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OBJECTIVE: To review the technical aspects of body composition assessment by dual-energy X-ray absorptiometry (DXA) and other methods based on the most recent scientific evidence. MATERIALS AND METHODS: This Official Position is a result of efforts by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and health care professionals with expertise in body composition assessment who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications. In this first part of the Official Position, the authors discuss the different methods and parameters used for body composition assessment, general principles of DXA, and aspects of the acquisition and analysis of DXA scans. CONCLUSION: Considering aspects of accuracy, precision, cost, duration, and ability to evaluate all three compartments, DXA is considered the gold-standard method for body composition assessment, particularly for the evaluation of fat mass. In order to ensure reliable, adequate, and reproducible DXA reports, great attention is required regarding quality control procedures, preparation, removal of external artifacts, imaging acquisition, and data analysis and interpretation.

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Composición Corporal , Absorciometría de Fotón/métodos , Brasil , Impedancia Eléctrica , Humanos , Reproducibilidad de los Resultados

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PURPOSE: To investigate the relationships between bone measures, vitamin D status and markers of glucose metabolism among diabetic and non-diabetic adults. METHODS: Cross sectional study with 298 adults (mean age 57.5 years, SD = 14.8; 44.3% male, 16.9% diabetic) participants of the Health Survey-São Paulo (ISA-Capital) 2014-2015. Blood samples were collected to assess serum glucose, insulin and 25 hydroxyvitamin D [25(OH)D] concentrations. Dual-energy x-ray absorptiometry (DXA) was performed to determine total body fat; total lean mass; full body bone mineral density (BMD); lumbar spine BMD and bone mineral content (BMC); and femur BMD and BMC. Fat mass index (FMI), lean mass index (LMI), quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment of insulin resistance (HOMA-IR) and of ß-pancreatic cell function (HOMA-ß) were calculated. Linear regression analysis were performed. RESULTS: Multiple bone measures were associated with markers of glucose metabolism in analyses adjusted by age and sex. However, after additional adjustments by LMI, FMI and serum 25(OH)D, only associations of lumbar spine BMC with HOMA-IR (ß = 0.167; p = 0.035) and QUICKI (ß = -1.879; p = 0.027) persisted, in the subgroup of diabetic participants. Analysis restricted to diabetic subjects revealed stronger correlations between bone parameters and markers of glucose metabolism. CONCLUSIONS: Our study observed positive associations between BMD and markers of insulin resistance among a sample of adults. Correlations were stronger among diabetic subjects, and some associations between bone and glucose metabolism were independent of adiposity. Findings reinforce the need of further research for better understanding the bidirectional and multifactorial crosstalk between glucose homeostasis and bone metabolism.

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Objective Recent research has investigated the possible inverse relationship between vitamin K intake and body fat. In addition, an increasing number of studies are supporting a key role for this vitamin in improving lipid profile and insulin sensitivity and reducing the risk of type 2 diabetes mellitus, but little is known about what mechanisms would be involved. Thus, the objective of this study was to investigate the relationship between vitamin K intake (in the form of phylloquinone - PK), body fat, lipid profile and markers of glucose homeostasis in adults and the elderly. Subjects and methods A cross-sectional study with 298 participants (46% men) in the São Paulo Health Survey 2014-2015. Spearman correlations were performed to evaluate the associations between vitamin K intake and the biochemical and body composition measures. Results Among normal-weight male adults (n = 15), PK intake presented a positive correlation with the quantitative insulin sensitivity check index (QUICKI) (r = 0.525; p = 0.045). Among men with high fat mass index (FMI) (n = 101), PK intake had a negative correlation with homeostasis model assessment estimate for ß-cell function (HOMA-ß) (r = -0.227; p = 0.022). In women with high FMI (n = 122), PK intake had a negative correlation with HOMA-ß (r = -0.199, p = 0.032) and insulin (r = -0.207, p = 0.026). No correlations were found between PK intake and lipid profile. Conclusions Our findings support a potential relationship among PK intake, body fat and markers of glucose homeostasis in adults and the elderly.

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Diabetes Mellitus Tipo 2 , Homeostasis , Resistencia a la Insulina , Tejido Adiposo , Adulto , Anciano , Índice de Masa Corporal , Estudios Transversales , Femenino , Glucosa , Humanos , Insulina , Lípidos , Masculino , Vitamina K

