Biomedical subjects

B R Bistrian

Publications and source records attributed to B R Bistrian.

At least 91 records · Page 5Linked to original sources

PubMed1994

DNA replication time accounts for tumor growth variation induced by dietary fat in a breast carcinoma model.

Female Fischer rats were pair-fed on diets containing either safflower oil (SO) or fish oil (FO) for 6 weeks. Implanted breast 13762 MAT tumors had a doubling times of 35.4 and 55.5 h in SO and FO rats, respectively (P < 0.001). Proliferation kinetics were measured in vivo by bromedeoxyuridine (BrdUrd) labeling and bivariate DNA/BrdUrd analysis by flow cytometry. After 1 h of pulsing, the labeling index was similar in both groups. However, 6 h later, tumor cells from FO rats had significantly lower relative movement of BrdUrd-labeled cells (0.78 vs. 0.91, P < 0.001). These results reflected a significantly longer S phase duration (15.0 vs. 9.1 h, P < 0.001) in FO rats and accounted for all the difference in tumor growth rates. This mechanism, which has not previously been reported, implies a significant role for fatty acids in DNA replication.

Animals↗

PubMed1994

Influence of interleukin-2 infusion on cell cycle kinetics in the Walker-256 carcinosarcoma.

The effect of recombinant human interleukin-2 (IL-2) on tumor cell cycle kinetics was evaluated in rats bearing the Walker-256 carcinosarcoma. Seven days after implantation, tumor-bearing rats were infused intravenously with IL-2 at a dose of 500 mg/kg body weight or 5% dextrose for 6 h. Tumor cell mean DNA synthesis time (TDNA), labeling index, potential doubling time (Tpot), and growth fraction (GF) were determined in vivo by use of bromodeoxyuridine (BrdUrd) pulse labeling and bivariate BrdUrd/DNA analysis using flow cytometry. IL-2 treatment significantly reduced the relative number of S-phase cells by 11.9% and increased the number of cells in the G0/G1 phase by 9.4%. The labeling index was reduced from 41.3 +/- 2.5% to 32.7 +/- 1.2% (P < .01). Estimates of TDNA derived from the change in BrdUrd movement relative to DNA content were not affected by IL-2 treatment. Based on these cytokinetic changes, IL-2 infusion significantly increased tumor Tpot from 15.3 +/- 0.3 h to 21.5 +/- 0.2 h (P < .001) and reduced GF from 1.01 +/- 0.07 to 0.83 +/- 0.01 (P < 0.001). The inhibitory effect of IL-2 infusion on tumor cell growth, which may be either direct or secondarily mediated by other factors, contrasts with other stimulatory effects of this cytokine on lymphoid cell proliferation.

Animals↗

PubMed1994

Fatty acid composition of lung, macrophage and surfactant phospholipids after short-term enteral feeding with n-3 lipids.

Utilization of enteral feeding modalities may prove clinically relevant for rapid modulation of lung phospholipid polyunsaturated fatty acids (PUFA) that serve as substrates for the formation of vasoactive dienoic eicosanoids. We compared the effects of short-term enteral feeding with formulations enriched with either fish (n-3) or corn (n-6) oil PUFA on the fatty acid composition of rat lung, alveolar macrophage and surfactant phospholipids. The diets were infused continuously for 72 h through a surgically placed gastroduodenal feeding catheter by a syringe pump. The n-3 PUFA derived from the fish oil enriched diet were readily incorporated into the phospholipid membranes of the alveolar macrophages, lung tissue and pulmonary surfactant. The relative percentages of the n-3 PUFA were significantly higher and individual and total n-6 PUFA significantly lower in the macrophage, lung and surfactant phospholipids from the n-3-supplemented rats in comparison with those present in the rats infused enterally with the n-6 diet or untreated, chow-fed rats (baseline). In contrast, there was a significant increase in linoleic acid (18:2n-6) without modification of arachidonic acid (20:4n-6) in the alveolar macrophages, lung tissue and surfactant from rats enterally receiving the n-6 diet relative to levels measured in the rats at baseline. The results suggest that short-term continuous delivery of n-3-enriched enteral preparations can foster rapid modification of membrane phospholipid PUFA composition of lung tissue, alveolar macrophages and lung surfactant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effects of systemic infusions of endotoxin, tumor necrosis factor, and interleukin-1 on glucose metabolism in the rat: relationship to endogenous glucose production and peripheral tissue glucose uptake.

