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Biomedical subjects

T P Stein

Publications and source records attributed to T P Stein.

At least 19 recordsLinked to original sources
PubMed1997

Weight loss, the gut and the inflammatory response in aids patients.

UNLABELLED: The objective of this study was to test the hypothesis that the integrity of the large bowel wall in AIDS patients is compromised in a manner that favours the chronic translocation of bacteria and/or products of bacterial metabolism into the bloodstream. When such translocation occurs, it induces a characteristic stress/inflammatory response in the body. Urinary butyrate, a unique product of colonic microbial metabolism, was used to assess gut wall permeability. Excretion of the pro-inflammatory cytokine IL-6 in the urine was used as a marker for the stress/inflammatory response. Four groups of subjects were studied, controls (n = 12), HIV + (n = 35) and AIDS patients with (n = 14) and without (n = 17) weight loss. RESULTS: measurable amounts of interleukin 6 (IL-6) and butyrate were found in the urine of all subjects. There were no significant differences in IL-6 excretion between the controls (0.68 +/- 0.64 pg/ml), asymptomatic HIV + subjects (0.59 +/- 0.37 pg/ml) and AIDS patients without weight loss (1.18 +/- 0.33 pg/ml) but IL-6 levels were significantly higher in the AIDS group with weight loss (4.02 +/- 1.26 pg/ml, P < 0.05). A similar pattern of results was found with interleukin 1 receptor antagonist (IL-1ra). Like IL-6 and (IL-1ra), urinary butyrate levels were increased in the AIDS patients with weight loss (2.83 +/- 0.67 mumol/l) relative to the controls (1.31 +/- 0.13 mumol/l, P < 0.05), with the HIV + patients (1.65 +/- 0.18 mumol/l) and AIDS patients without weight loss (1.90 +/- 0.22 mumol/l) falling in between. The data are consistent with a low, but chronic rate of bacteria and/or bacterial products seeping across a compromised colonic wall causing a chronic low stress response in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Human skeletal muscle protein breakdown during spaceflight.

Human spaceflight is associated with a loss of body protein. Excretion of 3-methylhistidine (3-MH) in the urine is a useful measurement of myofibrillar protein breakdown. Bed rest, particularly with 6 degrees head-down tilt, is an accepted ground-based model for human spaceflight. The objectives of this report were to compare 3-MH excretion from two Life Sciences shuttle missions (duration 9.5 and 15 days, n = 9) and from 17 days of bed rest (n = 7) with 6 degrees head-down tilt. The bed rest study was designed to mimic an actual Life Sciences spaceflight and so incorporated an extensive battery of physiological tests focused on the musculoskeletal system. Results showed that nitrogen retention, based on excretion of nitrogen in the urine, was reduced during both bed rest [from 22 +/- 1 to 1 +/- 5 mg N x kg(-1) x day(-1) (n = 7; P < 0.05)] and spaceflight [from 57 +/- 9 to 19 +/- 3 mg N x kg(-1) x day(-1) (n = 9; P < 0.05)]. 3-MH excretion was unchanged with either bed rest [pre-bed rest 5.30 +/- 0.29 vs. bed rest 5.71 +/- 0.30 micromol 3-MH x kg(-1) x day(-1), n = 7; P = not significant (NS)] or spaceflight [preflight 4.98 +/- 0.37 vs. 4.59 +/- 0.39 micromol 3-MH x kg(-1) x day(-1) in-flight, n = 9; P = NS]. We conclude that 1) 3-MH excretion was unaffected by spaceflight on the shuttle or with bed rest plus exercise, and 2) because protein breakdown (elevated 3-MH) was increased on Skylab but not on the shuttle, it follows that muscle protein breakdown is not an inevitable consequence of spaceflight.

Bed Rest↗
PubMed1996

Effect of fentanyl citrate anesthesia on protein turnover in patients with esophagectomy.

