RESUMO
A systematic review of the literature was performed in July 2011. Original papers based on longitudinal studies measuring spine, femoral neck, or total body bone mass by DXA were included (n = 17). Birth weight was positively associated with bone mass among children. The association was unclear among adolescents and weak among adults. This study aims to evaluate the association between birth weight and bone mass in future ages through a systematic review of literature and meta-analysis. A systematic review of the literature was performed in July 2011 in Medline, Web of Science and LILACS bases using key terms: ("birth size" OR "birth weight" OR birthweight OR prematurity OR premature OR "gestational age") AND (osteoporosis OR "bone mass" OR "bone density" OR "bone mineral density" OR "bone mineral content" OR "bone area") AND (longitudinal OR cohort). Original papers based on longitudinal studies measuring lumbar spine, femoral neck or total body bone mass by dual-emission X-ray absorptiometry (DXA) were included. A meta-analysis was performed using birth weight and bone mass density and/or content as continuous variables and adjusted for current height and/or weight. A total of 218 articles were retrieved from which 17 were selected and grouped into three categories according to age: studies with children; with adolescents and young adults, and studies with adults (older than 25). Five papers were included in the meta-analysis. Positive association between birth weight and bone mass was clear among children, unclear among adolescents, and weak among adults. The effect on bone mass content was stronger than those on body mass density regardless of age. Birth weight influences positively bone health in later life. Preventive health policies dealing with early-life modifiable risk factors, as birth weight, should be encouraged to attain an optimal peak bone mass as an strategy to decrease osteoporosis in the elderly.
Assuntos
Peso ao Nascer/fisiologia , Densidade Óssea/fisiologia , Osteoporose/fisiopatologia , Absorciometria de Fóton , Envelhecimento/fisiologia , Medicina Baseada em Evidências , Colo do Fêmur/fisiologia , Humanos , Vértebras Lombares/fisiologiaRESUMO
The aim of this study was to compare physical growth from birth to 2 years of age of babies born to women with or without gestational diabetes mellitus (GDM), among the subjects of the 2004 Pelotas Birth Cohort. Mothers who gave birth in 2004 in any of the five maternity wards in the city of Pelotas, Southern Brazil, were interviewed shortly after delivery by trained interviewers, using tested, pre-coded questionnaires. GDM diagnosis was self-reported. Child weight, length and abdominal circumference were measured, and adjusted weight-for-age, height-for-age and weight-for-height Z-scores were calculated at birth, 3, 12 and 24 months. We studied 4239 children. Offspring of GDM mothers (OGDM; n = 125) had lower gestational age (GA; P = 0.004), greater weight (P = 0.002) and greater abdominal circumference (P < 0.001) at birth. Prevalence of large for GA (LGA) was threefold higher among OGDM (18.4% v. 6.8%). Mean weight-for-age (0.48 v. -0.07; P < 0.001) and weight-for-height (0.94 v. 0.51; P < 0.001) Z-scores were also higher among OGDM. During the first 3 months, there was an abrupt catch-down among OGDM babies, who remained lighter than non-GDM offspring until the 24th month. LGA OGDM were heavier than LGA offspring of non-GDM mothers at birth, but had caught down with babies born with adequate weight for GA to non-GDM by 3 months, and showed similar growth patterns from thereon. OGDM show different growth patterns when compared to offspring of non-GDM mothers, which may be part of a causal pathway or constitute a risk marker for future obesity, impaired glucose tolerance and diabetes mellitus.
