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C R Jonas

Publications and source records attributed to C R Jonas.

11 recordsLinked to original sources
PubMed2001

Regulation of glutathione redox status in lung and liver by conditioning regimens and keratinocyte growth factor in murine allogeneic bone marrow transplantation.

BACKGROUND: Reactive oxygen species (ROS) and glutathione (GSH) depletion contribute to organ injury after bone marrow transplantation (BMT). Keratinocyte growth factor (KGF) ameliorates graft-versus-host disease (GVHD)-associated organ injury in murine BMT models. METHODS: B10.BR mice received total body irradiation (TBI; day -1) +/- cyclophosphamide (Cy; 120 mg/kg/day i.p., days -3 and -2), then were transplanted on day 0 with C57BL/6 bone marrow + spleen cells as a source of GVHD-causing T cells. KGF (5 mg/kg/day subcutaneously [s.c.]) or saline was given on days -6, -5, and -4. Lung and liver GSH and oxidized GSH disulfide (GSSG) levels were measured on days 0 and 5 and glutathione redox potential (Eh) calculated. Organ malondialdehyde (MDA) was determined on day 5 as an index of ROS-mediated lipid peroxidation. RESULTS: In lung, TBI+BMT oxidized GSH Eh and increased MDA. Cy further oxidized lung GSH Eh. In liver, neither BMT regimen altered GSH redox status or MDA. KGF prevented the decrease in lung GSH after TBI+Cy and decreased lung MDA after both TBI and TBI+Cy. KGF increased liver GSH levels and GSH Eh after TBI and GSH Eh after TBI+Cy. CONCLUSIONS: In murine allogeneic BMT, TBI oxidizes the lung GSH redox pool and Cy exacerbates this response by 5 days post-BMT. In contrast, liver GSH redox status is maintained under these experimental conditions. KGF treatment attenuates the Cy-induced decrease in lung GSH, decreases post-BMT lung lipid peroxidation, and improves liver GSH redox indices. KGF may have a therapeutic role to prevent or attenuate GSH depletion and ROS-mediated organ injury in BMT.

Animals↗
PubMed2000

Regulation of keratinocyte growth factor (KGF) and KGF receptor mRNAs by nutrient intake and KGF administration in rat intestine.

The aim of this study was to investigate the regulation of keratinocyte growth factor (KGF) and KGF receptor mRNAs by diet and KGF treatment in rat intestine. Fasting for three days up-regulated KGF and KGF receptor mRNA levels in ileum and increased KGF receptor mRNA expression in colon. KGF and KGF receptor mRNA levels returned toward control values with ad libitum refeeding but remained elevated when refeeding was limited to 25% of ad libitum intake. KGF treatment during nutrient repletion did not alter intestinal KGF mRNA levels but increased KGF receptor mRNA abundance in ileum and colon. We conclude that the increase in KGF and KGF receptor mRNAs induced by malnutrition may be an adaptive response to attenuate gut mucosal atrophy in this setting. The gut-trophic effects of KGF treatment may be mediated, in part, by up-regulation of the KGF receptor mRNA in small bowel and colon.

Analysis of Variance↗
PubMed2000

Plasma antioxidant status after high-dose chemotherapy: a randomized trial of parenteral nutrition in bone marrow transplantation patients.

