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1.
Br J Dermatol ; 172(3): 652-61, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25646772

RESUMO

Vitamin D can be synthesized following exposure to ultraviolet radiation (UVR), ingested in the diet or provided through oral supplementation. The medical literature frequently states that humans obtain most of their vitamin D from sunshine and that UVR exposure is essential to maintain vitamin D levels. A systematic review was conducted to determine the requirement for UVR in maintaining adequate (> 50 nmol L(-1) ) serum 25-hydroxyvitamin D [25(OH)D] levels. Studies reporting serum 25(OH)D during situations of negligible UVR exposure were sought. Forty-one studies (from a search yielding 42 698 articles) with a total of 4211 healthy adults met the inclusion criteria, providing 56 datasets from different population groups. Over 50% of subjects had > 50 nmol L(-1) 25(OH)D in 10 of 19 datasets reporting winter levels in areas with limited UVR. In addition, > 50% of subjects had adequate 25(OH)D levels in four of 12 datasets from polar regions during periods of negligible UVR, one of nine datasets documenting clothing-related minimal UVR and two of eight datasets detailing employment-related minimal UVR. The data demonstrate that many adults maintain adequate serum vitamin D levels despite negligible UVR exposure for several months. However, we acknowledge that preceding UVR exposure leading to vitamin D storage and delayed release may account for this maintenance of adequate serum vitamin D levels. There remains a need for further research on whether UVR exposure is required for longer-term maintenance of adequate vitamin D levels.


Assuntos
Raios Ultravioleta , Deficiência de Vitamina D/prevenção & controle , Vitamina D/análogos & derivados , Vestuário/efeitos adversos , Emprego , Feminino , Humanos , Masculino , Exposição à Radiação , Estações do Ano , Vitamina D/metabolismo , Deficiência de Vitamina D/sangue
2.
Placenta ; 34(12): 1223-31, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24183194

RESUMO

INTRODUCTION: Placental glutamine synthesis has been demonstrated in animals and is thought to increase the availability of this metabolically important amino acid to the fetus. Glutamine is of fundamental importance for cellular replication, cellular function and inter-organ nitrogen transfer. The objective of this study was to investigate the role of glutamate/glutamine metabolism by the isolated perfused human placenta in the provision of glutamine to the fetus. METHODS: Glutamate metabolism was investigated in the isolated dually perfused human placental cotyledon. U-¹³C-glutamate was used to investigate the movement of carbon and ¹5N-leucine to study movement of amino-nitrogen. Labelled amino acids were perfused via maternal or fetal arteries at defined flow rates. The enrichment and concentration of amino acids in the maternal and fetal veins were measured following 5 h of perfusion. RESULTS: Glutamate taken up from the maternal and fetal circulations was primarily converted into glutamine the majority of which was released into the maternal circulation. The glutamine transporter SNAT5 was localised to the maternal-facing membrane of the syncytiotrophoblast. Enrichment of ¹³C or ¹5N glutamine in placental tissue was lower than in either the maternal or fetal circulation, suggesting metabolic compartmentalisation within the syncytiotrophoblast. DISCUSSION: Placental glutamine synthesis may help ensure the placenta's ability to supply this amino acid to the fetus does not become limiting to fetal growth. Glutamine synthesis may also influence placental transport of other amino acids, metabolism, nitrogen flux and cellular regulation. CONCLUSIONS: Placental glutamine synthesis may therefore be a central mechanism in ensuring that the human fetus receives adequate nutrition and is able to maintain growth.


Assuntos
Glutamina/metabolismo , Troca Materno-Fetal , Modelos Biológicos , Placenta/metabolismo , Circulação Placentária , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Transporte Biológico , Isótopos de Carbono , Membrana Celular/metabolismo , Feminino , Desenvolvimento Fetal , Ácido Glutâmico/metabolismo , Humanos , Técnicas In Vitro , Cinética , Leucina/metabolismo , Isótopos de Nitrogênio , Perfusão , Placenta/irrigação sanguínea , Placenta/citologia , Gravidez , Trofoblastos/citologia , Trofoblastos/metabolismo
3.
Eur J Clin Nutr ; 67 Suppl 1: S71-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23299874

