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2.
Acta Physiol (Oxf) ; 213(2): 519-36, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25204637

RESUMO

AIM: To determine whether late gestation under- and overnutrition programme metabolic plasticity in a similar way, and whether metabolic responses to an obesogenic diet in early post-natal life depend on the foetal nutrition history. METHODS: In a 3 × 2 factorial design, twin-pregnant ewes were for the last 6 weeks of gestation (term = 147 days) assigned to HIGH (N = 13; 150 and 110% of energy and protein requirements, respectively), NORM (N = 9; 100% of requirements) or LOW (N = 14; 50% of requirements) diets. The twin offspring were raised on high-carbohydrate-high-fat (HCHF; N = 35) or conventional (CONV; N = 35) diets from 3 days to 6 months of age (around puberty). Then intravenous glucose (GTT; overnight fasted), insulin (ITT; fed) and propionate (gluconeogenetic precursor; PTT; both fed and fasted) tolerance tests were conducted to evaluate (hepatic) metabolic plasticity. RESULTS: Prenatal malnutrition differentially impacted adaptations of particularly plasma lactate followed by glucose, cholesterol and insulin. This was most clearly expressed during PTT in fasted lambs and much less during ITT and GTT. In fasted lambs, propionate induced more dramatic increases in lactate than glucose, and HIGH lambs became more hyperglycaemic, hyperlactataemic and secreted less insulin compared to the hypercholesterolaemic LOW lambs. Propionate-induced insulin secretion was virtually abolished in fasted HCHF lambs, but upregulated in fasted compared to fed CONV lambs. HCHF lambs had the greatest glucose-induced insulin secretory responses. CONCLUSION: Prenatal malnutrition differentially programmed glucose-lactate metabolic pathways and cholesterol homeostasis. Prenatal overnutrition predisposed for hyperglycaemia and hyperlactataemia, whereas undernutrition predisposed for hypercholesterolaemia upon exposure to an obesogenic diet. Prenatal overnutrition (not undernutrition) interfered with pancreatic insulin secretion by non-glucose-dependent mechanisms.


Assuntos
Dieta , Glucose/metabolismo , Hiperglicemia/metabolismo , Insulina/sangue , Ácido Láctico/metabolismo , Hipernutrição/metabolismo , Efeitos Tardios da Exposição Pré-Natal , Adaptação Fisiológica/fisiologia , Envelhecimento , Animais , Jejum/metabolismo , Feminino , Período Pós-Parto , Gravidez , Ovinos
3.
Eur Heart J ; 36(46): 3268-3275, 2015.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1062613

RESUMO

AIM:To assess clinical outcomes, efficacy, and safety according to sex during anticoagulation with apixaban compared with warfarin in patients with atrial fibrillation.METHODS AND RESULTS:Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) was a randomized, double-blind, placebo-controlled, multicentre trial that included 11 785 (64.7%) men and 6416 (35.3%) women with atrial fibrillation or flutter randomized to receive either warfarin or apixaban. The primary efficacy endpoint was stroke or systemic embolism; secondary efficacy endpoints were death from any cause and cardiovascular death. The primary safety endpoint was major bleeding; secondary safety endpoints were a composite of major bleeding and non-major clinically relevant bleeding. The risk of stroke or systemic embolism was similar in women vs. men [adjusted hazard ratio (adjHR): 0.91; 95% confidence interval (CI): 0.74-1.12; P = 0.38]. However, among patients with history of stroke or transient ischaemic attack, women had a lower risk of recurrent stroke compared with men (adjHR: 0.70; 95% CI: 0.50-0.97; P = 0.036). Women also had a lower risk of all-cause death (adjHR: 0.63; 95% CI: 0.55-0.73; P < 0.0001) and cardiovascular death (adjHR: 0.62; 95% CI: 0.51-0.75; P < 0.0001), and a trend towards less major bleeding (adjHR: 0.86; 95% CI: 0.74-1.01; P = 0.066) and major or non-major clinically relevant bleeding (adjHR: 0.89; 95% CI: 0.80-1.00; P = 0.049). The efficacy and safety benefits of apixaban compared with warfarin were consistent regardless of sex.CONCLUSION:In the ARISTOTLE trial, women had a similar rate of stroke or systemic embolism but a lower risk of mortality and less clinically relevant bleeding than men. The efficacy and safety benefits of apixaban compared with warfarin were consistent in men and women...


