Dynamics of oxidative/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease.

Insulin resistance, oxidative stress, and proinflammatory cytokines play a key role in pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of our study was to investigate the dynamics of oxidative/nitrosative stress in methionine-choline-deficient (MCD) diet -induced NAFLD in mice. Male C57BL/6 mice were divided into following groups: group 1: control group on standard diet; group 2: MCD diet for 2, 4, and 6 weeks (MCD2, MCD4, and MCD6, respectively). After treatment, liver and blood samples were taken for histopathology, alanine- and aspartate aminotransferase, acute phase reactants, and oxidative/nitrosative stress parameters. Liver malondialdehyde level was higher in all MCD-fed groups versus control group (p < 0.01), while nitrites + nitrates level showed a progressive increase. The activity of total superoxide dismutase and its isoenzymes was significantly lower in all MCD-fed groups (p < 0.01). Although catalase activity was significantly lower in MCD-fed animals at all intervals (p < 0.01), the lowest activity of this enzyme was evident in MCD4 group. Liver content of glutathione was lower in MCD4 (p < 0.05) and MCD6 group (p < 0.01) versus control. : Ferritin and C-reactive protein serum concentration were significantly higher only in MCD6 group. Our study suggests that MCD diet induces a progressive rise in nitrosative stress in the liver. Additionally, the most prominent decrease in liver antioxidative capacity is in the fourth week, which implies that application of antioxidants would be most suitable in this period, in order to prevent nonalcoholic steatohepatitis but not the initial NAFLD phase.

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity.

BACKGROUND: Stereotactic ablative body radiotherapy (SBRT, SABR) is being increasingly applied because of its high local efficacy, e.g., for small lung tumors. However, the optimum dosage is still under discussion. Here, we report data on 45 lung lesions [non-small cell lung cancer (NSCLC) or metastases] in 39 patients treated between 2009 and 2010 by SABR. PATIENTS AND METHODS: SABR was performed with total doses of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) prescribed to the 60% isodose line encompassing the planning target volume. Three-monthly follow-up CT scans were supplemented by FDG-PET/CT if clinically indicated. RESULTS: The median follow-up was 17 months. Local progression-free survival rates were 90.5% (all patients), 95.0% (NSCLC), and 81.8% (metastases) at 1 year. At 2 years, the respective local progression-free survival rates were 80.5%, 95.0%, and 59.7%. Overall survival rates were 71.1% (all patients), 65.4% (NSCLC), and 83.3% (metastases) at 1 year. Overall survival rates at 2 years were 52.7%, 45.9%, and 66.7%, respectively. Acute side effects were mild. CONCLUSION: With the moderate dose schedule used, well-tolerated SABR led to favorable local tumor control as in other published series. Standardization in reporting the dose prescription for SABR is needed to allow comparison of different series in order to determine optimum dosage.

Reduction of dosimetric impact of intrafractional prostate motion during helical tomotherapy.

BACKGROUND: In this study, the interplay between intrafractional prostate motion and helical tomotherapy (HT) radiation delivery with respect to treatment planning parameters, such as jaw size and pitch factor, was investigated. METHODS: Four treatment plans were created using two jaw widths (i.e., 1.05 and 2.5 cm) and two pitch factors (i.e., 0.287 and 0.574). A phantom with a slit for a film, attached to the motion platform, was used to simulate two-dimensional prostate motion in the superior-inferior and anterior-posterior directions. Doses were measured using gafchromic EBT films in the sagittal position. Each treatment plan was delivered to the static and dynamic phantom. Dose measurements performed with the dynamic phantom were quantitatively compared to static phantom doses in terms of dose-area histograms (DAH) for the planning target volume (PTV) and prostate, percentage of prostate and PTV receiving the prescription dose, and the minimum dose received by 95% of the prostate. RESULTS: Larger jaw width (2.5 cm) provided more adequate coverage of the PTV and prostate: D(95) of the moving prostate was 1.9 Gy for both plans with the jaw size 2.5 cm. When the jaw size was 1.05 cm, D(95) of the prostate and the PTV dropped to 1.5 Gy and 1.4 Gy, respectively. For a given jaw size, prostate and PTV dose coverage do not appear to be significantly dependent on the pitch factor. CONCLUSION: In the absence of an optimal motion management technique, the correct choice of the planning parameters is important to overcome larger under- and overdosage caused by intrafractional prostate motion during HT.

Possible implications of non-linear radiobiological effects for the estimation of radiation risk at low doses.