RESUMO

BACKGROUND/OBJECTIVES: There is wide variability in the shape and size of an individual and their body composition. This partly reflects inherent genetic differences, but to a large extent is determined by the extent to which their intake of energy and nutrients has adequately matched their needs over extended periods of time. SUBJECTS/METHODS: During childhood, the effective partitioning of nutrients to tissues reflects the hierarchy of demand for growth and maturation during critical periods of development. At all ages, the structural relationships at the molecular, cellular, tissue and whole-body levels are indicative of functional capability and the capacity to cope with internal and external stresses. RESULTS: Reliable measurements of body composition and their interpretation can mark health, be indicative of the risk of ill-health and be a direct cause of pathology and disease. The bioelectrical impedance of the body has been used as an indirect measure for body composition, because it is a reflection of both its structural and functional characteristics, but the specifics of the relationships between these considerations still need to be determined. CONCLUSIONS: The measurement of bioelectrical impedance is simple to carry out and is non-invasive. It could be further refined and developed to fully explore and exploit its potential utility in practice.


Assuntos
Antropometria/métodos , Composição Corporal , Impedância Elétrica , Fenômenos Fisiológicos da Nutrição , Ciências da Nutrição , Projetos de Pesquisa , Estudos de Avaliação como Assunto , Humanos
4.
Dig Dis Sci ; 58(1): 33-41, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22899241

RESUMO

13C-Liver-function breath tests have been used in clinical diagnostics and, to a limited extent, to investigate hepatic function. From a practical perspective, tests such as the 13C-aminopyrine and 13C-methacetin breath tests are simple to administer, safe, and relatively inexpensive to perform. Surprisingly, they have not entered the mainstream of clinical practice, because they are perceived to lack the specificity and adequate precision needed to give accurate results in real time. The dynamic nature of 13C-liver-function breath tests, their possible versatility in terms of assessing a range of different liver functions, and the ease with which they can be repeated to follow relative changes in liver function with time, all imply the potential for wider clinical application. Therefore, there is a need for these tests to be critically evaluated and their potential clinical application be tested systematically against defined objectives. We describe refinements in the methodology of the tests and propose several situations in which currently reliable methods for assessment of liver function do not exist and where 13C-liver-function breath tests might be of use. We propose that use has been constrained by practical methodological considerations which could be addressed to offer tests better suited to routine application in the out-patient or community setting.


Assuntos
Testes Respiratórios/métodos , Hepatopatias/diagnóstico , Testes de Função Hepática/métodos , Fígado/metabolismo , Isótopos de Carbono , Humanos , Fígado/patologia , Hepatopatias/metabolismo
5.
Eur J Clin Nutr ; 64(5): 495-502, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20216560

RESUMO

BACKGROUND/OBJECTIVES: Vitamin B(12) (B(12)) deficiency is common in Indians and a major contributor to hyperhomocysteinemia, which may influence fetal growth, risk of type II diabetes and cardiovascular disease. The purpose of this paper was to study the effect of physiological doses of B(12) and folic acid on plasma total homocysteine (tHcy) concentration. SUBJECTS/METHODS: A cluster randomized, placebo-controlled, double-blind, 2 x 3 factorial trial, using the family as the randomization unit. B(12) was given as 2 or 10 microg capsules, with or without 200 microg folic acid, forming six groups (B(0)F(0), B(2)F(0), B(10)F(0), B(0)F(200), B(2)F(200) and B(10)F(200)). Plasma tHcy concentration was measured before and after 4 and 12 months of supplementation. RESULTS: From 119 families in the Pune Maternal Nutrition Study, 300 individuals were randomized. There was no interaction between B(12) and folic acid (P=0.14) in relation to tHcy concentration change and their effects were analyzed separately: B(0) vs. B(2) vs. B(10); and F(0) vs. F(200). At 12 months, tHcy concentration reduced by a mean 5.9 (95% CI: -7.8, -4.1) micromol/l in B(2), and by 7.1 (95% CI: -8.9, -5.4) micromol/l in B(10), compared to nonsignificant rise of 1.2 (95% CI: -0.5, 2.9) micromol/l in B(0). B(2) and B(10) did not differ significantly. In F(200), tHcy concentration decreased by 4.8 (95% CI: -6.3, -3.3) micromol/l compared to 2.8 (95% CI: -4.3, -1.2) micromol/l in F(0). CONCLUSION: Daily oral supplementation with physiological doses of B(12) is an effective community intervention to reduce tHcy. Folic acid (200 microg per day) showed no additional benefit, neither had any unfavorable effects.


