Metformin protects PC12 cells against oxygen-glucose deprivation/reperfusion injury

Oxidative stress has a causative role in ischemic reperfusion-induced cell death. Evidence has shown that metformin is capable to reduce ischemic reperfusion injuries. The current study investigated the effect of metformin on ischemia/reperfusion-induced apoptosis in PC12 cells by evaluation of Bcl-2 family proteins expression. Cells were exposed to a time-dependent in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) injury and then treated with metformin. The intracellular reactive oxygen species (ROS) levels were measured. Western blotting was used to examine the expression of anti- and pro-apoptotic proteins. Moreover, the number of apoptotic cell death was evaluated by TUNEL assay. Our results showed that metformin attenuated ROS generation, downregulated pro-apoptotic BAX expression, and upregulated expression of the Bcl-2 protein in the PC12 cells. Moreover, metformin reduced cell death under OGD/R condition which was confirmed by lower apoptotic cell death in the TUNEL assay. These findings suggest that neuroprotective effect of metformin on OGD/R-induced cell death is possibly mediated by inhibition of ROS-induced apoptosis pathway.     

Tubulin binding blocks mitochondrial voltage-dependent anion channel and regulates respiration

Regulation of mitochondrial outer membrane (MOM) permeability has dual importance: in normal metabolite and energy exchange between mitochondria and cytoplasm and thus in control of respiration, and in apoptosis by release of apoptogenic factors into the cytosol. However, the mechanism of this regulation, dependent on the voltage-dependent anion channel (VDAC), the major channel of MOM, remains controversial. A long-standing puzzle is that in permeabilized cells, adenine nucleotide translocase (ANT) is less accessible to cytosolic ADP than in isolated mitochondria. We solve this puzzle by finding a missing player in the regulation of MOM permeability: the cytoskeletal protein tubulin. We show that nanomolar concentrations of dimeric tubulin induce voltage-sensitive reversible closure of VDAC reconstituted into planar phospholipid membranes. Tubulin strikingly increases VDAC voltage sensitivity and at physiological salt conditions could induce VDAC closure at <10 mV transmembrane potentials. Experiments with isolated mitochondria confirm these findings. Tubulin added to isolated mitochondria decreases ADP availability to ANT, partially restoring the low MOM permeability (high apparent K_m for ADP) found in permeabilized cells. Our findings suggest a previously unknown mechanism of regulation of mitochondrial energetics, governed by VDAC and tubulin at the mitochondria–cytosol interface. This tubulin–VDAC interaction requires tubulin anionic C-terminal tail (CTT) peptides. The significance of this interaction may be reflected in the evolutionary conservation of length and anionic charge in CTT throughout eukaryotes, despite wide changes in the exact sequence. Additionally, tubulins that have lost significant length or anionic character are only found in cells that do not have mitochondria.     

Morphea, Diabetes Mellitus Type I, and Celiac Disease: Case Report and Review of the Literature

Abstract:  An 11-year-old girl with a history of diabetes mellitus type I and celiac disease presented with multiple, depressed patches of purple-brown skin on the right lower extremity and central back, with histopathologic features of early morphea. Though morphea may coexist with other autoimmune diseases, its presentation with both diabetes mellitus type I and celiac disease has not yet been described.     

Brain abscess in children, experience Of Mashad University

Objective： Brain abscesses continue to pose a problem in neurosurgery, and it is a serious life-threatening complication for several diseases. The objective of this research was to lock at the clinical profile of children suffering from brain abscess, predisposing conditions, microbiology and outcome of these patients. Methods： Ninety children aged less than 15 years were reviewed. The clinical presentation, predisposing factors, diagnosis, management and outcome were noted. There were 56（ 62.2% ） males and 34 （ 37.7% ） females. The mean age of presentation was 5.7 ± 4.2 years. Results： The mean duration of illness at the time of presentation was 10.6 ± 12.4 days. Typically patients presented with fever, vomiting, headache, neurological deficit, and seizures. The predisposing conditions found were cyanotic congenital heart disease in 18 （20 % ） of children, meningitis in 6 （6.7 % ）, Otitis or mastoiditis in 32 （35.5 % ）, Head trauma in 6 （ 6.7 % ）, previous intraeranial surgery in 8 （8.8 % ） and no underlying cause was found in 22 （24.4 % ） children. The most common microbe in children with cyanotic congenital heart disease was of the Streptococcus group （54 % ）. Computerized tomography confirmed the diagnosis and the most common location of the abscess was the parietal lobe of the cerebral hemisphere. That abscesses were larger than 2 cm in diameter where aspirated surgically. Excision was performed for eight children. Six children expired, two due to intracranial bleeding and the others due to severe cerebral edema and tentorial herniation. Complications were observed in 11 children out of which six had squeal and five had bemiparesis. Conclusion： Attention to hygiene of mouth and teeth in infant and child patients with cyanotic heart disease is very important in prevention of infectious brain diseases. We must also pay attention to ear-nose-throat diseases of children. That is very important the patients be examined again after treatment because of finding and trea     

