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Biomedical subjects

T Peter Stein

Publications and source records attributed to T Peter Stein.

12 recordsLinked to original sources
PubMed2006

Vitamin E: maternal concentrations are associated with fetal growth.

BACKGROUND: Few data exist on the effects of the 2 most abundant isomers of vitamin E (alpha- and gamma-tocopherols) on fetal growth. OBJECTIVE: We measured maternal plasma concentrations of alpha- and gamma-tocopherols and examined their relation with measures of fetal growth. We also examined the relation, controlled for associated maternal factors, of diet and supplement use to tocopherol concentrations at week 28 of gestation. DESIGN: A cohort of 1231 gravid women from Camden, NJ, was studied from entry to care (16.0 +/- 0.15 wk gestation); plasma tocopherol concentrations were measured at entry and at week 28. RESULTS: Plasma concentrations of alpha-tocopherol at entry and at week 28 were positively related to increased fetal growth (birth weight for gestation), a decreased risk of small-for-gestational-age births, and an increased risk of large-for-gestational-age births. Concentration of alpha-tocopherol at week 28 was positively related to use of prenatal multivitamins and dietary intake of vitamin E; concentration of gamma-tocopherol was related positively to dietary fat intake and negatively to multivitamin use. CONCLUSION: Early and late circulating concentrations of alpha-tocopherol are positively associated with fetal growth.

Adolescent↗
PubMed2006

Insights into muscle atrophy and recovery pathway based on genetic models.

PURPOSE OF REVIEW: Muscle atrophy is a pervasive problem that occurs with disuse, aging, and a myriad of disease conditions. The purposes of this review are to describe recent advances in studying muscle atrophy that have elucidated pathways involved at the molecular level; to compare different types of atrophy--primary (e.g. bed rest, immobilization) and secondary (when the atrophy is related to pathology as well as disuse, e.g. injury, sepsis etc.) and their multiple common features; to review progress in studying the recovery process and clinical status. RECENT FINDINGS: Major advances have been made at the molecular level. There are two phenotypes for muscle atrophy--primary, which is mainly related to disuse (e.g. bed), and secondary, when the atrophy is related to pathology as well as disuse. It appears that the two forms have multiple elements in common. Studies on the recovery process reveal a very complex sequence of events that are not the simple reverse of the muscle loss process. In contrast to the progress at the molecular level, progress in treating muscle atrophy or accelerating recovery has been disappointing. SUMMARY: Although nutritional supplementation and pharmacological agents continue to have the potential to minimize muscle atrophy, given its minimal risks, exercise sets a very high standard for treatment options when medically appropriate. Identification of pathways and control points offers the potential for new approaches.

Bed Rest↗
PubMed2006

Association of elevated serum ferritin levels and the risk of gestational diabetes mellitus in pregnant women: The Camden study.

OBJECTIVE- We examined the influence of a moderately elevated serum ferritin level at entry to care on the risk of gestational diabetes mellitus (GDM) and a possible mechanism (increased iron stores versus inflammation). RESEARCH DESIGN AND METHODS- In a prospective observational study with 1,456 healthy pregnant women in Camden, New Jersey, serum ferritin and anthropometric measurements were determined. Serum C-reactive protein (CRP) concentration was measured in a nested case-control study of 172 subjects. RESULTS- Women who developed GDM had a higher concentration of serum ferritin than women who did not develop GDM (P < 0.001). Elevated serum ferritin level (highest quintile) was significantly and positively correlated with prepregnant BMI and skinfold measurements. Women in the highest quintile of serum ferritin had a twofold increased risk of developing GDM adjusted for several known risk factors (adjusted odds ratio, 2.02 [95% CI 1.04-3.92], P < 0.05). Similar results were obtained with a nested case-control study, in which women in the highest tertile of serum ferritin (2.35 [1.06-5.22], P < 0.05) or CRP (2.67 [1.16-6.17], P < 0.001) had a greater than twofold increased risk of GDM. However, these effects were modified and became nonstatistically significant after additional adjustment for prepregnant BMI. CONCLUSIONS- Elevated serum ferritin concentrations early in gestation are associated with an increased risk of GDM. The association, at least in part, is mediated by the maternal fat mass and obesity. These data suggest a possible link between elevated serum ferritin and low-grade inflammation.

