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Biomedical subjects

J D Palombo

Publications and source records attributed to J D Palombo.

At least 37 records · Page 2Linked to original sources
PubMed1988

Decreased loss of liver adenosine triphosphate during hypothermic preservation in rats pretreated with glucose: implications for organ donor management.

Recent studies of human donor livers indicate an association between ex vivo hepatocellular adenosine triphosphate and posttransplant graft function. To test the hypothesis that prior glucose loading of donor liver would optimize its adenosine triphosphate production and adenylate energy charge during ex vivo organ preservation, adult male rats were randomized to receive either intravenous dextrose or saline for 44 h. After this infusion, a liver lobe was exposed and freeze-clamped (time 0). The remaining liver was quickly flushed, excised, and stored in Collins' II solution at 2 degrees C for 8 h. Additional lobes were freeze-clamped at 1, 4, and 8 h. Liver adenosine triphosphate, total nucleoside triphosphates, and energy charge losses were significantly reduced in the dextrose-treated rats in comparison with saline-treated rats during the first 4 h of preservation. Although the livers from rats receiving intravenous dextrose were able to generate lactate, their glycogen stores were not utilized appreciably, suggesting that exogenous glucose served as a substrate for anaerobic glycolysis. Unesterified choline levels of the fasted rat livers were significantly higher than those from the rats receiving intravenous dextrose by the first hour, indicative of increased membrane breakdown. These results indicate that prior infusion of glucose enhances the capacity of the ex vivo liver, presumably through the induction and stabilization of key glycolytic enzymes, to anaerobically generate adenosine triphosphate. Administration of glucose to liver donors before organ procurement may improve post-transplant graft function by reducing the loss of hepatocellular energy, retarding membrane damage, and fostering glycogen storage for use in the early postoperative period.

Adenosine Triphosphate↗
PubMed1987

Branched-chain amino acid administration in surgical patients. Effects on amino acid and fuel substrate profiles.

During the first five days following gastric bypass surgery, 15 patients received near isotonic amino acid solutions that varied in their branched-chain amino acid (BCAA) content and amino acid profiles (15.6%, 50%, or 100% BCAA solutions). Plasma valine concentrations were elevated in patients receiving 50% and 100% BCAA solutions. Plasma alanine concentrations were highest in patients receiving 50% BCAA. Plasma free fatty acids and blood lactate concentrations were unchanged by either the operation or BCAA administration. Serum glucose concentration was unaffected by the different amino acid administrations and followed the pattern induced by stress initially and later by starvation. beta-Hydroxybutyrate concentrations increased as starvation proceeded and were highest in patients receiving the 15.6% BCAA solution. Branched-chain amino acid-enriched solutions without additional energy may be administered safely to patients recovering from operative trauma. Plasma amino acid concentrations and fuel substrate profiles appear to follow metabolic patterns determined by the physiologic response to stress and starvation and can be affected by large quantities of BCAAs.

3-Hydroxybutyric Acid↗
PubMed1987

Effectiveness of orthotopic liver transplantation on the restoration of cholesterol metabolism in patients with end-stage liver disease.

The effects of end-stage liver disease and orthotopic liver transplantation on components that modulate cholesterol esterification in plasma were assessed. In comparison with healthy controls, patients with end-stage liver disease had significantly decreased concentrations of lecithin-cholesterol acyltransferase mass, apolipoprotein A-1, total phospholipids, and both total and esterified cholesterol. Elevated phosphatidylcholine and reduced lysophosphatidylcholine fractions indicated impairment of cholesterol esterification by lecithin-cholesterol acyltransferase. Constituent fatty acids of the patients' phospholipids and cholesterol esters manifested increased saturation and a concomitant reduction of polyunsaturated fatty acids, indicative of impaired hepatic elongation and desaturation of essential fatty acids. By the third month after hepatic replacement, the plasma concentrations of total cholesterol, phospholipids, lecithin-cholesterol acyltransferase, and apolipoprotein A-1 were comparable to those of the healthy subjects. Despite the improvement in cholesterol esterification and the rapid normalization of the enzyme and cofactor involved in this process, the percentage of phosphatidylcholine remained significantly higher and the percentages of lysophosphatidylcholine and esterified cholesterol remained significantly lower than in the healthy subjects at 6 mo. Phospholipid and cholesterol ester fatty acid patterns attained normalcy by the sixth month after transplant. We conclude that hepatic transplantation effectively restores cholesterol and essential fatty acid metabolism in patients with end-stage liver disease.

