Monosodium glutamate-induced obesity changed the expression and activity of glutathione S-transferases in mouse heart and kidney.

Obesity may affect activity and/or expression of enzymes participating in xenobiotics' detoxification and antioxidant defense. This study sought to investigate the activities and expression of cardiac and renal glutathione S-transferase (GST) isoforms in order to reveal possible differences between obese and control mice. For this purpose, mice with monosodium glutamate (MSG)-induced obesity were used as an experimental model. Obesity was induced in newborn male mice by repeated s.c. administration of MSG. At 8 months of age, mice were sacrificed and specific activity, protein and mRNA expressions levels of GSTs were analyzed in their heart and kidney. In hearts of obese mice, specific activity of GST was decreased by 51% compared to control. This reduction was accompanied by a decline in GSTP-class protein and Gstp1/2 mRNA expression levels. In contrast, specific activity of GST was elevated by 31% in kidney of obese mice and this increase was accompanied by upregulation of GSTA-class protein and Gsta1/2 mRNA expressions. Increased capacity of renal GSTs together with GSTA upregulation may serve as compensatory mechanism against elevated oxidative stress, which accompanies obesity. On the other hand, decreased cardiac GST activity in obese mice and GSTP downregulation may worsen the defense against oxidative stress and harmful xenobiotics.

Longterm treatment results of childhood medulloblastoma by craniospinal irradiation in supine position.

Medulloblastoma, a primitive neuroectodermal tumor growing in cerebellum, is one of the most sensitive to radiation therapy childhood brain tumors. The radiotherapy is an essential method of treatment for these tumours, but the surgery is the primary treatment of choice in medulloblastoma. I this study between January 1997 and March 2005 were post-operative irradiated a total number of 33 pediatric patients aged under 15 years (median age 8.7 years) with medulloblastoma. All tumors were histologically proved and were localizated infratentorially in the posterior fossa. All of the patients were irradiated with a dose of 24-36 Gy to the whole craniospinal axis and boost with conformal therapy restricted to the tumor bed to the total dose of 50-54 Gy (30-36 Gy "high risk", 24-30 Gy "standard risk" group). Chemotherapy received 26 patients (78%). Patients with craniospinal irradiation were placed in supine position and fixed by a vacuum-form body immobilizer and head mask. Irradiation was performed using standard fractionation (5 fractions per week) with a single dose of 1.5-1.8 Gy for craniospinal axis by photon beam (6 MV) of the linear accelerator. The median overall survival for the whole group was 55.3 months. The median of disease-free survival was 20.6 months, 8 patients (24%) died. In our study the statistical difference in survival rate between standard and high-risk patients with medulloblastoma was not shown. No relationship was found between survival and age, sex or tumor size. Endocrine deficits occurred in 45% (8 patients of the group were hypothyroid, 6 patients needed growth hormone replacement therapy, 1 patient had early puberty). This results (results of overall and disease-free survival) and side-effects of technique of craniospinal axis irradiation in supine position are comparable with results of technique in prone position. Further evaluation of the effectiveness of our therapy is not feasible due to the small number of patients.