Comparison of quality of life in patients with mitral valve replacement and mitral valve repair in Imam Ali Hospital during 2014 to 2020: a cross-sectional study.

OBJECTIVE: Mitral valve failure is one of the most common valvular heart diseases worldwide. Valve replacement and repair have an impact on the quality of life of patients. Therefore, the present study was conducted to compare the quality of life in patients with mitral valve replacement and those who underwent mitral valve repair. METHODS: In this cross-sectional study, we considered all cardiac patients with ischemic mitral insufficiency who underwent mitral valve repair and patients with a history of valve replacement in Imam Ali Hospital of Kermanshah between 2014 and 2020. Two Minnesota and general quality of life questionnaires along with a checklist for demographic variables were used for data collection. Data analysis was performed using SPSS version 21 software. RESULTS: The mean quality of life score based on the general quality of life scale in the valve repair group was 32.33 (SD = 2.29) and in the valve replacement group 32.89(SD = 2.60), (p = 0.917). Also, mean quality of life, as measured by the Minnesota MLHFQ was 60.89(SD = 17.67) in the valve repair group and 63.42 (SD = 12.13) in the valve replacement group (p = 0.308). The results showed that the average general quality of life was different in study groups regarding education. Tukey's post hoc test showed that the average general quality of life in illiterate people is significantly lower than in people with academic degrees (P-value = 0.001). CONCLUSION: The quality of life of the patients in both the valve repair and replacement groups was at an average level. There was no significant difference between the general quality of life and the Minnesota scales, suggesting that both tools can be effectively used to measure patients' quality of life. The study's findings can be valuable for monitoring patients, screening for conditions, and enhancing communication between doctors and patients.

The burden of headache disorders in the Eastern Mediterranean Region, 1990-2016: findings from the Global Burden of Disease study 2016.

OBJECTIVES: Using the findings of the Global Burden of Disease Study (GBD), we report the burden of primary headache disorders in the Eastern Mediterranean Region (EMR) from 1990 to 2016. METHODS: We modelled headache disorders using DisMod-MR 2.1 Bayesian meta-regression tool to ensure consistency between prevalence, incidence, and remission. Years lived with disability (YLDs) were calculated by multiplying prevalence and disability weight (DW) of migraine and tension-type headache (TTH). We assumed primary headache disorders as non-fatal, so their YLD is equal to disability-adjusted life years (DALYs). RESULTS: Migraine and TTH were the second and twentieth leading causes of YLDs in EMR. Between 1990 and 2016, the absolute YLD numbers of migraine and TTH increased from 2.3 million (95% uncertainty interval (UI): 1.5-3.2) to 4.7 million (95%UI: 3-6.5) and from 383 thousand (95%UI: 240-562) to 816 thousand (95%UI: 516-1221), respectively. During the same period, age-standardised YLD rates of migraine and TTH in EMR increased by 0.7% and 2.5%, respectively, in comparison to a small decrease in the global rates (0.2% decrease in migraine and TTH). The bulk of burden due to headache occurred in the 30-49 year age group, with a peak at ages 35-44 years. The age-standardised YLD rates of both headache disorders were higher in women with female to male ratio of 1.69 for migraine and 1.38 for TTH. All countries of the EMR except for Somalia and Djibouti had higher age-standardised YLD rates for migraine and TTH in compare to the global rates. Libya and Saudi Arabia had the highest increase in age-standardised YLD rates of migraine and TTH, respectively. CONCLUSION: The findings of this study show that primary headache disorders are a major and a growing cause of disability in EMR. Since 1990, burden of primary headache disorders has constantly been higher in EMR compared to rest of the world, which indicates that health systems in EMR must focus further on developing and implementing preventive and management strategies to control headache.

Air pollution, environmental chemicals, and smoking may trigger vitamin D deficiency: Evidence and potential mechanisms.

