenciones en PP y 14 para la monitorización del tratamiento y el seguimiento de estos pacientes. Se obtuvo más del 90% de aprobación para cada una de las recomendaciones por el grupo de endocrinólogos certificados que respondieron el cuestionario en línea. Conclusiones: Si bien se logró un alto grado de consenso para las recomendaciones para el diagnóstico, el tratamiento y la monitorización de la PP entre los endocrinólogos pediatras, el nivel de evidencia para la mayoría de estas recomendaciones resultó bajo.

Abstract Background: The Mexican Society of Pediatric Endocrinology presents recommendations for the diagnosis and treatment of precocious puberty (PP), a condition defined as the development of sexual characteristics due to an increase in pituitary gonadotropin secretion before 8 or 9 years of age in girls and boys, respectively. Methods: Three systematic reviews were conducted: controlled clinical trials on interventions for PP treatment, diagnostic tests, and observational studies on the long-term effects of PP. The quality evaluation and data extraction from the studies were conducted by two independent reviewers. The Scottish Intercollegiate Guidelines Network and the Oxford Center for Evidence-Based Medicine systems were used for grading the quality of evidence for recommendations on intervention and diagnosis, respectively. Recommendations were submitted to a consensus by a Delphi method and were validated by another 143 certified pediatric endocrinologists through an online questionnaire. Results: The group generated 12 recommendations on the diagnosis of PP, seven on the diagnosis of secondary causes of PP, eight on interventions for inhibition of puberty, five on other interventions for PP treatment, and 14 for the monitoring and follow-up of these patients. The online questionnaires submitted to certified pediatric endocrinologists showed more than 90% of approval for each one of the recommendations. Conclusions: Although a high degree of consensus for the recommendations for diagnosis, treatment, and monitoring of PP among pediatric endocrinologists was achieved, most of these recommendations showed a low level of evidence.

Diagnóstico de pubertad precoz / Diagnosis of precocious puberty: clinical guideline for the diagnosis and treatment of precocious puberty

Resumen La Sociedad Mexicana de Endocrinología Pediátrica elaboró una guía de práctica clínica para el diagnóstico y el tratamiento de la pubertad precoz. Este documento presenta recomendaciones relacionadas con el diagnóstico de pubertad precoz. La descripción detallada de la metodología para el desarrollo de esta guía y del sistema de gradación, así como la síntesis de la evidencia en la que se basa, pueden consultarse en este suplemento.

Abstract The Mexican Society of Pediatric Endocrinology developed a clinical practice guide for the diagnosis and treatment of precocious puberty. This document presents recommendations related to the diagnosis of precocious puberty. The detailed description of the methodology for the development of this guide and the grading system, as well as the synthesis of the evidence on which it is based can be accessed in this same supplement.

Diagnóstico de causas secundarias de pubertad precoz / Diagnosis of secondary causes of precocious puberty: Clinical guideline for the diagnosis and treatment of precocious puberty

Resumen La Sociedad Mexicana de Endocrinología Pediátrica elaboró una guía de práctica clínica para el diagnóstico y el tratamiento de la pubertad precoz. Este documento presenta recomendaciones relacionadas con el diagnóstico de causas secundarias de pubertad precoz central. La descripción detallada de la metodología para el desarrollo de esta guía y del sistema de gradación, así como la síntesis de la evidencia en la que se basa, pueden consultarse en este mismo suplemento.

Abstract The Mexican Society of Pediatric Endocrinology developed a clinical practice guide for the diagnosis and treatment of precocious puberty. This document presents recommendations related to the diagnosis of secondary causes of central PP. The detailed description of the methodology for the development of this guide and the grading system, as well as the synthesis of the evidence on which it is based can be consulted in this same supplement.

Inhibición de la pubertad / Puberty blockade: Clinical guideline for the diagnosis and treatment of precocious puberty

Resumen La Sociedad Mexicana de Endocrinología Pediátrica elaboró una guía de práctica clínica para el diagnóstico y el tratamiento de la pubertad precoz. Este documento presenta recomendaciones relacionadas con las intervenciones para inhibir la pubertad precoz central. La descripción detallada de la metodología para el desarrollo de esta guía y del sistema de gradación, así como la síntesis de la evidencia en la que se basa, pueden consultarse en este mismo suplemento.