RESUMO
BACKGROUND: Rapid weight gain in childhood may increase the risk of chronic adult diseases. Few studies have examined the effects of lifecourse weight gain on waist circumference (WC), hip circumference (HC), or waist-to-hip ratio (WHR). OBJECTIVE: To evaluate the effects of birthweight and weight gain from birth to age 23 years on WC, HC, and WHR in young adults. DESIGN: Population-based birth cohort study started in 1982. A sample of 856 individuals was examined in 2006. Conditional growth analyses were carried out with adjustment for confounders. WC and HC were also mutually adjusted. RESULTS: Weight gains during all age ranges studied (birthweight, 0-2, 2-4, 4-15, 15-18/19, and 18/19-23 years) were positively associated with WC and HC in both sexes. These effects were strongest from 4 to 15 years range (beta = 5.0 cm for both circumferences). Proxies for visceral adipose tissue (WHR and WC adjusted for HC) were associated with weight gain after 2 years in females and after 4 years in males. Subcutaneous adipose and muscular tissues, assessed by HC adjusted for WC, were associated with birthweight and weight gain from 0 to 2 years in both sexes, and again with weight gains from 4 to 18 years in males and 4 to 15 years in females. CONCLUSIONS: Weight gains in utero and in the first 2 years had long-term effects on HC, but weight gain after age 4 years was strongly associated with WC. Weight gains up to age 2 years may reduce cardiovascular risk associated with adult fat patterns in a middle-income setting.
Assuntos
Doenças Cardiovasculares/etiologia , Obesidade Abdominal/etiologia , Circunferência da Cintura/fisiologia , Relação Cintura-Quadril , Aumento de Peso/fisiologia , Adolescente , Fatores Etários , Peso ao Nascer/fisiologia , Composição Corporal/fisiologia , Índice de Massa Corporal , Brasil/epidemiologia , Doenças Cardiovasculares/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Obesidade Abdominal/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
Glucose transport in plasma membranes is the prototypic example of facilitated diffusion through biological membranes, and transport in erythrocytes is the most widely studied. One of the oldest and simplest models describing the kinetics of the transport reaction is that of alternating conformers, schematized in a cycle of four partial reactions where glucose binds and dissociates at two opposite steps, and the transporter undergoes transconformations at the other two opposite steps. The transport kinetics is entirely defined by the forward and backward rate constants of the partial reactions and the glucose and transporter concentrations at each side of the membrane, related by the law of mass action. We studied, in silico, the effect of modifications of the variables on the transient kinetics of the transport reaction. The simulations took into account thermodynamic constraints and provided results regarding initial velocities of transport, maximal velocities in different conditions, apparent influx and efflux affinities, and the turnover number of the transporter. The results are in the range of those experimentally reported. Maximal initial velocities are obtained when the affinities of the ligand for the transporter are the same at the extra- and intracellular binding sites and when the equilibrium constants of the transconformation steps are equal among them and equal to 1, independently of the obvious effect of the increase of the rate constant values. The results are well adjusted to Michaelis-Menten kinetics. A larger initial velocity for efflux than for uptake described in human erythrocytes is demonstrated in a model with the same dissociation constants at the outer and inner sites of the membrane. The larger velocities observed for uptake and efflux when transport occurs towards a glucose-containing trans side can also be reproduced with the alternating conformer model, depending on how transport velocities are measured.
RESUMO
The sarcoplasmic reticulum (SR) Ca-dependent adenosinetriphosphatase (Ca-ATPase) actively transports Ca2+ from the myoplasm to the SR lumen. Under optimal conditions a 2:1 stoichiometry of Ca transport/ATP hydrolysis has been observed, but lower stoichiometries have been reported under several circumstances. A lower stoichiometry under conditions of high Ca2+ load, although thermodynamically less efficient, could in theory increase the rate and the maximal amount of Ca uptake. We analysed, by computing simulation, the transient kinetics of a model of the SR Ca-ATPase with variable stoichiometry. The model is based on current experimental reports and includes the most relevant properties of the system. The results show an acceleration in the rate of Ca uptake, an increase in the net Ca transport, and an increase in the rate of [Ca2+] reduction in the medium, which might be physiologically useful to increase the rate of Ca pumping at high Ca load of the sarcoplasmic reticulum.
Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Cálcio/metabolismo , Simulação por Computador , Retículo Sarcoplasmático/enzimologia , Trifosfato de Adenosina/metabolismo , Animais , Transporte Biológico , Hidrólise , Modelos BiológicosRESUMO
The sarcoplasmic reticulum Ca-ATPase is fully activated when approximately 1 microM [Ca2+] saturates the two transport sites; higher [Ca] inhibits the ATPase by competition of Ca-ATP with Mg-ATP as substrates. Here we describe a novel effect of EGTA and other chelators, raising the possibility of an additional activating effect of Ca in the sub- or low microM range. Sarcoplasmic reticulum membranes were isolated from rabbit skeletal muscles. The ATPase activity was measured after incubation at 37 degreesC in 3 mM ATP, 3 mM MgCl2, 50 mM MOPS-Tris (pH 7.2), 100 mM KCl, and variable CaCl2, EGTA and calcimycin. In the absence of added EGTA and Ca the ATPase activity is high due to contaminant Ca. The determination of the ATPase activity in the presence of increasing amounts of EGTA, without added Ca, yields a decreasing sigmoidal function. Ki ranged between 20 and 100 microM, depending on the enzyme concentration. Pi production is linear with time for several [EGTA] yielding suboptimal ATPase activities, which are inhibited by thapsigargin. These suboptimal Ca-ATPase activities are inhibited by preincubation of the enzyme in EGTA, at pH 7.2. This effect increases upon increasing EGTA concentration and preincubation time. The inhibitory effect of the previous exposure of the enzyme to EGTA is partially but significantly reverted by increasing [Ca2+] during incubations. Calcimycin and EDTA have similar effects as EGTA when added in preincubations. The effect of calcimycin is fully reverted by optimal [Ca2+] in incubations. The effects of EGTA, EDTA and calcimycin in preincubation are not additive. The results suggest that an additional calcium, lost during preincubations from a site with affinity near 1 microM, is necessary for full activation of the ATPase.
Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Cálcio/metabolismo , Músculo Esquelético/metabolismo , Retículo Sarcoplasmático/metabolismo , Animais , Sítios de Ligação , Transporte Biológico Ativo , Calcimicina/farmacologia , Cálcio/farmacologia , ATPases Transportadoras de Cálcio/antagonistas & inibidores , Quelantes/farmacologia , Ácido Edético/farmacologia , Ácido Egtázico/farmacologia , Ativação Enzimática/efeitos dos fármacos , Técnicas In Vitro , Ionóforos/farmacologia , Cinética , Músculo Esquelético/efeitos dos fármacos , Coelhos , Retículo Sarcoplasmático/efeitos dos fármacosRESUMO
The phosphorylation of the sarcoplasmic reticulum Ca-ATPase (EC 3.6.1.38) with P(i) was characterized using Mn as a Mg analogue. Steady state and transient fluorescence and radioisotopic techniques were used; the affinities of Mn and P(i) for the enzyme and the rate constants of the phosphorylation and dephosphorylation reactions were determined, under several conditions. The reactions were carried out at pH 5.5 to minimize the binding of contaminant Ca to the transport sites, thus avoiding the use of Ca chelators. The apparent affinity of Mn binding at low [Mn] is larger in the absence of P(i) (35 microM) than in the presence of saturating P(i) (70 microM). On the contrary, the apparent affinity of Mn for the formation of the phosphoenzyme increases, from 1.5 mM to 0.15 mM, upon increasing [P(i)] in the millimolar range. The apparent affinty of P(i) for the formation of the phosphoenzyme also increases, from 2.2 mM to 0.2 mM, upon increasing [Mn] in the millimolar range. The equilibrium of the phosphoenzyme with the noncovalent Mn.P(i). Enzyme complex favors the covalent species. The simulation of a reaction model including the random binding of 2 Mn and I P(i) per mol of ATPase and a noncovalent complex in equilibrium with the phosphoenzyme, using a set of equilibrium constants deduced from the results, agree with the experimental data.
Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Manganês/metabolismo , Fosfatos/metabolismo , Retículo Sarcoplasmático/metabolismo , Animais , Sítios de Ligação , Simulação por Computador , Relação Dose-Resposta a Droga , Cinética , Manganês/farmacologia , Modelos Químicos , Fosforilação , Coelhos , Retículo Sarcoplasmático/enzimologia , Espectrometria de FluorescênciaRESUMO
Prolactin is a pituitary hormone with several functions, one of them, immunoregulatory. Patients with prolactinoma develop hyperprolactinemia. In the next two cases, patients with microprolactinoma, both autoimmune disease associated. First patient, male, with multiple sclerosis; the other one patient, female, with systemic lupus erythematosus. Treatment of hyperprolactinemia with bromocriptine was associated with satisfactory clinical evolution, and a reduction of dosage of immunosuppressor treatment. The patients with multiple sclerosis had neurological functions recovery and the patients with systemic lupus erythematosus had severe relapse of disease each time she dropped bromocriptine treatment. Pituitary function must be evaluated in autoimmune disease, to search alterations like hyperprolactinemia who influenced immune function.
