Calorie restriction promotes remyelination in a Cuprizone-Induced demyelination mouse model of multiple sclerosis

Metabolic Brain Disease - Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary...     

Dual effects of 3, 4-methylenedioxymethamphetamine （ecstasy） on survival and apoptosis of primary hippocampal neurons

BACKGROUND： 3, 4-methylenedioxymethamphetamine （MDMA, also known as ＂ecstasy＂） has been shown to exhibit neurotoxic effects on the hippocampus. However, exposure to sub-lethal insults of MDMA has been reported to result in neuroprotection. OBJECTIVE： To investigate the effects of MDMA on hippocampal neuronal viability, caspase-3 activity, and mRNA expression of the N-methyI-D-aspartate （NMDA） receptor 2B （NR2B） subunit. DESIGN, TIME AND SETTING： A cytological, in vitro experiment was performed at the Department of Anatomy, School of Medicine, and Department of Toxicology-Pharmacology, Faculty of Pharmacy Tehran University of Medical Sciences in 2008. MATERIALS： MDMA was extracted from ecstasy tablets, which were kindly supplied by the Pharmacology-Toxicology Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran. METHODS： Hippocampal neurons were isolated from Wistar rats at gestational day 18. Following primary culture, hippocampal neuronal viability was detected by MTT assay. Varying concentrations of MDMA （100-5 000 μmol/L） were used to determine lethal concentration 50 （LC50）, which was around 1 500 μmol/L. Five concentrations of MDMA below 1 500 μmol/L （100, 200, 400, 800, and 1 050 μmol/L） were used for the remaining experiments. After 24 hours of MDMA treatment, NR2B mRNA expression was detected by RT-PCR, and caspase-3 relative activity was determined by colorimetric assay. MAIN OUTCOME MEASURES： Hippocampal neuronal viability, caspase-3 activity, and NR2B mRNA expression. RESULTS： MDMA-induced neurotoxicity in hippocampal neuronal cultures was dose-dependent. In high concentrations （1 000-5 000μmol/L） of MDMA, neuronal viability was decreased. However, with a 500 μmol/L dose of MDMA, neuronal viability was significantly increased （P 〈 0.01）. Low concentrations of MDMA （200 and 400μmol/L） significantly decreased caspase-3 activity （P 〈 0.01）, whereas high concentrations of MDMA significantly increased caspase-3 activity （P 〈 0.01）. NR2B subunit mRNA expression was not significantly altered after 100 -1 050 μmol/L MDMA exposure. CONCLUSION： MDMA exhibits dual effects on hippocampal neuronal viability and caspase-3 activity. These effects are independent from NR2B subunit expression levels.     

Poly thymidine polymorphism and cystic fibrosis in a non-Caucasian population

Background: Cystic fibrosis is a monogenic recessive disorder found predominantly in Caucasian population. This disease arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In this study we consider poly T polymorphism c.1210-12T[5], c.1210-12T[7], c.1210-12T[9] (T₅, T₇, T₉) in the intron 8 of CFTR gene in normal individuals and cystic fibrosis patients in the north of Iran. Material and methods: 40 CF patients and 40 normal individuals were screened for poly T polymorphism in intron 8 of CFTR gene using Reverse Dot Blot method which was also used to detect p.Phe508del among CF patients. Results: T₇ allele is the most prevalent in both normal and CF patients. Its abundance is approximately 75%. T₉ and T₅ represent approximately 20% and 5% of alleles respectively. T₇/ T₇ genotype is the most present in both normal and CF patients with 72.5% and 60% prevalence respectively. p.Phe508del was present in 13 CFTR alleles belonging to 7 patients with either homozygote T₉/ T₉, T₇/ T₇ or compound heterozygote T₇/ T₉ genotypes. Conclusion: Contrary to the Caucasians, T₇ allele is more frequent in Northern Iranian CF patients. The presence of p.Phe508del and T₇ allele in the same framework is reported for the first time in this part of the world. Further investigations of other populations will help to understand whether p.Phe508del arose by selection pressure in this part of the world or was imported from European countries. The abundance of T₅, T₇, T₉ alleles indicates that this polymorphism can be used as one of the informative markers for detection of normal and mutant alleles in prenatal diagnosis or carrier assessment in families with previous history of the disease in regions with high degree of CFTR mutation heterogeneity.     

Insulin resistance in relation to inflammatory gene expression and metabolic features in apparently healthy obese individuals

International Journal of Diabetes in Developing Countries - The present study aimed to investigate the association of insulin resistance (IR) with inflammatory gene expression levels, metabolic...     