This study was performed to characterize and compare the actions of insulin on hepatic glucose production and peripheral glucose utilization during infusions of endotoxin, tumor necrosis factor (TNF), interleukin-1 (IL-1), and a combination of IL-1 and TNF in the rat. The euglycemic hyperinsulinemic clamp technique was combined with a primed-constant tracer infusion of high-performance liquid chromatography (HPLC)-purified 3H-3-glucose for estimation of whole-body glucose appearance and utilization rates; 14C-deoxyglucose (14C-DG) uptake was also measured in specific tissues following intravenous bolus administration. As expected, acute endotoxemia resulted in a significant reduction of glucose infusion during the clamp procedure (insulin concentration, 100 microU/mL), suggesting decreased insulin action. Similarly, infusion of TNF decreased the rate of glucose infusion necessary to maintain euglycemia. However, differences between endotoxin- and cytokine-treated rats were noted in whole-body glucose appearance (or disappearance) rates. Whereas endotoxin infusion predominantly decreased whole-body glucose uptake, suggesting diminished utilization in skeletal muscles, cytokine infusions were associated with a measurable hepatic glucose output despite hyperinsulinemia. In contrast, both cytokine and endotoxin administration decreased the rate of 14C-DG uptake by muscle tissue. These results demonstrate that TNF, IL-1, and endotoxin can induce a state of insulin resistance when infused continuously; the results also emphasize the complexity of regulation of glucose homeostasis during infection and sepsis.

Animals↗

PubMed1994

Effect of low and high amounts of a structured lipid containing fish oil on protein metabolism in enterally fed burned rats.

To determine the optimal fat intake and source in nutritional support, we measured the protein-sparing effects of a structured lipid (SL) derived from 60% medium-chain triglyceride (MCT) and 40% fish oil and a 50:50 soybean to safflower oil emulsion (long-chain triglyceride, LCT). Male Sprague-Dawley rats received an enteral diet for 7 d with either all nonprotein energy as dextrose (control diet) or 10% or 35% nonprotein energy as SL or LCT. The rats were burned on day 3. Indirect calorimetry and nitrogen balance were measured on day 2 (preburn) and days 4 and 6 (postburn). Respiratory quotient decreased postburn. There was a significant increase in total energy expenditure postburn, particularly with 35% LCT. Nitrogen balance was best without fat and 10% fat compared with 35% fat and with SL compared with LCT. These results confirm previous studies that fish oil-containing SLs possess protein-sparing effects in burn injury and that 10% SL seems optimal for nutritional support in burn injury.

Analysis of Variance↗

PubMed1994

The value of arm circumference measurements in assessing chronic energy deficiency in Third World adults.

OBJECTIVE: To assess the usefulness of mid-upper arm circumference (MUAC) as a substitute for body mass index (BMI: kg/m2) or an additional measure of adult nutritional state. DESIGN: Variously sampled adults aged 18-60 years from selected regions of five African countries, India, China and Papua New Guinea were measured. SUBJECTS: 2421 men and 3248 women were measured for their heights, weights and MUAC. Of these, 1569 men and 1905 women also had their triceps skinfold thickness measured, thus allowing additional estimates of muscle area circumferences and fat areas in the arm. RESULTS: MUAC and BMI were highly correlated in each national group; each group's MUAC differed from the overall mean MUAC at any BMI value by < 10%. Women's MUACs were smaller than men's at equivalent BMIs. Increases in MUAC with age were statistically significant but trivial. Muscle and fat measurements showed similar increases with BMI; a larger muscle mass in men explained their greater MUACs but muscle differences alone did not explain national variations in MUAC. The -1 SD MUAC value, taken as an independent measure of peripheral tissue wasting, readily distinguished those with a BMI < 16.0 from those with a BMI > 18.5; intermediate grades of BMI were poorly specified by MUAC values. CONCLUSION: MUAC values of 23.0 cm in men and 22.0 cm in women are useful cut-off points for simple screening of nutritional state. In combination with BMI it may provide a more refined classification of CED. This new combined classification scheme may be a better means of discriminating the at-risk underweight adults from those who are thin but not at risk.