Assuntos
Acidente Vascular Cerebral/prevenção & controle , Anticoagulantes , Fibrilação Atrial , Sexo , Varfarina
4.
J Thromb Haemost ; 12(9): 1401-12, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24942912

RESUMO

BACKGROUND: D-dimer is related to adverse outcomes in arterial and venous thromboembolic diseases. OBJECTIVES: To evaluate the predictive value of D-dimer level for stroke, other cardiovascular events, and bleeds, in patients with atrial fibrillation (AF) treated with oral anticoagulation with apixaban or warfarin; and to evaluate the relationship between the D-dimer levels at baseline and the treatment effect of apixaban vs. warfarin. METHODS: In the ARISTOTLE trial, 18 201 patients with AF were randomized to apixaban or warfarin. D-dimer was analyzed in 14 878 patients at randomization. The cohort was separated into two groups; not receiving vitamin K antagonist (VKA) treatment and receiving VKA treatment at randomization. RESULTS: Higher D-dimer levels were associated with increased frequencies of stroke or systemic embolism (hazard ratio [HR] [Q4 vs. Q1] 1.72, 95% confidence interval [CI] 1.14-2.59, P = 0.003), death (HR [Q4 vs. Q1] 4.04, 95% CI 3.06-5.33) and major bleeding (HR [Q4 vs. Q1] 2.47, 95% CI 1.77-3.45, P < 0.0001) in the no-VKA group. Similar results were obtained in the on-VKA group. Adding D-dimer level to the CHADS2 score improved the C-index from 0.646 to 0.655 for stroke or systemic embolism, and from 0.598 to 0.662 for death, in the no-VKA group. D-dimer level improved the HAS-BLED score for prediction of major bleeds, with an increase in the C-index from 0.610 to 0.641. There were no significant interactions between efficacy and safety of study treatment and D-dimer level. CONCLUSION: In anticoagulated patients with AF, the level of D-dimer is related to the risk of stroke, death, and bleeding, and adds to the predictive value of clinical risk scores. The benefits of apixaban were consistent, regardless of the baseline D-dimer level.


Assuntos
Fibrilação Atrial/complicações , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Tromboembolia/sangue , Administração Oral , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/sangue , Estudos de Coortes , Embolia/sangue , Feminino , Fibrinolíticos/química , Hemorragia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/sangue , Resultado do Tratamento , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem , Varfarina/uso terapêutico
5.
Acta Physiol (Oxf) ; 210(1): 110-26, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23746217

RESUMO

AIM: To investigate if late gestation under- or overnutrition has similar adverse impacts on visceral adiposity, metabolic and endocrine function in sheep, and if subsequent exposure to a high-fat diet in early post-natal life exaggerates the prenatal programming outcomes later in life. METHODS: Thirty-six twin-pregnant ewes were fed a NORM (fulfilling 100% of daily requirements for energy and protein), LOW (50% of NORM) or HIGH diet (150% of energy and 110% of protein requirements) during the last 6 weeks of gestation (term = 147 days). Post-natally, the twin lambs were subjected to a high-fat or a moderate diet until 6 months of age (around puberty), where metabolic and endocrine adaptability to fasting was examined, and subgroups of animals were killed. RESULTS: Animals exposed to either prenatal under- or overnutrition had reduced subcutaneous fat deposition when fed a high-fat diet, resulting in higher ratios of mesenteric and peri-renal fat relative to subcutaneous fat compared to controls. This was not related to prenatal influences on plasma glucose or insulin. Irrespective of the prenatal diet, high-fat-fed lambs underwent changes resembling the metabolic syndrome with higher plasma glucose, cholesterol, non-esterified fatty acids, triglyceride and lactate combined with abdominal obesity. Peri-renal fat appeared to be a particular target of a high-fat diet post-natally. CONCLUSION: Both prenatal under- and overnutrition predisposed for abdominal adiposity, apparently by reducing the expandability of subcutaneous adipose tissue and induced differential physiological adaptations to fasting. This study does not suggest that exposure to gestational overnutrition will provide a protective effect against development of hyperglycaemia later in life.


