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Bruce R Bistrian

Publications and source records attributed to Bruce R Bistrian.

16 recordsLinked to original sources
PubMed2003

Hyperglycemia induced by glucose infusion causes hepatic oxidative stress and systemic inflammation, but not STAT3 or MAP kinase activation in liver in rats.

The purpose of this study was to determine the effects of acute hyperglycemia induced by glucose infusion on oxidative stress, systemic inflammation, and several key signal intermediates in liver for the systemic inflammatory response in nonstressed rats. Rats received saline or glucose infusion (hyperglycemic clamp) for 3 hours. Rats without catheter insertion were included as an additional control for observing the effects of surgical stress. Levels of malondialdehyde (MDA) and total glutathione to assess oxidative stress were determined in liver and muscle. Proinflammatory cytokines including tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6, and alpha 1 acid glycoprotein (alpha1-AG) were determined in serum. The protein content and phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38 stress-activated protein kinase (p38), and signal transducer and activator of transcription-3 (STAT-3) were examined in the liver tissue with or without IL-6 stimulation. The results showed that acute hyperglycemia significantly increased MDA release and depleted total glutathione in liver but not in muscle. Hyperglycemia also significantly elevated the production of TNF, IL-1, and alpha1-AG, but not IL-6 in serum. However, hyperglycemia for 3 hours in vivo did not activate ERK1/2, p38 and STAT3 in liver, and also did not alter the response of these signal proteins to IL-6 stimulation. These data suggest that acute (3 hours) hyperglycemia causes hepatic oxidative stress and activates a low-grade systemic inflammation but does not affect key components of the IL-6 signaling pathway in liver.

Animals↗
PubMed2003

Immunonutrition: problematic or problem solving?

The addition of immune-modulating nutrients to enteral formulas has been examined in clinical trials and meta-analyses. Enhancing immunity through diet is generally done by adding n-3 fatty acids, arginine, and nucleotides to an otherwise nutritionally complete formula. Despite flaws in many studies, a consistent trend to reduced infectious complications has been seen with immunonutrition, especially in patients undergoing surgery for upper gastrointestinal cancer or trauma. In critical care populations, however, the results have been mixed. In this review, we analyze these studies and focus on select clinical points that may explain the variation. One common flaw has been a failure to deliver an adequate nutrition volume. Few patients, especially in the earliest studies, received even close to goal feeding. A minimum quantity of immunonutrition may be required for effective reduction in infections. When feeding volumes are low, immunonutrition is usually not better than an isonitrogenous control. In more recent studies, practitioners have been increasingly aggressive with enteral feeding, and this has been reflected in improved outcomes from immunonutrition. Early delivery of immunonutrition (preoperatively in surgical patients with cancer) might be particularly beneficial. Another consideration is illness severity: we discuss evidence that the use of immunonutrition in moderate illness is more likely to be helpful, whereas severe sepsis is probably beyond the reach of any nutritional intervention, and mild illness is more likely to improve irrespective of feeding. If future trials can consider these vital points, level 1 recommendations in favor of immunonutrition might be justified, although presently such evidence is lacking for most clinical indications.

Adjuvants, Immunologic↗
PubMed2002

The influence of medium-chain triglycerides on the stability of all-in-one formulations.

When mixed with parenteral nutrients as an all-in-one admixture, previous data have demonstrated that lipid emulsions composed of medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs) yield more stable formulations compared with those compounded with pure LCT lipid emulsions. We investigated the physical stability of various preparations of intravenous lipid emulsions as all-in-one admixtures. Each final lipid emulsion used to compound the all-in-one formulation was a 20% w/v mixture containing MCTs and LCTs as either a single emulsion containing both triglycerides, or an emulsion made extemporaneously from separate starting emulsions of pure MCT and LCT. The first emulsion was composed of a 50:50 (by weight) physical mixture of MCTs and LCTs, and consisted of 50% MCT:40% omega-6 LCT (soybean oil):10% omega-3 LCT (fish oil) that was available as a single 20% w/v lipid emulsion. The second and third emulsions were specially prepared from separate stock dispersions containing pure 20% w/v MCT and pure 20% w/v LCT (soybean oil) lipid emulsions, and were made in volume ratios of 75% MCT:25% omega-6 LCT and 50% MCT:50% omega-6 LCT, respectively. This was done in order to investigate whether the method of emulsion preparation and/or ratio of MCT to LCT influenced all-in-one admixture stability. Each all-in-one admixture was studied at four intervals over 30 h at room temperature conditions by light extinction (or obscuration) using a single-particle optical sensing (LE/SPOS) technique. The data, performed in duplicate at each interval, is expressed as the volume-weighted percent of fat (PFAT) globules >5 microm. The results confirm the stabilizing effects of MCTs when made as a physical oil mixture as a single lipid emulsion. However, stabilization is lost if the MCT and LCT emulsions are mixed from separate starting emulsions and then compounded as an all-in-one formulation. The extemporaneous mixing of commercial lipid emulsions is not recommended.

