RESUMO
In sepsis, excessive inflammation may lead to organ injury or a paradoxical immunosuppressed state where the host is unable to clear preexisting infection. Resolution of inflammation is the process which restores tissue homeostasis and ensures that a chronic cycle of infection/inflammation does not occur. Lipoxin A4 (LXA4) is one of a family of lipid mediators with novel inflammation resolution activity. We compared the actions of LXA4 to the stable 15-epi-16-(para-fluorophenoxy)-lipoxin A4 methyl ester (LXA4 analog) in the cecal ligation and puncture (CLP) model of sepsis. Both LXA4 compounds (at 7 µg/kg; i.v.) reduced plasma TNFα and IL-6 concentrations compared to rats given vehicle saline. Neither treatment altered plasma IL-10 compared to CLP given saline, but LXA4 analog, increased plasma IL-10 concentrations compared to rats given LXA4. LXA4 reduced blood bacterial load but the LXA4 analog did not. LXA4 increased 8 day survival and the LXA4 analog did not have a significant effect. To examine possible mechanisms for the differences, we investigated peritoneal leukocyte gene expression of iNOS and macrophage phagocytic ability. Only LXA4 increased the percentage of phagocytic peritoneal macrophages. LXA4 reduced neutrophil gene expression of iNOS compared to CLP rats given vehicle, while the LXA4 analog did not. Our results suggest that at doses which reduced systemic inflammation, only LXA4 inhibited bacterial spread and increased survival. This difference may be due to the shorter-lived compound being able to increase macrophage phagocytosis and reduce neutrophil iNOS expression.
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Lipoxinas/uso terapêutico , Sepse/tratamento farmacológico , Animais , Cromatografia Líquida , Macrófagos/efeitos dos fármacos , Masculino , Neutrófilos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Sepse/imunologia , Espectrometria de Massas em TandemRESUMO
Space flight is a new experience for humans. Humans adapt if not perfectly, rather well to life without gravity. There is a reductive remodeling of the musculo-skeletal system. Protein is lost from muscles and calcium from bones with anti-gravity functions. The observed biochemical and physiological changes reflect this accommodative process. The two major direct effects of the muscle loss are weakness post-flight and the increased incidence of low back ache pre- and post-flight. The muscle protein losses are compromised by the inability to maintain energy balance inflight. Voluntary dietary intake is reduced during space flight by ~20 %. These adaptations to weightlessness leave astronauts ill-equipped for life with gravity. Exercise, the obvious counter-measure has been repeatedly tried and since the muscle and bone losses persist it is not unreasonable to assume that success has been limited at best. Nevertheless, more than 500 people have now flown in space for up to 1 year and have done remarkably well. This review addresses the question of whether enough is now known about these three problems (negative energy balance, muscle loss and bone loss) for to the risks to be considered either acceptable or correctible enough to meet the requirements for a Mars mission.
Assuntos
Adaptação Fisiológica/fisiologia , Peso Corporal/fisiologia , Osso e Ossos/fisiologia , Músculo Esquelético/fisiologia , Voo Espacial , Animais , Astronautas , Gravitação , Humanos , Contramedidas de Ausência de PesoRESUMO
It is thought that autism could result from an interaction between genetic and environmental factors with oxidative stress as a potential mechanism linking the two. One genetic factor may be altered oxidative-reductive capacity. This study tested the hypothesis that children with autism have increased oxidative stress. We evaluated children with autism for the presence of two oxidative stress biomarkers. Urinary excretion of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-isoprostane-F2alpha (8-iso-PGF2alpha) were determined in 33 children with autism and 29 healthy controls. 8-iso-PGF2alpha levels were significantly higher in children with autism. The isoprostane levels in autistic subjects were variable with a bimodal distribution. The majority of autistic subjects showed a moderate increase in isoprostane levels while a smaller group of autistic children showed dramatic increases in their isoprostane levels. There was a trend of an increase in 8-OHdG levels in children with autism but it did not reach statistical significance. There was no significant correlation between the levels of the biomarkers and vitamin intake, dietary supplements, medicine, medical disorders, or history of regression. These results suggest that the lipid peroxidation biomarker is increased in this cohort of autistic children, especially in the subgroup of autistic children.