Abstract The Mexican Society of Pediatric Endocrinology developed a clinical practice guide for the diagnosis and treatment of precocious puberty. This document presents recommendations related to the interventions for the inhibition of central precocious puberty. The detailed description of the methodology for the development of this guide and the grading system, as well as the synthesis of the evidence on which it is based can be consulted in this same supplement.

Intervenciones adyuvantes en el manejo de la pubertad precoz / Adjuvant interventions in the treatment of precocious puberty: Clinical guideline for the diagnosis and treatment of precocious puberty

Resumen La Sociedad Mexicana de Endocrinología Pediátrica elaboró una guía de práctica clínica para el diagnóstico y el tratamiento de la pubertad precoz. Este documento presenta recomendaciones relacionadas con intervenciones adyuvantes en el tratamiento de la pubertad precoz distintas de la inhibición de la pubertad. La descripción detallada de la metodología para el desarrollo de esta guía y del sistema de gradación, así como la síntesis de la evidencia en la que se basa, pueden consultarse en este mismo suplemento.

Abstract The Mexican Society of Pediatric Endocrinology developed a clinical practice guide for the diagnosis and treatment of precocious puberty. This document presents recommendations related to the complementary interventions for the treatment of precocious puberty besides puberty blockade. The detailed description of the methodology for the development of this guide and the grading system, as well as the synthesis of the evidence on which it is based, can be consulted in this same supplement.

Monitorización durante el tratamiento de la pubertad precoz / Monitoring during the treatment of precocious puberty: Clinical guideline for the diagnosis and treatment of precocious puberty

Resumen La Sociedad Mexicana de Endocrinología Pediátrica elaboró una guía de práctica clínica para el diagnóstico y el tratamiento de la pubertad precoz. Este documento presenta recomendaciones relacionadas con la monitorización del tratamiento y el seguimiento de pacientes con pubertad precoz central. La descripción detallada de la metodología para el desarrollo de esta guía y del sistema de gradación, así como la síntesis de la evidencia en la que se basa, pueden consultarse en este mismo suplemento.

Abstract The Mexican Society of Pediatric Endocrinology developed a clinical practice guide for the diagnosis and treatment of precocious puberty. This document presents recommendations related to the monitorization of the treatment and follow-up of patients with central precocious puberty. The detailed description of the methodology for the development of this guide and the grading system, as well as the synthesis of the evidence on which it is based, can be consulted in this same supplement.

Síntesis de la evidencia / Synthesis of the evidence: Clinical guideline for the diagnosis and treatment of precocious puberty

Resumen Se realizaron tres revisiones sistemáticas para la formulación de las recomendaciones sobre diagnóstico, tratamiento y seguimiento de pacientes con pubertad precoz: intervenciones para el tratamiento de la pubertad precoz que incluyeran los desenlaces de talla final o casi final, salud mental, salud metabólica, salud ósea o éxito en el bloqueo; estudios observacionales comparativos que evaluaran desenlaces a largo plazo en sujetos con antecedentes de pubertad precoz; y por último, estudios de exactitud de prueba diagnóstica para pubertad.

Abstract Three systematic reviews were conducted to formulate the recommendations on diagnosis, treatment and follow-up of patients with precocious puberty: interventions for the treatment of precocious puberty that included the outcomes of final or near-final height, mental health, metabolic health, health bone, or blockade success; comparative observational studies evaluating long-term outcomes in subjects with a history of precocious puberty; and diagnostic test accuracy studies for puberty.

Resistin levels are not associated with obesity in central precocious puberty.