Adult↗
PubMed2006

Plasma protein synthesis after spaceflight.

INTRODUCTION: Astronauts land in a protein-depleted state. An anabolic phase takes place during the postflight period as muscle regains the lost protein. Yet where dietary intake has been measured after spaceflight, there does not appear to be any significant increase in dietary protein intake relative to preflight to provide additional amino acids to support muscles as they regain protein. We hypothesized that protein synthesis in other tissues is sub-optimal after spaceflight because of substrate competition for amino acids occurring between the muscles needing protein and other tissues. METHODS: We measured selected plasma protein synthesis rates before and after spaceflight on the Shuttle using the 15N glycine-hippuric acid method. The fractional protein synthesis rates (FSR) of four plasma proteins, fibrinogen, complement C-3, ceruloplasmin, and haptoglobin, were measured before and after a 16-d flight on the Space Shuttle. Data was obtained for four subjects. Preflight measurements of plasma protein synthesis rates were made 45 and 7 d before launch. Postflight measurements were done on the day of landing and 6 and 14 d later. RESULTS: Compared with preflight, plasma protein synthesis rates were reduced 6 d after landing. DISCUSSION: Plasma protein synthesis rates are depressed after spaceflight. The observations are consistent with amino acids being the limiting factor due to substrate competition between the muscles needing protein and other tissues.

Astronauts↗
PubMed2005

Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes.

BACKGROUND: It is not known how a low-carbohydrate, high-protein, high-fat diet causes weight loss or how it affects blood glucose levels in patients with type 2 diabetes. OBJECTIVE: To determine effects of a strict low-carbohydrate diet on body weight, body water, energy intake and expenditure, glycemic control, insulin sensitivity, and lipid levels in obese patients with type 2 diabetes. DESIGN: Inpatient comparison of 2 diets. SETTING: General clinical research center of a university hospital. PATIENTS: 10 obese patients with type 2 diabetes. INTERVENTION: Usual diets for 7 days followed by a low-carbohydrate diet for 14 days. MEASUREMENTS: Body weight, water, and composition; energy intake and expenditure; diet satisfaction; hemoglobin A1c; insulin sensitivity; 24-hour urinary ketone excretion; and plasma profiles of glucose, insulin, leptin, and ghrelin. RESULTS: On the low-carbohydrate diet, mean energy intake decreased from 3111 kcal/d to 2164 kcal/d. The mean energy deficit of 1027 kcal/d (median, 737 kcal/d) completely accounted for the weight loss of 1.65 kg in 14 days (median, 1.34 kg in 14 days). Mean 24-hour plasma profiles of glucose levels normalized, mean hemoglobin A1c decreased from 7.3% to 6.8%, and insulin sensitivity improved by approximately 75%. Mean plasma triglyceride and cholesterol levels decreased (change, -35% and -10%, respectively). LIMITATIONS: The study was limited by the short duration, small number of participants, and lack of a strict control group. CONCLUSION: In a small group of obese patients with type 2 diabetes, a low-carbohydrate diet followed for 2 weeks resulted in spontaneous reduction in energy intake to a level appropriate to their height; weight loss that was completely accounted for by reduced caloric intake; much improved 24-hour blood glucose profiles, insulin sensitivity, and hemoglobin A1c; and decreased plasma triglyceride and cholesterol levels. The long-term effects of this diet, however, remain uncertain.

Appetite↗
PubMed2005

Effect of hind limb muscle unloading on liver metabolism of rats.

In response to decreased use, skeletal muscle undergoes an adaptive reductive remodeling. There is a shift in fiber types from slow twitch to fast twitch fiber types. Associated with muscle unloading is an increased reliance on carbohydrate metabolism for energy. The hind limb suspended (HLS) rat model was used as the experimental model to determine whether skeletal muscle unloading had any impact on the liver. We used a combination of actual enzyme assays and microarray mRNA expression to address this question. The GenMAPP program was used to identify altered metabolic pathways. We found that the major changes in the liver with HLS were increases in the expression of genes involved in the generation of energy fuels for export, specifically gluconeogenesis and lipogenesis. The expression of mRNA was increased (P<0.05) for three of the four enzymes involved in the regulation of gluconeogenesis pathway (pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G-6-Pase). Actual assay of enzymatic activity, in micromol . min(-1) . mg protein(-1) showed G-6-Pase (0.14+0.01 vs 0.17+0.01 P<0.05), fructose 1,6, bisphophosphatase (0.048+0.002 vs 0.054+0.002, P<0.07), and PEPCK (0.031+0.002 vs 0.038+0.012 (P<0.05) to be increased. We conclude that 1) atrophied muscle is not the only tissue to be affected by HLS, as there is also a response by the liver; and 2) the major changes in liver substrate metabolism induced by HLS appear to be limited to glucose and triglyceride production. The increase in glycolytic capacity in disused muscle is paralleled by an increase in glucogenic capacity by the liver.