Assuntos
Envelhecimento/metabolismo , Jejum/metabolismo , Transtornos da Nutrição Fetal/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Gordura Intra-Abdominal/metabolismo , Hipernutrição/metabolismo , Adaptação Fisiológica , Animais , Feminino , Idade Gestacional , Resistência à Insulina , Gravidez , Ovinos
6.
Acta Physiol (Oxf) ; 210(1): 84-98, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23452307

RESUMO

AIM: Exposure to adverse intra-uterine conditions can predispose for metabolic disorders later in life. By using a sheep model, we studied (i) how programming of glucose-insulin homoeostasis during late gestation is manifested later in life depending on the early post-natal dietary exposure and (ii) whether dietary alteration in obese individuals can prevent adverse outcomes of early life programming. METHODS: During late gestation, twin-pregnant sheep were fed 100% (NORM) or 50% (LOW) of energy and protein requirements. After birth, offspring were exposed to a moderate (CONV) or high-carbohydrate-high-fat (HCHF) diet until around puberty. Offspring remaining thereafter (exclusively females) were fed a moderate diet until young adulthood. RESULTS: LOW lambs had increased insulin secretory responses during intravenous glucose tolerance tests indicative of reduced insulin sensitivity. HCHF lambs were hypertriglyceridaemic, 75% had mild pancreatic collagen infiltration, and their acute insulin secretory response and insulin clearance during intravenous glucose and insulin tolerance tests, respectively, were reduced. However, NORM-HCHF in contrast to LOW-HCHF lambs had normal glucose tolerance, indicating that later health outcomes are highly influenced by pre-natal nutrition. Dietary alteration normalized glucose-insulin homoeostasis in adult HCHF females, whereas late-gestation undernutrition (LOW) permanently depressed insulin sensitivity. CONCLUSION: Maintenance of glucose tolerance in sheep exposed to pre-natal undernutrition relied on pancreatic hypersecretion of insulin to compensate for reduced insulin sensitivity. A mismatching high-fat diet in early post-natal life interfered with this pancreatic hypersecretion resulting in reduced glucose tolerance. Early post-natal, but not late pre-natal, impacts on glucose-insulin homoeostasis could be reversed by dietary correction later in life.


Assuntos
Envelhecimento/metabolismo , Glicemia/metabolismo , Insulina/sangue , Desnutrição/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Medicina Baseada em Evidências , Feminino , Homeostase , Resistência à Insulina , Desnutrição/embriologia , Modelos Animais , Gravidez , Ovinos
7.
Food Chem ; 141(3): 2812-20, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23871028

RESUMO

Novel procedures for analytical authentication of organic plant products are urgently needed. Here we present the first study encompassing stable isotopes of hydrogen, carbon, nitrogen, oxygen, magnesium and sulphur as well as compound-specific nitrogen and oxygen isotope analysis of nitrate for discrimination of organically and conventionally grown plants. The study was based on wheat, barley, faba bean and potato produced in rigorously controlled long-term field trials comprising 144 experimental plots. Nitrogen isotope analysis revealed the use of animal manure, but was unable to discriminate between plants that were fertilised with synthetic nitrogen fertilisers or green manures from atmospheric nitrogen fixing legumes. This limitation was bypassed using oxygen isotope analysis of nitrate in potato tubers, while hydrogen isotope analysis allowed complete discrimination of organic and conventional wheat and barley grains. It is concluded, that multi-isotopic analysis has the potential to disclose fraudulent substitutions of organic with conventionally cultivated plants.