OBJECTIVE: To compare serum resistin concentrations between prepubertal girls with a BMI > 85th percentile and girls with precocious puberty (CPP) who have and have not undergone GnRH analog treatment. PATIENTS AND METHODS: This is a cross-sectional study in girls with a BMI > 85th percentile and a median age of 8 years. We included 31 girls with CPP who did not receive treatment (CPPoT), 23 girls with CPP who were treated with leuprolide (CPPT), 22 prepubertal girls and 24 pubertal girls. Anthropometric data and the fasting plasma concentrations of lipids, glucose, insulin, and resistin were measured. RESULTS: The z-BMI scores were similar among the groups (p = 0.344), and body fat percentage (BF%) was similar among CPPT, CPPoT and prepubertal girls (p = 0.151). Resistin and insulin levels were lower in girls with CPP (CPPT and CPPoT) than in prepubertal and pubertal girls (median resistin level: CPPT 11.8 pg/ml vs CPPoT 11 pg/ml vs prepubertal 16 pg/ml vs pubertal 16 pg/ml, p = 0.001; median insulin level: CPPT 10.7 µUI/mL vs CPPoT 10.2 µUI/mL vs prepubertal 14.4 µUI/mL vs pubertal 32 µUI/mL p = 0.02). ANCOVA analysis, after adjustments for pubertal stage, BF% and z-BMI, showed that CPP modifies resistin levels (F = 31.4; p = 0.0001) independently of these parameters (p < 0.05). CONCLUSIONS: In the group of girls with overweight or obesity, the resistin level was lower in girls with CPP than in prepubertal and pubertal girls. More studies are needed to understand the role of resistin in CPP patients.

Cardiometabolic Risk Indicators for Kidney Disease in Mexican Patients with Type 2 Diabetes.

INTRODUCTION: Kidney disease is one of the main complications in the diabetic patient. Risk factors such as obesity, dyslipidemia, and hyperglycemia have been associated with increased urinary albumin excretion (UAE) and decreased glomerular filtration rates (GFR). However, the data are inconsistent. The objective of this study was to identify the primary risk factors associated with kidney disease in Mexican patients with type 2 diabetes. METHODS: A cross-sectional study was done in 395 patients with type 2 diabetes from four primary-care clinics. From fasting venous blood samples, the serum creatinine, glucose, glycated hemoglobin (HbA1c), and lipid profiles were measured. The diagnosis of diabetic kidney disease (DKD) was made by measuring GFR with the CKD-EPI equation, and the UAE from the first morning urination, according to the KDIGO 2012 Guidelines. Weight and waist circumference (WC), as well as body composition through the method of bioimpedance, were measured. RESULTS: Fourteen percent of the study population was diagnosed with DKD. Higher age and higher triglyceride levels were associated with a greater risk of DKD (p <0.05). In a multivariate analysis, higher age (OR = 1.06, 95% CI 1.02-1.11), triglyceride level (OR = 2.4, 95% CI 1.18-4.92), WC (OR = 1.09, 95% CI 1.03-1.15), and smoking (OR 2.6, 95% CI 1.07-6.49) were associated to DKD. CONCLUSION: Higher triglyceride levels, greater WC, and smoking are risk factors associated to DKD. An early diagnosis and opportune treatment for several cardiometabolic risk factors associated to DKD and cardiovascular disease should be identified and treated.

Multimedia education program and nutrition therapy improves HbA1c, weight, and lipid profile of patients with type 2 diabetes: a randomized clinical trial.

