Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase.

Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of animals: (i) untreated lean (?/+) Zucker diabetic fatty (ZDF) rats; (ii) untreated obese diabetic (fa/fa) ZDF rats; and (iii) ZDF fa/fa rats treated with melatonin (20 mg/L) in drinking water. Urinary albumin excretion was measured weekly. After 4 wk of the treatment, the following parameters were determined in kidney cortex: Nox activity, expression of subunits of the enzyme, their phosphorylation and subcellular distribution. Histological studies were also performed. Compared to ?/+ controls, ZDF fa/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47(phox) subunits, elevated level of p47(phox) phosphorylation, and enlarged phospho-p47(phox) and p67(phox) content in membrane. Melatonin administration to ZDF fa/fa rats resulted in the improvement of renal functions, as manifested by considerable attenuation of albuminuria and some amelioration of structural abnormalities. The treatment turned out to nearly normalize Nox activity, which was accompanied by considerably lowered expression and diminished membrane distribution of regulatory subunits, that is, phospho-p47(phox) and p67(phox) . Thus, it is concluded that: (i) melatonin beneficial action against diabetic nephropathy involves attenuation of the excessive activity of Nox; and (ii) the mechanism of melatonin inhibitory effect on Nox is based on the mitigation of expression and membrane translocation of its regulatory subunits.

Recognition and Processing of Visual Information after Neuronavigated Transcranial Magnetic Stimulation Session.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a method of noninvasive and painless stimulation of the nervous system, which is based on Faraday's law of electromagnetic induction. Over the past twenty years, the TMS technique has been deployed as a tool for the diagnosis and therapy of neurodegenerative diseases, as well as in the treatment of mental disorders (e.g., depression). METHODS: We tested the inhibitory effects of repetitive TMS (rTMS) on reaction times to militarily relevant visual stimuli amidst distractors and on accompanying blood oxygenation level dependent (BOLD) signal functional magnetic resonance imaging (fMRI) in 20 healthy people. rTMS was applied over the visual cortices, V1, on both hemispheres with the inhibitory theta burst paradigm with the intensity of 70% of the active motor threshold fMRI in 20 healthy people. RESULTS: Analysis of the reaction time to visual stimuli after using TMS to the V1 visual cortex revealed an increase in the number of incorrect recognitions, and the reaction time was from 843 to 910 ms. In the subgroup of participants (n = 15), after the stimulation, there were significant reductions of BOLD signal in blood flow within V1 cortices. CONCLUSIONS: The studies of reaction times after the rTMS revealed the inhibitory effect of rTMS on the reaction times and recognition performance of significant (military) objects in the visual field.

A comparison of the remineralizing potential of dental restorative materials by analyzing their fluoride release profiles.

BACKGROUND: The accessibility of the remineralizing ions in teeth's environment is essential for their incorporation into caries-affected dentin. Novel bioglass-reinforced materials capable of releasing fluoride, calcium and phosphates may be particularly useful in the tissue remineralization process. A novel restorative material, ACTIVA BioActive-Restorative (Pulpdent Corp., Watertown, USA), is a hydrophilic resin-modified glassionomer cement (RMGIC) enriched with bioglass particles and fortified with a patented rubberized polymer resin. Its application in restorative dentistry may be significant, promoting remineralization of carious lesions. OBJECTIVES: The aim of the study was to compare the fluoride ion release profiles from a bioglass-reinforced RMGIC, a conventional glass-ionomer cement (GIC) and a nanohybrid restorative polymer resin. MATERIAL AND METHODS: The quantity of fluoride ions released from ACTIVA, Ketac Molar Quick Aplicap and Tetric EvoCeram was assessed using a fluoride-specific electrode. The surface characteristics of the preand post-experimental specimens were studied using a scanning electron microscope (SEM) and confocal microscope. An X-ray powder diffraction (XRD) analysis was additionally used to examine the chemical compositions of the dental materials. RESULTS: The greatest quantity of fluoride ions was freed from the GIC specimens (20.698-54.118 ppm), followed by the bioglass-reinforced RMGIC (from 1.236 to 15.552 ppm) and nanohybrid polymer resin (0.370-1.148 ppm). The pre-experimental specimens of the bioglass-reinforced RMGIC were porous, while the post-experimental specimens were smoother with visible micro-cracks. The XRD analysis of the bioglass particles confirmed that the material was composed mainly of fluoride (27.70 mass%), silicon (15.62 mass%), aluminum (5.91 mass%), and calcium (5.40 mass%). CONCLUSIONS: The fluoride ion release profile of ACTIVA was lower than the GIC Keta Molar Quick Aplicap, but significantly higher than the nanohybrid restorative polymer resin Tetric EvoCeram.