Beyond vitamin D (VD) effect on bone homeostasis, numerous physiological functions in human health have been described for this versatile prohormone. In 2016, 95% of the world's population lived in areas where annual mean ambient particulate matter (<2.5 µm) levels exceeded the World Health Organization guideline value (Shaddick et al., 2018). On the other hand, industries disperse thousands of chemicals continually into the environment. Further, considerable fraction of populations are exposed to tobacco smoke. All of these may disrupt biochemical pathways and cause detrimental consequences, such as VD deficiency (VDD). In spite of the remarkable number of studies conducted on the role of some of the above mentioned exposures on VDD, the literature suffers from two main shortcomings: (1) an overview of the impacts of environmental exposures on the levels of main VD metabolites, and (2) credible engaged mechanisms in VDD because of those exposures. To summarize explanations for these unclear topics, we conducted the present review, using relevant keywords in the PubMed database, to investigate the adverse effects of exposure to air pollution, some environmental chemicals, and smoking on the VD metabolism, and incorporate relevant potential pathways disrupting VD endocrine system (VDES) leading to VDD. Air pollution may lead to the reduction of VD cutaneous production either directly by blocking ultraviolet B photons or indirectly by decreasing outdoor activity. Heavy metals may reduce VD serum levels by increasing renal tubular dysfunction, as well as downregulating the transcription of cytochrome P450 mixed-function oxidases (CYPs). Endocrine-disrupting chemicals (EDCs) may inhibit the activity and expression of CYPs, and indirectly cause VDD through weight gain and dysregulation of thyroid hormone, parathyroid hormone, and calcium homeostasis. Smoking through several pathways decreases serum 25(OH)D and 1,25(OH)2D levels, VD intake from diet, and the cutaneous production of VD through skin aging. In summary, disturbance in the cutaneous production of cholecalciferol, decreased intestinal intake of VD, the modulation of genes involved in VD homeostasis, and decreased local production of calcitriol in target tissues are the most likely mechanisms that involve in decreasing the serum VD levels.

Prevalence and Years Lived with Disability of 310 Diseases and Injuries in Iran and its Neighboring Countries, 1990-2015: Findings from Global Burden of Disease Study 2015.

BACKGROUND: Due to significant achievements in reducing mortality and increasing life expectancy, the issue of disability from diseases and injuries, and their related interventions, has become one of the most important concerns of health-related research. METHODS: Using data obtained from the GBD 2015 study, the present report provides prevalence and years lived with disability (YLDs) of 310 diseases and injuries by sex and age in Iran and neighboring countries over the period 1990-2015. Age-standardized rates of all causes of YLDs are presented for both males and females in 16 countries for 1990 and 2015. We present the percentage of total YLDs for 21 categories of diseases and injuries, the percentage of YLDs for age groups, as well as the ranking of the most prevalent causes and YLDs from the top 50 diseases and injuries in Iran. RESULTS: In 2015, the burden of 310 diseases and injuries among the Iranian population was responsible for 8,357,878 loss of all-age total years, which is equal to 10.58% of total years lived per year. This differs from the neighboring countries, as it ranges from 9.05% in Turkmenistan to 13.36% in Russia. During the past 25 years, a remarkable decrease was observed in all-cause YLD rates in all 16 countries. Meanwhile, in all countries, the age-standardized rate of all causes of YLDs was higher in females than males. CONCLUSION: Based on our findings, one of the remarkable changes in NCDs observed among the studied age groups was increased rate of YLDs from mental disorders, which was replaced by musculoskeletal disorders in older age groups in 2015.

Disability-Adjusted Life-Years (DALYs) for 315 Diseases and Injuries and Healthy Life Expectancy (HALE) in Iran and its Neighboring Countries, 1990-2015: Findings from Global Burden of Disease Study 2015.