Drug Combinations↗
PubMed2002

The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells.

The antiproliferative effects of two commercial preparations of conjugated linoleic acid (CLA) and their constituent isomers, cis-9, trans-11 (c9,t11)-CLA, c9,c11-CLA, and t10,c12-CLA, were determined in vitro using human colorectal (HT-29, MIP-101) and prostate (PC-3) carcinoma cells adapted to serum-free medium. The antiproliferative effects of the preparations were dependent upon the type and concentration of CLA isomer present. The t10,c12-CLA isomer exhibited the greatest potency against colorectal cancer proliferation, and the c9,t11 and t10,c12 isomers were moderately effective against prostate cancer. The t10,c12 isomer induced caspase-dependent apoptosis in MIP-101 and PC-3 cells. The results are the first to demonstrate that physiologic levels of two CLA preparations, their constituent isomers, and the c9,t11-CLA elongation product, c11,t13-conjugated eicosadienoic acid, induce dose-dependent inhibitory effects on cancer proliferation in vitro. Novel CLA preparations may prove effective as chemopreventive supplements for individuals at risk of or diagnosed with colorectal or prostate cancer.

Apoptosis↗
PubMed2002

Disturbances in essential fatty acid metabolism in patients receiving long-term home parenteral nutrition.

Patients receiving home total parenteral nutrition (HTPN) are at risk for the development of essential fatty acid deficiency (EFAD). This study examined the essential fatty acid status of patients on long-term HTPN for gut failure. Serum phospholipid and triglyceride fatty acids were measured in 11 patients and 10 healthy volunteers. Patients had similar levels of linoleic acid (18:2w6) in serum triglyceride fatty acids but significantly lower levels of 18:2w6 in serum phospholipids compared to controls. Although there was accumulation of Mead acid (20:3w9) in both fatty acid fractions, the ratio of 20:3w9 to arachidonic acid (20:4w6) remained less than 0.2, reflecting an adequate essential fatty acid status in these patients. There were, however, substantial increases in 20:4w6 content in both triglyceride and phospholipid fractions in serum despite the lower levels of 18:2w6 in serum phospholipids, suggesting that an accelerated hepatic conversion of 18:2w6 to 20:4w6 occurs in HTPN patients, as well as the 20-carbon members of w3 (20:3w3) and w9 (20:3w9) families. The determination of optimal parenteral fat intakes should be investigated further as important priority in patients receiving long term HTPN.

Adult↗
PubMed2002

Patterns of plasma leptin and insulin concentrations in hospitalized patients after the initiation of total parenteral nutrition.

BACKGROUND: The regulation of leptin in patients with critical illness is poorly understood. Sex, diet, body mass, and cytokines may all play a role. OBJECTIVE: The aims of this study were to determine the factors influencing leptin concentrations in hospitalized patients beginning total parenteral nutrition (TPN) and whether a 3-d regimen of TPN would further increase plasma leptin concentrations above baseline. DESIGN: Twenty-six patients requiring TPN were enrolled in this prospective, nonintervention study. Only 20 (11 women and 9 men) completed all 3 d of TPN. RESULTS: Baseline plasma leptin in the TPN patients ranged from 62.5 to 1625 pmol/L ( +/- SD: 419 +/- 387; n = 26) and was not significantly different between men (444 +/- 494 pmol/L) and women (363 +/- 244 pmol/L). Baseline plasma insulin ranged from 76 to 695 pmol/L (271 +/- 188; n = 26) and was not correlated with plasma leptin. Leptin concentrations increased after 3 d of TPN, from 356 +/- 300 to 794 +/- 600 pmol/L (P < 0.05) in parallel with an increase in insulin from 257 +/- 187 to 979 +/- 917 pmol/L (P < 0.01) in the 20 patients who completed the study; however, the changes were not correlated when expressed as percentages. Although the men and women had insulin responses to feeding that were not significantly different, leptin concentrations did not increase significantly in men but increased 3-fold in women (to 1094 +/- 638 pmol/L; P < 0.01). CONCLUSIONS: Leptin regulation in patients with a critical illness differs substantially from that in healthy persons. The importance of glucose and insulin in leptin secretion remains unclear, especially in men.

Adult↗
PubMed2002

Inhibition of interleukin-6-activated janus kinases/signal transducers and activators of transcription but not mitogen-activated protein kinase signaling in liver of endotoxin-treated rats.