Assuntos
Grão Comestível/química , Alimentos Orgânicos/análise , Isótopos/análise , Plantas/química , Verduras/química , Fertilizantes/análise , Agricultura Orgânica
8.
Thromb Haemost ; 109(5): 769-86, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23636477

RESUMO

Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Cardiologia/normas , Cardiopatias/tratamento farmacológico , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/tratamento farmacológico , Anticoagulantes/efeitos adversos , Fibrilação Atrial/sangue , Fibrilação Atrial/tratamento farmacológico , Vias de Administração de Medicamentos , Cardiopatias/sangue , Cardiopatias/diagnóstico , Implante de Prótese de Valva Cardíaca/normas , Humanos , Intervenção Coronária Percutânea/normas , Resultado do Tratamento
10.
Methods Mol Biol ; 953: 121-41, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23073880

RESUMO

Plant tissue analysis is a valuable tool for evaluating the nutritional status and quality of crops and is widely used for scientific and commercial purposes. The majority of plant analyzes are now performed by techniques based on ICP spectrometry such as inductively coupled plasma-optical emission spectroscopy (ICP-OES) or ICP-mass spectrometry (ICP-MS). These techniques enable fast and accurate measurements of multielement profiles when combined with appropriate methods for sample preparation and digestion. This chapter presents state-of-the-art methods for digestion of plant tissues and subsequent analysis of their multielement composition by ICP spectrometry. Details on upcoming techniques, expected to gain importance within the field of multielement plant tissue analysis over the coming years, are also provided. Finally, attention is given to laser ablation ICP-MS (LA-ICP-MS) for multielement bioimaging of plant tissues. The presentation of the methods covers instructions on all steps from sampling and sample preparation to data interpretation.


Assuntos
Elementos Químicos , Especificidade de Órgãos , Plantas/metabolismo , Espectrofotometria Atômica/métodos , Micro-Ondas , Pressão , Estatística como Assunto
11.
Br J Nutr ; 109(11): 2098-110, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23069212

RESUMO

We have developed a sheep model to facilitate studies of the fetal programming effects of mismatched perinatal and postnatal nutrition. During the last trimester of gestation, twenty-one twin-bearing ewes were fed a normal diet fulfilling norms for energy and protein (NORM) or 50% of a normal diet (LOW). From day 3 postpartum to 6 months (around puberty) of age, one twin lamb was fed a conventional (CONV) diet and the other a high-carbohydrate-high-fat (HCHF) diet, resulting in four groups of offspring: NORM-CONV; NORMHCHF; LOW-CONV; LOW-HCHF. At 6 months of age, half of the lambs (all males and three females) were slaughtered for further examination and the other half (females only) were transferred to a moderate sheep diet until slaughtered at 24 months of age (adulthood). Maternal undernutrition during late gestation reduced the birth weight of LOW offspring (P<0·05), and its long-term effects were increased adrenal size in male lambs and adult females (P<0·05), increased neonatal appetite for fat-(P=0·004) rather than carbohydrate-rich feeds (P<0·001) and reduced deposition of subcutaneous fat in both sexes (P<0·05). Furthermore, LOW-HCHF female lambs had markedly higher visceral:subcutaneous fat ratios compared with the other groups (P<0·001). Postnatal overfeeding (HCHF) resulted in obesity (.30% fat in soft tissue) and widespread ectopic lipid deposition. In conclusion, our sheep model revealed strong pre- and postnatal impacts on growth, food preferences and fat deposition patterns. The present findings support a role for subcutaneous adipose tissue in the development of visceral adiposity, which in humans is known to precede the development of the metabolic syndrome in human adults.