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The renin-angiotensin system promotes oxidative stress, apoptosis, necrosis, fibrosis, and thus heart failure. Secretory renin plays a central role in these processes, initiating the generation of angiotensins. Nevertheless, alternative renin transcripts exist, which code for a cytosolically localized renin isoform (cyto-renin) that is cardioprotective. We tested the hypothesis that the protective effects are associated with a beneficial switch of metabolic and mitochondrial functions. To assess H9c2 cell mitochondrial parameters, we used the Seahorse XF analyser. Cardiac H9c2 cells overexpressing cyto-renin exhibited enhanced nonmitochondrial oxygen consumption, lactate accumulation, and LDH activity, reflecting a switch to more aerobic glycolysis known as Warburg effect. Additionally, mitochondrial spare capacity and cell respiratory control ratio were enhanced, indicating an increased potential to tolerate stress conditions. Renin knockdown induced opposite effects on mitochondrial functions without influencing metabolic parameters. Thus, the protective effects of cyto-renin are associated with an altered bioenergetic profile and an enhanced stress tolerance, which are favourable under ischaemic conditions. Therefore, cyto-renin is a promising new target for the prevention of ischaemia-induced myocardial damage.

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Cardiotónicos/metabolismo , Mitocondrias/metabolismo , Renina/metabolismo , Animales , Recuento de Células , Línea Celular , Respiración de la Célula , Metabolismo Energético , Glucólisis , L-Lactato Deshidrogenasa/metabolismo , Lactatos/metabolismo , Potencial de la Membrana Mitocondrial , Consumo de Oxígeno , Isoformas de Proteínas/metabolismo , Ratas

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Dronedarone improves microvascular flow during atrial fibrillation and reduces the infarct size in acute models of myocardial infarction. However, dronedarone might be harmful in patients with recent decompensated heart failure and increases mortality in patients with permanent atrial fibrillation. A pathophysiological explanation for these discrepant data is lacking. This study investigated the effects of dronedarone on gene and protein expression in the infarcted area and border zone in pigs subjected to anterior ischemia/reperfusion myocardial infarction. The ischemia/reperfusion myocardial infarction was induced in 16 pigs. Eight pigs were treated with dronedarone for 28 days after myocardial infarction, the remaining pigs served as control. Microarray-based transcriptome profiling and 2D-DIGE-based proteome analysis were used to assess the effects of dronedarone on left ventricular gene expression in healthy (LV), infarcted (MI), and border zone tissue. Selected targets were validated by RT-qPCR or immunoblot analyses, with special emphasize given to the transcriptome/proteome overlap. Combined "omics" analysis was performed to identify most significant disease and function charts affected by dronedarone and to establish an integrated network. The levels of 879 (BZ) or 7 (MI) transcripts and 51 (LV) or 15 (BZ) proteins were significantly altered by dronedarone, pointing to a substantial efficacy of dronedarone in the border zone. Transcriptome and proteome data indicate that dronedarone influences post-infarction remodeling processes and identify matricellular proteins as major targets of dronedarone in this setting. This finding is fully supported by the disease and function charts as well as by the integrated network established by combined "omics". Dronedarone therapy alters myocardial gene expression after acute myocardial infarction with pronounced effects in the border zone. Dronedarone promotes infarct healing via regulation of periostin and might contribute to the limitation of its expansion as well as cardiac rupture. Thus, there are no experimental hints that dronedarone per se has direct harmful effects after MI in ventricular tissue. Impact statement Dronedarone reduced the infarct size in models of acute myocardial infarction (MI). Here, we show that dronedarone attenuates many of the substantial changes in gene expression that are provoked by acute myocardial infarction (AMI) in pigs. Dronedarone modifies the expression of gene panels related to post-infarction cardiac healing and remodeling processes and, most remarkably, this occurs predominantly in the infarction border-zone and much less so in the vital or infarcted myocardium. Combined "omics" identified matricellular proteins and ECM as major dronedarone-regulated targets and emphasizes their relevance for Disease Charts and Tox Function Charts associated with tissue remodeling and cellular movement. The results demonstrate dronedarone's capability of regulating cardiac repair and remodeling processes specifically in the infarction border zone and identify underlying mechanisms and pathways that might be employed in future therapeutic strategies to improve long-term cardiac tissue function and stability.

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Fármacos Cardiovasculares/administración & dosificación , Dronedarona/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Remodelación Ventricular/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Immunoblotting , Análisis por Micromatrices , Proteoma/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Porcinos , Resultado del Tratamiento , Electroforesis Bidimensional Diferencial en Gel