BACKGROUND: Summary measures of health are essential in making estimates of health status that are comparable across time and place. They can be used for assessing the performance of health systems, informing effective policy making, and monitoring the progress of nations toward achievement of sustainable development goals. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) as main summary measures of health. We assessed the trends of health status in Iran and 15 neighboring countries using these summary measures. METHODS: We used the results of GBD 2015 to present the levels and trends of DALYs, life expectancy (LE), and HALE in Iran and its 15 neighboring countries from 1990 to 2015. For each country, we assessed the ratio of observed levels of DALYs and HALE to those expected based on socio-demographic index (SDI), an indicator composed of measures of total fertility rate, income per capita, and average years of schooling. RESULTS: All-age numbers of DALYs reached over 19 million years in Iran in 2015. The all-age number of DALYs has remained stable during the past two decades in Iran, despite the decreasing trends in all-age and age-standardized rates. The all-cause DALY rates decreased from 47,200 in 1990 to 28,400 per 100,000 in 2015. The share of non-communicable diseases in DALYs increased in Iran (from 42% to 74%) and all of its neighbors between 1990 and 2015; the pattern of change is similar in almost all 16 countries. The DALY rates for NCDs and injuries in Iran were higher than global rates and the average rate in High Middle SDI countries, while those for communicable, maternal, neonatal, and nutritional disorders were much lower in Iran. Among men, cardiovascular diseases ranked first in all countries of the region except for Bahrain. Among women, they ranked first in 13 countries. Life expectancy and HALE show a consistent increase in all countries. Still, there are dissimilarities indicating a generally low LE and HALE in Afghanistan and Pakistan and high expectancy in Qatar, Kuwait, and Saudi Arabia. Iran ranked 11th in terms of LE at birth and 12th in terms of HALE at birth in 1990 which improved to 9th for both metrics in 2015. Turkey and Iran had the highest increase in LE and HALE from 1990 to 2015 while the lowest increase was observed in Armenia, Pakistan, Kuwait, Kazakhstan, Russia, and Iraq. CONCLUSIONS: The levels and trends in causes of DALYs, life expectancy, and HALE generally show similarities between the 16 countries, although differences exist. The differences observed between countries can be attributed to a myriad of determinants, including social, cultural, ethnic, religious, political, economic, and environmental factors as well as the performance of the health system. Investigating the differences between countries can inform more effective health policy and resource allocation. Concerted efforts at national and regional levels are required to tackle the emerging burden of non-communicable diseases and injuries in Iran and its neighbors.

Trend of Socio-Demographic Index and Mortality Estimates in Iran and its Neighbors, 1990-2015; Findings of the Global Burden of Diseases 2015 Study.

BACKGROUND: The Global burden of disease and injuries study (GBD 2015) reports expected measures for years of life lost (YLL) based on socio-demographic index (SDI) of countries, as well as the observed measures. In this extended GBD 2015 report, we reviewed total and cause-specific deaths and YLL for Iran and all its neighboring countries between 1990 and 2015. METHODS: We extracted data from the GBD 2015 database. Observed YLL measures were calculated by multiplying the number of deaths by standard life expectancy at each age. SDI was a composite index, calculated based on income per capita, average years of schooling, and total fertility rate. The GBD world population was used for age standardization. RESULTS: All-ages crude death rate in Iran reduced from 665.6 per 100,000 population (95% uncertainty interval: 599.3-731.6) in 1990 to 487.2 (414.9-566.1) in 2015. The ratio of observed to expected YLL (O/E ratio) for all-causes ranged between 0.54 (Turkey) and 1.95 (Russia) in 2015. For Iran, the all-causes O/E ratio was less than 1 in all years (1990-2015), except 2003. However, cause-specific O/E ratio was more than 1 for some causes, including the top leading causes of YLL (ischemic heart disease, road injuries, and cerebrovascular disorders). Ischemic heart disease was the first or second cause of YLL in all comparator countries except Afghanistan. CONCLUSION: The leading YLL causes with high O/E ratios should be prioritized in public health efforts. In addition to research evidence, countries with low O/E ratios should be scrutinized to find feasible innovative interventions.

Prevalence and Incidence of Multiple Sclerosis in Tehran, Iran.