Assuntos
Ingestão de Alimentos , Preferências Alimentares , Desnutrição/complicações , Fenômenos Fisiológicos da Nutrição Materna , Obesidade Abdominal/etiologia , Complicações na Gravidez , Envelhecimento , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Peso ao Nascer , Dieta/veterinária , Feminino , Masculino , Modelos Animais , Gravidez , Ovinos
12.
Methods Mol Biol ; 860: 193-211, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22351179

RESUMO

Trace elements are unevenly distributed and speciated throughout the cereal grain. The germ and the outer layers of the grain have the highest concentrations of trace elements. A large fraction of the trace elements is therefore lost during the milling process. The bioavailability of the remaining trace elements is very low. This is usually ascribed to the formation of poorly soluble complexes with the phosphorus storage compound phytic acid. Hence, analysis of the total concentration of trace elements in grain tissues must be combined with a speciation analysis in order to assess their contribution to human nutrition. This chapter deals with the fractionation of anatomically very different cereal tissues. Procedures for microscaling of digestion procedures are outlined together with requirements for the use of certified reference materials in elemental profiling of grain tissue fractions. Methods for extraction and analysis of complexes containing trace elements in the grain tissue fractions are described. Finally, the chapter concludes with criteria for choice of chromatographic methods and setting of ICP-MS instrument parameters.


Assuntos
Cromatografia Líquida/métodos , Grão Comestível/química , Espectrometria de Massas/métodos , Espectrofotometria Atômica/métodos , Oligoelementos/análise
13.
Fundam Clin Pharmacol ; 25(5): 564-71, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21077944

RESUMO

Antiplatelet agents play an essential role in the treatment of acute coronary syndrome (ACS). Numerous clinical trials have established the value of antiplatelet therapies for ACS. Aspirin (ASA), thienopyridines and GP IIb/IIIa antagonists comprise the major classes of antiplatelet therapies demonstrated to be of benefit in the treatment of ACS. Thienopyridines are a class of drugs that function via inhibition of the adenosine diphosphate (ADP) P2Y12 platelet receptors. Currently, clopidogrel, a second generation thienopyridine, is the main drug of choice and the combination of aspirin and clopidogrel is administered orally for the treatment of ACS. Recently, a third generation of thienopyridines has been introduced represented by prasugrel that has demonstrated promising results in ACS patients treated with percutaneous coronary intervention (PCI). A number of nonthienopyridine oral antiplatelet drugs are under development, and one of them, ticagrelor has already been tested in a major phase III clinical trial, PLATO, with the inclusion of a broad spectrum of patients with ACS. The present review aims to discuss the present knowledge about the safety and efficacy of oral antiplatelet treatment of patients with ACS.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2/farmacologia , Antagonistas do Receptor Purinérgico P2/uso terapêutico , Síndrome Coronariana Aguda/fisiopatologia , Administração Oral , Plaquetas/fisiologia , Ensaios Clínicos como Assunto , Humanos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Antagonistas do Receptor Purinérgico P2/administração & dosagem , Antagonistas do Receptor Purinérgico P2/efeitos adversos , Tienopiridinas/administração & dosagem , Tienopiridinas/efeitos adversos , Tienopiridinas/farmacologia , Tienopiridinas/uso terapêutico
14.
Int J Clin Pract ; 63(4): 667-70, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19335707