PURPOSE: To evaluate the effect of a multimedia education program and nutrition therapy on metabolic control in patients with type 2 diabetes. RESEARCH QUESTION: What is the effect of a multimedia education program and nutritional therapy on metabolic control in type 2 diabetes? PATIENTS AND METHODS: A randomized clinical trial was conducted in 351 patients randomly assigned to either an experimental group receiving a multimedia diabetes education program (MDE) and nutrition therapy (NT) (NT + MDE: n = 173), or to a control group who received nutrition therapy only (NT: n = 178). At baseline, 7, 14, and 21 months, the glycated hemoglobin (HbA1c), glucose, cholesterol, triglycerides, LDL-cholesterol, and HDL-cholesterol were measured. Weight, body mass index (BMI), waist circumference (WC), fat percentage, fat and lean mass, systolic blood pressure (SBP), and diastolic (DBP) were also recorded. RESULTS: Glycated hemoglobin decreased in both groups, although the group with NT + MDE had a greater reduction, with a difference of -0.76% (95%CI -1.33 to -0.19) at 7 months and -0.73% (95%CI -1.37 to -0.09) at 21 months. Only in the NT + MDE did the glucose decrease at 7 (-41.2 mg/dL; 95%CI -52.0 to -30.5), 14 (-27.8 mg/dL; 95%CI -32.6 to -23.1), and 21 months (-36.6 mg/dL; 95%CI -46.6 to -26.6). Triglycerides and the atherogenic index decreased in both groups at 7 and 14 months; while only in the NT + MDE group did it decrease at 21 months. (p < 0.05). Weight decreased at 21 months in the NT + MDE group (-1.23, -2.29 at -0.16; p < 0.05). CONCLUSION: Nutrition therapy and a multimedia diabetes education program have a favorable impact on achieving metabolic control goals in type 2 diabetes.

High plasma adenosine levels in overweight/obese pregnant women.

We aim to investigate whether overweight/obese pregnant women have elevated plasma levels of adenosine associated with increased consumption of high-calorie food. Sixty women were included. They were divided into lean (n = 23 and n = 12) or overweight/obese (n = 7 and n = 18) non-pregnant and pregnant women, respectively. Clinical records and maternal blood samples were collected after informed consent. A self-reported dietary questionnaire was also completed. Plasma adenosine levels were determined with high-performance liquid chromatography. Biochemical parameters, including glucose, total protein, and lipid profile, were determined using standard colorimetric assays. Adenosine levels were higher in pregnant women than in non-pregnant women (18.7 ± 1.6 vs 10.8 ± 1.3 nM/µg protein, respectively, p < 0.0001). Overweight/obese pregnant women (21.9 ± 2.5 nM/µg protein) exhibited higher adenosine levels than lean pregnant (14.5 ± 1.0 nM/µg protein, p = 0.04) or non-pregnant women (11.7 ± 1.5 nM/µg protein, p = 0.0005). Also, pregnant women with elevated weight gain exhibited higher (26.2 ± 3.7 nM/µg protein) adenosine levels than those with adequate weight gain (14.9 ± 1.4 nM/µg protein, p = 0.03). These differences were not statistically significant compared with those of pregnant women with reduced weight gain (17.4 ± 2.1 nM/µg protein, p = 0.053). Body mass index and adenosine only in pregnant women were positively correlated (r = 0.39, p = 0.02). While, polyunsaturated fatty acid (PUFA) consumption was negatively correlated with plasma adenosine levels only in non-pregnant women (r = -0.33, p = 0.03). Pregnancy is associated with high plasma adenosine levels, which are further elevated in pregnant women who are overweight/obese. High PUFA intake might reduce plasma adenosine levels in non-pregnant women.

The Kv1.3 channel blocker Vm24 enhances muscle glucose transporter 4 mobilization but does not reduce body-weight gain in diet-induced obese male rats.

AIMS: Voltage-gated potassium channels 1.3 (Kv1.3) can be targeted to reduce diet-induced obesity and insulin resistance in mice. Since species-specific differences in Kv1.3 expression and pharmacology have been observed, we tested the effect of Vm24, a high-affinity specific blocker of Kv1.3 channels from Vaejovis mexicanus smithi, on body weight (BW), glucose tolerance and insulin resistance in diet-induced obese rats. MATERIALS AND METHODS: Young adult male Wistar rats were switched to a high-fat/high-fructose (HFF) diet. Eighteen days later animals were divided in two groups: vehicle and Vm24 group. Subcutaneous injections were applied every other day until sacrifice 2months later. An additional cohort was maintained on standard chow. KEY FINDINGS: The HFF diet promoted obesity. Treatment with Vm24 did not alter various metabolic parameters such as food intake, BW gain, visceral white adipose tissue mass, adipocyte diameter, serum glucose, leptin and thyroid hormone concentrations, brown adipose tissue mass or uncoupling protein-1 expression, and insulin tolerance. Vm24 did reduce basal and glucose-stimulated serum insulin concentrations, serum C-peptide concentration, increased QUICKI, and tended to lower HOMA-IR. Vm24 treatment did not change the activation of insulin receptor substrate-1, but enhanced protein-kinase B activation and membrane glucose-transporter 4 (GLUT4) protein levels in skeletal muscle. SIGNIFICANCE: In conclusion, in male rats, long-term blockade of Kv1.3 channels with Vm24 does not reduce weight gain and visceral adiposity induced by HFF diet; instead, it reduces serum insulin concentration, and enhances GLUT4 mobilization in skeletal muscle.

