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Objective Research examining associations between diet quality and obesity in Iranian adults is limited by small and non‐representative samples. This study examined associations between two diet quality indices and obesity risk in a nationally representative sample of Iranian adults and interactions by sex and area of residence. Methods Data on 18,307 adults (mean age 37 [SD 15.2] years) were used from the Iranian National Survey 2001–2003. Two diet quality indices (Healthy Eating Index 2015, HEI‐2015, and Diet Quality Index International, DQI‐I) were calculated from household 24‐h dietary recalls. Multi‐level regression analyses were used to examine the association between household diet quality and individual‐level obesity risk, with interaction terms for sex and area of residence. Results Higher household HEI‐2015 and DQI‐I were associated with higher risk of obesity (HEI‐2015: relative risk ratio: 1.04, 95% CI: 1.03, 1.05; DQI‐I: relative risk ratio: 1.02, 95% CI: 1.01, 1.02), with stronger effect sizes in adults living in rural areas. Conclusions Higher diet quality (HEI‐2015 and DQI‐I) was associated with higher obesity risk, which was stronger in adults living in rural areas. Due to the complexity of examining these associations in a Middle Eastern country undergoing a nutrition transition, longitudinal research is needed to confirm these findings.

Background During the first wave of COVID‐19, many Iranians were poisoned by ingesting hand sanitizers and/or alcoholic beverages to avoid viral infection. To assess whether the COVID‐19 pandemic resulted in an increased prevalence of accidental hand sanitizer/alcoholic beverage exposure in children and adolescents, we compared pediatric hospitalization rates during COVID‐19 and the previous year. For poisoning admissions during COVID‐19, we also evaluated the cause by age and clinical outcomes. Methods This retrospective data linkage study evaluated data from the Legal Medicine Organization (reporting mortalities) and hospitalization data from nine toxicology referral centers for alcohol‐poisoned patients (age 0 to 18 years) for the study period (February 23 to June 22, 2020) and the pre‐COVID‐19 reference period (same dates in 2019). Results Hospitalization rates due to ethanol and methanol exposure were significantly higher in 2020 (n = 375) than 2019 (n = 202; OR [95% CI] 1.9 [1.6, 2.2], p, During the first wave of COVID‐19 pandemic, Iran experienced the worldwide biggest methanol outbreak recorded to date. The outbreak triggered by consumption of toxic alcoholic beverages or hand sanitizers, partially motivated by the belief that ingestion would protect against COVID‐19 infection. Our study shows that children and adolescents were also affected, with 22 deaths due to methanol exposure recorded in 2020. These were significantly higher in Feb‐June 2020 (during COVID‐19), compared to the corresponding time period in 2019.

Objective: The aim of this study was to investigate the linear and nonlinear dose–response associations of animal-based dietary protein intake and risk of developing rheumatoid arthritis (RA). Methods: A systematic search of MEDLINE, Scopus and Embase was conducted up to October 2020. Observational studies that report risk estimates of RA for animal-based protein consumption were included. We calculated pooled relative risks (RRs) by using a random-effects model. Linear and non-linear dose–response analyses were performed to examine the dose–response relations between animal-based protein consumption and RA. Results: Seven cohort studies (n = 457,554) with 3545 incident cases and six case–control studies with 3994 cases and 5252 controls were identified. Highest compared with the lowest category of fish consumption was inversely associated with risk of RA (RR: 0.89; 95% CI, 0.80 to 0.99; I2 = 0%, n = 10). Also, a 100 g/day increment in fish intake was associated with a 15% decreased risk of RA. Dose–response analysis showed a modest U-shaped association between fish consumption and incidence of RA, with the lowest risk at a fish intake of 20–30 g/day (Pnon-linearity = 0.04). We found no significant association between consumption of red meat, poultry or dairy and the risk of RA. Conclusion: The present study revealed a significant reverse association between fish consumption and risk of RA. While we observed no association between red meat, dairy or poultry consumption and risk of RA. Further well-designed prospective studies are needed to support our findings.

Previous studies regarding the zinc status in attention-deficit/hyperactivity disorder (ADHD) yielded inconsistent results. Thus, the present meta-analysis was aimed to estimate the association between hair and serum/plasma zinc levels and ADHD. Online databases of Medline, EMBASE, and Scopus were searched up to October 2020 with no limitation in time and language. Weighted mean differences (WMDs) of hair and serum/plasma zinc levels were calculated using a random-effects model. Overall, 22 articles with 1280 subjects with ADHD and 1200 controls were included. The pooled effect size indicated that serum/plasma zinc levels in subjects with ADHD were not statistically different than their controls (WMD = − 1.26 µmol/L; 95% CI − 3.72, 1.20). Interestingly, the exclusion of one study from the analysis showed that people with ADHD significantly have lower circulating levels of zinc compared to their controls (WMD: − 2.49 µmol/L; 95% CI − 4.29, − 0.69). Also, the pooled effect size indicated that hair zinc levels in cases with ADHD were not statistically different than their controls (WMD = − 24.19 μg/g; 95% CI − 61.80, 13.42). Present meta-analysis raises the possibility that subjects with ADHD are prone to have declined levels of zinc levels. Based on current findings, screening the zinc levels in subjects with ADHD could be reasonable. Further well-designed studies are needed to clarify the role of zinc in the etiology of ADHD.