Assuntos
Transtorno Autístico/metabolismo , Desoxiguanosina/análogos & derivados , Dinoprosta/análogos & derivados , Peroxidação de Lipídeos , 8-Hidroxi-2'-Desoxiguanosina , Adolescente , Transtorno Autístico/urina , Biomarcadores/urina , Criança , Pré-Escolar , Estudos de Coortes , Desoxiguanosina/urina , Dinoprosta/urina , Feminino , Humanos , Masculino , Estresse Oxidativo/fisiologiaRESUMO
In response to decreased usage, skeletal muscle undergoes an adaptive reductive remodeling. This adaptive response has been found with disuse during human spaceflight, rat spaceflight, rat hind-limb unloading, bed rest, and aging. The reductive remodeling of skeletal muscle with disuse is largely independent of the reason for the disuse. The process involves more than a transition from slow to fast myosin fiber types. There are associated metabolic changes including a fuel shift toward glycolysis, decreased capacity for fat oxidation, and energy substrate accumulation in the atrophied muscles. Glycolysis is very effective for high-intensity short-duration acute activities, but if sustained output is needed, an energy profile where fat use is favored rather than compromised is desirable. For astronauts, there is a need to maintain as much functional capacity as possible during spaceflight for extravehicular activities. The shift toward increased activity of the glycolytic enzymes in atrophied muscle is accommodated by an increase in gluconeogenic capacity in the liver.
Assuntos
Músculo Esquelético/patologia , Transtornos Musculares Atróficos/metabolismo , Transtornos Musculares Atróficos/patologia , Animais , Astronautas , Glucose/metabolismo , Glicólise , Humanos , Metabolismo dos Lipídeos , Transtornos Musculares Atróficos/etiologia , Ratos , Voo EspacialRESUMO
Spaceflight and prolonged bed rest (BR) alter plasma hormone levels inconsistently. This may be due, in part, to prescription of heavy exercise as a countermeasure for ameliorating the adverse effects of disuse. The initial project was to assess exercise programs to maintain aerobic performance and leg strength during BR. The present study evaluates the effect of BR and the performance of the prescribed exercise countermeasures on plasma steroid levels. In a 30-day BR study of male subjects, the efficacy of isotonic (ITE, n = 7) or isokinetic exercise (IKE, n = 7) training was evaluated in contrast to no exercise (n = 5). These exercise countermeasures protected aerobic performance and leg strength successfully. BR alone (no-exercise group) did not change steroidogenesis, as assessed by the plasma concentrations of cortisol, progesterone, aldosterone, and free (FT) and total testosterone (TT). In the exercise groups, both FT and TT were decreased (P < 0.05): FT during IKE from 24 +/- 1.7 to 18 +/- 2.0 pg/ml and during ITE from 21 +/- 1.5 to 18 +/- 1 pg/ml, and TT during IKE from 748 +/- 68 to 534 +/- 46 ng/dl and during ITE from 565 +/- 36 to 496 +/- 38 ng/dl. The effect of intensive exercise countermeasures on plasma testosterone was not associated with indexes of overtraining. The reduction in plasma testosterone associated with both the IKE and ITE countermeasures during BR supports our hypothesis that intensive exercise countermeasures may, in part, contribute to changes in plasma steroid concentrations during spaceflight.