RESUMO

AZD6140, the first reversible oral P2Y(12) receptor antagonist, exhibits greater and more consistent inhibition of platelet aggregation than the irreversible thienopyridine clopidogrel. As a result of its reversible effect, AZD6140 may pose less risk for bleeding when antiplatelet treatment cannot be stopped at least 5 days before coronary artery bypass graft (CABG) surgery or other invasive procedures. The Dose conflrmation Study assessing anti-Platelet Effects of AZD6140 vs. clopidogRel in NSTEMI (DISPERSE2) trial showed overall comparable bleeding rates with antiplatelet treatment with AZD6140 90 mg twice daily or 180 mg twice daily vs. clopidogrel 75 mg once daily in 984 patients with non-ST-elevation acute coronary syndromes. A post hoc exploratory analysis of bleeding outcomes in the subset of 84 patients undergoing CABG in DISPERSE2 suggests reduced risk for total bleeding (41% and 58% vs. 62%), all major bleeding (38% and 50% vs. 62%), and life-threatening bleeding (22% and 38% vs. 54%) with AZD6140 90 mg (n = 32) and 180 mg (n = 26) vs. clopidogrel (n = 26) respectively. Trends suggested that major bleeding rates were reduced with AZD6140 (combined groups) vs. clopidogrel when treatment was stopped < or = 5 days prior to surgery (39% vs. 63%, p = 0.15) but not when treatment was stopped > 5 days before surgery (50% vs. 60%). This observation is consistent with the reversible binding of AZD6140 to the P2Y(12) receptor. Further prospective studies are planned to assess the relationship between this potential clinical benefit of AZD6140 and the reversibility of its antiplatelet effects.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Adenosina/análogos & derivados , Hemorragia/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Síndrome Coronariana Aguda/complicações , Adenosina/efeitos adversos , Adenosina/uso terapêutico , Idoso , Ensaios Clínicos como Assunto , Clopidogrel , Ponte de Artéria Coronária , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Fatores de Risco , Ticagrelor , Ticlopidina/efeitos adversos , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Resultado do Tratamento
15.
Domest Anim Endocrinol ; 34(4): 419-31, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18289824

RESUMO

This study investigated whether undernutrition (UN) during late fetal life can programme the subsequent adult life adaptation of glucose homeostasis and metabolism during pregnancy and lactation. Twenty-four primiparous experimental ewes were used. Twelve had been exposed to a prenatal NORM level of nutrition (maternal diet approximately 15 MJME/d) and 12 to a LOW level of nutrition (maternal diet approximately 7 MJME/d) during the last 6 weeks pre-partum. The experimental ewes were subjected to two intravenous glucose tolerance tests (IGTT) in late gestation (one prior to (G-IGTT) and one by the end of a feed restriction period (RG-IGTT)), and a third around peak lactation (L-IGTT). LOW had lower basal insulin concentrations during lactation, and significantly decreased absolute insulin secretion during the L-IGTT in spite of similar glucose tolerance, indicating increased insulin sensitivity in LOW during lactation. There was no effect of prenatal UN on glucose tolerance during G-IGTT, however, during RG-IGTT LOW was more glucose intolerant and apparently more insulin resistant compared to NORM. In conclusion, UN during late fetal life in sheep impairs subsequent pancreatic insulin secretory capacity during adult life, and reduces plasticity of down-regulation of insulin secretion in response to a metabolic challenge. Furthermore, prenatal UN appears to programme mechanisms, which in young adult females can shift the insulin hypersensitivity observed during early lactation into an insulin resistance observed during late gestation and feed restriction. Early postnatal UN caused by lowered milk intake in early postnatal life may have contributed to these phenomena.


Assuntos
Adaptação Fisiológica , Glucose/metabolismo , Lactação/metabolismo , Prenhez , Gravidez/metabolismo , Fenômenos Fisiológicos da Nutrição Pré-Natal , Ovinos/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Peso ao Nascer/fisiologia , Peso Corporal , Ácidos Graxos não Esterificados/sangue , Feminino , Teste de Tolerância a Glucose , Homeostase/fisiologia , Insulina/sangue , Leite/metabolismo , Ovinos/crescimento & desenvolvimento , Ovinos/fisiologia
16.
Animal ; 2(4): 574-81, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22443572