Animals↗
PubMed2005

Oxidative stress, diet, and the etiology of preeclampsia.

BACKGROUND: A current theory holds that oxidative stress, ie, an imbalance between maternal prooxidants and antioxidants, is a component of preeclampsia. It is uncertain whether such an imbalance occurs before clinical recognition of the syndrome or whether it is related to diet. OBJECTIVE: We measured urinary excretion of the isoprostane 8-iso-prostaglandin F(2alpha), which is an indicator of oxidative damage to lipids, and the total antioxidant power, which is a global measure of antioxidant status, at the entry to prenatal care. We also examined the relation of these indexes to diet during pregnancy. DESIGN: A cohort of 307 gravidae from Camden, NJ, was studied from entry to prenatal care (at 15.0 +/- 0.49 wk gestation). Measures of the maternal diet were obtained by 24-h recall. RESULTS: Risk of preeclampsia was increased 5-fold with higher urinary isoprostane excretion and decreased 3-fold with higher total antioxidant power. Over the course of pregnancy, there were significant trends for an association of higher isoprostane excretion with increased consumption of energy-adjusted fat, polyunsaturated fat, and polyunsaturated fatty acids (n-3, n-6, and linoleic and linolenic fatty acids), whereas total antioxidant power was not related to diet. CONCLUSIONS: Increased urinary excretion of isoprostane and decreased antioxidant production is an imbalance that is consistent with oxidative stress, and it precedes clinical recognition of preeclampsia. The maternal diet is an underlying factor that provides an environment for free radical generation.

Adolescent↗
PubMed2003

Protein turnover in atrophying muscle: from nutritional intervention to microarray expression analysis.

PURPOSE OF REVIEW: In response to decreased usage, skeletal muscle undergoes adaptive reductive remodeling due to the decrease in tension on the weight bearing components of the musculo-skeletal system. This response occurs with uncomplicated disuse (e.g. bed rest, space flight), as a secondary consequence of several widely prevalent chronic diseases for which activity is reduced (e.g. chronic obstructive pulmonary disease and chronic heart failure) and is part of the aging process. The problem is therefore one of considerable clinical importance. RECENT FINDINGS: The impaired function and exercise intolerance is related more to the associated muscle wasting rather than to the specific organ system primarily impacted by the disease. Progress has continued in describing the use of anabolic drugs and dietary manipulation. The major advance in the field has been: (i) the discovery of the atrogin-1 gene and (ii) the application of microarray expression analysis and proteomics with the objectives of obtaining comprehensive understanding of the pathways changed with disuse atrophy. SUMMARY: Disuse atrophy is a common clinical problem. There is a need for therapeutic interventions that do not involve exercise. A better understanding of the changes, particularly at the molecular level, could indicate hitherto unsuspected sites for nutritional and pharmacological intervention.

Exercise Tolerance↗
PubMed2003

Association of glutathione peroxidase activity with insulin resistance and dietary fat intake during normal pregnancy.

Glutathione peroxidase (GPx) is one of the most important antioxidant enzymes in humans. We studied the relationship between erythrocyte GPx activity and fasting serum insulin, plasma glucose, and C-peptide, estimates of insulin resistance from the homeostasis model of assessment as well as dietary fat intake in 408 normotensive nondiabetic pregnant women from Camden, NJ. GPx activity and the metabolic parameters were determined at entry to care (16 wk of pregnancy) and during the third trimester. GPx activity and the levels of insulin resistance increased significantly between entry and the third trimester. Statistically significant associations, all positive, were observed between GPx activity and fasting insulin (beta = 0.009, P < 0.001), glucose (beta = 0.975, P < 0.05), C-peptide (beta = 1.537, P < 0.01), and insulin resistance from the homeostasis model of assessment (beta = 0.209, P < 0.01). Dietary intakes of fat and polyunsaturated fatty acids were positively correlated with GPx activity as well. African Americans had significantly higher GPx activity, dietary fat, and polyunsaturated fatty acid intake than Hispanics and Caucasians. In conclusion, we demonstrated that normal pregnancy is associated with increased GPx activity and insulin resistance. There are ethnic differences in antioxidant response and dietary fat intake. Our findings suggest a potential link among antioxidant defenses, insulin resistance, and dietary fat intake.

