Synergistic Antiparkinsonian Effect of Flunarizine, Glibenclamide and B Vitamins in a Rate 6-Hydroxydopamine Model; The Role of Malondialdehyde

Background: The current study evaluated the effects of a combination of flunarizine (flu) a calcium channel blocker, glibenclamide (Glib), a KATP channels blocker and B vitamins (B com) on the behavioral symptoms of 6-hydroxydopamine (6-OHDA)-induced model of Parkinson disease to evaluate the synergistic antiparkinsonian effects of the drugs and supplements. Also the level of malondialdehyde (MDA) was measured in blood and brain suspensions to find probable neuroprotective mechanism of these materials. Methods: 6-OHDA was injected into striatum of rats by stereotaxic surgery. Pretreatment with flu, Glib and B com was started before the surgery and continued to three weeks after the surgery. Development and severity of Parkinson disease were evaluated by the conventional behavioral tests. MDA values were measured spectrophotometrically, using thiobarbituric acid test and the MDA standard curve. Results: Pretreatment with a combination of flu, Glib and B com ameliorated the behavioral symptoms of Parkinson disease. The effect of the combination was significantly more potent than those of flu, Glib or B com, solely. Pretreatment with the combination or using only Glib or B com separately, reduced the level of MDA in blood and brain, significantly. However, the effect of the combination was significantly more potent than those of Glib or B com, solely. Conclusions: Since the severity of the behavioral symptoms in the 6-OHDA-induced model of Parkinson disease reflects the degree of the lesion in substantia nigra (SN) dopaminergic neurons, it is suggested that using the combination had neuroprotective effects. The obtained data suggest a synergistic neuroprotective and antiparkinsonian effect for flu, Glib and B com. At least, a part of this effect was mediated through inhibition of oxidative stress. Keywords: 6-Hydroxydopamine, Flunarizine, Glibenclamide: B Vitamins, Behavioral Symptoms, Malondialdehyd

Prevalence and intensity of catastrophic health care expenditures in Iran from 2008 to 2015: a study on Iranian household income and expenditure survey.

BACKGROUND: Households exposure to catastrophic health expenditure is a valuable measure to monitor financial protection in health sector payments. The present study had two aims: first, to estimate the prevalence and intensity of catastrophic health expenditures (CHE) in Iran. Second, to investigate main factors that influence the probability of CHE. METHODS: CHE is defined as an occasion in which a household's out-of-pocket (OOP) spending exceeds 40% of the total income that remains after subtraction of living expenses. This study used the data from eight national repeated cross-sectional surveys on households' income and expenditure. The proportion of households facing CHE, as a prevalence measure, was estimated for rural and urban areas. The intensity of CHE was also calculated using overshoot and mean positive overshoot (MPO) measures. The factors affecting the CHE were also analyzed using logistic random effects regression model. We also used ArcMap 10.1 to display visually disparities across the country. RESULTS: An increasing number of Iranians has been subject to catastrophic health care costs over the study period in both rural and urban areas (CHE = 2.57% in 2008 and 3.25% in 2015). In the same period, the overshoot of CHE and the mean positive overshoot ranged from 0.26% to 0.65% and from 12.26% to 20.86%, respectively. The average absolute monetary value of OOP spending per month has been low in rural areas over the years, but the prevalence of CHE has been higher than urban areas. Generally put, rural settlement, higher income, receiving inpatient and outpatient services, and existence of elderly people in the household led to increase in CHE prevalence (p < 0.05). Interestingly, provinces with more limited geographical and cultural accessibility had the lowest CHE. CONCLUSIONS: According to the findings, Iran's healthcare system has failed to realize the aim of five-year national development plan regarding CHE prevalence (1% CHE prevalence according to the plan). Therefore, revision of financial health care protection policies focusing on pre-payments seems mandatory. For instance, these policies should extend the interventions that target low-income populations particularly in rural areas, provide more coverage for catastrophic medical services in basic benefit packages, and develop supplementary health insurance

Synergistic Antiparkinsonian Effect of Flunarizine, Glibenclamide and B Vitamins in a Rat 6-Hydroxydopamine Model; The Role of Malondialdehyde

