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B R Bistrian

Publications and source records attributed to B R Bistrian.

At least 55 records · Page 3Linked to original sources
PubMed1999

Endotoxin-induced inhibition of growth hormone receptor signaling in rat liver in vivo.

The bacterial lipopolysaccharide endotoxin induces a catabolic response characterized by resistance to multiple anabolic hormones. The objective of this study was to determine the effects of endotoxin on the GH signaling pathway in rat liver in vivo. After the iv injection of Escherichia coli endotoxin (1 mg/kg), there was a progressive decrease in liver STAT5 (signal transducer and activator of transcription-5) tyrosine phosphorylation in response to GH (40% decrease 6 h after endotoxin), which occurred in the absence of a change in abundance of the STAT5 protein. Endotoxin resulted in a rapid 40-fold increase in liver Janus family kinase-2 (JAK2) messenger RNA, followed by a 2-fold increase in JAK2 protein abundance. This was associated with a 50% decrease in phosphorylated/total JAK2 after GH stimulation. GH receptor abundance was unchanged, suggesting a postreceptor site of endotoxin-induced GH resistance. Rat complementary DNAs for three members of the suppressor of cytokine signaling gene family were cloned [cytokine-inducible sequence (CIS), suppressor of cytokine signaling-2 (SOCS-2), and SOCS-3] and, using these probes, messenger RNAs for SOCS-3 and CIS were shown to be increased 10- and 4-fold above control values, respectively, 2 h after endotoxin infusion. The finding of endotoxin inhibition of in vivo STAT5 tyrosine phosphorylation in response to a supramaximal dose of GH in the absence of a change in GH receptor abundance or total GH-stimulated JAK2 tyrosine phosphorylation provides the first demonstration of acquired postreceptor GH resistance. We hypothesize that this may occur through a specificity-spillover mechanism involving the induction of SOCS genes by cytokines released in response to endotoxin and subsequent SOCS inhibition of GH signaling.

Animals↗
PubMed1999

Enteral nutrition: just a fuel or an immunity enhancer?

Based on a review of randomized, controlled clinical trials, enteral feeding improves septic morbidity in critically ill and/or malnourished patients. Enteral feeding may be better than parenteral feeding, but a definitive study is not available. Immune-enhancing diets further improve septic morbidity in critically ill and/or malnourished patients. Active components identified include arginine, glutamine, and omega-3 fats, but the relative efficacy of any single immune enhancing component versus their combination is impossible to state based on the presently available evidence.

Critical Illness↗
PubMed1998

Effect of continuous enteral medium-chain fatty acid infusion on lipid metabolism in rats.

This study compared (i) the relative effects of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT), (ii) the influence of amount of MCT, and (iii) the impact of medium-chain fatty acid position, on plasma and lymphatic triglycerides and portal vein free fatty acids. The animals were fed approximately at 250 kcal/kg.day for 20 h. The lymph from lymphatic duct and blood from portal vein and systemic circulation were collected. The results showed that feeding 100% MCT for 20 h was sufficiently long to reduce significantly the level of linoleic acid in portal vein fatty acids and plasma and lymph triglycerides. However, this alteration induced by MCT feeding was partially prevented by adding LCT to the diet. The level of arachidonic acid was significantly reduced in plasma triglycerides by any of the diets containing medium-chain fatty acids compared to 100% LCT. When feeding MCT only, palmitoleic acid, presumably reflecting de novo lipogenesis, was increased in lymphatic triglycerides and portal vein fatty acids. Total saturated fatty acids as a total percentage of total fatty acids were also significantly increased in plasma and lymphatic triglycerides and portal vein fatty acids. Thus, when linoleic acid is limiting, the conversion of MCT into long-chain fatty acids by de novo lipogenesis is likely to be an important metabolic route. Providing LCT with MCT or 2-monodecanoin appears to limit this pathway.

Animals↗
PubMed1998

Metabolism of dietary alpha-linolenic acid vs. eicosapentaenoic acid in rat immune cell phospholipids during endotoxemia.