BACKGROUND: Tehran is the capital of Iran with an increasing Multiple Sclerosis (MS) incidence. A retrospective population-based study was conducted to evaluate the status of MS prevalence and MS incidence trends in Tehran Province, Iran. METHODS: A population-based study was conducted from 1991 to 2014 in Tehran Province, the capital city of Iran based on Iranian MS Society (IMSS) registry system. A structured questionnaire design to cover the important epidemiological variables, related at the individual level for MS. A Monte Carlo Permutation method was utilized to test whether the apparent change in MS trends during 1991-2014 was statistically significant. RESULTS: MS incidence was significantly increased during our study period. The annual percent change (APC) was 12.8% in women during 1991 to 2004 and 12.5% in men during the same period. The point prevalence of MS was 101.39 per 100000 populations in 2014. The age-adjusted prevalence rates were 134.03 and for male patients were 42.45 per 100000. CONCLUSION: MS prevalence and incidence in Tehran are markedly rising, it is crucial to elucidate the causes of the increasing trends and implement efficient policies lowering disease burden.

Multiple sclerosis and air pollution exposure: Mechanisms toward brain autoimmunity.

The association between neurodegenerative diseases and environmental exposures, in particular air pollution, has been noticed in the last two decades, but the importance of this environmental factor in multiple sclerosis (MS) pathogenesis has not been considered extensively. However, recent evidence suggests that major mechanisms involved in MS pathogenesis, such as inflammatory factors expression, free radicals overproduction, the blood brain barrier (BBB) breakdown, neuroinflammation, vitamin D deficiency and mitochondrial dysfunction could also occur due to exposure to air pollutants. A prospective hypothesis is suggested here in which exposure to air pollutants may initiate destructive mechanisms inducing inflammatory-oxidative cascades, reduction of immunological self-tolerance and neurodegeneration leading to brain autoimmunity.

Multiple Sclerosis Epidemiology in East Asia, South East Asia and South Asia: A Systematic Review.

BACKGROUND: Multiple sclerosis (MS) is one of the most common chronic immune-mediated diseases of the human central nervous system and an important cause of non-traumatic neurologic disability among young population in several countries. Recent reports from East Asia, South East Asia and South Asia have proposed a low to moderate prevalence of MS in these countries. METHODS: A literature review search was carried out in December 2014 in Medline, Embase, Scopus and Cochrane library to recover original population-based studies on MS epidemiology in East Asia, South East Asia and South Asia countries published between January 1, 1950 and December 30, 2014. We intended search strategies using the key words: multiple sclerosis, prevalence, incidence and epidemiology. Based on our inclusion criteria, 68 epidemiologic studies were included in this systematic review. RESULTS: The most extensively used diagnostic criteria in the studies were McDonald's criteria. Most studies were performed in a multi-center hospital setting. The female to male ratio varied and ranged from 0.7 in India to 9.0 in China. The mean age at disease onset ranged from the lowest age of 25.3 in Iran to the highest age of 46.4 in China. MS prevalence ranged from 0.77 in 100,000 populations in Hong Kong (1999) to 85.80 in 100,000 in Iran (2013). CONCLUSIONS: Advances in MS registries around the globe allow nationwide population-based studies and will allow worldly comparisons between the prevalence and incidence in different regions that are provided to monitor estimation.

Behavioral despair associated with a mouse model of Crohn's disease: Role of nitric oxide pathway.

Crohn's disease (CD) is associated with increased psychiatric co-morbidities. Nitric oxide (NO) is implicated in inflammation and tissue injury in CD, and it may also play a central role in pathogenesis of the accompanying behavioral despair. This study investigated the role of the NO pathway in behavioral despair associated with a mouse model of CD. Colitis was induced by intrarectal (i.r.) injection of 2,4,6-trinitrobenzenesulfonic acid (10mg TNBS in 50% ethanol). Forced swimming test (FST), pharmacological studies and tissues collection were performed 72 h following TNBS administration. To address a possible inflammatory origin for the behavioral despair following colitis induction, tumor necrosis factor-alpha (TNF-α) level was measured in both the hippocampal and colonic tissue samples. In parallel, hippocampal inducible nitric oxide synthase (iNOS) and nitrite level were evaluated. Pharmacological studies targeting the NO pathway were performed 30-60 min before behavioral test. Colitis was confirmed by increased colonic TNF-α level and microscopic score. Colitic mice demonstrated a significantly higher immobility time in the FST associated to a significant increase of hippocampal TNF-α, iNOS expression and nitrite content. Acute NOS inhibition using either Nω-nitro-l-arginine methyl ester (a non-specific NOS inhibitor) or aminoguanidine hydrochloride (a specific iNOS inhibitor) decreased the immobility time in colitic groups. Moreover, acute treatment with both NOS inhibitors decreased the TNF-α level and nitrite content in the hippocampal samples. This study suggests that the NO pathway may be involved in the behavioral effects in the mouse TNBS model of CD. These findings endow new insights into the gut-brain communication during the development of colonic inflammation, which may ultimately lead to improved therapeutic strategies to combat behavior changes associated with gastrointestinal disorders.