Adolescent↗

PubMed1994

[Influences of tumor necrosis factor-alpha on protein metabolism and cell-cycle kinetics in malignant tumor].

Sprague-Dawley rats, subcutaneously inoculated with Walker 256 carcinosarcoma, were injected intraperitoneally with recombinant human TNF-alpha at a dose of 4.75 x 10(6) U/kg for 3 consecutive days. Protein metabolism and cell-cycle kinetics of the tumor were studied. The results showed a significant decrease in tumor volume and weight in comparison with control. TNF resulted in significant decrease in tumor protein fractional synthesis rate (25.3% +/- 3.5%.d-1 versus control 42.9% +/- 2.7%.d-1, P < 0.01), protein synthesis (0.20 +/- 0.05 g/d versus control 1.14 +/- 0.20 g/d, P < 0.001) and fractional growth rate (24.3% +/- 2.1%.d-1 versus control 35.8% +/- 2.3%.d-1, P < 0.01), but no change of tumor protein fractional degradation rate. TNF also resulted in remarkable decline in labelling index (30.8% +/- 4.2% versus control 44.7% +/- 4.2%, P < 0.01) and G1 phase increase (6.0% +/- 1.3% versus control 12.2% +/- 2.5%, P < 0.01) of tumor cells, 6 hours after injection of bromodeoxyuridine, by flow cytometry. The results indicate that TNF inhibits tumor growth as a result of decreases in tumor cell DNA and protein syntheses.

Animals↗

PubMed1994

Is total parenteral nutrition immunosuppressive?

Total parenteral nutrition (TPN) has been a major advance in patient therapeutics, particularly for critically ill patients. Incorrect administration of TPN, however, primarily through excessive use of energy, either as dextrose or lipid, is an underappreciated risk factor that leads to serious complications in nutritional support. Even a modest degree of uncontrolled hyperglycemia induced by TPN appears to increase the risk of infection, usually to a level that can nullify any potential benefit of feeding. Rapid and/or excessive lipid administration can interfere with the reticuloendothelial system function, which may also predispose the patient to serious infection. The goals of nutritional support in the critically ill are to provide ample protein at 1.5 to 2.0 g/kg body weight/day, while limiting calories to approximately the patient's resting energy expenditure, which optimally supports the metabolic response to injury. Repleting the critically ill, malnourished patient with calories in excess of the patient's energy expenditure is not effective, but rather increases the likelihood of an adverse outcome.

Body Weight↗

PubMed1993

Thermogenesis secondary to transdermal water loss causes growth retardation in essential fatty acid-deficient rats.

Manifestations of essential fatty acid (EFA) deficiency in rats include growth retardation and increased transdermal water loss. The extra metabolic energy requirement could be caused by greater evaporative water loss from the skin surface. To test this hypothesis, 38 weanling rats were randomly assigned to one of two environments, control (CE) at 20 degrees C and 40% humidity or warm/humid (WHE) at 30 degrees C and 90% humidity. Half of the 20 CE rats were fed an EFA-adequate diet and the other 10 an EFA-deficient diet; the 18 WHE rats were also equally partitioned to the two diets. CE and WHE animals were independently group-fed to maintain equal energy intakes within each environment. Weight gain at 90 days was lower for CE EFA-deficient rats than for CE EFA-adequate rats (P < .0001). Growth rates in the WHE to 140 days did not differ. Mean weights at 90 days were as follows: CE EFA-adequate, 196 g; CE EFA-deficient, 148 g; WHE EFA-adequate, 148 g; WHE EFA-deficient, 135 g. In both CE and WHE animals, the triene/tetraene ratio of both serum and liver phospholipids (PL) was 100-fold greater for EFA-deficient versus EFA-adequate diets. PL fatty acids of liver in CE and WHE EFA-deficient rats contained 2.09 and 1.92 micrograms of 20:3 omega 9 per micrograms phosphorus (Pi), respectively, compared with 0.03 and 0.02 microgram 20:3 omega 9/micrograms Pi in CE and WHE EFA-adequate rats. These results indicate equivalent degrees of EFA deficiency in the two environments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of fish oil on glucose metabolism in the interleukin-1 alpha-treated rat.