Short-term (i.e., 3 d) continuous enteral feeding of diets containing eicosapentaenoic (EPA) and gamma-linolenic (GLA) polyunsaturated fatty acids (PUFA) to endotoxemic rats reduces the levels of arachidonic acid (AA) and linoleic acid (LA) in alveolar macrophage (AM) and liver Kupffer and endothelial (K&E) cell phospholipids with attendant decreases in prostaglandin formation by these cells in vitro. Diets that contain alpha-linolenic acid (LNA) as a substrate for endogenous formation of EPA may not be as effective in facilitating these immune cell modifications given the limited activity of delta6 desaturase. In the present study we compared the effectiveness of an LNA-enriched diet vs. an (EPA + GLA)-enriched diet to displace phospholipid AA from AM and liver K&E cells in vivo in endotoxemic rats fed enterally for 3 or 6 d. We determined the fatty acid composition of AM and K&E cell phospholipids by gas chromatography. We found that AM and K&E cells from rats that had received the EPA + GLA diet for 3 d had significantly (P < 0.001) higher mole percentage of EPA and the GLA metabolite, dihomoGLA, than corresponding cells from rats given the LNA diet or a control diet enriched with LA. Rats given the LNA diet had relatively low levels of stearidonic acid, EPA and other n-3 PUFA, while rats given the LA diet had low levels of GLA and dihomoGLA. We conclude that diets enriched with LNA or LA may not be as effective as those enriched with EPA + GLA for purposes of fostering incorporation of EPA or dihomoGLA into and displacement of AA from macrophage phospholipids under pathophysiologic conditions commonly found in acutely septic patients.

Animals↗
PubMed1998

Effects of dietary protein and tumor necrosis factor on components of the insulin-like growth factor-I pathway in the colon and small intestine in protein-depleted rats.

Intestinal cell growth is markedly affected by nutrient intake and the presence of cytokines. Since insulin-like growth factor-I (IGF-I) is an important hormone regulator of intestinal proliferation, this study examined the effects of dietary protein content and tumor necrosis factor (TNF) on mRNA levels of IGF-I, IGF-I receptor, IGF binding protein-3 (IGFBP-3), and IGFBP-4 and on the histology of the colon, jejunum, and ileum in protein-malnourished rats. After 2 weeks of feeding a 2% casein diet, rats continued on the 2% casein diet or were refed with a 20% casein diet and received daily intraperitoneal injections of either TNF (50 microg/kg) or saline for 4 days. The abundance of mRNA in the intestine was determined by RNA dot-blot analysis, and morphology measurements were performed by light microscopy. Simultaneous refeeding with the 20% casein diet and administration of TNF led to a modest increase in IGF-I and IGFBP-4 mRNA abundance in the colon. However, in the jejunum and ileum, refeeding had no effect but TNF caused a decrease in IGF-I and IGFBP-3 mRNA levels in malnourished rats. Refeeding with the 20% casein diet resulted in relatively modest histologic changes, which were greater in the colon versus the small intestine. The decreased magnitude of histologic changes in the order of the colon, ileum, and jejunum may reflect a response to a gradient of amino acid availability from intraluminal nutrients. These data demonstrate that TNF has distinct effects on colon and small intestine mRNA, but these mild changes had only a slight impact in the colon and did not translate into identifiable histologic changes in the small intestine. Combined protein restriction and TNF administration had only a modest effect on intestinal mRNA levels and mucosal histology.

Animals↗
PubMed1998

Role of the systemic inflammatory response syndrome in the development of protein-calorie malnutrition in ESRD.

Chronic activation of the systemic inflammatory response is a common and unifying factor in many end-stage illnesses, particularly end-stage renal disease. Protein-calorie malnutrition and hypoalbuminemia, which are prominent features of end-stage renal disease, develop as a consequence of this syndrome. Recognition of this relationship can assist in the development of new approaches to the successful management of protein-calorie malnutrition developing in the course of end-stage renal disease.

Cytokines↗
PubMed1998

Appropriate nutritional support in acute and complicated Crohn's disease.