Assuntos
Suplementos Nutricionais , Ácido Fólico/uso terapêutico , Homocisteína/sangue , Hiper-Homocisteinemia/tratamento farmacológico , Deficiência de Vitamina B 12/tratamento farmacológico , Vitamina B 12/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Adulto , Criança , Método Duplo-Cego , Família , Feminino , Ácido Fólico/farmacologia , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/etiologia , Índia , Masculino , Vitamina B 12/farmacologia , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/complicações , Complexo Vitamínico B/farmacologia
6.
Public Health Nutr ; 11(12): 1229-37, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18298884

RESUMO

OBJECTIVE: Women of lower educational attainment have less balanced and varied diets than women of higher educational attainment. The diets of women are vital to the long-term health of their offspring. The present study aimed to identify factors that influence the food choices of women with lower educational attainment and how women could be helped to improve those choices. DESIGN: We conducted eight focus group discussions with women of lower educational attainment to identify these factors. We contrasted the results of these discussions with those from three focus group discussions with women of higher educational attainment. SETTING: Southampton, UK. SUBJECTS: Forty-two white Caucasian women of lower educational attainment and fourteen of higher educational attainment aged 18 to 44 years. RESULTS: The dominant theme in discussions with women of lower educational attainment was their sense that they lacked control over food choices for themselves and their families. Partners and children exerted a high degree of control over which foods were bought and prepared. Women's perceptions of the cost of healthy food, the need to avoid waste, being trapped at home surrounded by opportunities to snack, and having limited skill and experience with food, all contributed to their sense they lacked control over their own and their family's food choices. CONCLUSIONS: An intervention to improve the food choices of women with lower educational attainment needs to increase their sense of control over their diet and the foods they buy. This might include increasing their skills in food preparation.


Assuntos
Comportamento de Escolha , Dieta/normas , Escolaridade , Preferências Alimentares/psicologia , Saúde da Mulher , Adolescente , Adulto , Atitude Frente a Saúde , Comportamento Alimentar , Feminino , Grupos Focais , Humanos , Fenômenos Fisiológicos da Nutrição/fisiologia , Reino Unido , Adulto Jovem
7.
Diabetologia ; 51(1): 29-38, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17851649

RESUMO

AIMS/HYPOTHESIS: Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B12, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years. METHODS: In the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B12, tHcy and methylmalonic acid (MMA) at 18 and 28 weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6 years. RESULTS: Two-thirds of mothers had low vitamin B12 (<150 pmol/l), 90% had high MMA (>0.26 micromol/l) and 30% had raised tHcy concentrations (>10 micromol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28 weeks predicted higher offspring adiposity and higher HOMA-R (both p < 0.01). Low maternal vitamin B12 (18 weeks; p = 0.03) predicted higher HOMA-R in the children. The offspring of mothers with a combination of high folate and low vitamin B12 concentrations were the most insulin resistant. CONCLUSIONS/INTERPRETATION: Low maternal vitamin B12 and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India.


Assuntos
Ácido Fólico/sangue , Vitamina B 12/sangue , Tecido Adiposo/metabolismo , Antropometria , Composição Corporal , Índice de Massa Corporal , Criança , Feminino , Homocisteína/sangue , Humanos , Resistência à Insulina , Masculino , Ácido Metilmalônico/sangue , Gravidez , Complicações na Gravidez
8.
Placenta ; 28(5-6): 445-52, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-16904742