Adult↗
PubMed1987

Cutaneous application of safflower oil in preventing essential fatty acid deficiency in patients on home parenteral nutrition.

Essential fatty acid deficiency (EFAD) is observed in patients with massive bowel resection who are placed on home parenteral nutrition (HPN). We investigated the use of cutaneously applied safflower oil to prevent EFAD. Five subjects on HPN supplemented with intravenous (IV) fat emulsions underwent a three-phase study: 1) no IV fat emulsions for 4 wk; 2) cutaneous safflower oil for 4-6 wk; 3) oral safflower oil for 4 wk. Fatty acid profiles (FAP) of plasma were obtained during each phase. Significant decreases in linoleic and arachidonic acid occurred by the end of phase 1 and the triene:tetraene ratio rose from a baseline value of 0.1 to 0.5. This ratio returned to 0.2 by the end of phase 2 and significant increases in linoleic and arachidonic acid occurred. Only one of five subjects completed the oral phase (3). Cutaneous safflower oil may improve plasma FAP but adequacy of tissue stores remains unanswered. Liver function tests need to be monitored if this treatment modality is utilized.

Administration, Cutaneous↗
PubMed1986

Short-term administration of parenteral glucose-lipid mixtures improves protein kinetics in portacaval shunted rats.

The efficacy of various total parenteral nutrition regimens administered for 72 h in supporting the rat after portacaval anastomosis was evaluated. All animals that received amino acid-containing formulas had significantly improved nitrogen balance (p less than 0.05), albumin synthetic rates (p less than 0.05), and serum albumin concentration (p less than 0.05) compared with animals receiving dextrose only. Rats that received the mixed-fuel system containing amino acids, dextrose, and lipid had significantly improved leucine flux and whole body protein synthesis (p less than 0.05) compared with animals that received dextrose only, or amino acids and dextrose. Diets composed of dextrose only, amino acids and dextrose, or amino acids and dextrose with the addition of currently available long-chain triglyceride lipid emulsion induced abnormal morphologic changes in the liver. No hepatic morphologic changes were evident in rats that received an isocaloric mixed-fuel regimen containing medium- and long-chain triglycerides. The results suggest that mixed-fuel systems containing amino acids and dextrose with lipids are superior to formulas containing dextrose only, or dextrose with amino acids. The improved liver morphology observed in animals given the lipid emulsion system containing medium- and long-chain triglycerides suggests that medium-chain triglycerides may provide an additional benefit in supporting the patient with liver dysfunction.

Amino Acids↗
PubMed1985

Comparison of different techniques for estimating rates of protein synthesis in vivo in healthy and bacteraemic rats.

Previous studies have reported that use of a flooding dose of radiolabelled amino acid is a more precise technique than the constant infusion of tracer quantities for determining rates of protein synthesis in rapidly turning-over tissues in the rat. However, there has been little direct investigation comparing different methods under comparable conditions. Initially, 12 healthy male Sprague-Dawley rats, weighing approx. 100 g, were randomized to receive either a bolus intravenous injection of 100 mumol of L-leucine (containing 30 microCi of [1-14C]leucine)/100 g body wt., or a continuous 2 h tracer infusion of [14C]leucine. In the second phase of the experiment, 12 additional rats were intravenously injected with 1 X 10(8) colony-forming units of Pseudomonas aeruginosa and 16 h later randomized to receive one of two infusions described above. Total protein synthesis as well as fractional synthesis rates were determined in liver, rectus muscle and whole body. Synthesis rates measured in liver, muscle and whole body were significantly higher in bacteraemic rats than in healthy rats. The flooding-dose methodology gave significantly higher estimates of protein synthesis in the liver, skeletal muscle and whole body than did the continuous-infusion method using direct measurement of the acid-soluble fraction from the respective tissue. Indirect estimates of whole-body protein synthesis based on plasma enrichments and stochastic modelling gave the lowest values.

Animals↗
PubMed1985

Stability of cimetidine hydrochloride in a total nutrient admixture.