Possible implications of the effects of low LET radiation on the induction of cancer at low doses are studied. Low dose hypersensitivity and adaptive response were identified as candidates which may give a non-linear dose effect curve for acute exposures, whereas adaptive response may influence protracted exposures. In this paper acute exposures are studied. Several radiobiological reports on studies with mammalian cell lines have indicated the presence of a hypersensitive region in the radiation survival response at low doses followed by an increase in radioresistance. The two step clonal expansion (TSCE) model for the process of carcinogenesis was adapted in such a way that cell killing after acute radiation induces increased clonal expansion for some time and thus gives a promoting effect of radiation. As a first step, the Radiation Effects Research Foundation (RERF) data on the lung cancer incidence are fitted to study how such a model would influence the assessment of the cancer risk at low doses.

Alterations in magnesium and oxidative status during chronic emotional stress.

Magnesium and oxidative status were investigated in young volunteers exposed to chronic stress (political intolerance, awareness of potential military attacks, permanent stand-by duty and reduced holidays more than 10 years) or subchronic stress consisting of everyday mortal danger in military actions lasting more than 3 months. Significant decreases in plasma ionized Mg2+, total Mg and ionized Ca2+ concentrations were found in both groups. Similarly, both study groups exhibited oxidative stress as assessed by increased plasma superoxide anions and malondialdehyde and modified antioxidant defense. There were no significant differences between the two stress groups. A negative correlation between magnesium balance and oxidative stress was observed suggesting that the same etiological factor (chronic stress) initiate decreases in both free and total magnesium concentrations and simultaneously increase oxidative stress intensity. These findings support the need for magnesium supplementation with antioxidant vitamins for people living in conditions of chronic stress.

Characterization of plasma magnesium concentration and oxidative stress following graded traumatic brain injury in humans.

Plasma magnesium, calcium, and oxidative status were investigated in 31 male casualties with traumatic brain injury (TBI) during a 7-day posttraumatic period. The study group consisted of eight patients with mild closed head injury (Glasgow Coma Scale score [GCS] of 13-15), 10 patients with extensive penetrating head injury (GCS 4-6), and 13 patients with blast injuries but without direct head trauma. The latter group was included since previous experimental and clinical data have confirmed the development of indirect brain trauma in patients with blast injuries. Patients with multiple injuries were not included. Significant declines in plasma divalent cations were found in GCS 4-6 patients immediately after TBI and persisting for the entire 7-day study period. Similar changes in magnesium, but not calcium, were present in the GCS 13-15 and the blast injury groups, but only up until day 3 after injury. Alterations in lipid peroxidation products and superoxide anions were also observed following TBI. Increased lipid peroxidation was noted in all three groups over the entire posttraumatic period while increases in superoxide anion generation occurred transiently immediately following TBI. Thereafter, in the GCS 13-15 and blast injury groups, superoxide anions subsequently normalized, whereas in extensive head injury (GCS 4-6), superoxide anion generation significantly declined. A negative correlation between magnesium balance and oxidative stress was observed in all patients immediately after injury persisting in GCS 4-6 patients to the end of the observation period. Our findings suggest an interrelationship between magnesium changes and blood oxidants/antioxidants after TBI, which could be of both diagnostic and prognostic value in patients with neurotrauma.

Influence of low level laser irradiation on biochemical processes in brainstem and cortex of intact rabbits.

The influence of low level laser (LLL) irradiation at wavelength at 660 and 904 nm on oxidative stress (lipid peroxidation activity-LP, production of superoxide anion radicals-NBT reduction), activity of enzymes of antioxidative defense (superoxide dismutase-SOD, glutathione reductase-GR) and functional activity of sodium pump (Na+K+ ATPase) in relation with applied wavelength of LLL was investigated. The investigation was performed at the adult rabbits (n = 21) classificated in three groups: control group (C), the group of rabbits irradiated with LLL wavelength 904 nm (CL1) and the group of rabbits irradiated with LLL wavelength 660 nm (CL2). The irradiation was performed in the upper cervical region in the anatomical projection of the brainstem. It was established that LLL induced oxidative stress in the brainstem and the cortex of treated rabbits, independently of applied wavelength of laser beams. The registrated changes in functional activity of sodium pump were dependent on the applied wavelength. The irradiation at 904 nm caused the significant increase of the substrate uptake rate of sodium pump in the brainstem tissue. The irradiation at 660 nm caused the "competitive inhibition" of the sodium pump. Decrease of norepinefrine content in the brainstem of treated rabbits pointed on the indirect mechanism of functional activity of sodium pump as well as the oxidative stress.