Biomedical subjects

W Souba

Publications and source records attributed to W Souba.

5 recordsLinked to original sources

PubMed1999

Alteration in enterocyte gene expression may explain structural and functional changes following glutamine supplemented parenteral nutrition.

Following extensive bowel resection, the intestinal tract undergoes a variety of adaptive responses to enhance bowel function. The purpose of this study was to determine the effect of glutamine-supplemented parenteral nutrition on mucosal cellularity and gut function. In addition, enterocyte gene expression of two relevant systems was also characterized and related to the structural and functional changes that occurred. Male Wistar rats underwent a 60% small bowel resection and jugular vein catheterization and were randomized into two groups. The control group (n = 10) received a standard intravenous nutritional solution and the study group (n = 10) received a similar solution but enriched with alanylglutamine dipeptide. After 7 days blood was taken for amino acid analysis, and bowel was harvested to determine mucosal morphology and expression of mucosal cell glutaminase and IGF-I mRNA. Mesentery lymphnodes were cultured to determine the presence of bacteria and thus access bacteria translocation. Serum glutamine concentration and mucosal architecture were maintained in the study group compared to the controls. Seventy percent of lymphnodes were cultured positive in control vs. only 20% in the study group (P < 0.05). Jejunal mucosal glutaminase and ileum mucosal IGF-I mRNA increased twofold and threefold respectively compared to control animals. Parenteral nutrition supplemented with alanyl-glutamine dipeptide supports mucosal cellularity and regional immune function in rodents following intestinal resection, These alterations are associated with enhanced enterocyte expression of glutaminase and IGF-I. These changes may facilitate the structural and functional alterations which were observed in the glutamine treated animals.

Animals↗

PubMed1996

Safety and efficacy of total parenteral nutrition delivered via a peripherally inserted central venous catheter.

Central venous catheters for total parenteral nutrition (TPN) have traditionally been inserted via direct cannulation of the subclavian vein, but this technique requires physician participation and is associated with well-described complications. We report the single largest institutional experience with peripherally inserted central venous catheters (PICC lines) used exclusively for TPN in non-intensive care unit patients. From July 1991 to March 1994, 135 PICC lines were placed in 126 patients via the antecubital vein, advanced into the central venous system, and used only for TPN. Complication rates were determined and compared with those for TPN administered through a subclavian vein-inserted central catheter. Patient demographics were similar in each group with respect to age, type of disease process, acuity of illness, and indications for nutrition support. A cumulative number of 1381 TPN days (mean = 11 days per patient) comprised the PICC line experience. Comparison was made with 135 successive standard (subclavian) central lines inserted in 105 patients for TPN administration (1056 TPN days, mean = 10 days per patient). There was no difference in the overall rate of complications between the two groups. There were no major complications that prolonged hospitalization (eg, catheter-related sepsis or pneumothorax) in the PICC group compared with three such complications in the standard group. PICC lines can be used safely and effectively for TPN and are associated with an acceptable rate of complications.

Adult↗

PubMedDate not supplied

Inhibition of pulmonary microvascular endothelial glutamine transport by glucocorticoids and endotoxin.

BACKGROUND: During septic states, the lungs produce increased amounts of glutamine, an event that is mediated by both endotoxin and glucocorticoid hormones and is presumed to be due to accelerated intracellular glutamine biosynthesis. Because enhanced net glutamine release in vivo could also be due to a decrease in cellular uptake, we assayed glutamine transport in cultured rat microvascular pulmonary endothelial cells. METHODS: The effect of Escherichia coli endotoxin (LPS, 1 microgram/mL), various cytokines, and dexamethasone (DEX, 0.1 mumol/L) on glutamine transport activity was studied in rat lung microvascular endothelial cells grown in varying glutamine concentrations (0, 0.1, 0.5, and 2 mmol/L). Experiments were also performed in cells treated with cycloheximide, actinomycin D, or chelerythrine chloride. RESULTS: More than 90% of glutamine transport was mediated by the Na+ -dependent transport system ASC. DEX and LPS inhibited endothelial glutamine uptake in a time- and dose-dependent manner, a response that was only observed with incubation medium contained the lower concentrations of glutamine. Neither DEX nor LPS altered transport activity in cells cultured in medium containing 2 mmol glutamine/L. There was no synergistic or additive effect when both compounds were added together. The cytokines tumor necrosis factor alpha, interleukin (IL) 1, IL-2, and IL-6 did not alter glutamine transport. both DEX and LPS inhibited glutamine transport by decreasing transporter maximal transport velocity (Vmax) without affecting transporter affinity (Km). Cycloheximide and actinomycin D abrogated the inhibition of transport activity that was observed in DEX- or LPS-treated cells, whereas the protein kinase C inhibitor chelerythrine chloride had no effect on either control or stimulated glutamine transport. CONCLUSIONS: These data suggest that DEX and LPS "down-regulate" glutamine uptake by lung microvascular endothelial cells by inducing the synthesis of an inhibitory protein that modulates the activity of the system ASC protein. This response in vitro appears to be influenced by the extracellular glutamine concentration. This decrease in microvascular endothelial glutamine transport may be one mechanism by which net lung glutamine release is enhanced during critical illness.