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BACKGROUND: Heart failure is associated with altered gene expression and DNA methylation. De novo DNA methylation is associated with gene silencing, but its role in cardiac pathology remains incompletely understood. We hypothesized that inhibition of DNA methyltransferases (DNMT) might prevent the deregulation of gene expression and the deterioration of cardiac function under pressure overload (PO). To test this hypothesis, we evaluated a DNMT inhibitor in PO in rats and analysed DNA methylation in cardiomyocytes. METHODS AND RESULTS: Young male Wistar rats were subjected to PO by transverse aortic constriction (TAC) or to sham surgery. Rats from both groups received solvent or 12.5 mg/kg body weight of the non-nucleosidic DNMT inhibitor RG108, initiated on the day of the intervention. After 4 weeks, we analysed cardiac function by MRI, fibrosis with Sirius Red staining, gene expression by RNA sequencing and qPCR, and DNA methylation by reduced representation bisulphite sequencing (RRBS). RG108 attenuated the ~70% increase in heart weight/body weight ratio of TAC over sham to 47% over sham, partially rescued reduced contractility, diminished the fibrotic response and the downregulation of a set of genes including Atp2a2 (SERCA2a) and Adrb1 (beta1-adrenoceptor). RG108 was associated with significantly lower global DNA methylation in cardiomyocytes by ~2%. The differentially methylated pathways were "cardiac hypertrophy", "cell death" and "xenobiotic metabolism signalling". Among these, "cardiac hypertrophy" was associated with significant methylation differences in the group comparison sham vs. TAC, but not significant between sham+RG108 and TAC+RG108 treatment, suggesting that RG108 partially prevented differential methylation. However, when comparing TAC and TAC+RG108, the pathway cardiac hypertrophy was not significantly differentially methylated. CONCLUSIONS: DNMT inhibitor treatment is associated with attenuation of cardiac hypertrophy and moderate changes in cardiomyocyte DNA methylation. The potential mechanistic link between these two effects and the role of non-myocytes need further clarification.

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Cardiomegalia/genética , Cardiomegalia/fisiopatología , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , Metilación de ADN/efectos de los fármacos , Metilación de ADN/genética , Ftalimidas/farmacología , Triptófano/análogos & derivados , Análisis de Varianza , Animales , Islas de CpG/genética , Modelos Animales de Enfermedad , Fibrosis , Regulación de la Expresión Génica , Insuficiencia Cardíaca/metabolismo , Imagen por Resonancia Magnética , Masculino , Miocardio/patología , Miocitos Cardíacos/metabolismo , Ratas , Ratas Wistar , Análisis de Secuencia de ARN , Arterias Torácicas/cirugía , Triptófano/farmacología , Función Ventricular

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OBJECTIVES: This study aimed to investigate the relationship between 25-hydroxyvitamin D (25(OH)D), osteocalcin, markers of glucose metabolism, and obesity-related parameters among adolescents. METHODS: This was a cross-sectional study with 198 adolescents age 14-18 years. Weight, height, and waist and hip circumferences were measured, as well as the following biochemical parameters: serum 25(OH)D, parathyroid hormone (PTH), total (tOC) and undercarboxylated (ucOC) osteocalcin, adiponectin, leptin, glucose, and insulin. The homeostasis model of assessment estimate of insulin resistance (HOMA-IR) and ß-cell function (HOMA-ß) and quantitative insulin sensitivity check index (QUICKI) were calculated. Student's t test, analysis of variance (ANOVA), Pearson's correlation, and linear regression models were performed. RESULTS: Overweight was observed in 42.6% of the sample. This group presented significantly higher PTH, leptin, insulin, HOMA-IR, and HOMA-ß and lower 25(OH)D, adiponectin, tOC, ucOC, and QUICKI than normal-weight subjects. 25(OH)D was positively correlated with ucOC and adiponectin and negatively associated with body mass index (BMI), weight, and waist circumference (p < 0.05 for all). The association between 25(OH)D and ucOC was also observed in the multiple regression analysis, adjusted for age, BMI, and season of the year (partial r2 = 0.071, p < 0.0001). 25(OH)D and ucOC were not associated with markers of glucose metabolism. However, leptin was strongly correlated with insulin, HOMA-IR, HOMA-ß, and QUICKI (p < 0.0001 for all). CONCLUSION: The present study demonstrated that undercarboxylated osteocalcin is related to 25(OH)D and adiponectin concentrations. Both ucOC and 25(OH)D were lower in overweight and obese adolescents, reinforcing the importance of fighting obesity. Although a relationship of ucOC and 25(OH)D with markers of glucose metabolism was not observed, leptin has shown to be the hormone most related to energy homeostasis.

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Adipoquinas/metabolismo , Tejido Adiposo/metabolismo , Huesos/metabolismo , Glucosa/metabolismo , Osteocalcina/metabolismo , Vitamina D/metabolismo , Adipoquinas/genética , Adolescente , Biomarcadores , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Masculino , Hormona Paratiroidea , Estaciones del Año , Transducción de Señal/fisiología