Fish oil has been demonstrated to ameliorate many of the responses to infection. This study was conducted to determine whether fish oil feeding could modify the alterations of glucose metabolism induced by interleukin-1 alpha (IL-1 alpha) infusion in the rat. Male Sprague-Dawley rats were pair-fed for 5 weeks on two experimental diets in which the source of fat was either fish oil or soybean oil and provided 20% of calories; the diets were isonitrogenous and isocaloric. After 5 weeks of feeding, rats from both diet regimens were further divided into two subgroups to receive a 3-hour infusion of either 0.1% albumin in saline or 0.1% albumin in saline containing IL-1 alpha. A total of 20 micrograms/kg IL-1 alpha was administered, and half the dose of IL-1 alpha was given as a bolus and the remaining portion (10 micrograms/kg) was continuously infused into the jugular vein. During the last 2 hours of IL-1 alpha infusion, a primed constant infusion of D-(6-3H)glucose and D-(U-14C)glucose was combined to determine the effects of IL-1 alpha and diet on glucose kinetics. Plasma levels of glucose and insulin, energy expenditure, and respiratory quotient were also measured. IL-1 alpha significantly increased concentrations of plasma insulin and the percentage of glucose carbon recycling, confirming previous findings. Concentrations of glucose and insulin with IL-1 alpha treatment were significantly higher in soybean oil- fed animals compared with fish oil-fed animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1993

Nutrition support and the human immunodeficiency virus (HIV).

Nutritional support of patients with HIV or acquired immune deficiency syndrome (AIDS) has many similarities to other disease states in that the same nutritional products and techniques are used. Some patients with HIV, and many with AIDS without secondary infection, experience a metabolic milieu similar to patients with cancer cachexia. In providing dietary counselling to the HIV patient, we encounter many of the obstacles that must be overcome to improve nutrition in cancer: anorexia, gastrointestinal discomfort, lethargy, and poor nutrient utilization, which limit the ability for nutritional repletion. When a secondary infection is superimposed on HIV, patients resemble more highly catabolic trauma patients or patients in the intensive care unit (ICU), where, despite aggressive efforts to feed, there is usually a net nitrogen wasting leading to the more rapid development of cachexia. However, even in this setting, feeding will limit substantially net catabolism when compared to total starvation. Because the nutritional needs of HIV patients vary greatly, individual strategies have to be designed as the patient moves through the stages of disease. Patients are generally able to consume adequate nutrition either as regular food or dietary supplements during the latency period of viral replication. Once secondary infections become prevalent, artificial diets administered by tube or by vein may be required during the period of active secondary infections, with dietary supplements often helpful during more quiescent periods. Patients with HIV are among the most challenging for clinicians providing nutritional support. Knowledge from treatment of patients with other diseases may be useful, but more data must be gathered on the unique aspects of aetiology and treatment of the anorexia, malabsorption, and ultimate wasting associated with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Hepatic utilization of exogenous nucleotide precursors for restoration of ATP after cold ischemia in rats.

The study objective was to assess hepatic utilization of exogenous adenosine or adenine to enhance ATP recovery in rat liver after cold ischemia. ATP was measured noninvasively by 31P nuclear magnetic resonance (NMR) in perfused livers before and after 18 h of cold ischemia. The hepatocellular concentration of ATP during the initial postischemic reperfusion without adenosine or adenine coinfusion was 60% of that in fresh liver. The ATP increased significantly (P < 0.001) to 139% and 82% of baseline in postischemic livers coinfused for 90 min with adenosine or adenine (final concentration, 1 mmol/L), respectively. Less than 0.5% of the excess adenosine was catabolized to uric acid. In conclusion, adenosine and, to a lesser extent, adenine are salvaged by liver after extended cold ischemia to enhance ATP restoration. Provision of these ATP precursors, as components of an enteral formulation may facilitate the repletion of liver ATP and foster early resumption of liver function after an ischemic insult.