Glucocorticoids curtail stimuli-induced CREB phosphorylation in TRH neurons through interaction of the glucocorticoid receptor with the catalytic subunit of protein kinase A.

PURPOSE: Corticosterone prevents cold-induced stimulation of thyrotropin-releasing hormone (Trh) expression in rats, and the stimulatory effect of dibutyryl cyclic-adenosine monophosphate (dB-cAMP) on Trh transcription in hypothalamic cultures. We searched for the mechanism of this interference. METHODS: Immunohistochemical analyses of phosphorylated cAMP-response element binding protein (pCREB) were performed in the paraventricular nucleus (PVN) of Wistar rats, and in cell cultures of 17-day old rat hypothalami, or neuroblastoma SH-SY5Y cells. Cultures were incubated 1h with dB-cAMP, dexamethasone and both drugs combined; their nuclear extracts were used for chromatin immunoprecipitation; cytosolic or nuclear extracts for coimmunoprecipitation analyses of catalytic subunit of protein kinase A (PKAc) and of glucocorticoid receptor (GR); their subcellular distribution was analyzed by immunocytochemistry. RESULTS: Cold exposure increased pCREB in TRH neurons of rats PVN, effect blunted by corticosterone previous injection. Dexamethasone interfered with forskolin increase in nuclear pCREB and its binding to Trh promoter; antibodies against histone deacetylase-3 precipitated chromatin from nuclear extracts of hypothalamic cells treated with tri-iodothyronine but not with dB-cAMP + dexamethasone, discarding chromatin compaction as responsible mechanism. Co-immunoprecipitation analyses of cytosolic or nuclear extracts showed protein:protein interactions between activated GR and PKAc. Immunocytochemical analyses of hypothalamic or SH-SY5Y cells revealed diminished nuclear translocation of PKAc and GR in cells incubated with forskolin + dexamethasone, compared to either forskolin or dexamethasone alone. CONCLUSIONS: Glucocorticoids and cAMP exert mutual inhibition of Trh transcription through interaction of activated glucocorticoid receptor with protein kinase A catalytic subunit, reducing their nuclear translocation, limiting cAMP-response element binding protein phosphorylation and its binding to Trh promoter.

Comparative effect of human and Trypanosoma cruzi calreticulin in wound healing.

In orthopaedics, the use of factors that enhance granulation tissue formation and prevent or delay new bone regeneration is sometimes desirable. Calreticulin (CRT), a unique endoplasmic reticulum luminal Ca(2+) -binding chaperone widely distributed in eukaryotic cells, is involved in many cellular functions. Among them, CRT has an important influence in cutaneous wound healing and diverse processes associated with cutaneous repair, inhibition of angiogenesis, promotion of cell adhesion and antitumour effect. One of the molecules involved in several aspects of the host-parasite interplay is Trypanosoma cruzi calreticulin (TcCRT), which is highly homologous to human calreticulin (HuCRT). Here, recombinant (r)HuCRT and rTcCRT are compared on their abilities to affect fibroblast behaviour in a scratch plate assay, and wound healing in in vivo skin rat models. In molar terms, rTcCRT is three orders of magnitude more efficient than rHuCRT in increasing proliferation and migration of human fibroblasts in vitro. A similar effect was observed in vivo on rat skin wounds and inhibition of bone gap bridging in rabbit unicortical bone osteotomies.