The stability of cimetidine hydrochloride in a total nutrient admixture was studied. A total nutrient admixture composed of 5% amino acid injection, 20% dextrose injection, and 3% intravenous fat emulsion was prepared aseptically in four 2-L ethylene-vinyl acetate bags. Cimetidine hydrochloride injection was added to three of the admixtures to yield final cimetidine concentrations of 600, 1200, and 1800 mg per 1500 mL of admixture; the fourth admixture served as a control. At 0, 24, and 48 hours, cimetidine content was measured by high-performance liquid chromatography, and the admixtures were tested for pH and visually inspected for signs of creaming, oiling out, or phase separation. Particle-size distribution in the admixtures was compared with that in 20% intravenous fat emulsion. No appreciable changes in cimetidine concentration or pH occurred over 48 hours, and no visual changes were observed. Particle sizes were comparable to those in the 20% intravenous fat emulsion control except in the admixture containing cimetidine hydrochloride 600 mg, which had significantly more particles larger than 9.9 microns at 48 hours. In the total nutrient admixture studied, cimetidine hydrochloride in concentrations up to 1800 mg per 1500 mL was stable for 24 hours at room temperature, and the lipid emulsion was apparently not altered during this period by cimetidine.

Chromatography, High Pressure Liquid↗
PubMed1984

Improvement in amino acid use in the critically ill patient with parenteral formulas enriched with branched chain amino acids.

To assess the value of BCAA enriched solutions in patients under stress, we studied five critically ill, intensive care unit patients requiring total parenteral nutrition. Two complete feeding solutions were compared: one containing 15.6 per cent of the amino acids as BCAA and the other enriched to contain 50 per cent as BCAA. These solutions were prepared to be isocaloric and isonitrogenous and were administered in consecutive 24 hour periods. The order of administration was determined randomly. In the last ten hours of each infusion day, 50 microcuries of L-[1-14C]leucine were added to the solution to estimate leucine kinetics. Increased plasma leucine appearance (from 3.92 +/- 0.48 to 6.26 +/- 0.51 millimoles per hour, p less than 0.05), oxidation (from 0.83 +/- 0.23 to + 1.41 +/- 0.33 millimoles per hour, p less than 0.05) and net leucine balance (from + 0.48 +/- 0.23 to + 1.41 +/- 0.33 millimoles per hour, p less than 0.05) were found in patients while receiving the solution enriched to contain 50 per cent of the amino acids as BCAA. Plasma leucine, isoleucine and valine concentrations were also significantly increased with administration of the BCAA enriched solution, whereas plasma levels of glycine, tyrosine and phenylalanine were significantly reduced. These changes represent a normalization of plasma amino acid levels with administration of BCAA enriched solution. In addition, the improved net leucine balance observed during administration of BCAA suggests patients have an improved protein balance while receiving BCAA enriched solutions.

Aged↗
PubMed1983

Alterations in tyrosine and protein kinetics produced by injury and branched chain amino acid administration in rats.

1. To determine whether the alterations in amino acid metabolism after injury were a result of changes in protein synthesis, whole body tyrosine and individual tissue protein kinetics were estimated 24 h after three different forms of stress in rats. 2. In addition, injured rats were either starved or infused with 180 mg of nitrogen/day (as branched chain amino acids or L-alanine) to ascertain whether the mechanism and degree of nitrogen sparing were unique to branched chain amino acid administration or whether they could be attributed to the infusion of alpha-amino nitrogen. 3. In the more catabolic types of injury, increased nitrogen loss during starvation appeared to be due to both an increased plasma amino acid appearance and a greater percentage being oxidized. Rates of tyrosine incorporation into whole body protein were also enhanced and could be explained in part by increases in the fractional synthesis rate of hepatic non-secretory protein. 4. Both branched chain amino acid and L-alanine administration reduced endogenous tyrosine oxidation and improved nitrogen balance. However, branched chain amino acid administration significantly increased amino acid incorporation into whole body protein and fractional synthetic rates of skeletal muscle, kidney and hepatic non-secretory protein. 5. It is concluded that the catabolic response to severe injury is consistent with increased rates of plasma amino acid appearance and branched chain amino acid administration spares body protein by improving amino acid utilization for whole body protein synthesis.

Alanine↗
PubMedDate not supplied

Perfusion with lipopolysaccharide negative blood eliminates lipopolysaccharide induced lung injury.