Allergic contact dermatitis to mafenide acetate: a case series and review of the literature

Burn patients with extensive involvement of body surface area (BSA >30%) represent a challenge in wound treatment. Multiple topical agents may be used for cleansing, barrier protection, and antimicrobial control leading to complications of contact and/or irritant dermatitis, which may further complicate re-epithelization and eventual wound healing. We present 4 patients who sustained extensive burns during Operation Iraqi Freedom/Operation Enduring Freedom and later developed contact dermatitis to mafenide acetate, a common topical antimicrobial used in burn care treatment, also known as Sulfamylon (alpha-amino-p-toluenesulfonamide monoacetate). All patients who were patch tested to mafenide acetate 7% solution were positive. A rechallenge with mafenide acetate resulted in recrudescence of the eruption in 2 out of the 4 patients. Though cutaneous reactions to mafenide acetate were reported by Yaffe and Dressler in 1969, the most recent case reports are from 1995. This paper presents more recent examples of cutaneous reactions to mafenide acetate, while also reviewing the literature.     

蜂王浆对女性2型糖尿病患者血糖控制及氧化应激因素的作用：一项随机临床试验

Objective:It has been proposed that royal jelly has antioxidant properties and may improve oxidative stress and glycemic control.Therefore,we investigated the effects of royal jelly supplementation in diabetic females.Methods:In this pilot,parallel design randomized clinical trial,50 female volunteers with type2 diabetes were randomly allocated to the supplemented(25,cases)and placebo(25,cases)groups,based on random block procedure produced by Random Allocation Software,given a daily dose of 1,000 mg royal jelly soft gel or placebo,respectively,for 8 weeks.Before and after intervention,glycemic control indices,antioxidant and oxidative stress factors were measured.Results:After royal jelly supplementation,the mean fasting blood glucose decreased remarkably(163.05142.51 mg/dL vs.149.68±42.7 mg/dL).Royal jelly supplementation resulted in significant reduction in the mean serum glycosylated hemoglobin levels(8.67%±2.24%vs.7.05%±1.45%,P=0.001)and significant elevation in the mean insulin concentration(70.28±29.16 pmol/L vs.86.46±27.50 pmol/L,P=0.01).Supplementation significantly increased erythrocyte superoxidase dismutase and glutathione peroxidase activities and decreased malondialdehyde levels(P0.05).At the end of study,the mean total antioxidant capacity elevated insignificantly in both groups.Conclusions:On the basis of our findings,it seems that royal jelly supplementation may be beneficial in controlling diabetes outcomes.Further studies with larger sample size are warranted.     

The association between dietary antioxidants and adipokines level among obese women

AimAdipokines are associated with several oxidative stress-related diseases and pathologic conditions. We aimed to assess the association between antioxidants and adipokines in obese adults.Methods and MaterialsIn this cross-sectional study, a total of 160 obese women were included. Body composition and anthropometric characteristics were measured. Dietary intakes were assessed by 3-day, 24-h dietary recall. Blood samples were obtained following an overnight fasting. Serum concentrations of adipokines including progranulin, retinol binding protein 4 (RBP4) and Angiopoietin-related growth factor 6 (ANGPTL6) was measured using an enzyme-linked immunosorbent assay. ANCOVA and the linear regression model analysis was performed to assess the relationship between Progranulin, RBP4, AnGPTL6, and antioxidants.ResultsMean age of included women was 39.31 ± 12.10. Mean and standard deviation for BMI was 35.05 ± 4.26 in this obese population. There was a positive significant association between ANGPTL6 and vitamin D intake (p < 0.001). Also, there was a marginal association between RBP4 and vitamin A (p = 0.063) intake, but after adjustment age, and fat mass, we found a significant association (p = 0.008). However, the associations between dietary antioxidants, progranulin, and ANGPTL6 were not statistically significant.ConclusionsANGPTL6 and RBP4 levels directly associated with dietary vitamins D and A intake, respectively. But, according to the results, the association between ANGPTL6 and vitamin D was bidirectional. The suggested associations probably can be useful in the development of interventional studies for management of chronic diseases.