RESUMO

The human fetus requires more glycine than any other amino acid but placental glycine transfer to the fetus is insufficient to meet fetal demand. L-Serine could represent a major metabolic source of glycine for the human fetus but little is known about the kinetics and physiology of L-serine uptake by the human placenta. We have characterised the amino acid transport systems involved in the uptake of L-serine by the microvillous membrane of the human placental syncytiotrophoblast and compared the uptake rates to those of glycine. L-Serine uptake into microvillous membrane (MVM) vesicles was primarily mediated by system A (MeAIB inhibitable) and system L (BCH inhibitable). Further characterisation using specific substrates of LAT1 and LAT2 found the pattern of L-serine uptake was consistent with that expected for uptake mediated by LAT2. Uptakes were performed with tracer levels of (14)C-L-serine, physiological levels of L-serine, or with physiological levels of amino acids. As amino acid concentrations rose, the proportion of uptake by System L decreased while uptake by uncharacterised Na(+)-independent systems increased. Uptake of Lserine into MVM vesicles had a V(max) of 2.1+/-0.4 nmol/mg protein/min, which was significantly higher than for glycine (V(max) 1.0+/-0.2 nmol/mg protein/min). This indicates that MVM vesicles have a higher uptake capacity for L-serine than glycine, despite a greater demand for glycine over serine for fetal protein synthesis. Further studies are now required to define the fate of L-serine taken up by the placenta and its importance for the fetus.


Assuntos
Microvilosidades/metabolismo , Placenta/metabolismo , Serina/metabolismo , Sistema A de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+L de Transporte de Aminoácidos/genética , Transporte Biológico/genética , Feminino , Cadeias Leves da Proteína-1 Reguladora de Fusão/genética , Humanos , Proteínas de Neoplasias/genética , Gravidez , Trocador de Sódio e Cálcio/genética
9.
Arch Dis Child ; 91(8): 706-10, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16861489

RESUMO

Malnutrition (underweight) contributes to approximately 60% of all child deaths, yet health professionals, policy makers, and donor agencies often fail to recognise its relevance to child survival. There is a need for the paediatric community to champion the importance of adequate nutrition for normal growth and development, and of placing sufficient emphasis on the prevention and treatment of malnutrition. Many severely malnourished children die from inappropriate treatment. Case fatality rates of 25-30% are commonly found and in some hospitals as many as 50-70% will die. Many of these deaths are avoidable. Weaknesses in health systems, inappropriate training of doctors and nurses, inadequate supervision, and lack of support for staff all contribute to compromised quality of care. The International Union of Nutritional Sciences, with support from the International Pediatric Association, Launched a global Malnutrition Task Force in 2005. The main objective is to ensure that an integrated system of prevention and treatment of malnutrition is actively supported as a fundamental aspect of care, and becomes an integral part of all training programmes.


Assuntos
Transtornos da Nutrição Infantil/mortalidade , Pediatria , Administração de Caso , Criança , Serviços de Saúde da Criança , Transtornos da Nutrição Infantil/terapia , Previsões , Saúde Global , Humanos , Papel do Médico , Guias de Prática Clínica como Assunto , Prática Profissional , Prognóstico
10.
Eur J Clin Nutr ; 60(2): 197-202, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16278695

RESUMO

OBJECTIVE: To explore the effect of birth weight on urea kinetics in young healthy children. DESIGN: Observational study. SETTING: Tertiary center for treatment of malnutrition. SUBJECTS: A total of 17 male children, 6-24 months old, who had recovered from malnutrition. INTERVENTIONS: Urea kinetics were measured using stable isotope methodology with [(15)N(15)N]-urea over 36 h. RESULTS: Birth weight was negatively related to urea hydrolysis after controlling for the intake of protein (adjusted R (2 ) = 0.91, P = 0.001) and separately for energy intake (adjusted R (2) = 0.95, P = 0.001), age (adjusted R (2) = 0.90, P = 0.001) and rate of weight gain (adjusted R (2) = 0.91, P = 0.001). There was a tendency for higher urea production in the children with lower birth weight after controlling for nitrogen intake (adjusted R (2) = 0.93, P = 0.099), and separately for age (adjusted R (2) = 0.94, P = 0.06) and rate of weight gain (adjusted (R (2) = 0.92, P = 0.096). Urea excretion was not significantly related to birth weight. CONCLUSIONS: The salvaging of urea nitrogen following urea hydrolysis contributed significantly more to the nitrogen economy in children with lower birth weight compared to those with higher birth weight. This may be as a result of reductive adaptation in the children with lower birth weight as a consequence of inappropriate prenatal nutrition and growth.