The objectives of this study were to determine whether high doses of fentanyl anesthesia reduced the surgical stress level and to elucidate the effect of fentanyl anesthesia on protein turnover after esophagectomy. Seventeen male patients with esophageal cancer were divided into two groups, conventional anesthesia (CA) and fentanyl anesthesia (FA). The FA patients received 134.0 +/- 15.3 microg/kg fentanyl citrate and the CA patients 15.7 +/- 7.4 microg/kg fentanyl during the surgery. Protein turnover was measured by the method of bolus infusion of [15N]glycine (1 g). High dose of fentanyl anesthesia reduced cortisol levels during the surgery (CA 38.0 +/- 13.8 pg/ml vs FA 13.5 +/- 2.4, P < 0.05) and interleukin-6 levels in the plasma after the surgery (P < 0.02). The postoperative nitrogen retention was greater with fentanyl anesthesia than with conventional anesthesia. Both protein synthesis and breakdown rates were increased with fentanyl anesthesia, while they were unaltered in CA patients. Postoperative fibrinogen synthesis rate was greater with FA than with CA (CA 51.1 +/- 9.2%/day vs FA 100.9 +/- 14.0, P < 0.01). The protein turnover and fibrinogen synthesis data suggested a shorter duration of shock phase in FA patients than in CA patients. We concluded that a high dose of fentanyl anesthesia reduced surgical stress levels and shortened the postoperative shock phase, resulting in a nitrogen-sparing effect.

Acute-Phase Proteins↗
PubMed1996

Supplementation with gum arabic fiber increases fecal nitrogen excretion and lowers serum urea nitrogen concentration in chronic renal failure patients consuming a low-protein diet.

In chronic renal failure (CRF), plasma concentrations of the products of protein metabolism are increased. Current dietary management is to prescribe a decrease in protein intake. The use of dietary fiber to increase fecal excretion of retained metabolites in CRF may be a beneficial adjunct to a low-protein diet (LPD). Colonic bacteria ferment dietary fiber, providing them with energy for growth and nitrogen incorporation, in turn, increasing nitrogen excretion in feces. Sixteen CRF patients consuming an LPD were randomly assigned to receive a supplement of a highly fermentable fiber, gum arabic (50 g/d), or a placebo (1 g pectin/d) in a prospective, single-blind, crossover design. Fecal bacterial mass and fecal nitrogen content were significantly increased during supplementation with gum arabic compared with the baseline LPD or supplementation with pectin. Serum urea nitrogen was significantly decreased during supplementation with gum arabic compared with the baseline LPD or supplementation with pectin. Nitrogen balance did not change significantly.

Adult↗
PubMed1996

Energy expenditure in rhesus monkeys (Macaca mulatta) during spaceflight using doubly labeled water (2H2(18)O).

The mean daily energy expenditure rates of three rhesus monkeys (Macaca mulatta) were determined during spaceflight on the joint US-Russian Cosmos 2044 and 2229 missions by the doubly labeled water (2H2(18)O) method. In-flight values were compared with ground data obtained from seven measurements taken from six chair-adapted control monkeys. The mean energy expenditure for the ground control determinations was 94.5 +/- 6.4 kcal.kg-1.day-1 (n = 6). The mean in-flight energy expenditure, 55.1 +/- 8.0 kcal.kg-1.day-1 (n = 3), was significantly less than the mean ground control value (P < 0.05). These data suggest that energy expenditure in restrained rhesus monkeys is significantly reduced during spaceflight.

Animals↗
PubMed1996

Diet and nitrogen metabolism during spaceflight on the shuttle.

Human spaceflight is associated with a loss of body protein. To investigate this problem, dietary intake, nitrogen balance, the whole body protein, and fibrinogen protein synthesis rates were measured on the crews of two Spacelab Life Sciences (SLS) shuttle missions before, during, and after spaceflight. The first mission, SLS-1, lasted 9.5 days, and the second, SLS-2, lasted 15 days. The 15N-glycine method was used for the protein synthesis measurements. The following results were obtained. 1) There was a rapid decline in weight for the first 5 days and then the body weight appeared to stabilize. 2) The mean energy intake preflight was 39.0 +/- 2.5 kcal x kg-1 x day-1 (n = 10). There was a sharp drop in dietary intake on flight day 1, with recovery by the second day, and then energy intake was constant at 30.4 +/- 1.5 kcal x kg-1 x day-1 (n = 12) for the remainder of the flight period (P < 0.05). 3) Nitrogen retention was decreased during flight, with the magnitude of the decrease lessening toward the end of the mission. The daily mean nitrogen balance changed from 58 +/- 9 mg x kg-1 x day-1 (n = 9) preflight to 16 +/- 3 mg N x kg-1 x day-1; P < 0.05; n = 11) in flight, corresponding to a loss of approximately 1 kg of lean body mass over 14 days. 4) Whole body protein synthesis was increased early in flight and on recovery, as was fibrinogen synthesis. We conclude that 1) the rapid readjustment and stabilization of energy intake and the improved nitrogen retention with increasing flight duration are consistent with a rapid metabolic accommodation to the novel environment; and that 2) the increased protein turnover indicates that a metabolic stress response is an important factor in this adjustment process.