Animals↗

PubMedDate not supplied

Lipopolysaccharide and tumor necrosis factor stimulate lung microvascular arginine uptake, a response attenuated by dexamethasone.

BACKGROUND: Lipopolysaccharide (LPS), tumor necrosis factor-alpha, (TNF), and glucocorticoids can modulate endothelial nitric oxide (NO) production. L-Arginine is the exclusive precursor for NO biosynthesis, suggesting that NO generation and arginine transport are intimately linked. METHODS: To further study this relationship, we examined the effects of LPS, TNF, and dexamethasone (DEX) on arginine uptake by rat lung microvascular endothelial cells. The transport of radiolabeled arginine was assayed in confluent cells grown in 24-well plates. RESULTS: The bulk (> 90%) of arginine transport was mediated by the Na(+)-independent carriers System y+ and System b0,+. Arginine transport was stimulated independently by LPS and TNF, a response first observed at 10 hours. Together, both agents exerted an additive effect on carrier-mediated uptake. The LPS- and TNF-induced increase in arginine transport activity was blocked by cycloheximide and actinomycin D, indicating the requirement for RNA and protein synthesis. The enhancement in transport activity was primarily due to an increase in Systems y+ maximal transport capacity (Vmax) with no change in transporter affinity and little change in System b0,+ activity. Treatment of cells with dexamethasone inhibited arginine transport activity in a time- and dose-dependent manner, an event that was abrogated by both actinomycin D and cycloheximide. The combination of DEX and LPS and TNF abrogated each other's antagonistic effects. CONCLUSIONS: These data indicate that LPS and TNF additively stimulate arginine transport in lung microvascular endothelial cells via a pathway that requires de novo protein synthesis (possibly of the transporter protein itself) and that this response is attenuated by DEX.

Animals↗

PubMedDate not supplied

Adjuvant high-dose interferon alfa-2b in patients with high-risk melanoma.

We performed an analysis of toxicity and survival in stage III melanoma patients receiving adjuvant interferon alfa-2b (IFN). This was a retrospective single-arm analysis of 40 patients with stage III melanoma who received (IFN) administered at maximum tolerated doses of 20 mU/m2/day intravenously (i.v.) for 1 month and 10 mU/m2 three times per week subcutaneously (s.c.) for 48 weeks. Toxicity in our series is comparable to that experienced in the Eastern Cooperative Oncology Group (ECOG) 1684 trial, except for higher rates of dose-limiting myelosuppression and hepatotoxicity. All 40 patients experienced constitutional symptoms, but only 14/40 (35%) experienced grade 3 to 4 symptoms. Of the 40 patients, 36 (90%) experienced neurologic symptoms, but only seven (17.5%) experienced grade 3 to 4 neurotoxicity. Two patients stopped treatment because of severe psychiatric symptoms; one patient attempted suicide, and a psychosis developed in another. Thirty-nine (97.5%) patients experienced myelosuppression; 31 (77.5%) developing grade 3 to 4 myelosuppression. Hepatotoxicity was evident in 39 (97.5%) patients, and 26 (65%) experienced grade 3 to 4 hepatotoxicity. Three patients (7.5%) experienced mild renal toxicity. At a median follow-up of 27 months from initiation of therapy, there have been 19 relapses (47.5% disease-free survival [DFS]) and 10 deaths (75% OS) resulting from progression of disease. The DFS compares with the treatment arm in ECOG 1684 at 27 months, but overall survival is higher in our series of patients at the same time point. In a single program setting, IFN can be administered with similar side effects and outcome profiles seen in multi-institutional studies. Modifications in the induction regimen resulted in notably higher hematologic and hepatic toxicities but did not preclude administering further therapy and did not result in increased attrition rate among patients: only nine patients (22.5%) had their treatment stopped as a result of IFN-related toxicity. In comparison, 26% of patients had to have their treatment discontinued because of toxicity in ECOG 1684.

Adult↗