Assuntos
Doenças Autoimunes/imunologia , Hiperprolactinemia/imunologia , Adulto , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Bromocriptina/uso terapêutico , Antagonistas de Dopamina/uso terapêutico , Feminino , Humanos , Hiperprolactinemia/complicações , Hiperprolactinemia/tratamento farmacológico , MasculinoRESUMO
The Ca2(+)-dependent adenosinetriphosphatase (Ca2(+)-ATPase) from the sarcoplasmic reticulum (SR) of rat skeletal muscles is phosphorylated by inorganic phosphate (Pi) in the absence of Ca2+. The reaction can be described by the following simplified scheme: [formula: see text] where E-P is a covalent, acid-stable and ADP-insensitive phosphoenzyme, and E.Pi is a noncovalent and acid-labile complex. The reaction is Mg2(+)-dependent. Membrane fragments deposited on Millipore filters were successively perfused with two solutions, at constant flow. The effluent samples were analyzed. The perfused solutions were Ca2+ free and always contained 40% dimethylsulfoxide (DMSO), plus other reactants. Following the successive perfusion of solutions without and with [32P]Pi, 32P binding is only detected in the presence of Mg2+, indicating the formation of the phosphoenzymes (E.Pi and E-P). Following perfusions of the phosphoenzymes with 5% trichloroacetic acid, 32P release indicates the amount of the acid-labile moiety (E.Pi). After phosphorylations, the filters were washed with acid and unlabeled Pi, and the remaining radioactivity was measured to evaluate the acid-stable phosphoenzyme (E-P). The acid-labile and acid-stable phosphoenzymes amounted, respectively, 0.72 +/- 0.12, and 1.48 +/- 0.10 nmol of Pi/mg of protein ( +/- S.E., n = 5), after phosphorylations with 20 microM Pi. The results indicate: (1) The method allowed the evaluation of the acid-labile intermediate of the SR Ca2(+)-ATPase cycle. Keq = k2/k-2), in the above scheme, approaches 2.0. (2) The substrate of the phosphorylation reaction, in the presence of DMSO, is likely to be the Mg.Pi complex, since Mg2+ is necessary for step 1 in the above scheme.
Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Músculos/enzimologia , Fosfoproteínas/metabolismo , Retículo Sarcoplasmático/enzimologia , Animais , Membrana Celular/enzimologia , Dimetil Sulfóxido/farmacologia , Concentração de Íons de Hidrogênio , Magnésio/farmacologia , Filtros Microporos , Fosfatos/metabolismo , Fosforilação , RatosRESUMO
The activation of the Ca2+-independent (basal) ATPase from rat skeletal muscle microsomes is demonstrated in the presence of enough Ca2+ to provide the simultaneous activation of the (Ca2+ + Mg2+)-ATPase. It was achieved taking advantage of the delayed inorganic phosphate (Pi) release due to the formation of a phosphoenzyme complex during the Ca2+-dependent enzymatic cycle, which is evidenced in fast experiments. The microsomes were immobilized on a filter and perfused at constant flow with an incubation medium which was briefly interrupted with a pulse of appropriate reactants to activate the ATPases, at 2 degrees C. Successive samples were collected after passing through the filter, at approx. 0.1 s intervals. The Pi effluent profile coincides with the pattern of the pulse when it activates only the Ca2+-independent ATPase, it appears delayed when the pulse activates only extra Pi production by the (Ca2+ + Mg2+)-ATPase, and it includes a rapid and a delayed component when both Ca2+-independent and Ca2+-dependent ATPases are activated simultaneously by the pulse.