Assuntos
Peso ao Nascer/fisiologia , Proteínas Alimentares/administração & dosagem , Transtornos da Nutrição do Lactente/dietoterapia , Transtornos da Nutrição do Lactente/urina , Ureia/metabolismo , Adaptação Fisiológica , Fatores Etários , Pré-Escolar , Proteínas Alimentares/farmacocinética , Humanos , Lactente , Cinética , Masculino , Isótopos de Nitrogênio , Ureia/urina , Aumento de Peso/fisiologia
11.
Eur J Appl Physiol ; 94(3): 262-7, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15765242

RESUMO

This study compared protein turnover in ten young female gymnasts [10.3 (0.5) years] engaged in regular intense physical training with ten age-matched controls [9.4 (0.6) years)]. Nitrogen flux ( Q), protein synthesis (PS), protein degradation (PD) and net protein turnover (NPB = PS-PD) were measured following a single oral dose of [(15)N]-glycine. The habitual dietary intake of each subject was assessed using a 7-day food record, with food portions being weighed before ingestion. The gymnasts had a low total energy intake which was unbalanced in the proportions of lipid, carbohydrate and protein. Protein flux was 7.19 (0.35) g.kg(-1).day(-1) in the gymnasts and 7.53 (0.81) g.kg(-1).day(-1) in the controls; protein synthesis was 6.06 (0.27) g.kg(-1).day(-1 )in the gymnasts and 6.53 (0.74) g.kg(-1).day(-1) in the controls; protein degradation was 5.45 (0.38) g.kg(-1).day(-1) in the gymnasts and 5.27 (0.74) g.kg(-1).day(-1) in the controls. All data are presented as means and standard errors of the mean (SEM). There were no statistical differences for protein flux, protein synthesis or protein degradation between the two groups. However, NPB was lower (-14%) in the trained gymnasts than in the control group ( P <0.05), which might be explained by a greater protein ingestion in the control group on the day of the protocol ( P <0.05). These results show that in pre- and early pubertal female gymnasts intense training does not exert a demonstrable effect on protein turnover.


Assuntos
Ginástica/fisiologia , Educação Física e Treinamento , Proteínas/metabolismo , Puberdade/fisiologia , Criança , Ingestão de Energia , Feminino , Humanos
12.
J Physiol ; 554(Pt 2): 497-504, 2004 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-14578485

RESUMO

Protein restriction in rat pregnancy programmes the development of elevated systolic blood pressure and vascular dysfunction in the offspring. A recent study has shown that hypertension is reversed by maternal glycine supplementation. Whether this protective effect is exerted directly on the embryo and fetus, or indirectly via effects on the mother, is unknown although we have previously shown abnormalities in the maternal vasculature. We tested the hypothesis that dietary glycine repletion would reverse endothelial dysfunction in protein-restricted pregnant rat dams using wire myography. Impaired acetylcholine- (P < 0.01) and isoprenaline-induced (P < 0.05) vasodilatation in isolated mesenteric arteries (MA) from protein-restricted pregnant dams was accompanied by reduced vascular nitric oxide (NO) release (P < 0.05). Dietary glycine supplementation reversed vascular dysfunction in MA (P < 0.05) and improved NO release thus potentially protecting the maternal circulation. The impaired NO release in the MA of low protein diet dams was not accompanied by reduced eNOS mRNA expression, suggesting that eNOS activity was altered. Protein restriction did not alter the vascular function of a conduit artery, the thoracic aorta. These results provide evidence that adequate provision of glycine, a conditionally essential amino acid in pregnancy, may play a role in the vascular adaptations to pregnancy, protecting the fetus from abnormal programming of the cardiovascular system.


Assuntos
Dieta com Restrição de Proteínas/efeitos adversos , Glicina/uso terapêutico , Doenças Vasculares/dietoterapia , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Proteínas Alimentares/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Glicina/farmacologia , Técnicas In Vitro , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Óxido Nítrico Sintase/fisiologia , Óxido Nítrico Sintase Tipo III , Gravidez , Ratos , Ratos Wistar , Doenças Vasculares/fisiopatologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
13.
J Thromb Haemost ; 1(10): 2179-85, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14521602