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Repouso em Cama/efeitos adversos , Transtornos Traumáticos Cumulativos/sangue , Transtornos Traumáticos Cumulativos/fisiopatologia , Exercício Físico , Esforço Físico , Testosterona/sangue , Simulação de Ausência de Peso/efeitos adversos , Adaptação Fisiológica , Adulto , Transtornos Traumáticos Cumulativos/etiologia , Hormônios/sangue , Humanos , Masculino , Aptidão FísicaRESUMO
Bed rest is associated with a loss of protein from the weight-bearing muscle. The objectives of this study are to determine whether increasing dietary branched-chain amino acids (BCAAs) during bed rest improves the anabolic response after bed rest. The study consisted of a 1-day ambulatory period, 14 days of bed rest, and a 4-day recovery period. During bed rest, dietary intake was supplemented with either 30 mmol/day each of glycine, serine, and alanine (group 1) or with 30 mmol/day each of the three BCAAs (group 2). Whole body protein synthesis was determined with U-(15)N-labeled amino acids, muscle, and selected plasma protein synthesis with l-[(2)H(5)]phenylalanine. Total glucose production and gluconeogenesis from alanine were determined with l-[U-(13)C(3)]alanine and [6,6-(2)H(2)]glucose. During bed rest, nitrogen (N) retention was greater with BCAA feeding (56 +/- 6 vs. 26 +/- 12 mg N. kg(-1). day(-1), P < 0.05). There was no effect of BCAA supplementation on either whole body, muscle, or plasma protein synthesis or the rate of 3-MeH excretion. Muscle tissue free amino acid concentrations were increased during bed rest with BCAA (0.214 +/- 0.066 vs. 0.088 +/- 0.12 nmol/mg protein, P < 0.05). Total glucose production and gluconeogenesis from alanine were unchanged with bed rest but were significantly reduced (P < 0.05) with the BCAA group in the recovery phase. In conclusion, the improved N retention during bed rest is due, at least in part, to accretion of amino acids in the tissue free amino acid pools. The amount accreted is not enough to impact protein kinetics in the recovery phase but does improve N retention by providing additional essential amino acids in the early recovery phase.
Assuntos
Aminoácidos de Cadeia Ramificada/uso terapêutico , Repouso em Cama , Suplementos Nutricionais , Adulto , Alanina/metabolismo , Aminoácidos/administração & dosagem , Aminoácidos de Cadeia Ramificada/administração & dosagem , Proteínas Sanguíneas/biossíntese , Dieta , Gluconeogênese , Humanos , Fígado/metabolismo , Masculino , Proteínas Musculares/biossíntese , Proteínas Musculares/metabolismo , Nitrogênio/metabolismo , Proteínas/metabolismoRESUMO
Alteration of metabolism has been suggested as a major limiting factor to long-term space flight. In humans and primates, a negative energy balance has been reported. The metabolic response of rats to space flight has been suggested to result in a negative energy balance. We hypothesized that rats flown in space would maintain energy balance as indicated by maintenance of caloric intake and body mass gain. Further, the metabolism of the rat would be similar to that of laboratory-reared animals. We studied the results from 15 space flights lasting 4 to 19 d. There was no difference in average body weight (206 +/- 13.9 versus 206 +/- 14.8 g), body weight gain (5.8 +/- 0.48 versus 5.9 +/- 0.56 g/d), caloric intake (309 +/- 21.0 versus 309 +/- 20.1 kcal/kg of body mass per day), or water intake (200 +/- 8.6 versus 199 +/- 9.3 mL/kg of body mass per day) between flight and ground control animals. Compared with standard laboratory animals of similar body mass, no differences were noted. The observations suggested that the negative balance observed in humans and non-human primates may be due to other factors in the space-flight environment.
Assuntos
Peso Corporal , Ingestão de Líquidos/fisiologia , Ingestão de Alimentos/fisiologia , Ingestão de Energia/fisiologia , Voo Espacial , Adaptação Fisiológica , Animais , Astronautas , Feminino , Humanos , Masculino , Modelos Animais , Necessidades Nutricionais , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos SHR , Ausência de PesoRESUMO
Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.