Multiple Sclerosis Epidemiology in Middle East and North Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple sclerosis (MS) is one of the most common neurological disorders and a leading cause of nontraumatic disability in young adults in many countries. Recent reports from the Middle East and North Africa have suggested a moderate to high risk of MS in these countries. METHODS: A literature search was performed in August 2014 in MEDLINE, EMBASE, and IMEMR to retrieve original population-based studies on MS epidemiology in the Middle East and North African countries published between 1st January 1985 and 1st August 2014. We designed search strategies using the key words: MS, prevalence, incidence, and epidemiology. According to the inclusion criteria, 52 studies were included in this systematic review. RESULTS: McDonald's criteria were the most widely used diagnostic criteria in the studies. Most studies were conducted in single hospital-based centers with a defined catchment area. The female/male ratio ranged from 0.8 in Oman to 4.3 in Saudi Arabia. MS prevalence ranged from 14.77/100,000 population in Kuwait (2000) to 101.4/100,000 in Turkey (2006). The overall MS prevalence in the region was 51.52/100,000. The mean age at disease onset ranged from 25.2 years in Kuwait to 32.5 years in Northeastern Iran, with an overall estimate of 28.54 years. CONCLUSIONS: Recent advances in MS registries will allow nation-wide studies and temporal comparisons between countries, provided that age- and sex-standardized estimates are available.

Potential impact of air pollution on multiple sclerosis in Tehran, Iran.

BACKGROUND: Multiple sclerosis (MS) incidence has dramatically increased in Tehran, Iran. The health impact of air pollution in Tehran underscores the attention to a possible association to this environmental risk factor. In this study, the authors aimed to analyze the spatial distribution of prevalent MS cases and their association with the spatial patterns of air pollution. METHODS: Patient records meeting McDonald's criteria for definite MS diagnosis with disease onset during 2003-2013 were obtained. Next, the location of 2,188 patients was successfully geo-referenced within Tehran metropolis by geographic information system (GIS) bureau of Iran's post office based on their phone numbers. A cluster analysis was performed using the average nearest neighbor index (ANNI) and quadrat analysis. The long-term exposures of MS patients to particulate matter (PM10), sulfur dioxide (SO2), nitrogen oxide (NO), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were estimated using the previously developed land use regression models. RESULTS: Prevalent MS cases had a clustered pattern in Tehran. A significant difference in exposure to PM10, SO2, NO2, and NOx (p < 0.001) was observed in MS cases compared with controls. CONCLUSION: This study revealed the potential role of long-term exposure to air pollutants as an environmental risk factor in MS.

A further TWEAK to multiple sclerosis pathophysiology.

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF super family that controls many cellular activities including proliferation, migration, differentiation, apoptosis, and inflammation by binding to fibroblast growth factor-inducible 14 (Fn14), a highly inducible cell surface receptor. Recent studies have indicated that TWEAK-Fn14 axis signaling may contribute to chronic autoimmune diseases. TWEAK expression via microglia in cortical lesions, presence of TWEAK(+) macrophages in inflamed leptomeninges, and absence of TWEAK/Fn14 expression in healthy brain implicates importance of this pathway in pathogenesis of multiple sclerosis lesions. TWEAK-Fn14 axis blockade has also shown promise in various multiple sclerosis animal models. Stimulation of the TWEAK/Fn14 pathway can result in activation of both canonical and noncanonical NF-κB signaling and could also stimulate mitogen-activated protein kinase (MAPK) signaling pathways. Here, we have reviewed evidence of the possible role of TWEAK-Fn14 axis in pathophysiology of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) via neuroinflammation, tissue remodeling, blood-brain barrier (BBB) disruption, neurodegeneration, and astrogliosis.