OBJECTIVES: Endotoxin-induced cytokines, such as interleukin-6, mediate systemic inflammatory responses through multiple cellular signaling pathways. Interleukin-6 is also responsible for the synthesis of acute phase proteins. Recent studies have shown that endotoxin can inhibit signal transducers and activators of transcription (STAT)-3 tyrosine phosphorylation in cultured cells, suggesting that this effect may limit the synthesis of acute phase proteins. The purpose of this study was to examine the effects of endotoxin on interleukin-6 activation of STATs and mitogen-activated protein (MAP) kinase pathways in rat liver in vivo. DESIGN: Controlled laboratory study. SETTING: Medical school laboratory. SUBJECTS: Specific pathogen-free male Sprague Dawley rats. INTERVENTIONS: Under anesthesia, interleukin-6 was injected into the portal vein of rats 4 hrs after the bolus intravenous administration of endotoxin (1 mg/kg) or saline. The effects of interleukin-6 on key intermediates in early steps of the interleukin-6 signaling pathway, including janus kinase-1, gp 130, the interleukin-6 receptor, STAT1, and STAT3, were examined in both saline and endotoxin-treated rats. MEASUREMENTS AND MAIN RESULTS: In endotoxin-treated rats, there was significant inhibition of interleukin-6 activation of janus kinase-1, gp 130, the interleukin-6 receptor, STAT1, and STAT3. These signaling changes were associated with decreased tissue abundance of interleukin-6 receptors and STAT3. In contrast to its effects on the janus kinase/STAT pathways, interleukin-6 activation of MAP kinases (extracellular signal-regulated kinase-1, extracellular signal-regulated kinase-2, and p38) was unaffected by endotoxin. CONCLUSIONS: The pathway-specific inhibition of interleukin-6 signaling responses in the liver may be an important determinant of the pathophysiologic consequences of endotoxin exposure.

Animals↗
PubMedDate not supplied

Iron deficiency anemia in patients receiving home total parenteral nutrition.

BACKGROUND: Certain patients receiving home total parenteral nutrition (HPN) are likely to develop iron-deficiency anemia because of inadequate absorption or chronic iron loss from gastrointestinal lesions. The objective of this study was to examine the incidence and prevalence of iron deficiency anemia in patients on long-term HPN (>6 months) and to investigate both the efficacy of and rate of adverse reactions to parenteral iron dextran therapy. METHODS: The records of 55 patients treated with HPN for >6 months between January 1, 1994 and December 31, 1999 were examined. RESULTS: Thirty patients (55%) had evidence of iron-deficiency anemia. Ten patients were diagnosed at the initiation of HPN, and in 20 patients, iron deficiency developed after receiving HPN. The time between initiation of HPN and development of anemia ranged from 2 to 97 months (mean 28.8+/-26.2 months). Mild iron loss from the gastrointestinal tract seemed to be the predominant reason for iron deficiency. Regular treatment with small amounts of iron in HPN appeared to be safe and efficacious, with no reported side effects. Total dose infusion of iron was associated with adverse reactions in as many as 25% of these patients, although all reactions were mild and self-limited. CONCLUSIONS: Iron-deficiency anemia is common in patients receiving chronic HPN. Regular small doses of iron in HPN formula, rather than total dose infusion, is the preferred treatment.

Adult↗
PubMedDate not supplied

Clinical aspects of essential fatty acid metabolism: Jonathan Rhoads Lecture.

The clinical implications of the metabolism of the 2 essential fatty acids, linoleic and alpha-linolenic acid, are most clearly related to the membrane phospholipid concentrations of their elongation and desaturation products, arachidonic, eicosapentaenoic, and docosahexaenoic acid. Levels of these very long chain polyunsaturated fatty acids can be altered by diet, prematurity, and disease which can affect growth (nutritional repletion) and the intensity and character of systemic inflammation as well as cognitive and visual function in infants.

Adult↗
PubMedDate not supplied

New Food and Drug Administration requirements for inclusion of vitamin K in adult parenteral multivitamins.

The newly amended requirements by the Food and Drug Administration (FDA) for an effective adult parenteral multivitamin drug product increase the amounts of vitamins B1, B6, C, and folic acid currently in the product to better meet estimated needs, and specifies the inclusion of 150 microg of vitamin K. Infuvite Adult Multiple Vitamins for Infusion is the first adult parenteral multivitamin product to meet the revised FDA requirements. The inclusion of vitamin K in adult parenteral multivitamin products is intended to afford patients a consistent daily supply of vitamin K approximating usual levels of intake. This is a change to clinical practice in the United States, where vitamin K has not been included in adult parenteral vitamin preparations, and physicians prescribe vitamin K separately. The reformulation of adult parenteral multivitamins required by the FDA raises questions about the potential impact that inclusion of vitamin K will have on patient management. One clinical practice change is that patients on parenteral nutrition receiving Infuvite Adult should no longer need weekly subcutaneous (SC) or intramuscular (IM) vitamin K injections. In addition, the consistent and modest level of vitamin K provided by the reformulated adult parenteral multivitamins may make it easier for physicians to maintain the desired level of hypoprothrombinemia (low levels of prothrombin) in those patients also on anticoagulant therapy with warfarin. However, for physicians accustomed to administering vitamin K separately, it is important to highlight that it may be more difficult to titrate anticoagulant therapy, especially among patients receiving dual feeding or vitamin K from another source. If marketed globally, these clinical practice issues may be more pronounced outside of the United States, where dual feeding is common, and patients may receive vitamin K from other sources.

Adult↗