Oxidative stress and nitrate/nitrite (NOx) status following citrulline supplementation in type 2 diabetes: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The pathogenesis of diabetes is accompanied by oxidative stress. Citrulline can be considered as a potent antioxidant. The present study aimed to examine the effects of citrulline supplementation on the status of oxidative stress and serum levels of nitrite/nitrate (NOx) in patients suffering from type 2 diabetes (T2DM). METHODS: The present study comprises a double-blind placebo-controlled randomised clinical trial. The study subjects include 54 patients with T2DM chosen from specialised clinics of Tabriz University of Medical Sciences. The patients were allocated to one of the placebo or intervention groups. The patients in the placebo and the intervention group received one sachet of microcrystalline cellulose or l-citrulline (3 g), respectively, every day for 2 months. Malondialdehyde (MDA), glutathione peroxidase (GPx), total antioxidant capacity (TAC), superoxide dismutase (SOD), serum levels of fasting blood sugar (FBS), citrulline and NOx were assessed before and after the intervention. RESULTS: Forty-five patients completed the trial. Significant decreases were found in serum levels of FBS and MDA. Serum levels of TAC, citrulline and NOx in the intervention group increased compared to those of the placebo group, after adjusting the data for the baseline values and confounders. Differences between and within the two groups were statistically nonsignificant for GPx and SOD at the end of the study. Body mass index and energy intake were not changed significantly after the intervention. CONCLUSIONS: The results of the present study show the positive effects of citrulline supplementation with respect to attenuating FBS levels and oxidative stress, as well as boosting NOx status, in patients with T2DM.

Healing potential of Iranian traditional medicinal plants on burn wounds in alloxan-induced diabetic rats

Malva sylvestris, Punica granatum, Amygdalus communis, Arnebia euchroma and Scrophularia deserti are important medicinal plants in Iranian traditional medicine (Unani) whose have been used as remedy against edema, burn, and wound and for their carminative, antimicrobial and anti-inflammatory activities. The ethanol extracts of M. sylvestris and P. granatum flowers, A. communis leaves, A. euchroma roots and S. deserti stems were used to evaluate the burn healing activity in alloxan-induced diabetic rats. Burns were induced in Wistar rats divided into nine groups as following; Group-I: normal rats were treated with simple ointment base (control), Group-II: diabetic rats were treated with simple ointment base (control), Groups-III and -VII: diabetic rats were treated with simple ointment base containing of extracts (diabetic animals), Groups VIII: diabetic rats were treated with simple ointment base containing of mixed extracts, Group-IX: diabetic rats received the standard drug (Silver Sulfadiazine). The efficacy of treatments was evaluated based on wound area, epithelialization time and histopathological characteristics. Wound contraction showed that there is high significant difference between the different groups (p<0.001). At the 18th day, A. euchroma, S. deserti, A. communis and mixed extract ointment treated groups healed 80-90%. At the 9th and 18th days the experiment, the best results were obtained with A. communis and standard drug, when compared to the other groups as well as to the controls. It may be concluded that almond leaves (sweet and bitter) formulated in the simple ointment base is effective in the treatment of burns and thus supports its traditional use.

Successful elimination of non-neural cells and unachievable elimination of glial cells by means of commonly used cell culture manipulations during differentiation of GFAP and SOX2 positive neural progenitors (NHA) to neuronal cells.

BACKGROUND: Although extensive research has been performed to control differentiation of neural stem cells - still, the response of those cells to diverse cell culture conditions often appears to be random and difficult to predict. To this end, we strived to obtain stabilized protocol of NHA cells differentiation - allowing for an increase in percentage yield of neuronal cells. RESULTS: Uncommitted GFAP and SOX2 positive neural progenitors - so-called, Normal Human Astrocytes (NHA) were differentiated in different environmental conditions to: only neural cells consisted of neuronal [MAP2+, GFAP-] and glial [GFAP+, MAP2-] population, non-neural cells [CD44+, VIMENTIN+, FIBRONECTIN+, MAP2-, GFAP-, S100beta-, SOX2-], or mixture of neural and non-neural cells.In spite of successfully increasing the percentage yield of glial and neuronal vs. non-neural cells by means of environmental changes, we were not able to increase significantly the percentage of neuronal (GABA-ergic and catecholaminergic) over glial cells under several different cell culture testing conditions. Supplementing serum-free medium with several growth factors (SHH, bFGF, GDNF) did not radically change the ratio between neuronal and glial cells--i.e., 1,1:1 in medium without growth factors and 1,4:1 in medium with GDNF, respectively. CONCLUSION: We suggest that biotechnologists attempting to enrich in vitro neural cell cultures in one type of cells - such as that required for transplantology purposes, should consider the strong limiting influence of intrinsic factors upon extracellular factors commonly tested in cell culture conditions.

New evidence for a gating action of norepinephrine in central neuronal circuits of mammalian brain.

Many previous studies have examined the effects of norepinephrine (NE) on neuronal responsiveness to synaptic inputs and putative transmitter substances and have described differential depressant actions of NE on stimulus evoked versus spontaneous discharge such that the "signal to noise" ratio of threshold responses was increased. In the present studies, similar experimental strategies employing a combination of microiontophoresis, single unit recording and afferent pathway stimulation in intact anesthetized and brain tissue slice preparations have revealed noradrenergic "gating" actions whereby weak or subthreshold synaptic stimuli can evoke threshold neuronal responses in the presence of iontophoretically applied NE or following electrical stimulation of the locus coeruleus. Overall, these results suggest that potentially threshold excitatory and inhibitory synaptic inputs may normally arrive at central neurons but appear weak or absent except during behavioral conditions favoring the synaptic release of NE. As such, these findings provide evidence that signal to noise ratio may not be the only potential modulatory action expressed by NE in noradrenergic target circuits of the mammalian brain.