RESUMO

This experiment investigates the effects of maternal nutrient restriction in late gestation on the offsprings' postnatal metabolism and performance. Forty purebred Shropshire twin lambs born to ewes fed either a high-nutrition diet (H) (according to standard) or a low-nutrition (L) diet (50% during the last 6 weeks of gestation) were studied from birth until 145 days of age. In each feeding group, two different sires were represented, 'growth' (G) and 'meat' (M), having different breeding indices for the lean : fat ratio. Post partum all ewes were fed the same diet. Lambs born to L-ewes had significantly lower birth weights and pre-weaning growth rates. This was especially pronounced in L-lambs born to the M-ram, which also had markedly lower pre-weaning glucose concentrations than the other three groups of lambs. L-lambs converted milk to live weight with an increased efficiency in week 3 of life. Their glucose concentrations and growth rates were both increased. Plasma glucose concentrations in LM-lambs became similar to those observed in H-lambs post-weaning. However, LM-lambs continued to be lighter than the other groups throughout the experimental period and were unable to compensate for the reduced weight at birth despite having the highest daily fractional growth rates. LG-lambs had the highest plasma glucose concentrations of all four groups of lambs, and they indeed reached body weights comparable to those of the H-lambs by 145 days of age. The increased growth rate post-weaning in L-lambs was not reflected in fat deposition, as L-lambs had lower fat deposition than H-lambs. This may relate to the lower plasma insulin levels found in the L-lambs than in the H-lambs. In conclusion, a 50% reduction of maternal nutrient supply in the last 6 weeks of gestation reduces the birth weight and pre-weaning growth of the offspring due to lower milk intake. Growth rates can be restored when an adequate post-weaning diet is provided, but the prenatal nutrition may programme postnatal metabolism differentially depending on genotype, thus affecting the ability of the ad libitum-fed lamb to achieve a given body weight by a certain age.

17.
Endocrinology ; 149(3): 1163-72, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18048493

RESUMO

The relationships between reduced size at birth, increased activity of the hypothalamic-pituitary-adrenal (HPA) axis, and increased risk of disease in adulthood are well described in singletons but are much less clear in twins. This may be because the physiological processes underlying reduced size at birth are different in singletons and twins. Periconceptional undernutrition can cause altered activity of the fetal and postnatal HPA axis without altering size at birth. However, the independent effects of periconceptional undernutrition and twinning on activity of the maternal and fetal HPA axes are not well described. We therefore studied maternal and fetal HPA axis function during late gestation in twin and singleton sheep pregnancies, either undernourished around conception or fed ad libitum. We found that twinning led to suppressed baseline HPA axis function and decreased adrenal sensitivity to ACTH stimulation but increased fetal pituitary ACTH response both to direct stimulation by CRH (ACTH area under the curve response: 29.7 +/- 2.2 vs. 17.1 +/- 1.6 ng/min x ml, P < 0.01) and to decreased cortisol negative feedback. In contrast, periconceptional undernutrition resulted in a decreased pituitary response (ACTH area under the curve response: 19.4 +/- 1.6 vs. 26.1 +/- 2.2 ng/min x ml, P = 0.02) but no difference in adrenal response. Thus, the HPA axis function of twin sheep fetuses in late gestation is very different from that of control and undernourished singletons. If the HPA axis is an important mediator between fetal adaptations and adult disease, these data may help explain why the relationship between fetal growth and postnatal physiology and disease risk is inconsistent in twins.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiologia , Desnutrição/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiologia , Prenhez/fisiologia , Gravidez Múltipla/fisiologia , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Animais , Arginina Vasopressina/farmacologia , Hormônio Liberador da Corticotropina/farmacologia , Feminino , Feto/fisiologia , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Gravidez , Ovinos , Gêmeos
19.
Am J Physiol Endocrinol Metab ; 293(2): E548-57, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17505050