Crohn's disease is frequently complicated by protein-calorie malnutrition. Four common clinical presentations of Crohn's disease include acute exacerbations or flares of disease, intestinal obstruction, fistulizing disease, and perianal disease. In this review, we examine the role of nutritional support in these clinical scenarios. Nutritional support is important for maintaining functional status and preventing loss of lean tissue. Determinants of lean-tissue loss include severity of underlying injury, baseline nutritional status, and duration of inadequate nutrition. One of the clinically useful measures of nutritional status is the nutritional risk index (NRI) defined on the basis of the serum albumin and weight loss. Nutritional support is important in severely malnourished patients (NRI < 83). Enteral nutrition is the route of choice, provided there are no contraindications to using the gastrointestinal tract. In acute exacerbations of Crohn's disease, enteral nutrition also has a role in the primary management of disease although it is not as effective as corticosteroids in inducing remission. The mechanisms are poorly understood and the most effective enteral formulation needs to be determined. Total parenteral nutrition is justified in severely malnourished Crohn's disease patients who are unable to tolerate enteral feeding or in whom enteral feeding is contraindicated. More clinical studies are needed on the assessment of malnutrition in Crohn's disease, the effects of nutritional management on functional status, and the timing of nutritional intervention.

Acute Disease↗
PubMed1998

Nutrition support for patients after cardiopulmonary bypass: required modifications of the TPN solution.

OBJECTIVE: This study was designed to identify the unique metabolic characteristics of patients undergoing cardiopulmonary bypass (CPB) surgery who require postoperative parenteral nutrition. SUMMARY BACKGROUND DATA: Patients undergoing CPB surgery occasionally develop postoperative complications that result in the need for nutrition support. Although enteral nutrition is generally the preferred feeding route, symptomatic hyperlipasemia has been described in critically ill CPB patients receiving enteral nutrition proximal to the ligament of Treitz. In such instances, enteral feeding must be temporarily discontinued or severely curtailed, thereby necessitating the initiation of parenteral nutrition for full or partial support. METHODS: The period from 1988 through 1993 during which time 4091 CPB procedures were performed was reviewed. Data were retrospectively collected on 208 (5%) of the patients who underwent CPB who developed postoperative complications that necessitated the initiation of parenteral nutrition (PN) support. A random sample of 79 patients who underwent CPB who did not require PN were selected as controls. RESULTS: Patients requiring PN after CPB were significantly older and had a higher prevalence of diabetes and metabolic complications, specifically volume overload, hyponatremia, metabolic alkalosis, uremia, and hyperglycemia, than those patients who did not require PN after CPB. In addition, patients requiring PN after CPB were significantly more hypotensive and required more vasopressive drugs during the first 24 to 48 hours after surgery than control patients. CONCLUSIONS: In patients with postoperative complications after CPB, PN is often necessary to correct the metabolic characteristics of overhydration, hyponatremia, uremia, hyperglycemia, and alkalosis.

Aged↗
PubMed1997

The new dietary fats in health and disease.

Lipids are an integral part of the routine diet of patients and the general public. In this article, the physiologic properties of various dietary lipids are reviewed, beginning with those most commonly consumed-the long-chain triglycerides (LCTs) and extending to those with special purposes: the short- and medium-chain triglycerides. The nutritional dietary management of patients typically includes physical mixtures of lipids. Recently, structured triglycerides (STs), which combine advantages from conventional fats with those of special purposes, have become available. STs are currently developed by interesterifying a mixture of conventional fats and oils, usually with medium-chain triglycerides, to achieve a specific fatty acid profile. This results in a triglyceride containing combinations of short-, medium-, and long-chain fatty acids on a single glycerol backbone. They have unique chemical, physical, or physiologic properties that are not observed by simply blending mixtures of the starting fats and oils. A number of STs are under intense laboratory and clinical investigation in models of cancer, burns, and immune dysfunction. Much interest in the fatty acids resides in the sn-2 position on the glycerol molecule. This is because the fatty acid in the sn-2 position of triglycerides is preferentially absorbed as the 2-monoglyceride and serves as the template for reesterification by intestinal cells to re-form triglycerides. The sn-2 fatty acids are also preferentially preserved as components of chylomicrons and very-low-density lipoprotein particles for ultimate incorporation in tissue membranes. Technology is evolving to create STs with a selected fatty acid in this sn-2 position. For instance, incorporating linoleic, arachidonic, or eicosapentaenoic acid at the sn-2 position is being evaluated for the specific objective of modulating serum cholesterol concentrations and essential fatty acid absorption (a review of this work is included).