Adenine↗

PubMed1993

Rapid incorporation of fish or olive oil fatty acids into rat hepatic sinusoidal cell phospholipids after continuous enteral feeding during endotoxemia.

Therapeutic modalities that downregulate macrophage and endothelial production of eicosanoid mediators by displacing membrane arachidonic acid (20:4 omega 6) may benefit patients at increased risk of septic complications. The objective of this study in rats was to assess the incorporation of fish or olive oil fatty acids into hepatic Kupffer and endothelial (K&E) cell phospholipids after 4 d of continuous enteral feeding during endotoxemia. Either endotoxin (ETX) (0.5-1 mg-1.day-1) or vehicle was infused intravenously during the last 72 h. Dietary fish and olive oil fatty acids were rapidly incorporated into both K&E and plasma phospholipids irrespective of ETX cotreatment. Rats infused with the fish oil-enriched diet had a significantly lower relative percent of both K&E linoleic acid (18:2 omega 6) and 20:4 omega 6, whereas rats infused with the olive oil-enriched diet only had a lower relative percent of 18:2 omega 6 compared with control rats receiving corn oil. Provision of specific dietary lipids by continuous enteral infusion may prove efficacious for the rapid modulation of hepatic sinusoidal cell membrane fatty acids under either normal or endotoxemic conditions.

Animals↗

PubMed1993

Evaluation of antitumor effect of tumor necrosis factor in terms of protein metabolism and cell cycle kinetics.

To determine the significance of protein breakdown in regulating tumor growth and to better understand the antitumor mechanism of tumor necrosis factor in vivo, we measured the effects of a 6-h constant intravenous infusion of human recombinant tumor necrosis factor-alpha (rHuTNF) on tumor protein metabolism and cell cycle kinetics in rats bearing the Walker-256 carcinosarcoma. Protein metabolism was investigated with the use of [14C]leucine infusion; estimates of tumor cell cycle kinetics were obtained in vivo by use of 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling and bivariate BrdUrd/DNA analysis by flow cytometry. Reduction in tumor growth by rHuTNF was associated with a dose-dependent increase in tumor proteolysis but no change in tumor protein synthesis. At the cellular level, rHuTNF had a significant cytostatic effect on G2/M cells and caused a marked decrease in the fraction of cells capable of BrdUrd uptake. Release of BrdUrd, an indicator of cell death, was noted in only 7.5% of tumor cells labeled at the beginning of rHuTNF infusion. These results suggest that either tumor protein breakdown may influence cell cycle activity by regulating cytoplasmic protein mass or that tumor proteolysis may be a compensatory mechanism for limiting cytoplasmic size when cellular division is interrupted suddenly.

Animals↗

PubMed1992

Tumor and host response to arginine and branched chain amino acid-enriched total parenteral nutrition. A study involving Walker 256 carcinosarcoma-bearing rats.

The metabolic effects of total parenteral nutrition (TPN) solutions containing different profiles of individual amino acids were investigated in the rats bearing Walker 256 carcinosarcoma. The rats were subcutaneously inoculated with 10(7) tumor cells and 6 days later were continuously infused intravenously for 8 days with three different TPN solutions. The experimental and control solutions were composed of high concentrations of branched chain amino acids (BCAA) and arginine (high Arg + BCAA TPN), high concentrations of BCAA (high BCAA TPN) and regular amino acids (regular TPN), respectively, and were isonitrogenous, isocaloric, and isovolemic. Rats receiving subcutaneous injection of saline rather than tumor cells received high Arg + BCAA TPN as pair-fed controls. The flooding dose method of 14C-leucine was used for the analysis of protein synthesis. With the feeding of high Arg + BCAA TPN, the tumor-bearing rats revealed a smaller increase of tumor volume and lower tumor fractional rates of growth (Kg) and synthesis (Ks) as well as protein synthesis (PS), compared with the high BCAA TPN and regular TPN in tumor-bearing rats. There were no significant differences of Ks and PS in liver and muscle between TPN groups, whereas tumor-bearing rats infused with high Arg + BCAA TPN displayed higher levels of whole-body Ks and PS than other TPN groups in tumor-bearing rats and pair-fed nontumorous rats. Except for liver RNA content which showed a lower level in tumor-bearing rats with high Arg + BCAA TPN, no other differences of DNA and RNA contents were found in tumor, liver, and muscle of the different TPN groups. The current results indicate that individual amino acids can influence tumor growth and protein metabolism, and that arginine, in combination with BCAA, may reduce tumor growth through a reduction in protein synthesis.