Adult↗
PubMed1995

The effect of insulin-like growth factor-1 on protein metabolism and hepatic response to endotoxemia in parenterally fed rats.

To determine the influence of insulin-like growth factor-1 (IGF-1) on nitrogen loss and hepatic response to critical illness, 34 male Sprague-Dawley rats (190-230 g) were randomized to receive parenteral nutrition (PN) only (Ctrl), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), or PN plus LPS plus rhIGF-1 (IGF-1) at 3 mg/kg/day for 48 hr. Prior to randomization, all animals underwent iv cannulation and 30 hr of adaptation to PN. All animals received isocaloric and isonitrogenous PN (glucose 170 kcal/kg/day and nitrogen 1.1 g/kg/day) and were kept NPO except for water ad libitum. [15N]glycine was infused in all animals for determination of liver fractional synthetic rate. Cumulative nitrogen balance during endotoxemia was significantly different from each other (+72 +/- 42, -217 +/- 131, -114 +/- 137 mg/kg/48 hr for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001). Endotoxin significantly increased the urinary 3-methylhistidine/creatinine ratio (0.24 +/- 0.05, 0.55 +/- 0.12, 0.48 +/- 0.17 for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001); however, IGF-1 did not significantly reduce the ratio. Endotoxin induced a significant increase in liver fractional synthetic rate (29 +/- 8, 56 +/- 18, 64 +/- 12%/day for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.01) and depressed hepatic cytochrome P450 concentration (0.54 +/- 0.19, 0.22 +/- 0.07, 0.19 +/- 0.07 nmol/mg protein, respectively; ANOVA, P < 0.05) and ethoxycoumarin O-deethylase (ECOD) activity (103 +/- 73, 29 +/- 13, 17 +/- 11, pmol/mg/min, respectively; ANOVA, P < 0.01); however, rhIGF-1 did not significantly alter these hepatic variables during endotoxin infusion. Recombinant human insulin-like growth factor-1 significantly improved nitrogen balance without compromising hepatic response as measured by liver fractional synthetic rate, cytochrome P450 concentration, and ECOD activity in endotoxemic parenterally fed rats.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1995

Effect of growth hormone and protein intake on tumor growth and host cachexia.

BACKGROUND: Growth hormone supplementation has been shown to stimulate muscle protein synthesis and to improve nitrogen balance in a variety of catabolic states. The role of growth hormone to support the tumor-bearing host is complicated by the risk that growth hormone or its intermediaries may stimulate tumor growth. The purpose of this study is to examine the effect of growth hormone supplementation in tumor-bearing rats. This is studied in the protein-fed and protein-starved state in an attempt to isolate a selective benefit for the host over the tumor. METHODS: Forty Lewis rats bearing a metastatic mammary adenocarcinoma (MAC-33) were divided into four groups: one receiving a regular diet plus saline solution, one receiving a regular diet plus growth hormone (1 IU/kg/day), one receiving protein-depleted diet plus saline solution, and one receiving a protein-depleted diet plus growth hormone. After 25 days of growth hormone treatment, animals were killed to determine primary tumor size, tumor/carcass ratio, host organ composition, pulmonary metastasis, and serum amino acid levels. RESULTS: The tumor/carcass ratio was decreased as a result of growth hormone treatment in both the protein-fed and protein-starved groups. Growth hormone supplementation resulted in increased carcass weight, muscle weight, and muscle protein content in the protein-fed, tumor-bearing animals (p < 0.05). In the protein-starved, tumor-bearing rats growth hormone supplementation resulted in a significant decrease in tumor volume and tumor protein content. Amino acid analysis suggests that the amino acid tyrosine is a rate-limiting substrate for tumor cell proliferation in this model. CONCLUSIONS: Growth hormone has a differential effect on tumor and host growth in the protein-fed and protein-starved state. Growth hormone supplementation inhibited tumor growth in protein-deprived animals. This is most likely accomplished indirectly by limiting amino acid substrate availability to the tumor.

Adenocarcinoma↗
PubMed1995

Decreased protein synthesis during dry saturation diving.