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The (pro)renin receptor [(P)RR, ATP6AP2] is a multifunctional transmembrane protein that activates local renin-angiotensin systems, but also interacts with Wnt pathways and vacuolar H+ -ATPase (V-ATPase) during organogenesis. The aim of this study was to characterize the role of ATP6AP2 in the cell cycle in more detail. ATP6AP2 down-regulation by siRNA in renal As4.1 cells resulted in a reduction in the rate of proliferation and a G0/G1 phase cell cycle arrest. We identified a number of novel target genes downstream of ATP6AP2 knock-down that were related to the primary cilium (Bbs-1, Bbs-3, Bbs-7, Rabl5, Ttc26, Mks-11, Mks-5, Mks-2, Tctn2, Nme7) and the cell cycle (Pierce1, Clock, Ppif). Accordingly, the number of cells expressing the primary cilium was markedly increased. We found no indication that these effects were dependent of V-ATPase activity, as ATP6AP2 knock-down did not affect lysosomal pH and bafilomycin A neither influenced the ciliary expression pattern nor the percentage of ciliated cells. Furthermore, ATP6AP2 appears to be essential for mitosis. ATP6AP2 translocated from the endoplasmatic reticulum to mitotic spindle poles (pro-, meta- and anaphase) and the central spindle bundle (telophase) and ATP6AP2 knock-down results in markedly deformed spindles. We conclude that ATP6AP2 is necessary for cell division, cell cycle progression and mitosis. ATP6AP2 also inhibits ciliogenesis, thus promoting proliferation and preventing differentiation.

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Cilios/genética , Organogénesis/genética , ATPasas de Translocación de Protón/genética , Receptores de Superficie Celular/genética , ATPasas de Translocación de Protón Vacuolares/genética , Ciclo Celular/genética , Diferenciación Celular/genética , Línea Celular , Proliferación Celular/genética , Retículo Endoplásmico/genética , Regulación del Desarrollo de la Expresión Génica , Técnicas de Inactivación de Genes , Humanos , Mitosis/genética , Renina/genética , Sistema Renina-Angiotensina/genética , Vía de Señalización Wnt/genética

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Intravenous pamidronate is widely used to treat children with osteogenesis imperfecta (OI). In a well-studied protocol ('standard protocol'), pamidronate is given at a daily dose of 1 mg per kg body weight over 4 h on 3 successive days; infusion cycles are repeated every 4 months. Here, we evaluated renal safety of a simpler protocol for intravenous pamidronate infusions (2 mg per kg body weight given in a single infusion over 2 h, repeated every 4 months; 'modified protocol'). Results of 18 patients with OI types I, III, or IV treated with the modified protocol for 12 months were compared to 18 historic controls, treated with standard protocol. In the modified protocol, mild transient post-infusion increases in serum creatinine were found during each infusion but after 12 months serum creatinine remained similar from baseline [0.40 mg/dl (SD: 0.13)] to the end of the study [0.41 mg/dl (SD: 0.11)] (P = 0.79). The two protocols led to similar changes in serum creatinine during the first pamidronate infusion [modified protocol: +2% (SD: 21%); standard protocol: -3% (SD: 8%); P = 0.32]. Areal lumbar spine bone mineral density Z-scores increased from -2.7 (SD: 1.5) to -1.8 (SD: 1.4) with the modified protocol, and from -4.1 (SD: 1.4) to -3.1 (SD: 1.1) with standard protocol (P = 0.68 for group differences in bone density Z-score changes). The modified pamidronate protocol is safe and may have similar effects on bone density as the standard pamidronate protocol. More studies are needed with longer follow-up to prove anti-fracture efficacy.

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Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Osteogénesis Imperfecta/tratamiento farmacológico , Administración Intravenosa , Adolescente , Densidad Ósea/efectos de los fármacos , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Fracturas Óseas/epidemiología , Fracturas Óseas/prevención & control , Estudio Históricamente Controlado , Humanos , Inyecciones Intramusculares , Masculino , Osteogénesis Imperfecta/epidemiología , Pamidronato

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UNLABELLED: In the heart, secretory renin promotes hypertrophy, apoptosis, necrosis, fibrosis, and cardiac failure through angiotensin generation from angiotensinogen. Thus, inhibitors of the renin-angiotensin system are among the most potent drugs in the treatment of cardiac failure. Renin transcripts have been identified encoding a renin isoform with unknown targets and unknown functions that are localized to the cytosol and mitochondria. We hypothesize that this isoform, in contrast to secretory renin, exerts cardioprotective effects in an angiotensin-independent manner. Cells overexpressing cytosolic renin were generated by transfection or obtained from CX(exon2-9)renin transgenic rats. Overexpression of cytosolic renin reduced the rate of necrosis in H9c2 cardiomyoblasts and in primary cardiomyocytes after glucose depletion. These effects were not mediated by angiotensin generation since an inhibitor of renin activity did not influence the in vitro effects. siRNA-mediated knockdown of endogenous cytosolic renin increased the rate of necrosis and aggravated the pro-necrotic effects of glucose depletion. Isolated perfused hearts obtained from transgenic rats overexpressing cytosolic renin exhibited a 50% reduction of infarct size after ischemia-reperfusion injury. Cytosolic renin is essential for survival, both under basal conditions and during glucose starvation. The protective effects are angiotensin-independent and contrary to the known actions of secretory renin. KEY MESSAGES: A cytosolic isoform of renin with unknown functions is expressed in the heart. Cytosolic renin diminishes ischemia induced damage to the heart. The protective effects of cytosolic renin contradict the known function of secretory renin. The effects of cytosolic renin are not mediated via angiotensin generation. Renin-binding protein is a potential target for cytosolic renin.