RESUMO

Effects of moderate maternal undernourishment during late gestation on the intermediary metabolism and maturational changes in young lambs were investigated. 20 twin-bearing sheep, bred to two different rams, were randomly allocated the last 6 wk of gestation to either a NORM diet [barley, protein supplement, and silage ad libitum approximately 15 MJ metabolizable energy (ME)/day] or a LOW diet (50% of ME intake in NORM, offered exclusively as silage approximately 7 MJ ME/day). Post partum, ewes were fed to requirement. After weaning, lambs were fed concentrate and hay ad libitum. At 10 and 19 wk of age, lambs were subjected to an intravenous glucose tolerance test (IGTT) followed by 24 h of fasting. Heat energy (HE) was determined in a respiration chamber at 9 or 20 wk of age. LOW lambs had a lower birth weight and continued to be lighter throughout the experiment. Glucose tolerance did not differ between groups. However, 19-wk-old LOW lambs secreted less insulin during IGTT, released more NEFA, and tended to have lower leptin during fasting than NORM. Surprisingly, several metabolite and hormone responses during IGTT and fasting were greatly influenced by the paternal heritage. In conclusion, when lambs entered adolescence (19 wk) programming effects of late prenatal malnutrition on the glucose-insulin homeostasis and metabolism were manifested: LOW lambs had less insulin-secretory capacity, but this was apparently compensated for by increased target tissue sensitivity for insulin, and adipose lipolytic capacity increased during fasting. Thereby, glucose may be spared through increased lipid oxidation, but overall energetic efficiency is apparently deteriorated rather than improved.


Assuntos
Transtornos da Nutrição Fetal/metabolismo , Idade Gestacional , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Peso ao Nascer , Ingestão de Alimentos/fisiologia , Jejum/metabolismo , Feminino , Desenvolvimento Fetal/fisiologia , Teste de Tolerância a Glucose , Crescimento , Masculino , Troca Materno-Fetal , Gravidez , Ovinos
20.
J Nutr Health Aging ; 11(1): 75-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17315085

RESUMO

INTRODUCTION: Nutritional status among stroke patients has received limited attention despite the fact, that it may have an influence on clinical outcome. Previous studies have estimated that 15-20 % of patients suffer from malnutrition in the acute phase of stroke, but so far no studies have focused on the late rehabilitation phase after stroke in the patients own home, where the attention on nutrition may be reduced. AIMS: To determine the prevalence of malnutrition during 6 months of stroke rehabilitation, and to investigate the association between nutritional status, functional recovery, length of stay in hospital and infectious complications. SUBJECTS AND METHODS: 89 patients with ischemic stroke consecutively admitted to a geriatric stroke rehabilitation unit had their nutritional status evaluated in the hospital at 1 week and 5 weeks after stroke, and in their own home at 3 months and 6 months. Nutritional status was evaluated by body weight, body mass index (BMI), mid upper arm circumference (MAC), triceps skinfold thickness (TSF) and serum concentrations of albumin and transferrin. Malnutrition was defined if the patients had 2 or more abnormal nutritional variables. RESULTS: We found a significant increase in albumin from 1 week to 6 months (P < 0.0001), and a significant increase in transferrin form 5 weeks to 6 months (P < 0.05). There was no significant change in weight or BMI from 1 week to 6 months. The number of patients with 2 or more abnormal nutritional variables was 31 (35 %) at 1 week and was reduced to 20 (22 %) at 6 months. CONCLUSION: 35 % of elderly patients with ischemic stroke admitted to a geriatric rehabilitation unit were malnourished 1 week after stroke. Particularly serum proteins and body fat were affected. Follow-up of nutritional variables showed improvement for serum proteins, and 22 % of the patients were malnourished 6 months after stroke.


Assuntos
Proteínas Sanguíneas/análise , Desnutrição/epidemiologia , Estado Nutricional , Desnutrição Proteico-Calórica/epidemiologia , Acidente Vascular Cerebral/complicações , Idoso , Antropometria , Biomarcadores/sangue , Feminino , Humanos , Tempo de Internação , Masculino , Desnutrição/sangue , Desnutrição/etiologia , Desnutrição Proteico-Calórica/sangue , Desnutrição Proteico-Calórica/etiologia , Fatores de Risco , Albumina Sérica/análise , Dobras Cutâneas , Reabilitação do Acidente Vascular Cerebral , Fatores de Tempo , Transferrina/análise
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