Changes in metabolism during saturation dives have been reported; however, these changes have not been well defined. This study was conducted to determine the effect of saturation diving on protein metabolism. Whole body protein synthesis was measured by the ammonia and urea endpoint methods, following a single oral dose of 15N-glycine in 11 Navy divers 33.9 +/- 1.9 yr of age. The divers were fed a controlled diet throughout the three trials. Trial I was on the surface, and trials II and III were during dry saturation dives at 0.56 MPa. The protein synthesis results in gram protein per kilogram lean body mass per day, least square mean +/- SD: [formula: see text]. Under the conditions of this series of dry saturation dives, protein synthesis was depressed by up to 30-50% for the urea and ammonia endpoint methods, respectively. An estimate of liver protein synthesis was made by measuring the incorporation of the 15N label into plasma fibrinogen. The 15N enrichment of fibrinogen glycine and the hippurate precursor for fibrinogen were decreased significantly. This dramatic decrease in protein synthesis was observed despite positive nitrogen balance in these divers. Although further investigation is needed to elucidate the mechanism, the decrease in the incorporation of 15N glycine into fibrinogen suggests alteration in liver nitrogen metabolism at 0.56 MPa.

Adult↗
PubMed1994

Spaceflight and protein metabolism, with special reference to humans.

Human space missions have shown that human spaceflight is associated with a loss of body protein. Specific changes include a loss of lean body mass, decreased muscle mass in the calves, decreased muscle strength, and changes in plasma proteins and amino acids. The major muscle loss is believed to be associated with the antigravity (postural) muscle. The most significant loss of protein appears to occur during the first month of flight. The etiology is believed to be multifactorial with contributions from disuse atrophy, undernutrition, and a stress type of response. This article reviews the results of American and Russian space missions to investigate this problem in humans, monkeys, and rats. The relationship of the flight results with ground-based models including bedrest for humans and hindlimb unweighting for rats is also discussed. The results suggest that humans adapt to spaceflight much better than either monkeys or rats.

Amino Acids↗
PubMed1994

Excretion of IL-6 by astronauts during spaceflight.

Ascent to and living under the microgravity conditions found during spaceflight is an unfamiliar environment for humans. The adaptation to the space environment may be perceived by the body as a stress. On the ground, stress results in increased cytokine activity. The objective of this study was to determine whether spaceflight is associated with increased cytokine activity. The mean daily urinary interleukin-6 (IL-6) excretion rate was measured on 24-h urine pools collected from four payload crew members from 11 days before launch to 7 days after landing for a total of 27 days. In addition, in-flight data were obtained from two orbiter crew members. The experiment was conducted before, during, and after the 1991 9.5-day SLS-1 (Columbia) space shuttle mission. Dietary intake and urine output were monitored continuously for the 27-day period for the four payload crew. Results are as follows: 1) urinary IL-6 excretion and cortisol excretion were increased on the 1st day of spaceflight, suggesting an acute-phase response; 2) elevated levels of IL-6 were not found in the urine on any other days before or during flight; and 3) two of the subjects had markedly increased IL-6 excretion rates after landing.

Diet↗
PubMed1994

Development of insulin resistance by astronauts during spaceflight.

Human spaceflight is associated with the loss of body protein. On Earth, insulin is an important factor in the regulation of muscle protein synthesis and breakdown. The objectives of this study were to determine whether insulin resistance occurs in spaceflight, and if the development of insulin resistance is related to the protein loss. The urinary C-peptide excretion rate was used as a marker for insulin secretion. The experiment was conducted before, during and after the 1991 9.5-d SLS-1 (Columbia) Space Shuttle mission. Dietary intake and urine output were monitored continuously for the four payload crewmembers from 11 d before launch to 7 d after landing for a total of 27 d. Data were obtained on the four payload crewmembers. Results were as follows: 1) the mean inflight C-peptide excretion rates were significantly lower than either the pre- or postflight rates (p < 0.05); and 2) the inflight nitrogen balance decreased as C-peptide excretion increased.

Adult↗
PubMed1994

Substrate cycling in lean and obese Zucker rats.

The objective of this study was to compare substrate cycling in lean and obese Zucker rats under conditions where there was (i) a nominal excess or (ii) a deficit in energy intake. Protein turnover was assessed by measuring protein synthesis and breakdown using 15N glycine as the tracer. Glucose/glucose-6-phosphate cycling was calculated from the difference in the glucose appearance rates measured using 2-D- and 6,6-D2-labeled glucose. Information on triglyceride/fatty acid cycling was obtained by measuring free fatty acid kinetics using 1-13C palmitate and glycerol kinetics using 5-D glycerol. Neither protein synthesis or breakdown or glucose cycling rates were significantly different between lean and obese Zucker rats. The relative rate of the triglyceride/fatty acid cycle was higher in the obese rat as a consequence of increased adiposity. Increased intake increased glucose cycling and decreased lipid cycling in both lean and obese rats. The findings indicate that substrate cycling is not different in obese rats and therefore is not a significant factor by which such animals maintain their severely obese state.