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Cardiotónicos/metabolismo , Isquemia Miocárdica/prevención & control , Necrosis/prevención & control , Renina/metabolismo , Angiotensinógeno/metabolismo , Animales , Células Cultivadas , Citosol/metabolismo , Glucosa/metabolismo , Corazón/fisiopatología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Isoformas de Proteínas/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Ratas , Ratas Sprague-Dawley , Ratas Transgénicas , Ratas Wistar , Renina/antagonistas & inhibidores , Renina/biosíntesis , Renina/genética , Sistema Renina-Angiotensina/fisiología

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Dronedarone has been demonstrated to be harmful in patients with recent decompensated heart failure. Furthermore, a PALLAS study reported that dronedarone therapy increases mortality rates in patients with permanent atrial fibrillation. Although a pathophysiological explanation for these finding remains to be elucidated, the long term effects of dronedarone on myocardial structure and stability have been suggested. The aim of the present study was to determine whether dronedarone therapy affects left ventricular (LV) function in a chronic model of myocardial infarction (MI). An anterior MI was induced in 16 pigs. Of these animals, eight pigs were then treated with dronedarone for 1 week prior to, and 4 weeks following MI, the remaining pigs served as controls. LV angiography was performed 4 weeks after MI to determine the LV ejection fraction (LVEF). A post­mortem magnetic resonance imaging scan of the LV was then performed on the two groups (n=6) to determine the volume and size of the induced MI. Dronedarone therapy did not affect systemic and intracardiac hemodynamic parameters or LVEF during the follow­up assessment. Of note, dronedarone had no negative effect on the total infarct volume and size and did not induce lethal proarrhythmic effects following the induced anterior MI. Therefore, the results suggested that dronedarone did not increase the volume or size of induced anterior MI and did not affect LV performance. Thus, dronedarone therapy was observed to be safe in a porcine model of anterior MI.

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Amiodarona/análogos & derivados , Antiarrítmicos/farmacología , Imagen por Resonancia Magnética , Infarto del Miocardio/diagnóstico , Amiodarona/efectos adversos , Amiodarona/farmacología , Animales , Antiarrítmicos/efectos adversos , Biomarcadores , Vasos Coronarios/patología , Modelos Animales de Enfermedad , Dronedarona , Electrocardiografía , Hemodinámica , Imagenología Tridimensional , Imagen por Resonancia Magnética/métodos , Masculino , Infarto del Miocardio/etiología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Porcinos , Función Ventricular Izquierda

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OBJECTIVES: To evaluate the usefulness of vertebral morphometry in identifying unreferred vertebral fractures and correlate potential risk factors. SUBJECTS AND METHODS: Female patients above 45 years, postmenopausal for at least 2 years, diagnosed with osteoporosis and undergoing treatment for at least three months were considered eligible. All of them underwent bone densitometry and vertebral morphometry performed by concomitant DXA. The presence of fractures was defined between T7 and L4; only moderate and severe fractures were considered for analysis. All volunteers were submitted to laboratory tests, anthropometry and responded a questionnaire on their lifestyle habits and medical history. RESULTS: Thirty two (17%) out of the 188 female patients presented with at least one vertebral fracture, among whom only 4 (12.5%) were previously aware of the fracture. The fractures were mainly located on the thoracic spine. Nine patients had severe fractures (28.1%), whereas 23 had moderate fractures (71.9%). On average, patients with fractures were 5 years older and weighed 5 kilograms less than those without fractures. The creatinine clearance was on average 9 mL/min less in patients with vertebral fracture. The assessment of vertebral fractures by morphometry is a fast, accurate and complementary method associated with low radiation exposure for identifying moderate and severe vertebral fractures. Predisposition to vertebral fractures does not depend solely on BMD.