Absorption↗
PubMed1997

Tissue-specific effects of chronic dietary protein restriction and gastrostomy on the insulin-like growth factor-I pathway in the liver and colon of adult rats.

Dietary protein restriction decreases plasma concentrations of insulin-like growth factor-I (IGF-I) and reduces IGF-I mRNA levels in the liver. In addition to the actions of systemic IGF-I, locally produced IGF-I is thought to mediate autocrine and paracrine growth effects in the colon. The objectives of the present study were to investigate the IGF-I pathway in the colon and liver of adult rats under conditions of dietary protein restriction, surgical stress, and dietary protein repletion. Two groups of rats were placed on either a 20% or 2% casein diet for 19 days. Two additional groups of rats underwent gastrostomy after a 2% casein diet for 2 weeks, and then were either kept on the 2% casein diet or changed to a 20% casein diet until day 19. Dietary protein restriction reduced plasma concentrations of IGF-I and IGF-binding proteins (IGFBPs) and hepatic IGF-I mRNA content, while increasing colonic IGF-I receptor mRNA. Gastrostomy in protein-depleted animals had no effect on hepatic IGF-I mRNA, but led to a marked increase in colonic IGF-I mRNA levels. Dietary protein repletion resulted in a decrease in colonic IGF-I receptor mRNA. The distinct effects of dietary protein depletion and operative stress on the IGF pathway in the colon as compared with the liver may serve to maintain the level of IGF-I signaling in the colon by autocrine or paracrine mechanisms under these conditions.

Animals↗
PubMed1997

Insulin-like growth factor-I improves glucose utilization in tumor necrosis factor-treated rats under hyperinsulinemic-euglycemic conditions.

The purpose of this study was to determine the effects of insulin-like growth factor-I (IGF-I) on glucose metabolism in normal and tumor necrosis factor (TNF)-treated rats under euglycemic and hyperinsulinemic conditions. During a hyperinsulinemic clamp (10 mU/kg.min), rats further received either saline or IGF-I (3.33 micrograms/kg.min) infusion for 2 hours. Glucose kinetics were determined with [3H-3]-glucose. Glucose utilization in peripheral tissues was examined by glucose uptake using [14C-2]-deoxyglucose (14C-DG) and by glycogen content in select tissues. The results showed that TNF infusion significantly decreased the rate of glucose infusion required to maintain euglycemia. TNF decreased glycogen content significantly in liver and marginally in abdominis muscle. TNF also decreased glucose uptake in muscle, although the decrease was only statistically significant compared with IGF-I infusion. In addition, TNF significantly reduced plasma IGF-I concentration. However, during hyperinsulinemic and euglycemic conditions, exogenous IGF-I significantly increased glucose uptake in muscle and glycogen storage in the liver and abdominis muscle in both saline- and TNF-treated groups. IGF-I normalized each of the effects of TNF in the rats, including those on plasma IGF-I, glucose uptake in muscle, and glycogen content in liver and abdominis muscle. These data suggest that under hyperinsulinemic and euglycemic conditions, TNF-treated rats, although resistant to insulin, have a normal response to IGF-I, indicating that the TNF-induced defect in the insulin pathway may not be a step in the IGF-I pathway.

Animals↗
PubMed1997

Mechanisms of host wasting induced by administration of cytokines in rats.

This study determined the effects of chronic administration of the two principal proximate cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), on host wasting in rats. The effects were compared with those observed in a matched pair-fed group to distinguish the contribution from anorexia. Both TNF and IL-1 produced weight loss, net nitrogen loss, and skeletal muscle catabolism and increased liver weight. Such effects were independent from and additive to those resulting from semistarvation. However, under equivalent nutritional conditions, TNF infusion led to a greater effect on muscle protein catabolism and liver weight and caused liver protein anabolism, whereas only the group receiving IL-1 had altered glucose metabolism in the postabsorptive state. Tachyphylaxis was seen in the response of food intake over time after administration of IL-1. These actions define the two principal mechanisms for the development of protein calorie malnutrition that occur because of cytokine action, anorexia producing semistarvation and an increased net protein catabolic rate reducing anabolic efficiency.

Animals↗