Amino Acids, Branched-Chain↗

PubMed1992

Influence of omega-3 fatty acids on splanchnic blood flow and lactate metabolism in an endotoxemic rat model.

Alteration in regional blood flow is important in the pathogenesis of organ failure during endotoxemia and sepsis. In particular, intestinal ischemia is thought to enhance the translocation of bacteria into the systemic circulation. We used radioactive microspheres to measure the influence of two intravenous (IV) dietary fats (vegetable oil containing high levels of omega-6 fatty acids, and fish oil containing high levels of omega-3 fatty acids) on regional blood flow during low-dose Escherichia coli endotoxin infusion (0.1 mg/100 g body weight [BW]) in a rat model. Despite absence of changes in the cardiac output, blood flow rates to the small and large intestines, stomach, and pancreas, and also to the skin and skeletal muscle were significantly reduced after 18 hours of endotoxin infusion in the rats fed standard vegetable oil. Short-term IV feeding during a period of 40 hours with an isonitrogenous, isocaloric nutrient solution containing fish oil as the only lipid source normalized intestinal perfusion and increased blood flow to the liver and spleen. Low-dose endotoxin infusion also resulted in significant increases in glucose, lactate, and pyruvate concentrations. In comparison to standard vegetable fat emulsion, fish oil significantly reduced these parameters. A second experiment was conducted to measure lactate kinetics. Based on the dilution of U-14C-lactate, fish oil feeding was associated with higher lactate clearance than standard vegetable oil feeding during the endotoxin infusion. We conclude that short-term IV feeding with fish oil improves intestinal perfusion and portal blood flow, improves glucose tolerance, and increases lactate clearance in a low-dose endotoxin rat model.

Animals↗

PubMed1992

Reevaluation of current transfusion practices in patients in surgical intensive care units.

Widespread interest in the complications associated with packed red blood cell (PRBC) transfusions has led to the scrutiny of traditional transfusion practices. Recently, attempts have been made to define more clearly the indications for PRBC transfusions in patients, particularly those who are critically ill. At present, however, transfusions continue to be ordered based on a hemoglobin level less than 10 g/dL. We report herein the impact on oxygen consumption of PRBC transfusions administered for a hemoglobin concentration less than 10 g/dL in 30 surgical intensive care unit patients who were euvolemic and hemodynamically stable. For the group as a whole, transfusion had a negligible effect on oxygen consumption. Fifty-eight percent of all such transfusions failed to change oxygen consumption by greater than 10% and could therefore be considered of questionable benefit.

Adult↗

PubMed1992

Could the oxygen cost of breathing be used to optimize the application of pressure support ventilation?

Pressure support ventilation (PSV) is a new ventilator modality that augments spontaneous inspiratory pressure with selected levels of positive airway pressure. There is presently considerable interest in its use in the management of critically ill, ventilator-dependent patients. The optimal method for application has not yet been established. This study investigated the effects of PSV on the oxygen cost of breathing (OCOB), a clinically applicable technique for quantitating the work of breathing. The OCOB and other bedside variables of pulmonary function were measured during PSV in ventilator-dependent patients where weaning was limited by an inability to sustain respiratory work. Nine studies were performed in 8 patients in the surgical intensive care unit. The OCOB, tidal volume (VT), respiratory rate (RR), and minute ventilation (VE) were measured at various levels of pressure support. The OCOB was calculated from the difference in oxygen consumption (VO2) during mechanical and spontaneous ventilation both at CPAP and with PSV. With increasing levels of PSV, the OCOB was observed to steadily decrease from 22% to 8% (p < 0.001). There were also statistically significant increases in VT and decreases in RR. VE appeared not to be influenced. The results of this study suggest that the bedside measurement of the OCOB may be an accurate, simple, and reproducible method of titrating the level of applied pressure support in order to optimize respiratory work.

Aged↗