Animals↗
PubMed1993

Effect of tumor burden on futile glucose and lipid cycling in tumor-bearing animals.

Futile cycling of metabolic substrates may play an important role in the development of cancer cachexia. To determine the effect of tumor burden on futile glucose and lipid cycling, 64 female Lewis/Wistar rats were randomized to control (non-tumor-bearing), small tumor burden, or large tumor burden groups (MAC-33 mammary adenocarcinoma). After 5 or 25 days of tumor growth, animals received a 5-day period of parenteral nutrition (158 kcal/kg/day) followed by a 6-hr infusion of the stable isotopes glucose-2-d and glucose-6,6-d2 or [C13]palmitate. The heavy glucose isotopes glucose-2-d and glucose-6,6-d2 are labeled with deuterium at the 2-carbon position and doubly labeled with deuterium at the 6-carbon position, respectively, to obtain differential molecular weights. No increase in glucose or lipid cycling was observed in animals with small tumor burdens. In contrast, a significant increase in plasma rate of appearance (Ra) of glucose-2-d (1377 +/- 136 mg/hr vs 947 +/- 54 mg/hr), Ra of glucose-6,6-d2 (810 +/- 88 mg/hr vs 510 +/- 24 mg/hr), and total glucose cycling (548 +/- 57 mg/hr vs 416 +/- 28 mg/hr) was seen in animals with large tumor burdens compared to control animals (P < 0.05). Although a trend toward increased lipid cycling was seen in tumor-bearing versus control animals, this change was not significant. Thus, futile cycling of glucose was significantly elevated in animals with large tumor burdens and may cause significant energy wasting to contribute to the development of cachexia in the tumor-bearing host.

Adenocarcinoma↗
PubMed1993

Glycerol kinetics with parenteral lipid emulsions (long-chain triglycerides, medium-chain triglycerides, and structured lipids) in rats.

Several studies have reported that parenteral lipid emulsions containing medium-chain triglycerides (MCT) and structured lipids (SL) are better utilized than those containing long-chain triglycerides (LCT). The objective of this study was to test the hypothesis that parenteral LCT require more extensive modification via hydrolysis and reesterification (triglyceride-free fatty acid [TG-FFA] recycling) for effective utilization, whereas MCT and SL do not. As an index of TG-FFA cycling activity, we measured glycerol and palmitate kinetics in rats (204 to 243 g) fed parenterally one of three isocaloric (250 kcal/kg/d) isonitrogenous (1.5 g N/kg/d) diets with half of the nonprotein energy from glucose and the rest from either LCT, LCT plus MCT, or SL for 5 days. Two experiments were performed. On day 5, rats were given a 7-to 8-hour infusion of either 5H2 Glycerol and 1-14C Palmitate bound to albumin to measure palmitate and glycerol kinetics (experiment 1), or U-13C glucose to determine the proportion of endogenous glycerol production derived from glucose (experiment 2). Data are presented as means +/- SEM. Endogenous glycerol production was significantly higher with LCT (11.33 +/- 2.89 mmol/kg/h) than with SL (2.91 +/- 0.62 mmol/kg/h). The value for the physical mixture of LCT plus MCT (5.46 +/- 1.29 mmol/kg/h) fell midway between that for LCT and SL (P = NS). There were no significant differences in palmitate kinetics or oxidation. The increased glycerol production is due to the mobilization of endogenous triglyceride and is consistent with a higher rate of TG-FFA cycling being involved in the metabolism of LCT than of SL.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Effect of spaceflight on human protein metabolism.

Nitrogen balance and the whole body protein synthesis rate were measured before, during, and after a 9.5-day spaceflight mission on the space shuttle Columbia. Protein synthesis was measured by the single-pulse [15N]glycine method. Determinations were made 56, 26, and 18 days preflight, on flight days 2 and 8, and on days 0, 6, 14, and 45 postflight. We conclude that nitrogen balance was decreased during spaceflight. The decrease in nitrogen balance was greatest on the 1st day when food intake was reduced and again toward the end of the mission. An approximately 30% increase in protein synthesis above the preflight baseline was found for flight day 8 for all 6 subjects (P < 0.05), indicating that the astronauts showed a stress response to spaceflight.

Body Mass Index↗
PubMed1992

Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats.

The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated. Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days. On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine. Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis rates. The following results were obtained. 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum. 2) Glutamine supplementation attenuated these changes. 3) There were no visible changes to the colon either from glutamine supplementation or sepsis. 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis. 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats.

Animals↗