BACKGROUND: Chemotherapy and radiation therapy result in increased free radical formation and depletion of tissue antioxidants. It is not known whether parenteral nutrition (PN) administered during bone marrow transplantation (BMT) supports systemic antioxidant status. OBJECTIVE: The aims of the study were to determine 1) whether high-dose chemotherapy decreases concentrations of major circulating antioxidants in patients undergoing BMT and 2) whether administration of standard PN maintains systemic antioxidant concentrations compared with PN containing micronutrients and minimal lipids alone. DESIGN: Twenty-four BMT patients were randomly assigned to receive either standard PN containing conventional amounts of dextrose, amino acids, micronutrients, and lipid (120 kJ/d) or a solution containing only micronutrients (identical to those in standard PN) and a small amount of lipid (12 kJ/d). Plasma antioxidant status was measured before conditioning therapy and serially at days 1, 3, 7, 10, and 14 after BMT. RESULTS: Plasma glutathione (GSH) and alpha- and gamma-tocopherol concentrations decreased and the GSH redox state became more oxidized after conditioning chemotherapy. Plasma cysteine concentrations were unchanged, whereas cystine concentrations increased. Plasma vitamin C and zinc concentrations and GSH peroxidase activity increased over time. Plasma alpha-tocopherol concentrations were lower in patients given standard PN. There were no differences in other plasma antioxidants between groups. CONCLUSIONS: A significant decline in GSH-glutathione disulfide, cysteine-cystine, and vitamin E status occurs after chemotherapy and BMT. Standard PN does not improve antioxidant status compared with administration of micronutrients alone. Further evaluation of PN formulations to support patients undergoing high-dose chemotherapy and BMT are needed.

Adult↗
PubMed1999

Keratinocyte growth factor enhances glutathione redox state in rat intestinal mucosa during nutritional repletion.

Malnutrition decreases tissue levels of glutathione (GSH), a major endogenous antioxidant that detoxifies reactive oxygen species and promotes cell growth. This study determined the effects of the gut trophic peptide keratinocyte growth factor (KGF) on intestinal mucosal GSH concentrations and redox state in malnourished rats. Adult rats were food-deprived for 3 d, then consumed food ad libitum or 25% of ad libitum intake for 3 d with daily intraperitoneal administration of saline or KGF (5 mg.kg-1.d-1). Mucosal GSH and glutathione disulfide (GSSG) concentrations, crypt depth and total mucosal height were measured in the jejunum, ileum and colon. In the 25% of ad libitum-refed, saline-treated group, mucosal GSH was lower in all gut tissues (42% in jejunum, 38% in ileum, and 57% in colon), and the GSH/GSSG ratio was lower in the jejunum and ileum compared to that in the ad libitum-refed controls. KGF treatment with ad libitum refeeding increased GSH/GSSG in the jejunum, ileum and colon. Furthermore, in 25% of ad libitum refeeding, KGF normalized jejunal, ileal and colonic mucosal GSH content and significantly increased the mucosal GSH/GSSG ratio relative to rats treated with saline. Increased crypt depth and total mucosal height induced by KGF and feeding could be explained in part by increased mucosal GSH content. KGF treatment improved gut mucosal glutathione redox state in malnourished, refed rats. These data provide evidence that gut trophic hormones and food intake may independently support gut mucosal glutathione antioxidant capacity during nutritional repletion.

Animals↗
PubMed1997

Adjunctive therapies in nutritional support.

The need for new therapeutic approaches to improve the metabolic and clinical efficacy of nutritional therapy has been increasingly emphasized. The field of nutrition support of catabolic, malnourished, or hospitalized patients is rapidly evolving in response to the beneficial effects observed with adjunctive therapies in animal models and in emerging clinical investigations. Enteral nutrition is being increasingly administered, and enteral diets are being tested to improve gut structure and function. Adjunctive therapies in enteral and parenteral nutrition are being actively investigated. These include administration of recombinant growth factors and anabolic steroid hormones (e.g., growth hormone, oxandrolone); conditionally essential amino acids (e.g., arginine, glutamine); novel lipid products (e.g., structured lipids, fish oils); nutrient antioxidants (e.g., vitamins C and E); and combinations of these approaches. It is likely that current methods of enteral and parenteral nutrition support will evolve in response to the results of these research studies.

Amino Acids, Essential↗
PubMed1995

Vitamin E in plasma and milk of lactating women with insulin-dependent diabetes mellitus.