We investigated whether perfusion with control blood improves pulmonary functions compromised by lipopolysaccharide (LPS) infusion. This was an animal study in a research laboratory at a university hospital by using Sprague-Dawley rats (n = 19), each weighing 325 to 350 g. All animals were pretreated with a 24 hour infusion of either LPS (5 mg/kg) or vehicle, after which, excised lungs were reperfused for 2 hours with either LPS+ or control blood. Three groups were studied: (1) group S (n = 6); LPS pretreated lungs reperfused with LPS containing blood to mimic persistent sepsis, (2) group N (n = 6); LPS pretreated lungs reperfused with control blood to mimic the removal of the septic blood components, and (3) group C (n = 7); vehicle pretreated lungs reperfused with normal blood as a control. Blood gas exchange, shunt fraction (Qs/Qt), alveolar-arterial oxygen gradient (A-aDO2), and variables for lung mechanics were measured. Leukosequestration was quantified with a myeloperoxidase (MPO) assay. The PO2 (mm Hg) values at 90 min after reperfusion in groups S, N, and C were 67.8 +/- 7.0*, 85.2 +/- 9.2, and 90.1 +/- 7.5, respectively (*p < 0.05; vs. group N and C). In addition to PO2, A-aDO2 and Qs/Qt significantly deteriorated in group S. MPO activity in the lungs after LPS infusion was significantly higher than that after vehicle infusion (1.7 +/- 0.3 vs. 0.12 +/- 0.04 units/g tissue; p < 0.001). Subsequent reperfusion with LPS+ blood (group S) increased MPO activity to 3.1 +/- 0.6 (p < 0.05), but reperfusion with normal blood (group N) caused a significant decrease to 1.1 +/- 0.2 (p < 0.05). MPO activity in group C did not significantly change compared with those after vehicle infusion. Reperfusion with control blood normalized lung function compromised by pretreatment with LPS and significantly reduced leukosequestration. These results favor the possibility that the removal of LPS+ blood components may eliminate septic lung injury.

Animals↗
PubMedDate not supplied

Cyclic vs continuous enteral feeding with omega-3 and gamma-linolenic fatty acids: effects on modulation of phospholipid fatty acids in rat lung and liver immune cells.

UNLABELLED: Arachidonic acid (AA) present in lung and liver immune cell phospholipids is the precursor of eicosanoids that promote neutrophil margination, leading to tissue injury and inflammation. Administration of novel enteral formulations low in linoleic acid (LA) and containing eicosapentaenoic acid (EPA) from fish oil and gamma-linolenic acid (GLA) from borage oil displaces AA and promotes cell formation of eicosanoids with reduced inflammatory potential. The present study was undertaken to determine whether or not short-term provision of enteral diets containing GLA, EPA, or both in a cyclic fashion modulated the fatty acid composition of rat alveolar macrophage (AM) and liver Kupffer and endothelial (K&E) cell phospholipids in vivo to the extent achieved during continuous feeding. METHODS: Rats were isocalorically fed through a gastrostomy catheter for 3 or 6 days with high-fat, low-carbohydrate diets that were enriched with either LA (diet A), EPA (diet B), or EPA + GLA (diet C). The rats were randomized by infusion modality, ie, continuous vs cyclic (14 hours feeding with 10 hours fasting daily) feeding. AM and K&E were isolated and phospholipid fatty acid profiles were determined by gas chromatography. RESULTS: The dietary effects on AM and K&E cell phospholipid fatty acids for a given feeding period were not significantly influenced by the infusion modality. AM and K&E cells from rats receiving either diet B or diet C for 3 days had significantly lower AA and LA and higher EPA and dihomo-GLA (DHGLA), respectively, than rats given diet A regardless of the infusion modality. The mole % of EPA and DHGLA in K&E cells were higher after 6 vs 3 days of cyclic feeding with diet C. Using the eicosanoid precursor ratio (EPA + DHGLA/AA), the potential for generation of AA-derived eicosanoids was lower in rats given die B or C vs diet A regardless of infusion modality. DISCUSSION: Given the rapid changes in lung and liver immune cell phospholipid fatty acids, short-term provision of EPA and GLA-enriched diets cyclically or continuously may prove clinically relevant for modulating the fatty acid composition and potential eicosanoid formation by these cells.

Adipose Tissue↗