Background: The current study evaluated the effects of a combination of flunarizine (flu) a calcium channel blocker, glibenclamide (Glib), a KATP channels blocker and B vitamins (B com) on the behavioral symptoms of 6-hydroxydopamine (6-OHDA)-induced model of Parkinson disease to examine the synergistic antiparkinsonian effects of the drugs and supplements. Also the level of malondialdehyde (MDA) was measured in blood and brain suspensions to find probable neuroprotective mechanism of these materials. Methods: 6-OHDA was injected into striatum of rats by stereotaxic surgery. Pretreatment with flu, Glib and B com was started before the surgery and continued to three weeks after the surgery. Development and severity of Parkinson disease were evaluated by the conventional behavioral tests. MDA values were measured spectrophotometrically, using thiobarbituric acid test and the MDA standard curve. Results: Pretreatment with a combination of flu, Glib and B com ameliorated the behavioral symptoms of Parkinson disease. The effect of the combination was significantly more potent than those of flu, Glib or B com, solely. Pretreatment with the combination or using only Glib or B com separately, reduced the level of MDA in blood and brain, significantly. However, the effect of the combination was significantly more potent than those of Glib or B com, solely. Conclusions: Since the severity of the behavioral symptoms in the 6-OHDA-induced model of Parkinson disease reflects the degree of the lesion in substantia nigra (SN) dopaminergic neurons, it is suggested that using the combination had neuroprotective effects. The obtained data suggest a synergistic neuroprotective and antiparkinsonian effect for flu, Glib and B com. At least, a part of this effect was mediated through inhibition of oxidative stress. Keywords: 6-Hydroxydopamine, Flunarizine, Glibenclamide: B Vitamins, Behavioral Symptoms, Malondialdehyd

Haplotype Analysis of RAGE Gene Polymorphisms and Association with Increased Risk of Diabetic Nephropathy

Background: The present study aimed at evaluating the association between the -429T/C and - 374T/A polymorphisms of RAGE (Receptor for Advanced Glycation End Products) gene promoter and diabetic nephropathy as well as examining its possible application as candidate markers of diabetic nephropathy among the population of Qazvin, Iran. Methods: In this study, the diabetic patients were divided into the two groups of with or without nephropathy. The frequency of genotype and allele were determined using TETRA-Primer ARMSPCR. Hardy-Weinberg equilibrium test and correlation of polymorphisms, odds ratio (OR), and FAMHAP software were used for haplotype analysis. Results: Based on our data, the CC genotype of -429T/C polymorphism may play a protective role against the development of nephropathy (OR=0.586, 95%; CI: 0.158-2.167) while, the AA genotype may be associated with increased risk of the disease (OR=1.889, 95%; CI: 0.454-7.854). Allele’s analysis revealed that the C allele of -429T/C polymorphism maybe protective against the appearance of nephropathy (OR=0.794, 95%; CI: 0.48-1.314) whereas, the A allele may be related to increased risk for nephropathy (OR=1.452, 95%; CI: 0.783-2.695). Haplotype analysis demonstrated that there was no significant correlation between the two -429T/C and -374T/A SNPs (χ2=5.125, p value=0.135). However, it was found that the CA haplotype may have a protective effect against the development of nephropathy (OR=0.48, 95%; CI: 0.14-1.64) while, the TA haplotype may increase the risk of the disease (OR=2.06, 95%; CI:1.01-4.23). Conclusion: Overall, no correlation between the -374T/A and -429T/C polymorphisms and the haplotypes in RAGE gene and the occurrence of diabetic nephropathy, was established. Keywords: Nephropathy, Type 2 Diabetes, Haplotype, Receptor for Advanced Glycation End Products, SNP, Iran Citation: Tavakoli A, Salahshourifar I, Hajialilo

Normobaric hyperoxia preconditioning attenuates streptozotocin - induced impairments in spatial learning

Introduction: A large body of evidence points to oxidative stress as prime candidate mediating the behavioral impairments and memory deficits in Alzheimer's disease (AD). It has been demonstrated that hyperoxia preconditioning activates complex endogenous neuroprotective mechanisms including an increase in capacity of antioxidant defence mechanisms. The aim of this study was to investigate the beneficial effects of normobaric hyperoxia preconditioning in streptozotocin (STZ)- induced memory impairment in rats. Materials and Methods: Male Wistar rats were first exposed to air with high oxygen concentration (>90%) or atmospheric air for 24 hours and then STZ (3 mg/kg) was bilaterally infused in lateral ventricles of the brain. Two weeks later Morris Water Maze (MWM) test was performed to assess spatial learning and memory consolidation. Results: STZ increased escape latency (P<0.05), distance and number of crossed quadrants (P<0.05) especially on 1st and 2nd days. However, hyperoxia preconditioning significantly attenuated STZ-induced learning and memory deficits during training sessions in the MWM (P<0.05). Preconditioning also increased time spent and swimming distance in the target quadrant in probe test (P<0.05). However, hyperoxia preconditioning had no effect on the swimming speed. Conclusion: Hyperoxia preconditioning significantly attenuated STZ-induced impairments in spatial learning and memory. These results suggest that hyperoxia may have a potential therapeutic effect at the early stage of AD and possibly the prevention of memory deficits