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Absorciometría de Fotón , Osteoporosis Posmenopáusica/diagnóstico por imagen , Fracturas de la Columna Vertebral/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Densidad Ósea , Femenino , Humanos , Estilo de Vida , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/lesiones , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Fracturas de la Columna Vertebral/epidemiología , Encuestas y Cuestionarios , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/lesiones

RESUMEN

Objectives To evaluate the usefulness of vertebral morphometry in identifying unreferred vertebral fractures and correlate potential risk factors. Subjects and methods Female patients above 45 years, postmenopausal for at least 2 years, diagnosed with osteoporosis and undergoing treatment for at least three months were considered eligible. All of them underwent bone densitometry and vertebral morphometry performed by concomitant DXA. The presence of fractures was defined between T7 and L4; only moderate and severe fractures were considered for analysis. All volunteers were submitted to laboratory tests, anthropometry and responded a questionnaire on their lifestyle habits and medical history. Results Thirty two (17%) out of the 188 female patients presented with at least one vertebral fracture, among whom only 4 (12.5%) were previously aware of the fracture. The fractures were mainly located on the thoracic spine. Nine patients had severe fractures (28.1%), whereas 23 had moderate fractures (71.9%). On average, patients with fractures were 5 years older and weighed 5 kilograms less than those without fractures. The creatinine clearance was on average 9 mL/min less in patients with vertebral fracture. The assessment of vertebral fractures by morphometry is a fast, accurate and complementary method associated with low radiation exposure for identifying moderate and severe vertebral fractures. Predisposition to vertebral fractures does not depend solely on BMD. .

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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteterapia , Psicoterapia de Grupo , Esquizofrenia/terapia , Resultado del Tratamiento

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A better education and training of clinical investigators and their teams is one of the factors that could foster the development of clinical research in Europe, a key objective of the Innovative Medicines Initiative (IMI). PharmaTrain (an IMI programme on training in medicines development), and European Clinical Research Infrastructures Network (ECRIN) have joined forces to address this issue. An advisory group composed of representatives of universities, pharmaceutical companies and other organisations met four times between June 2011 and July 2012. This resulted in a position paper proposing a strategy to improve and harmonize clinical investigator training in Europe, and including a detailed syllabus and list of learning outcomes. Major recommendations are the establishment of minimal and mutually recognized certification requirement for investigators throughout the EU and the creation of a European platform to provide a suitable course and examination infrastructure.

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Os autores abordam a importância do cálcio e da vitamina D na alimentação de crianças e adolescentes, ressaltando as consequências de sua deficiência na dieta. Descrevem as fontes mais ricas nesses elementos e as doses recomendadas em cada faixa etária, destacando a situação insatisfatória encontrada no Brasil. Finalmente, tratam da suplementação tanto do cálcio como da vitamina D no dia-a-dia da população infanto-juvenil...

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Humanos , Masculino , Femenino , Niño , Adolescente , Adolescente , Calcio , Vitamina D

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PURPOSE: To evaluate the usefulness of the cyp1a1ren-2 transgenic rat model of inducible hypertension for studies of the development and regression of cardiac hypertrophy. MATERIALS AND METHODS: Cyp1a1ren-2 rats received a diet containing 0% or 0.167% indole-3-carbinonl (I3C) for 4 weeks to induce hypertension. Cardiac magnetic resonance imaging (MRI) at 7 T was performed every second week for 10 weeks to measure left ventricular mass and the ejection fraction. Concomitantly, in six cyp1a1ren-2 rats blood pressure was recorded telemetrically. RESULTS: Plasma prorenin concentrations rose from 138 ± 38 to 15,490 ± 3990 ng/angiotensin I/mL/h (P < 0.001) in I3C-treated transgenic rats and returned to basal levels after cessation of I3C. Mean blood pressure increased to a plateau of 169 ± 11 mmHg by the second week of induction. After cessation of I3C (day 28), arterial pressure dropped to values slightly below those prior to induction within 4 days (basal: 106 ± 7 mmHg, day 32: 103 ± 21 mmHg; NS). At day 28, left ventricular mass was increased by 39% vs. 4% in controls (P < 0.001) without changes of the ejection fraction. Cardiac hypertrophy was completely reversed at day 70, as evaluated by MRI. CONCLUSION: The cyp1a1ren-2 transgenic rat is a useful model to study reversal and healing in the absence of surgical interventions.

Asunto(s)

Citocromo P-450 CYP1A1/genética , Modelos Animales de Enfermedad , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/etiología , Imagen por Resonancia Cinemagnética/métodos , Animales , Humanos , Ratas , Ratas Transgénicas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad

RESUMEN

This study aimed to elucidate the role of the AT(2) receptor (AT(2)R), which is expressed and upregulated in the adrenal zona glomerulosa (ZG) under conditions of increased aldosterone production. We developed a novel transgenic rat (TGR; TGRCXmAT(2)R) that overexpresses the AT(2)R in the adrenal gland, heart, kidney, brain, skeletal muscle, testes, lung, spleen, aorta, and vein. As a consequence the total angiotensin II (Ang II) binding sites increased 7.8-fold in the kidney, 25-fold in the heart, and twofold in the adrenals. The AT(2)R number amounted to 82-98% of total Ang II binding sites. In the ZG of TGRCXmAT(2)R, the AT(2)R density was elevated threefold relative to wild-type (WT) littermates, whereas AT(1)R density remained unchanged. TGRCXmAT(2)R rats were viable and exhibited normal reproduction, blood pressure, and kidney function. Notably, a slightly but significantly reduced body weight and a moderate increase in plasma urea were observed. With respect to adrenal function, 24-h urinary and plasma aldosterone concentrations were unaffected in TGRCXmAT(2)R at baseline. Three and 14 days of Ang II infusion (300 ng·min(-1)·kg(-1)) increased plasma aldosterone levels in WT and in TGR. These changes were completely abolished by the AT(1)R blocker losartan. Of note, glomerulosa cell proliferation, as indicated by the number of Ki-67-positive glomerulosa cells, was stimulated by Ang II in TGR and WT rats; however, this increase was significantly attenuated in TGR overexpressing the AT(2)R. In conclusion, AT(2)R in the adrenal ZG inhibits Ang II-induced cell proliferation but has no obvious lasting effect on the regulation of the aldosterone production at the investigated stages.

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Aldosterona/fisiología , Modelos Animales , Ratas Transgénicas , Receptor de Angiotensina Tipo 2/metabolismo , Zona Glomerular/fisiología , Angiotensina II/fisiología , Animales , Proliferación Celular , Regulación de la Expresión Génica/fisiología , Ratas , Regulación hacia Arriba , Zona Glomerular/citología

RESUMEN

OBJECTIVE: Information regarding nutrition and body composition in patients diagnosed with osteogenesis imperfecta (OI) is scarce. In the present study, nutritional status, bone mineral density, and biochemical parameters of subjects with OI were evaluated. METHODS: Patients with type I OI (n = 13) and type III OI (n = 13) and healthy controls (n = 8) were selected. Nutritional status and bone mineral density were assessed by a 3-d food diary and dual-energy X-ray absorptiometry at the lumbar spine, respectively. Body mass index, serum albumin, calcium, creatinine, cross-linked C-telopeptide, parathyroid hormone, and 25-hydroxivitamin D(3) were also evaluated. RESULTS: Patients with OI had lower bone mineral density (P < 0.05 versus controls). Patients with type III OI had the highest body mass index (P < 0.05 versus patients with type I OI and controls) and the lowest lean body mass (P < 0.05 versus patients with type I OI and controls). In patients with OI, the number of fractures was positively correlated with body mass index (r = 0.581, P = 0.002) and the percentage of body fat (r = 0.451, P = 0.027) and negatively correlated to lean body mass (r = -0.523, P = 0.009). Even when taking dietary supplements, 58% and 12% of subjects with OI did not achieve the calcium and vitamin D recommendations, respectively. CONCLUSIONS: Body composition is a risk factor for bone fractures in subjects with OI. Individualized nutritional support is recommended not only to improve body composition but also to potentiate pharmacologic and physical therapies.

Asunto(s)

Composición Corporal , Densidad Ósea , Fracturas Óseas/prevención & control , Necesidades Nutricionales , Apoyo Nutricional , Obesidad/complicaciones , Osteogénesis Imperfecta/terapia , Tejido Adiposo , Adolescente , Adulto , Compartimentos de Líquidos Corporales , Índice de Masa Corporal , Calcio/administración & dosificación , Calcio/sangre , Calcio/deficiencia , Estudios de Casos y Controles , Suplementos Dietéticos , Femenino , Fracturas Óseas/etiología , Humanos , Masculino , Estado Nutricional , Obesidad/sangre , Osteogénesis Imperfecta/sangre , Osteogénesis Imperfecta/complicaciones , Prevalencia , Vitamina D/administración & dosificación , Vitamina D/sangre , Deficiencia de Vitamina D/epidemiología , Adulto Joven

RESUMEN

OBJECTIVE: Hypertension is a risk factor for arterial thrombosis. We investigated the effects of angiotensin II (ANG II)-dependent hypertension on the platelet proteome. METHODS AND RESULTS: Hypertension was induced in cyp1a1ren-2 transgenic rats by feeding indole-3-carbinol (n = 10) and in Fischer 344 rats by subcutaneously infusing ANG II (n = 7). After 14 days of hypertension (SBP 180 mmHg) and 10 days after normalization of blood pressure, changes in the platelet proteome were assessed by two-dimensional differential in-gel electrophoresis. In a subset of animals (n = 4), repeated blood withdrawals were performed. Of 1040 protein spots, 45 displayed hypertension-associated changes (>1.5-fold, P < 0.01) in both models (34 increased, 11 decreased). All were reversible within 10 days. Thirty-eight spots were identified by mass spectrometry and assigned to 20 distinct proteins. The majority of spots with increased intensity constituted protein fragments. Repeated blood withdrawals and stimulation of megakaryocytopoiesis by a thrombopoietin receptor agonist induced changes in the same protein spots but in the opposite direction to those induced by ANG II-dependent hypertension. CONCLUSION: ANG II-dependent hypertension is associated with enhanced protein degradation in platelets. As these changes are reversible, the proteins identified might be used to develop a biomarker for monitoring recent blood pressure history.