RESUMO

AIMS: The aim of this study was to investigate associations between coronary heart disease risk and polymorphisms in the coagulation factor (F)VII gene in participants of a large prospective study. METHODS: One thousand nine hundred and fifty-seven men were genotyped for four FVII polymorphisms, -670A-->C, -402G-->A, a 10 base pair insertion at -323 (0 > 10) in the promoter, and R353Q in the structural gene. Associations among genotypes and estimated haplotypes, plasma FVII levels, and coronary heart disease risk were evaluated, and the function of the promoter polymorphisms was assessed in reporter gene assays. RESULTS: The -670A-->C and -402G-->A polymorphisms were in complete allelic association. The haplotype containing -670C and -402A (frequency =0.23) was associated with significantly increased plasma FVII coagulant activity and increased risk of an initial coronary event, particularly acute myocardial infarction, which remained after correction for conventional risk factors. In contrast, the -323 insertion and Q353 alleles (frequency =0.11 and 0.10, respectively) were associated with decreased plasma FVII levels, but hazard ratios for coronary events in carriers of these alleles were not significantly different from unity. In transiently transfected hepatoma cells, increased basal expression of the reporter gene was directed by a promoter fragment with rare haplotype -670C/-630G/-402A rather than by a promoter fragment with common haplotype -670A/-630A/-402G; -402A was not responsible for this effect. CONCLUSIONS: The promoter haplotype, -670C/-630G/402A, was associated with significantly increased plasma FVII coagulant activity, risk of an initial coronary event, particularly acute myocardial infarction, and reporter gene expression.


Assuntos
Doença das Coronárias/genética , Fator VII/genética , Alelos , Carcinoma Hepatocelular/metabolismo , Células Cultivadas , Éxons , Fator VII/biossíntese , Genes Reporter , Genótipo , Haplótipos , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Modelos de Riscos Proporcionais , Risco , Transfecção
14.
J Thromb Haemost ; 1(6): 1220-7, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12871323

RESUMO

Factor (F)VII plays a critical role in initiation of coagulation. Several segments within the 5' flanking region of the FVII gene were previously demonstrated to recognize hepatic nuclear proteins, but few have been identified. To identify a regulatory protein binding the nuclear hormone response region (-237 to -200) of the FVII 5' flanking region and demonstrate that the interaction is functional. Electrophoretic mobility shift assays and mutation analysis showed that ARP1, an orphan nuclear hormone receptor, interacted with two regions of the FVII 5' flanking region, the hepatic nuclear factor 4 binding region (-77 to -47) and the nuclear hormone response region (-237 to -200). Transfection experiments demonstrated that reporter gene expression was decreased from vectors including the nuclear hormone response segment compared with that containing only the minimal promoter between positions -109 and +1, and that ARP1 also repressed expression through an interaction with the minimal promoter. These data indicate a role for ARP1 in transcriptional modulation of the FVII gene.


Assuntos
Região 5'-Flanqueadora/genética , Proteínas de Ligação a DNA/metabolismo , Fator VII/genética , Receptores de Esteroides , Fatores de Transcrição/metabolismo , Transcrição Gênica/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Sítios de Ligação , Fator II de Transcrição COUP , Fatores de Transcrição COUP , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/fisiologia , Genes Reporter , Fator 4 Nuclear de Hepatócito , Humanos , Fosfoproteínas/genética , Regiões Promotoras Genéticas , Receptores de Glucocorticoides/genética , Elementos de Resposta , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Transfecção
15.
Eur J Clin Nutr ; 57(1): 69-74, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12548299

RESUMO

OBJECTIVES: To establish the prevalence of the risk of undernutrition, using criteria similar to those used by the Malnutrition Advisory Group (MAG), in people aged 65 y and over, and to identify relationships between risk of undernutrition and health and demographic characteristics. DESIGN: A cross-sectional nationally representative sample of free-living and institutionalized older people in the UK (65 y of age and over). Secondary analysis of the National Diet and Nutrition Survey based on 1368 people aged 65 y and over. RESULTS: About 14% (21% in those living in institutions) were at medium or high risk of undernutrition based on a composite measure of low body mass index and recent reported weight loss. Having a long-standing illness was associated with a statistically significantly increased risk of undernutrition (odds ratio: men 2.34, 95% CI 1.20-4.58; women 2.98; 1.58-5.62). The risk of undernutrition increased: in women reporting bad or very bad health status; in men living in northern England and Scotland; for those aged 85 y and older; for those hospitalized in the last year, and those living in an institution. Lower consumption of energy, meat products or fruit and vegetables and lower blood measures of zinc, vitamins A, D, E and C were associated with statistically significantly increased risk of undernutrition. CONCLUSIONS: A substantial proportion of the older population of the UK is at risk of undernutrition. High-risk subjects are more likely to have poorer health status. It is unlikely that the individuals at high risk are being detected currently, and therefore effective care is not being provided, either in the community or in institutions.