Medical podcasting in Iran; pilot, implementation and attitude evaluation.

Podcasting has become a popular means of transferring knowledge in higher education through making lecture contents available to students at their convenience. Accessing courses on media players provides students with enhanced learning opportunities. Development of teaching methods able to cope with ever-changing nature of medicine is crucial to train the millennium students. Pharmacology education in Tehran University of Medical Sciences has been based on lectures so far; our aim was to implement a pilot study to evaluate the advantages and disadvantages of offering the course contents as podcasts as well as evaluating whether such program can be feasible in our educational program. 46% of students downloaded the podcast according to our download center. 48% favored usage of both internet and DVD-ROM concurrently. Overall 96% of students perceived that podcasting had a positive impact on their learning in pharmacology course. Our results indicate that most of attendants proposed the positive yields of podcasting despite low usage of it, mainly as a pre-class preparing tool.

Estradiol reduces depressive-like behavior through inhibiting nitric oxide/cyclic GMP pathway in ovariectomized mice.

Estradiol decline has been associated with depressive-like behavior in female mice and NO has been suggested to play a major role in the pathogenesis of major depression. This study was conducted to investigate the antidepressant-like effects of acute estradiol administration in female ovariectomized (OVX) mice and the possible role of nitric oxide (NO)/cyclic GMP (cGMP) pathway. To this end, bilateral ovariectomy was performed in female mice and different doses of estradiol were injected alone or in combination with non-specific NO synthase (NOS) inhibitor (L-NAME), selective neural NOS (nNOS) inhibitor (7-NI), an NO precursor (L-arginine) or selective phosphodiesterase type 5 inhibitor (sildenafil). The duration of immobility was recorded in the forced swimming test (FST) to assess the depressive behavior. Moreover, hippocampal levels of NO were determined in select groups. 10 days following the procedure, OVX mice showed significantly prolonged immobility time in comparison with the sham group. Estradiol (3, 10, and 30 µg/kg, s.c.), when injected 1 h prior to FST, exerted antidepressant-like effects in OVX mice. Both L-NAME (30 mg/kg, i.p.), and 7-NI (50 mg/kg, i.p.) significantly reduced the immobility times of OVX mice. Administration of a sub-effective dose of L-NAME (10mg/kg), 15 min after a sub-effective dose of estradiol (1 µg/kg, s.c.) had a robust antidepressant-like effect in OVX mice. Also a sub-effective dose of 7-NI (25 mg/kg), 30 min after a sub-effective dose of estradiol (1 µg/kg, s.c.) showed antidepressant-like effect in OVX mice. Both the NO precursor L-arginine (750 mg/kg, i.p.) and the cGMP-specific phosphodiesterase type 5 inhibitor sildenafil (5 mg/kg, i.p.), 30 min before estradiol treatment, prevented the antidepressant-like effect of a potent dose of estradiol (10 µg/kg, s.c.) in OVX mice. The present findings suggest that suppression of the NO synthase/NO/cGMP pathway may be involved in the antidepressant-like effects of estradiol in OVX mice.

NMDA receptor involvement in antidepressant-like effect of pioglitazone in the forced swimming test in mice.