We measured levels of plasma and milk alpha-tocopherol in women with insulin-dependent diabetes mellitus (IDDM), women without IDDM, and healthy reference women. Milk collections were made at 7, 14, 42, and 84 days postpartum; blood was collected at 3, 14, and 42 days. Postprandial glucose at 80 min was used to describe metabolic control of women with IDDM postpartum. There was no difference between the groups for plasma alpha-tocopherol, which was within normal reported levels. Tocopherol (micrograms/g lipid) decreased by approximately 50% in all groups between 7 and 14 days. The trend for milk tocopherol was similar when expressed as micrograms/dl. Metabolic control did not have a significant effect on mean milk or plasma alpha-tocopherol. We have shown that this group of women with IDDM produced a milk with vitamin E content similar to control and reference women. We conclude that the infant of the breast-feeding woman with IDDM who is in good metabolic control during pregnancy and who receives good prenatal counseling most likely receives adequate vitamin E from the mother's milk.

Blood Platelets↗
PubMedDate not supplied

Enteral nutrition and keratinocyte growth factor regulate expression of glutathione-related enzyme messenger RNAs in rat intestine.

BACKGROUND: Malnutrition is associated with increased reactive oxygen species (ROS) formation and depletion of the critical antioxidant glutathione (GSH) in the intestine. The malnutrition-induced decrease in gut GSH levels is prevented by recombinant keratinocyte growth factor (KGF) administration. We investigated whether enzymes that are induced by oxidants and modulate tissue GSH supply are regulated by enteral nutrients or KGF at the messenger RNA (mRNA) level. METHODS: Adult rats were fasted for 3 days alone or fasted for 3 days then refed ad libitum. In a second model, rats were fasted for 3 days and then refed ad libitum or 25% of ad libitum intake with daily intraperitoneal saline or recombinant KGF (5 mg/kg/d) for 3 subsequent days. mRNA levels for gamma-glutamylcysteine synthetase (gamma-GCS), gamma-glutamyl transpeptidase (gamma-GT), glutathione-S-transferase Ya-subunit, gastrointestinal glutathione peroxidase (GI-GPx), and non-selenium-dependent glutathione peroxidase (ns-GPx) were determined in ileum and colon by ribonuclease protection assay. RESULTS: Fasting increased ileal gamma-GCS, ns-GPx, and glutathione-S-transferase mRNAs (by 36%, 165%, and 130% of controls) and decreased GI-GPx mRNA (to 55% of controls). In the colon, mRNAs for GSH-related enzymes were unchanged by fasting or refeeding. Prolonged enteral nutrient restriction (25% refeeding after a 3-day fast) increased gamma-GCS and glutathione-S-transferase mRNAs (by >270% of controls), decreased GI-GPx mRNA (to <50% of controls) in ileum and colon and increased ns-GPx mRNA (by 180%) in colon. KGF treatment increased ns-GPx mRNA in the ileum and colon and glutathione-S-transferase mRNA in the colon (by >200% of controls). CONCLUSIONS: Enteral nutrient intake regulates GSH-related enzyme mRNA levels in the intestine, which may contribute to the decrease in mucosal GSH during malnutrition. Increased ns-GPx and glutathione-S-transferase mRNA levels during malnutrition and with KGF administration may increase detoxifying functions in the gut under these conditions.

Analysis of Variance↗
PubMedDate not supplied

Interactions between nutrients and peptide growth factors in intestinal growth, repair, and function.

Several lines of evidence demonstrate that general nutritional status, specific nutrients (eg, zinc, glutamine), and certain trophic growth factors (eg, growth hormone, insulin-like growth factor I, keratinocyte growth factor, and glucagon-like peptide-2) have important interactions relevant for intestinal growth and function. Adequate nutritional status is critical for endogenous growth factor synthesis in the gut and other tissues and is an important mediator of organ responsiveness to exogenous growth factor administration. Both endogenously synthesized and exogenously administered growth factors upregulate nutrient uptake and utilization by gut mucosa, skeletal muscle, and other organs. Emerging data from both animal and human studies indicate that combinations of selected growth factors and specific nutrients may improve the growth, adaptation, and repair of the intestinal mucosa. Additional studies to determine basic mechanisms of nutrient-growth factor interactions and the safety and efficacy of treatment with combinations of specific nutrients and recombinant growth factors are needed. Results of these investigations should define new methods for support of the intestinal tract during short bowel syndrome (SBS), catabolic illness, and malnutrition.

Animals↗