Assuntos
Nível de Saúde , Distúrbios Nutricionais/epidemiologia , Estado Nutricional , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Doença Crônica/epidemiologia , Estudos Transversais , Feminino , Avaliação Geriátrica , Inquéritos Epidemiológicos , Humanos , Masculino , Distúrbios Nutricionais/sangue , Distúrbios Nutricionais/etiologia , Inquéritos Nutricionais , Razão de Chances , Prevalência , Fatores de Risco , Reino Unido/epidemiologia
17.
Arch Dis Child ; 87(6): 522-5, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12456554

RESUMO

BACKGROUND: Diets rich in lipid are used to provide energy density in treating children with severe malnutrition, but the extent to which their digestion and absorption can cope with the load effectively is uncertain. AIM: To determine the extent of impaired digestion or absorption, in three groups of eight malnourished children (aged 5-23 months) using isotopic probes of the predominant fatty acids in coconut and corn oil used to fortify the diet. METHODS: Each child received oral doses of one of three (13)C labelled triglycerides (trilaurin, triolein, or trilinolein). The recovery of (13)C label in stool either as triglyceride (TAG) or fatty acid (FA), was used to assess digestion and absorption. In a separate test, the recovery of label in stool following an oral dose of [(13)C]-glycocholate was measured to assess bile salt malabsorption. RESULTS: The median recovery of label in stool was 9% (range 1-29%) of administered dose. Following treatment there was a reduction in stool (13)C excretion for the labelled TAG (<1%). In half the subjects, label was recovered as TAG in stool (median 0.6%, range 0-44%). Most label in stool was recovered as FA (median 30%, range 0-100%). Following [(13)C]-glycocholate, label was recovered in excess in about one third of studies. CONCLUSION: Abnormalities in the gastrointestinal handling of lipid were observed in over 50% of children with severe malnutrition, reflecting problems in absorption, although impaired solubilisation or hydrolysis could also be contributory factors. The underlying lesion improves as treatment progresses, leading to concomitant improvement in function.


Assuntos
Dieta , Digestão/fisiologia , Transtornos da Nutrição do Lactente/metabolismo , Metabolismo dos Lipídeos , Síndromes de Malabsorção/metabolismo , Isótopos de Carbono , Sistema Digestório/metabolismo , Ácidos Graxos/metabolismo , Ácido Glicocólico/metabolismo , Humanos , Lactente , Triglicerídeos/metabolismo
18.
J Epidemiol Community Health ; 56(9): 684-7, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12177085

RESUMO

OBJECTIVE: To assess differences in birth weight between all first and second generation South Asian babies born in Southampton, and trends since 1957. DESIGN: Retrospective, cohort study. SETTING: Birth records for babies born in Southampton from 1957 to 1996 were searched to identify all babies born of South Asian origin (including from the Indian subcontinent, East Africa, and elsewhere). MAIN OUTCOME MEASURES: All information recorded in the birth record about the mother and baby was extracted. RESULTS: 2395 full term (>37 weeks; mean birth weight 3110; 95%CI 3092 to 3129) singleton births were identified. Detailed analysis was restricted to mothers either born in the Indian subcontinent (India, Pakistan, or Bangladesh (1435)) or United Kingdom (283). Mean birth weight and % low birth weight (<2500 g) were 3133 g (95%CI 3108 to 3157) and 7.5%, for first generation babies and 3046 g (2992 to 3099) and 11.7% for second generation babies. There was no trend over time to increased average birth weight in either first or second generation babies. Adjusting for other factors that were statistically significantly related to birth weight (gender, gestational age, mother's age, maternal weight at 15 weeks, parity, and mother's ethnic group) did not alter the trends. CONCLUSIONS: For that group in the UK who derive from the Indian subcontinent, average birth weight is significantly less than the national average. There has not been any increase in the average birth weight over the past 40 years, and the birth weight of babies of women who were born in the UK are no greater. The persistence of lower than desirable birth weight may result long term in higher than average rates of diabetes and heart disease in these groups.