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Desoxiguanosina/análogos & derivados , Dinoprosta/análogos & derivados , Estresse Oxidativo , Voo Espacial , Ausência de Peso/efeitos adversos , 8-Hidroxi-2'-Desoxiguanosina , Animais , Biomarcadores , Dano ao DNA , Desoxiguanosina/metabolismo , Membrana Eritrocítica/metabolismo , F2-Isoprostanos/metabolismo , Humanos , Peroxidação de Lipídeos , Oxidantes , Roedores , Fatores de TempoRESUMO
In response to decreased usage skeletal muscle undergoes an adaptive reductive remodeling due to the decrease in tension on the weight bearing components of the musculo-skeletal system. Accompanying a shift in fiber type is an increased reliance of carbohydrate metabolism and decreased reliance on fat for energy. These responses have been found with both space flight and ground based models of disuse atrophy including the chronically adapted rodent hind limb suspended (HLS) rat (1, 4-7, 10, 11). In addition, after space flight, the ability of soleus muscle homogenates to oxidize palmitate is decreased. We have previously shown that expression of the mRNA of enzymes involved in beta-oxidation is reduced in the soleus muscle of HLS rats. At the same time mRNA expression of enzymes involved in glycolysis was increased. This study extends these observations to address the question of whether the decrease in beta-oxidation is caused by a reduction in the capacity of the pathway to oxidize fat or the regulation is effected before fatty acids enter the mitochondria, i.e. the reduced capacity of the fatty acid oxidation pathway is because less fat is available for oxidation. The two key steps involved in fatty acid uptake into the cells are lipoprotein lipase and the transport of the free fatty acids produced by lipoprotein lipase into the cell via the carnitine acyltransferase system.
RESUMO
UNLABELLED: Compared with men, women appear to have a decreased sympathetic nervous system (SNS) response to stress. The two manifestations where the sexual dimorphism has been the most pronounced involve the response of the SNS to fluid shifts and fuel metabolism during exercise. The objectives of this study were to investigate whether a similar sexual dimorphism was found in the response to spaceflight. To do so, we compared catecholamine excretion by male and female astronauts from two similar shuttle missions, Spacelab Life Sciences 1 (SLS1, 1991) and 2 (SLS2, 1993) for evidence of sexual dimorphism. To evaluate the variability of the catecholamine response in men, we compared catecholamine excretion from the two SLS missions against the 1996 Life and Microgravity Sciences Mission (LMS) and the 1973 Skylab missions. RESULTS: No gender- or mission-dependent changes were found with epinephrine. Separating out the SLS1/2 data by gender shows that norepinephrine excretion was essentially unchanged with spaceflight in women (98 +/- 10%; n = 3) and substantially decreased with the men (41 +/- 9%; n = 4, P < 0.05). Data are a percentage of mean preflight value +/- SE. Comparisons among males demonstrated significant mission effects on norepinephrine excretion. After flight, there was a transient increase in norepinephrine but no evidence of any gender-specific effects. We conclude that norepinephrine excretion during spaceflight is both mission and gender dependent. Men show the greater response, with at least three factors being involved, a response to microgravity, energy balance, and the ratio of carbohydrate to fat in the diet.
Assuntos
Dieta , Epinefrina/urina , Norepinefrina/urina , Caracteres Sexuais , Voo Espacial , Metabolismo Energético , Feminino , Humanos , Cinética , Masculino , Nitrogênio/urina , Estados Unidos , United States National Aeronautics and Space Administration , Redução de Peso , Ausência de PesoRESUMO
OBJECTIVE: To evaluate changes in resting energy expenditure (REE) as well as protein and carbohydrate metabolism in dogs with osteosarcoma (OSA). ANIMALS: 15 weight-stable dogs with OSA that did not have other concurrent metabolic or endocrine illness and twelve 1-year-old sexually intact female Beagles (control dogs). PROCEDURES: Indirect calorimetry was performed on all dogs to determine REE and respiratory quotient (RQ). Stable isotope tracers (15N-glycine, 4.5 mg/kg of body weight, IV; 6,6-deuterium-glucose, 4.5 mg/kg, IV as a bolus, followed by continuous-rate infusion at 1.5 mg/kg/h for 3 hours) were used to determine rate of protein synthesis and glucose flux in all dogs. Dual-energy x-ray absorptiometry (DEXA) scans were performed to determine total body composition. RESULTS: Accounting for metabolic body size, REE in dogs with OSA was significantly higher before and after surgery, compared with REE of healthy control dogs. The RQ values did not differ significantly between groups. Dogs with OSA also had decreased rates of protein synthesis, increased urinary nitrogen loss, and increased glucose flux during the postoperative period. CONCLUSIONS AND CLINICAL RELEVANCE: Alterations in energy expenditure, protein synthesis, urinary nitrogen loss, and carbohydrate flux were evident in dogs with OSA, similar to results documented in humans with neoplasia. Changes were documented in REE as well as protein and carbohydrate metabolism in dogs with OSA. These changes were evident even in dogs that did not have clinical signs of cachexia.