RATIONALE: Previously, we showed that pioglitazone exerts its antidepressant-like effect through peroxisome proliferator-activated receptor gamma receptors and demonstrated the possible involvement of calcium-dependent nitric oxide synthase inhibitors. Based upon the in vitro results, pioglitazone reduces N-methyl-D-aspartate (NMDA)-mediated calcium currents in hippocampal neurons. OBJECTIVE: In this study, we evaluated the involvement of the NMDA receptor (NMDAR) on the antidepressant-like effect of pioglitazone in the forced swimming test (FST) in mice. METHOD: After the assessment of locomotor activity in the open-field test, mice were forced to swim individually and the immobility time of the last 4 min was evaluated. Pioglitazone was administered orally with doses of 5, 10, and 20 mg/kg 4 h before FST. To assess the involvement of NMDARs in the possible antidepressant-like effect of pioglitazone, a selective glutamate receptor agonist, NMDA (75 mg/kg, intraperitoneally [i.p.] or 20 ng/mouse, intracerebroventricularly [i.c.v.]), was administered before pioglitazone (20 mg/kg). To further determine a possible role of NMDARs in this effect, a noncompetitive antagonist of the NMDA, MK-801 (0.05 mg/kg, i.p. or 100 ng/mouse, i.c.v.), was coadministered with pioglitazone (10 mg/kg) 4 h prior to FST. RESULTS: Pioglitazone (20 mg/kg) administered 4 h prior to FST significantly reduced the immobility time. Coadministration of the noneffective doses of pioglitazone and MK-801 revealed an antidepressant-like effect in FST. Moreover, NMDA significantly reversed the antidepressant-like effect of pioglitazone administered 4 h prior to FST. CONCLUSION: The antidepressant-like effect of pioglitazone in the FST is mediated partly through NMDAR signaling. This study provides a new approach for the treatment of depression.

Voltage-dependent calcium channel and NMDA receptor antagonists augment anticonvulsant effects of lithium chloride on pentylenetetrazole-induced clonic seizures in mice.

Although lithium is still a mainstay in the treatment of bipolar disorder, its underlying mechanisms of action have not been completely elucidated. Several studies have shown that lithium can also modulate seizure susceptibility in a variety of models. In the present study, using a model of clonic seizures induced with pentylenetetrazole (PTZ) in male Swiss mice, we investigated whether there is any interaction between lithium and either calcium channel blockers (CCBs: nifedipine, verapamil, and diltiazem) or N-methyl-D-aspartate (NMDA) receptor antagonists (ketamine and MK-801) in modulating seizure threshold. Acute lithium administration (5-100mg/kg, ip) significantly (P<0.01) increased seizure threshold. CCBs and NMDA receptor antagonists also exerted dose-dependent anticonvulsant effects on PTZ-induced seizures. Noneffective doses of CCBs (5mg/kg, ip), when combined with a noneffective dose of lithium (5mg/kg, ip), exerted significant anticonvulsant effects. Moreover, co-administration of a noneffective dose of either MK-801 (0.05mg/kg, ip) or ketamine (5mg/kg, ip) with a noneffective dose of lithium (5mg/kg, ip) significantly increased seizure threshold. Our findings demonstrate that lithium increases the clonic seizure threshold induced by PTZ in mice and interacts with either CCBs or NMDA receptor antagonists in exerting this effect, suggesting a role for Ca(2+) signaling in the anticonvulsant effects of lithium in the PTZ model of clonic seizures in mice.

Determination of sensitivity of male Wistar rats to an equal dose of ketamine/xylazine injection at anesthetic dose in a chronic model of hypernatremia in comparison with control group.

OBJECTIVE: To determine the sensitivity to an equal dose of ketamine/xylazine injection at anesthetic dose in a chronic model of hypernatremia. METHODS: This study was conducted at the Department of Physiology, Zanjan University of Medical Science, Zanjan, Iran in 2004. Sixty male Wistar rats, weighing 250 +/- 20 g were randomly allocated to 3 groups. The control group was provided with tap water, and first and second test groups consumed 1% and 2% salt concentrations for 144 hours. One hundred mg/kg ketamine and 10 mg/kg xylazine were used as an anesthetic agent. The measured anesthetic parameters comprises of righting reflex latency, required time for establishment of animal's immobility, immobility period, required time for appearance of animal's mobility and complete re-establishment of the righting reflex. RESULTS: The required time for inhibition of the righting reflex and animal's mobility in the second group was significantly shorter than the first and control groups. Immobility period, required time for appearance of animal's mobility and complete re-establishment of the righting reflex in the second group were significantly longer than the first and control groups. CONCLUSION: Hypernatremia increases the speed of transition from different steps of ketamine/xylazine anesthesia with significant delay in immobility period and recovery from anesthesia in rats, hence, anesthetic dose reduction in hypernatremia is necessary.