Assuntos
Peso ao Nascer , Etnicidade , Recém-Nascido de Baixo Peso , Adulto , Antropometria , Sudeste Asiático/etnologia , Inglaterra/epidemiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Paridade , Gravidez , Estudos Retrospectivos
19.
Proc Nutr Soc ; 61(1): 131-6, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12002787

RESUMO

Chronic infection with HIV type 1 is associated with alterations in macronutrient metabolism, specifically elevated plasma lipids, glucose and reduced insulin sensitivity. These alterations are most severe in patients at the later stages of AIDS, indicating a relationship with disease progression. Recently, a metabolic syndrome, termed lipodystrophy, has been described in successfully-treated HIV patients in whom the altered macronutrient metabolism of HIV infection appears to be amplified markedly, with concurrent alterations in adipose tissue patterning. This syndrome presents a paradox, as before the development of highly-active antiretroviral therapy (HAART) the most severe perturbations in metabolism were observed in the sickest patients. Now, the patients that respond well to therapy are showing metabolic perturbations much greater than those seen before. The implications of this syndrome are that, whilst life expectancy may be increased by reducing viral load, there are concomitant increases in the risk of cardiovascular disease, diabetes and pancreatitis within this patient population. The aetiology of the syndrome remains unclear. In a collaborative trial with the Chelsea and Westminster Hospital in London we have used stable-isotope-labelled fatty acids to examine the hypothesis that treatment with HAART causes a delayed clearance of dietary lipid from the circulation, resulting in the retention of lipid within plasma and the downstream changes in insulin and glucose homeostasis. This hypothesis would indicate a role for low-fat diets, exercise and drugs that reduce plasma lipid or insulin resistance, in modulating the response to antiretroviral therapy in HIV infection.


Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Gorduras na Dieta/metabolismo , Infecções por HIV/tratamento farmacológico , Lipodistrofia/induzido quimicamente , Gorduras na Dieta/farmacocinética , Progressão da Doença , Infecções por HIV/metabolismo , Humanos , Lipodistrofia/fisiopatologia , Síndrome , Carga Viral
20.
West Indian med. j ; 50(4): 282-287, Dec. 2001.
Artigo em Inglês | LILACS | ID: lil-333339

RESUMO

In Trinidad and Tobago, cardiovascular disease and Type 2 diabetes mellitus are important causes of morbidity and mortality, and birth weight is significantly less than reference standards. Lower birth weight is associated with increased risk of these diseases. Variation in birth weight is due, in part, to deposition of adipose tissue in the foetus during the last trimester at the same time that maternal plasma triacylglycerol (TAG) increases. We conducted a pilot cross-sectional analysis of maternal plasma lipid status and birth weight in healthy, non-pregnant, primigravida Trinidadian women. Non-pregnant and pregnant women, in their second and third trimesters, and at term, were recruited at random from an antenatal clinic. Adult and umbilical cord plasma TAG, non-esterified fatty acids (NEFA) and phosphatidylcholine (PC) concentrations were determined from gas chromatographic analysis of fatty acids. Maternal height, weight, skinfold thickness and infant birth weight were measured. The infants born to Afro-Trinidadian and Indo-Trinidadian women were of low to normal birth weight (medians 3.07 and 3.22 kg, respectively). At term, plasma TAG concentration was approximately two fold (p < 0.05) greater than for non-pregnant women. The increment between 30-34 weeks was 1.5 to 1.9 fold lower than reported in other populations. There was a strong relationship (r = 0.8771, p = 0.019) between maternal and cord plasma TAG and NEFA, but not PC concentrations. There was no significant relationship between maternal TAG concentration at term and birth weight. The result suggests an impaired ability to increase plasma TAG concentrations during late gestation.


Assuntos
Adulto , Feminino , Humanos , Gravidez , Lipídeos/sangue , Fosfatidilcolinas , Trinidad e Tobago , Peso ao Nascer , Gravidez , Projetos Piloto , Estudos Transversais , Idade Gestacional , População Negra , População Branca , Sangue Fetal , Ácidos Graxos Insaturados/sangue , Triglicerídeos/sangue
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