Assuntos
Neoplasias Ósseas/veterinária , Doenças do Cão/metabolismo , Osteossarcoma/veterinária , Absorciometria de Fóton/veterinária , Animais , Neoplasias Ósseas/metabolismo , Calorimetria Indireta/veterinária , Cães , Metabolismo Energético/fisiologia , Feminino , Glucose/análise , Glucose/metabolismo , Glicina/sangue , Glicina/metabolismo , Glicina/urina , Masculino , Osteossarcoma/metabolismoRESUMO
A loss in fat mass is a common response to centrifugation and it results in low circulating leptin concentrations. However, rats adapted to hypergravity are euphagic. The focus of this study was to examine leptin and other peripheral signals of energy balance in the presence of a hypergravity-induced loss of fat mass and euphagia. Male Sprague-Dawley rats were centrifuged for 14 days at gravity levels of 1.25, 1.5, or 2 G, or they remained stationary at 1 G. Urinary catecholamines, urinary corticosterone, food intake, and body mass were measured on Days 11 to 14. Plasma hormones and epididymal fat pad mass were measured on Day 14. Mean body mass of the 1.25, 1.5, and 2 G groups were significantly (P < 0.05) lower than controls, and no differences were found in food intake (g/day/100 g body mass) between the hypergravity groups and controls. Epididymal fat mass was 14%, 14%, and 21% lower than controls in the 1.25, 1.5, and 2.0 G groups, respectively. Plasma leptin was significantly reduced from controls by 46%, 45%, and 65% in the 1.25, 1.5, and 2 G groups, respectively. Plasma insulin was significantly lower in the 1.25, 1.5, and 2.0 G groups than controls by 35%, 38%, and 33%. No differences were found between controls and hypergravity groups in urinary corticosterone. Mean urinary epinephrine was significantly higher in the 1.5 and 2.0 G groups than in controls. Mean urinary norepinephrine was significantly higher in the 1.25, 1.5 and 2.0 G groups than in controls. Significant correlations were found between G load and body mass, fat mass, leptin, urinary epinephrine, and norepinephrine. During hypergravity exposure, maintenance of food intake is the result of a complex relationship between multiple pathways, which abates the importance of leptin as a primary signal.
Assuntos
Ingestão de Alimentos , Gravitação , Hormônios/fisiologia , Leptina/biossíntese , Animais , Catecolaminas/urina , Corticosterona/urina , Epididimo/patologia , Epinefrina/urina , Hormônios/sangue , Insulina/sangue , Leptina/metabolismo , Masculino , Norepinefrina/urina , Ratos , Ratos Sprague-Dawley , Análise de Regressão , Fatores de TempoRESUMO
OBJECTIVE: DNA is susceptible to oxidation and is constantly being damaged and repaired in living cells. The most abundant of the nucleoside oxidation products is 8-oxo-7,8 dihydro-2 deoxyguanosine (8 OH-dG). Our objective was to determine whether oxidative damage to DNA, as measured by 8 OH-dG, is increased with poor pregnancy outcome. METHOD: We utilized a case-control design to study oxidative damage to DNA during an ongoing prospective study. Cases (n = 18) included all women giving birth to a low-birth-weight (< 2500 g) or growth-restricted (< 10th centile) or preterm infant (< 37 completed weeks). Controls (n = 34) were selected at random from women with normal pregnancies. Urine samples were obtained early in the third trimester (28 +/- 2 weeks) and normalized to creatinine. Diet was assessed at three points during pregnancy. RESULTS: Cases had significant (p < 0.05) increases in maternal urinary 8 OH-dG excretion at week 28, when all cases were considered and when cases were defined as those who delivered a low-birth-weight infant. 8OH-dG excretion, in turn, correlated positively with saturated fat in the maternal diet. CONCLUSION: This study suggests that gravidas with poor pregnancy outcome have increased oxidative damage to their DNA early in the third trimester of pregnancy.