The effects of simvastatin on ischemia-reperfusion injury of sciatic nerve in adult rats

Severe ischemia to nerve results in fiber degeneration and reperfusion results in oxidative injury to endothelial cells and augments fiber degeneration. Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, the most widely used lipid-lowering drugs, have been demonstrated to play a neuroprotective role. So we evaluated the effectiveness of simvastatin in protecting sciatic nerve from ischemia-reperfusion injury using the model of experimental nerve ischemia. Sixty adult male Sprague-Dawley rats weighing 250-300 g were used. They were divided into ten groups (N=6 per group). We used ischemia model in these groups by occluding the femoral artery and vein with a silk suture 6-0 using slipknot technique. All ischemia groups were rendered in ischemic for 3 h reperfused for various times of zero (0 h), 3 h (3 hour reperfusion), 7 days (7 day reperfusion), 14 days (14 day reperfusion). Half of the groups had experimental simvastatin (1 mg/kg) i.v. injection treatment via tail vein 1 h before ischemia. The other half experienced only ischemia-reperfusion as control groups. After euthanasia, histological samples were taken from distal part of the sciatic nerve. Sections were cut at 5 microm and then were stained with H and E and modified trichrome. We used H and E stain for edema and trichrome gomori for ischemic fiber degeneration. Samples were observed to assess their fiber degeneration and edema changes. By observation the level of fiber degeneration and endoneurial edema were also decreased in these recent groups (in both ischemia and reperfusion duration). In conclusion, pre-ischemic administration of simvastatin exhibits neuroprotective properties in ischemia-reperfusion nerve injury.     

The cannabinergic system is implicated in the upregulation of central NGF protein by psychotropic drugs

Rationale  

Studies on the regulation of nerve growth factor (NGF) levels by psychotropics are limited in scope and the mechanism(s) remain elusive which merit further elucidation.     

An Iranian male with syringoid eccrine carcinoma misdiagnosed as basal cell carcinoma: a case report

Syringoid carcinoma (syringoid eccrine carcinoma, or eccrine epithelioma) is a rare cutaneous tumor with some controversy regarding its correct definition. This tumor shows a slow growth and has often been for many years, some decades before diagnosis. It may also be difficult to differentiate from its benign counterpart (syringoma) or other adnexal carcinoma and cutaneous metastasis. There have been limited case reports of syringoid carcinoma in foreign literatures but none from Iran. Here we report a case of syringoid carcinoma in a 52 year-old Iranian man. Syringoid eccrine carcinoma is a very rare and uncommon diagnosed tumor thought to be derived from eccrine sweat apparatus. It locally invasive, destructive and often shows recurrence. It may also be difficult to differentiate from metastatic adenocarcinoma.     

Nitric oxide and c-Jun N-terminal kinase are involved in the development of dark neurons induced by inflammatory pain

Dark neurons, whose morphological characteristics are consistent with those of cells undergoing apoptosis, are generated in vivo as an acute or delayed consequence of several pathological situations and lesions. The present study was designed to evaluate whether inflammatory pain induced by injection of formalin to the rat hind paw lead to the formation of dark neurons in the dorsal horn of the lumbar spinal cord in rat. Since nitric oxide (NO) and c-Jun N-terminal Kinase (JNK) pathway are involved in the mechanisms of pain generation and degenerative neuronal alteration, their roles were also considered. The methods used spectrophotometrical analysis of the serum nitrite (metabolite of NO) and histological procedures for detection of dark neurons, following induction of inflammatory pain. According to the results, injection of formalin led to an increase of the serum nitrite level in both concentration and time-dependent manners. Visual inspections of the lumbar spinal cord sections showed that, on day 5, following chronic injections of 5% formalin, numbers of dark neurons were significantly increased. Acute and chronic administration of 1% or 2.5% formalin did not induce any remarkable neuronal alterations in the dorsal horn of the lumbar spinal cord. Daily intrathecal administration of quercetin (inhibitor of JNK pathway) 100 microg/rat, or 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO; NO scavenger) 30 mug/rat before injection of 5% formalin led to a reliable reduction in the number of dark neurons. These results indicate that induction of inflammatory pain for longer periods may result in a serious central disorder. Pretreatment with neutralizers or inhibitors of NO and JNK may exert a neuroprotective effect in this regard.     

Comparison of 1,2-propanediol and ethylene glycol for cryopreservation of slow-cooled mouse zygotes and their subsequent development

Purpose : This study was conducted on cryoprotective activity of ethylene glycol (ETG) and propanediol (PROH) on cleavage rate of mouse zygotes. Methods : Mouse oocytes were excised from fallopian tube of gonadotropin-treated mice, then inseminated with spermatozoa. After 16.5–17.5 h, zygotes were randomly allocated into three groups; control, toxicity, and frozen. In the latter, zygotes were slowly cooled with ETG and PROH similar to those used for human embryo cryopreservation. The survived zygotes cultured for 120 h and their later stages of development were compared with nonfrozen embryos. Results : The toxicity test showed that no differences were observed in cleavage rate between exposed and nonexposed embryos. The survival and expanded hatching blastocyst rate of embryos frozen with PROH was significantly better than with ETG (92.8 vs. 58.2% and 68.2 vs. 39.1%, respectively). Conclusions : ETG does not appear to be a good alternative to the classical PROH for freezing of mouse zygotes.