ERK1/2 pathway is involved in renal gluconeogenesis inhibition under conditions of lowered NADPH oxidase activity.

The aim of this study was to elucidate the mechanisms involved in the inhibition of renal gluconeogenesis occurring under conditions of lowered activity of NADPH oxidase (Nox), the enzyme considered to be one of the main sources of reactive oxygen species in kidneys. The in vitro experiments were performed on primary cultures of rat renal proximal tubules, with the use of apocynin, a selective Nox inhibitor, and TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a potent superoxide radical scavenger. In the in vivo experiments, Zucker diabetic fatty (ZDF) rats, a well established model of diabetes type 2, were treated with apocynin solution in drinking water. The main in vitro findings are the following: (1) both apocynin and TEMPOL attenuate the rate of gluconeogenesis, inhibiting the step catalyzed by phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme of the process; (2) in the presence of the above-noted compounds the expression of PEPCK and the phosphorylation of transcription factor CREB and ERK1/2 kinases are lowered; (3) both U0126 (MEK inhibitor) and 3-(2-aminoethyl)-5-((4-ethoxyphenyl)methylene)-2,4-thiazolidinedione (ERK inhibitor) diminish the rate of glucose synthesis via mechanisms similar to those of apocynin and TEMPOL. The observed apocynin in vivo effects include: (1) slight attenuation of hyperglycemia; (2) inhibition of renal gluconeogenesis; (3) a decrease in renal PEPCK activity and content. In view of the results summarized above, it can be concluded that: (1) the lowered activity of the ERK1/2 pathway is of importance for the inhibition of renal gluconeogenesis found under conditions of lowered superoxide radical production by Nox; (2) the mechanism of this phenomenon includes decreased PEPCK expression, resulting from diminished activity of transcription factor CREB; (3) apocynin-evoked inhibition of renal gluconeogenesis contributes to the hypoglycemic action of this compound observed in diabetic animals. Thus, the study has delivered some new insights into the recently discussed issue of the usefulness of Nox inhibition as a potential antidiabetic strategy.

NADPH oxidase inhibitor, apocynin, improves renal glutathione status in Zucker diabetic fatty rats: a comparison with melatonin.

Apocynin (4'-hydroxy-3'-methoxyacetophenone) is the most commonly used NADPH oxidase (Nox) inhibitor. However, its application raises serious controversies, as the compound has been reported to reveal some prooxidative effects. The aim of this study was to elucidate apocynin action on glutathione, the main intracellular antioxidant, metabolism in kidneys of Zucker diabetic fatty (ZDF) rat, a well established model of diabetes type 2. Additionally, apocynin effects were compared with those of melatonin. The experiments were performed on five groups of animals: (1) untreated lean (?/+) ZDF rats, (2) ZDF ?/+ rats treated with apocynin (2 g/l) in drinking water, (3) untreated obese diabetic (fa/fa) ZDF rats, (4) ZDF fa/fa rats treated with apocynin (2 g/l) in drinking water, and (5) ZDF fa/fa rats treated with melatonin (20 mg/l) in drinking water. After 8weeks of the treatment, the following parameters were measured in kidneys: NADPH oxidase activity, the rate of hydroxyl free radicals (HFR) production, GSH and GSSG content and the activities of the enzymes of glutathione metabolism: γ-glutamylcysteine synthetase (GCS), glutathione reductase (GR) and glutathione peroxidase (GPx). Compared to ?/+ controls, ZDF fa/fa rats exhibited increased Nox activity, accelerated HFR generation and dramatically lowered GSH/GSSG ratio accompanied by increased GPx and diminished GCS activities. In case of diabetic animals, apocynin treatment resulted in attenuation of both Nox activity and HFR production, restoration of control GSH/GSSG ratio (due to both an increase in GSH and a decline in GSSG content), normalization of GPx activity and a slight increase in GCS activity. Similar observations were made upon melatonin application to ZDF fa/fa rats. Thus, it is concluded that, in the diabetic model studied, apocynin extends a beneficial effect on renal glutathione homeostasis. The mechanism of this phenomenon involves attenuation of glutathione peroxidase activity, which is overstimulated under conditions of oxidative stress accompanying diabetes.