Assuntos
Dano ao DNA/fisiologia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Recém-Nascido Prematuro/fisiologia , Estresse Oxidativo/fisiologia , Resultado da Gravidez , 8-Hidroxi-2'-Desoxiguanosina , Estudos de Casos e Controles , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Humanos , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido , Fenômenos Fisiológicos da Nutrição/fisiologia , Gravidez , Estudos Prospectivos , Fatores Socioeconômicos , População UrbanaRESUMO
OBJECTIVE: The objective of this study was to determine whether differences in urinary proinflammatory cytokines, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha), exist between migraineurs and nonheadache control subjects, and between nonhormonal migraine and menstrual migraine. Any differences noted would expand and clarify a neuroimmune hypothesis of migraine pathogenesis and lead to future diagnostic markers or therapeutic options or both for the disorder. BACKGROUND: Current theories of migraine pathogenesis focus on biochemical abnormalities in the central nervous system resulting in sterile inflammation of meningeal blood vessels. Vasoactive substances involved in this process may include substance P, calcitonin gene-related peptide, neurokinin A, serotonin, and nitric oxide. Immune cell products, such as histamine, leukotrienes, and cytokines, also have vascular inflammatory properties. METHODS: A study of proinflammatory cytokines, IL-1beta, IL-6, and TNF-alpha, was undertaken in menstrual migraineurs. During and outside of menses, 24-hour urine samples of 19 women with migraine were taken during a menstrual migraine, a nonmenstrual migraine, and a headache-free day, and compared with 24-hour urine samples taken of 10 nonheadache controls during and outside of menses. RESULTS: A neuroimmune mechanism for migraine was tested with expected increases in proinflammatory cytokines tested during a migraine. This hypothesis was not validated. Mean IL-6 levels were increased in all three samples of migraineurs versus controls, but did not achieve statistical significance. No differences were found in IL-1beta levels between samples. Interestingly, marked differences were found in TNF-alpha values in menstrual migraineurs. Twelve (63%) of 19 migraineurs had at least one urine sample with undetectable TNF-alpha levels, whereas none of the 20 samples given by the 10 nonheadache controls in this study had undetectable levels. Thirty-two samples from men with cluster headache and nonheadache control subjects in prior studies had detectable levels. CONCLUSIONS: This deficiency of TNF-alpha levels in women with migraine may signal a disordered neuroimmune communication network and predisposition to migraine.
Assuntos
Interleucina-1/urina , Interleucina-6/urina , Menstruação , Transtornos de Enxaqueca/etiologia , Transtornos de Enxaqueca/urina , Fator de Necrose Tumoral alfa/deficiência , Feminino , Humanos , Menstruação/urina , Fator de Necrose Tumoral alfa/urinaRESUMO
We tested the generally accepted concept that increased gluconeogenesis (GNG) and endogenous glucose production (EGP) are the main reasons for postabsorptive hyperglycemia in patients with type 2 diabetes mellitus (T2DM). GNG was measured with the (2)H(2)O method by use of both the C5-to-C2 ratio (C5/C2, with gas chromatography-mass spectrometry) and the C5-to-(2)H(2)O ratio (C5/(2)H(2)O, with isotope ratio mass spectrometry), and EGP was measured with 3-[(3)H]glucose in 27 patients with T2DM [13 with fasting plasma glucose (FPG) >10 mM and 14 with FPG <10 mM] and in 7 weight- and age-matched nondiabetic controls. The results showed 1) that GNG could be determined accurately with (2)H(2)O by using either C5/C2 or C5/(2)H(2)O; 2) that whereas after an overnight fast of 16 h, GNG was higher in the entire group of patients with T2DM than in controls (6.4 vs. 5.0 micromol. kg(-1). min(-1) or 60.4 vs. 51.4% of EGP, P < 0.02), GNG was within normal limits (less than the mean +/- 2 SD of controls or <65.3%) in 11/14 (79%) patients with mild to moderate hyperglycemia (FPG <10 mM) and in 5/13 (38%) of patients with severe hyperglycemia (FPG 10-20 mM); 3) that elevated GNG in T2DM was associated with a 43% decrease in prehepatic insulin secretion, i.e., with hepatic insulin deficiency; and 4) that FPG correlated significantly with glucose clearance (insulin resistance) (r = 0.70) and with GNG (r = 0.50) or EGP (r = 0.45). We conclude 1) that peripheral insulin resistance is at least as important as GNG (and EGP) as a cause of postabsorptive hyperglycemia in T2DM and 2) that GNG and EGP in T2DM are increased under conditions of significant hepatic insulin deficiency and thus probably represent a late event in the course of T2DM.