Adult↗
PubMed2002

Protein kinetics in stable heart failure patients.

Heart failure (HF) is a slow progressive syndrome characterized by low cardiac output and peripheral metabolic, biochemical, and histological alterations. Protein loss and reduced protein turnover occur with aging, but the consequences of congestive HF (CHF) superimposed on the normal aging response are unknown. This study has two objectives: 1) to determine whether there was a difference between older age-matched controls and those with stable HF (i.e., ischemic pathology) in whole body protein turnover and 2) to determine whether protein metabolism in liver and skeletal muscle protein turnover is impacted by CHF. We measured the whole body protein synthesis rate with a U-(15)N-labeled algal protein hydrolysate in 10 patients with CHF and in 10 age-matched controls. Muscle fractional synthesis rate of lateral vastus muscle was determined with [U-(13)C]alanine on muscle biopsies obtained by a standard percutaneous needle biopsy technique. Fractional synthesis rates of five plasma proteins of hepatic origin (fibrinogen, complement C-3, ceruloplasmin, transferrin, and very low-density lipoprotein apoliprotein B-100) were determined by using (2)H(5)-labeled l-phenylalanine as tracer. Results showed that whole body protein synthesis rate was reduced in CHF patients (3.09 +/- 0.19 vs. 2.25 +/- 0.71 g protein x kg(-1) x day(-1), P < 0.05) as was muscle fractional synthesis rate (3.02 +/- 0.58 vs. 1.33 +/- 0.71%/day, P < 0.05) and very low-density lipoprotein apoliprotein B-100 (265 +/- 25 vs. 197 +/- 16%/day, P < 0.05). CHF patients were hyperinsulinemic (9.6 +/- 3.1 vs. 47.0 +/- 7.8 microU/ml, P < 0.01). The results were compared with those found with bed rest patients. In conclusion, protein turnover is depressed in CHF patients, and both skeletal muscle and liver are impacted. These results are similar to those found with bed rest, which suggests that inactivity is a factor in depressed protein metabolism.

Aged↗
PubMed2002

FFA cause hepatic insulin resistance by inhibiting insulin suppression of glycogenolysis.

Free fatty acids (FFA) have been shown to inhibit insulin suppression of endogenous glucose production (EGP). To determine whether this is the result of stimulation by FFA of gluconeogenesis (GNG) or glycogenolysis (GL) or a combination of both, we have determined rates of GNG and GL (with (2)H(2)O) and EGP in 16 healthy nondiabetic volunteers (11 males, 5 females) during euglycemic-hyperinsulinemic (~450 pM) clamping performed either with or without simultaneous intravenous infusion of lipid plus heparin. During insulin infusion, FFA decreased from 571 to 30 micromol/l (P < 0.001), EGP from 15.7 to 2.0 micromol x kg(-1) x min(-1) (P < 0.01), GNG from 8.2 to 3.7 micromol x kg(-1). min(-1) (P < 0.05), and GL from 7.4 to -1.7 micromol x kg(-1). min(-1) (P < 0.02). During insulin plus lipid/heparin infusion, FFA increased from 499 to 1,247 micromol/l (P < 0.001). EGP decreased 64% less than during insulin alone (-5.1 +/- 0.7 vs. -13.7 +/- 3.4 micromol x kg(-1). min(-1)). The decrease in GNG was not significantly different from the decrease of GNG during insulin alone (-2.6 vs. -4.5 micromol x kg(-1). min(-1), not significant). In contrast, GL decreased 66% less than during insulin alone (-3.1 vs. -9.2 micromol x kg(-1). min(-1), P < 0.05). We conclude that insulin suppressed EGP by inhibiting GL more than GNG and that elevated plasma FFA levels attenuated the suppression of EGP by interfering with insulin suppression of GL.

Adult↗