Asunto(s)

Angiotensina II/metabolismo , Plaquetas/metabolismo , Hipertensión/metabolismo , Proteoma/metabolismo , Aldosterona/metabolismo , Animales , Animales Modificados Genéticamente , Humanos , Indoles/farmacología , Masculino , Espectrometría de Masas/métodos , Proteómica/métodos , Ratas , Ratas Endogámicas F344 , Renina/metabolismo , Factores de Riesgo

RESUMEN

OBJETIVO: Investigar os níveis séricos e a prevalência de inadequação da ingestão dietética de folato e das vitaminas B6 e B12, identificando os alimentos contribuintes para a ingestão desses nutrientes. MÉTODOS: Estudo observacional, transversal, em adolescentes de 16 a 19 anos, de ambos os sexos, conduzido em Indaiatuba (SP). Coletou-se o registro alimentar de 3 dias não consecutivos. A dieta habitual foi estimada pela remoção da variabilidade intrapessoal, e a prevalência de inadequação da ingestão, pelo método da estimated average requirement como ponto de corte. As análises bioquímicas de folato, B6 e B12 foram conduzidas de acordo com os métodos aceitos na literatura. RESULTADOS: O estudo foi conduzido com 99 adolescentes, a maioria do sexo feminino (58,6 por cento), com média de idade de 17,6 (desvio padrão, DP 0,9) anos. As médias da concentração sérica de folato, B6 e B12 foram de 9,2 (DP 3,4) ng/mL, 18,7 (DP 5,1) nmol/L e 397,5 (DP 188,4) pg/mL, respectivamente; e a prevalência de inadequação da ingestão das vitaminas foi de 15,2, 10,2 e < 1 por cento, respectivamente. Os alimentos que mais contribuíram para a ingestão dos nutrientes foram, para folato: pão francês, macarrão e feijões; para B6: arroz branco, carne de frango e carne bovina; e para B12: carne bovina magra, leite integral e carne bovina gorda. CONCLUSÕES: As prevalências de inadequação de folato, B6 e B12 mostraram-se baixas, possivelmente em decorrência da melhoria do acesso e da disponibilidade de alimentos, fontes dietéticas das vitaminas. Os feijões, presentes na dieta tradicional brasileira, ainda estão entre os principais alimentos que contribuíram para a ingestão de folato, mesmo após a fortificação mandatória com ácido fólico no Brasil.

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OBJECTIVE: To investigate serum concentrations and the prevalence of inadequate folate intake and also vitamin B6 and vitamin B12 intakes and to identify those foods that make a major contribution to intake levels of these nutrients. METHODS: This was a cross-sectional, observational study of adolescents of both sexes aged 16 to 19 years from the town of Indaiatuba, SP, Brazil. Data collection was by non-consecutive 3-day dietary record. The samples’ habitual diet was estimated by removing intraindividual variability, and the prevalence rates of inadequate intakes were calculated using the estimated average requirement as cutoff points. Biochemical assays for folate, vitamin B6 and vitamin B12 were conducted in accordance with the methods accepted in the literature. RESULTS: The study sample comprised 99 adolescents, the majority of whom were female (58.6 percent), with a mean age of 17.6 [standard deviation, (SD) 0.9]. Mean serum concentrations for folate, vitamin B6 and vitamin B12 were 9.2 (SD 3.4) ng/mL, 18.7 (SD 5.1) nmol/L and 397.5 (SD 188.4) pg/mL, respectively; and the prevalence rates of inadequate intake for these vitamins were 15.2, 10.2 and < 1 percent, respectively. The foods that made a major contribution to vitamin intakes were French bread, pasta and beans for folate; white rice, chicken and beef for vitamin B6; and lean beef, whole milk and fatty beef for vitamin B12. CONCLUSIONS: The prevalence rates of inadequate folate, vitamin B6 and vitamin B12 intakes were low, which is possibly the result of improved access to and availability of foods that are dietary sources of these vitamins. Beans, which are a part of the traditional Brazilian diet, remain one of the primary food items that contribute to folate intake, even after mandatory fortification with folic acid in Brazil.

Asunto(s)

Adolescente , Femenino , Humanos , Masculino , Adulto Joven , Encuestas sobre Dietas , Conducta Alimentaria , Ácido Fólico/sangre , /sangre , /sangre , Brasil , Estudios Transversales , Registros de Dieta , Ingestión de Energía , Ácido Fólico/administración & dosificación , Valor Nutritivo , /administración & dosificación , /administración & dosificación , Vitaminas/administración & dosificación