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Diabetes Mellitus Tipo 2/metabolismo , Gluconeogênese/fisiologia , Hiperglicemia/metabolismo , Idoso , Glicemia/biossíntese , Deutério , Jejum/fisiologia , Ácidos Graxos não Esterificados/sangue , Feminino , Glucagon/sangue , Glucose/farmacocinética , Glicólise/fisiologia , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Insulina/metabolismo , Resistência à Insulina/fisiologia , Secreção de Insulina , Corpos Cetônicos/sangue , Masculino , Pessoa de Meia-Idade , TrítioRESUMO
Space flight is a new experience for man. Tension on the weight-bearing components of the musculo-skeletal system is greatly reduced, as is the work required for movement. The body responds by a reductive remodelling of the musculo-skeletal system. Protein is lost from muscles with anti-gravity functions. The rate of Ca loss from the weight-bearing bones is about 1 % per month. Voluntary dietary intake is reduced during space flight by about 20 %. These adaptations to weightlessness leave astronauts ill-equipped for life with gravity when they return to earth. Rates of energy expenditure are similar to that expected on the ground for comparable activities. Protein intake is adequate in flight but may be limiting after space flight due to substrate competition between repleting muscle and other anabolic processes. The most serious nutritional problem is the inability to maintain energy balance on missions with high exercise requirements. The poor dietary intake is probably a consequence of engineering-imposed environmental constraints. The low levels of lighting in the space vehicle may not be enough to promote vitamin D synthesis. Nevertheless, the evidence suggests that a normal well-balanced diet with plenty of fluids will be as healthy in space as on earth. The long-term goal of the manned space programme is to develop the means of sustaining human life beyond earth. This will involve the development of technologies to grow food, maintain a breathable atmosphere and recycle waste products with the only external input being energy.
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BACKGROUND: Maternal growth on the basis of knee height occurs in nearly 50% of pregnant teenagers and is associated with greater gestational weight gain and accrual of subcutaneous fat in the mother but lower fetal growth compared with nongrowing teenagers and mature pregnant women. OBJECTIVE: The objective of this study was to determine whether leptin is a biomarker for continued maternal growth. DESIGN: Leptin concentrations were measured in 162 growing and nongrowing teenage gravidas (aged =18 y) and in mature gravidas (aged 19-29 y) from the Camden Study at 2 time points during pregnancy and 1 time point postpartum. RESULTS: Growing teenagers had leptin concentrations that increased with gestation and were higher at 28 wk gestation and postpartum than in nongrowing teenagers and mature gravidas. The differences were related to a leptin surge between entry into the study (16.9 wk) and week 28, primarily in still-growing gravidas. Leptin-surge quartiles were associated with higher knee-height velocity and weight gain, increased skinfold thicknesses in late pregnancy (28 wk) and early postpartum (4-6 wk), and changes in postpartum weight and body mass index. For the highest quartile, low birth weight increased >5-fold, fetal growth restriction increased >6-fold, and infant birth weight decreased by approximately 200 g. Gravidas who developed pregnancy-induced hypertension showed a different pattern-higher leptin concentrations at entry and week 28, no difference in the leptin surge, and no postpartum difference in leptin concentration. CONCLUSION: A leptin surge by week 28 appears to mark reduced mobilization of maternal fat stores that is associated with maternal growth on the basis of knee height during adolescent pregnancy.
