Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice.

One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms - bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression.

[Parenteral glutamine does not improve the nutritional status in patients during high-dose chemotherapy and autologous peripheral stem cell transplantation]. / Parenterální glutamin nezlepsuje nutricní stav nemocných v prubehu vysokodávkové chemoterapie s autologní transplantací periferních kmenových bunek.

BACKGROUND AND AIM: High-dose chemotherapy is aggressive treatment modality adversely affecting both energy/protein demands and oral intake/resorption of nutrients. Aminoacid glutamine is known for its' proteoanabolic effect and as an energy source for enterocytes and immune system. Nutritional parameters have been studied in a controlled, randomised, double-blinded trial of parenteral glutamine supplementation of autologous stem cell transplant patients. METHODS: Forty consecutive patients with haematological and solid cancer and multiple sclerosis were treated from 1999 to 2001 by high-dose chemotherapy with autologous stem cell transplantation. Patients were randomly assigned either for parenteral administration of 30 g of alanyl-glutamine dipeptide (Dipeptiven, Fresenius-Kabi) or isonitrogenous glutamine-free amino acid solution from day +1 to day +14 or to discharge from hospital. Patients were closely monitored from admission to day +100. Nutritional parameters included: oral dietary intake, body weight, body composition, energy expenditure, concentration of serum proteins and nitrogen balance. Parenteral nutrition in dose of 26.5 kcal/kg and 1 g of aminoacid/kg was given to patients who did not reach adequate oral intake for 5 days and withheld after three consecutive days of adequate intake. RESULTS: Nutritional assessment on admission differed according to the method used but no parameter of nutrition predicted the clinical course of treatment. Inadequate oral intake period lasted (mean +/- SD) 6.8 +/- 5.9 days, average length of stay being 17.5 +/- 3.9 days. Patients were unable to use sipping of enteral feed. Resting energy expenditure neither on admission nor in critical period differed from predicted value. Serum protein concentrations significantly decreased on discharge with normalisation as soon as to day +28, correlating inversely with changes in extracellular water content. Nitrogen urine loss was 10-16 g/day. Only 42.5% of patients were treated with parenteral nutrition. Cumulative nitrogen balance at day +9 was -30.7 +/- 24.1 g N. Body weight at day +28 significantly decreased (-2.94 +/- 4.4 kg), mostly consisting of loss of pure body cell mass. Glutamine supplementation did not improve any of the listed nutritional parameters. CONCLUSIONS: High-dose chemotherapy with autologous stem cell transplantation causes proteocatabolism of medium severity. Nutritional status of patients cannot be improved by the mode and dosage of parenteral glutamine used in our study. Optimal nutritional monitoring and treatment for this group of patients is suggested.