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Desenvolvimento Embrionário e Fetal , Crescimento , Leptina/sangue , Gravidez na Adolescência/fisiologia , Adolescente , Adulto , Biomarcadores , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Dobras Cutâneas , Aumento de PesoRESUMO
A 15N-glycine tracer technique was used to study protein turnover in four Russian cosmonauts and two U.S. astronauts who had spent long time aboard the Russian orbital station MIR. As was shown, in space flight protein synthesis falls by 46% on the average, which substantially exceeds estimations made on the basis of data about bed-rested human subjects. Reduction in protein synthesis during space flight is connected with the negative energy balance; therefore, it appears imperative to keep balance between energy intake (foodstuffs) and expenditure by cosmonauts on long-term mission.
Assuntos
Ritmo Circadiano/fisiologia , Metabolismo Energético/fisiologia , Biossíntese de Proteínas , Voo Espacial , Humanos , Exposição Ocupacional , Fatores de Tempo , Ausência de PesoRESUMO
The objectives of this study were to assess oxidant damage during and after spaceflight and to compare the results against bed rest with 6 degrees head-down tilt. We measured the urinary excretion of the F(2) isoprostane, 8-iso-prostaglandin (PG) F(2alpha), and 8-oxo-7,8-dihydro-2 deoxyguanosine (8-OH DG) before, during, and after long-duration spaceflight (4-9 mo) on the Russian space station MIR, short-duration spaceflight on the shuttle, and 17 days of bed rest. Sample collections on MIR were obtained between 88 and 186 days in orbit. 8-iso-PGF(2alpha) and 8-OH DG are markers for oxidative damage to membrane lipids and DNA, respectively. Data are mean +/- SE. On MIR, isoprostane levels were decreased inflight (96. 9 +/- 11.6 vs. 76.7 +/- 14.9 ng. kg(-1). day(-1), P < 0.05, n = 6) due to decreased dietary intake secondary to impaired thermoregulation. Isoprostane excretion was increased postflight (245.7 +/- 55.8 ng. kg(-1). day(-1), P < 0.01). 8-OH DG excretion was unchanged with spaceflight and increased postflight (269 +/- 84 vs 442 +/- 180 ng. kg(-1). day(-1), P < 0.05). On the shuttle, 8-OH DG excretion was unchanged in- and postflight, but 8-iso-PGF(2alpha) excretion was decreased inflight (15.6 +/- 4.3 vs 8.0 +/- 2.7 ng. kg(-1). day(-1), P < 0.05). No changes were found with bed rest, but 8-iso-PGF(2alpha) was increased during the recovery phase (48.9 +/- 23.0 vs 65.4 +/- 28.3 ng. kg(-1). day(-1), P < 0.05). The changes in isoprostane production were attributed to decreased production of oxygen radicals from the electron transport chain due to the reduced energy intake inflight. The postflight increases in the excretion of the products of oxidative damage were attributed to a combination of an increase in metabolic activity and the loss of some host antioxidant defenses inflight. We conclude that 1) oxidative damage was decreased inflight, and 2) oxidative damage was increased postflight.
Assuntos
Oxidantes/farmacologia , Voo Espacial , 8-Hidroxi-2'-Desoxiguanosina , Repouso em Cama , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Dinoprosta/análogos & derivados , Dinoprosta/urina , Ingestão de Energia , F2-Isoprostanos , Decúbito Inclinado com Rebaixamento da Cabeça/fisiologia , HumanosRESUMO
The mean daily energy expenditure rates of two rhesus monkeys (Macaca mulatta) were determined during spaceflight on the joint U.S./Russian Bion 11 mission by the doubly labeled water (DLW, 2H218O) method. Control values were obtained from two studies performed under flight-like conditions (n = 4). The mean inflight energy expenditure for the two Bion 11 monkeys was 81.3 kcal/kg/day, which was higher than that seen previously. The average energy expenditure (77.6 +/- 4.4 kcal/kg/day) for the four ground control monkeys was slightly lower than had been measured previously.