Background: Coronavirus disease 2019 (COVID-19) is spreading rapidly and has affected millions of people worldwide. Comorbid diseases have complicated the course of infection and increased mortality. Myasthenia gravis (MG) affects the neuromuscular junctions (NMJs) and can compromise respiratory muscle action, leading to worse clinical outcomes in individuals infected with the COVID-19 theoretically. In this study, the aim is to assess the pattern of COVID-19 infection in patients with MG based on several factors. Methods: This was a prospective cohort study following 150 patients with MG over a six-month period. The patients were monitored for the development of signs and symptoms of the COVID-19 infection. Results: Comparison of the patients infected with COVID-19 with MG and those not infected was performed independently based on age, duration since MG diagnosis, status of thymectomy, and current clinical status of MG disease. Data analysis did not reveal increased susceptibility or increased severity of COVID-19 illness based the criteria assessed. Conclusion: COVID-19 related deaths and susceptibility were not related to age, thymectomy status, and disease duration in patients with MG.

Background Although a large body of literature reported the beneficial effects of omega-3 fatty acids (omega-3 FAs) consumption on adipokines levels, but recent findings from clinical trials are not univocal. The aim of this systematic review and meta-analysis was to evaluate the effect of omega-3 FAs supplements on adipokines. Methods We searched Medline, Web of Science, Scopus, Embase, and Cochrane Library from inception to August 2020 without any particular language limitations. Outcomes were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) estimated from Hedge's g and random effects modeling. Results Fifty-two trials involving 4,568 participants were included. Omega-3 FAs intake was associated with a significant increase in plasma adiponectin levels (n = 43; 3,434 participants; SMD: 0.21, 95% CI: 0.04, 0.37; p = 0.01; I-2= 80.14%). This meta-analysis indicates that supplementing participants with omega-3 fatty acids more than 2000 mg daily and more than 10 weeks resulted in a significant and more favorable improvement in plasma adiponectin levels. However, omega-3 FAs intake had no significant effect on leptin levels (SMD: -0.02, 95% CI: -0.20, 0.17, I-2= 54.13%). Conclusion The evidence supports a beneficial effect of omega-3 FAs intake on serum adiponectin levels but does not appear to impact on leptin concentrations. Larger well-designed RCTs are still required to evaluate the effect of omega-3 FAs on leptin in specific diseases. info:eu-repo/semantics/publishedVersion

Abstract. Some studies indicated poor vitamin D level in NAFLD which is independently correlated with severity of steatosis. Low 25(OH) D3 levels are associated with an impaired lipid profile. Impaired levels and function of vaspin and omentin, which are adipokines, have been demonstrated in NAFLD patients. This study determined the relationship between vitamin D and serum liver enzymes, ultrasound findings, some adipokines, atherogenic index of plasma (AIP) and visceral adiposity index (VAI) in patients with NAFLD in a cross-sectional study. This study was a cross-sectional study in eighty-three NAFLD patients (57 males and 26 females). Plasma levels of omentin-1e-1, vaspin were measured. Anthropometric indices metabolic status was assessed. Visceral adiposity index and atherogenic index of plasma were calculated according to suggested formula. Anthropometric indices, lipid profiles, liver enzymes as well as abdominal ultrasonography and the status of vitamin D were assessed. The results showed that aspartate aminotransferase (AST) (44.22 ± 8.5 IU/L vs. 40.19 ± 8.75 IU/L, p-value = 0.039) AIP (0.767 ± 0.142 vs. 0.6417 ± 0.139, p

Cytokine release syndrome with rituximab has been reported in certain diseases, however, it is rarely reported in MS patients treated with rituximab. The treating physician should suspect the syndrome when typical signs and symptoms appear.

Background Glucagon-like peptide-1 (GLP-1), a gut-derived incretin hormone, plays a pivotal role in glucose-induced insulin secretion. Currently, the role of incretin hormones in the pathogenesis of cirrhosis is not clearly defined. This study aimed to investigate circulating levels of GLP-1 in liver cirrhosis and its association with the severity of liver disease. Methods A total of 80 participants including 39 patients with a definite diagnosis of liver cirrhosis and 41 healthy controls recruited in this cross-sectional study. Circulating levels of GLP-1 were determined using the ELISA method. The severity of liver cirrhosis was assessed according to the Child-Pugh, MELD (i), MELD-Na, MELD New, and UK end-stage liver disease score (UKELD) criteria. Results The mean age of patients and healthy subjects was 42.51 ± 12.80 and 42.07 ± 10.92 years, respectively (p value = .869). The mean MELD (i), MELD-Na, MELD New, UKELD, and Child-Pugh scores were 14.36 ± 4.26, 15.26 ± 4.81, 14.74 ± 4.66, 52.33 ± 3.82, and 7.28 ± 1.50, respectively. In this study, circulating levels of GLP-1 were statistically lower in cirrhotic patients compared with healthy controls (95.26 ± 17.15 vs 111.84 ± 38.14 pg/mL; p value = .017). Conclusion Larger prospective studies are needed to explore the incretin effect in cirrhosis patients compared with healthy individuals.

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of insulin resistance, is the most common cause of chronic liver. The present study aimed to investigate the roles of vaspin and omentin-1 in the NAFLD-related pathology including IR, inflammation and elevated blood pressure.This cross-sectional study was conducted among 83 NAFLD patients in Jahrom, Iran. Plasma levels of omentin-1, vaspin, hs-CRP and IL-6 were measured. Anthropometric indices, lipid profiles, liver enzymes as well as abdominal ultrasonography were assessed.Partial correlations controlling for age and sex showed significant positive correlation between vaspin and fasting blood sugar (FBS), insulin, HOMA-IR, and hs-CRP. It has been observed that omentin negatively correlated with glucose levels. Moreover, a marginally significant association has been found between omentin levels and systolic blood pressure (SBP).This study shows that vaspin and omentin-1 are associated with inflammation, insulin resistance and serum glucose levels in patients with NAFLD.Oboljenje ne-alkoholna masna jetra (NAFLD) je posledica promene na jetri usled insulinske rezistencije je najčešći uzrok hroničnog oboljenja jetre. Ovaj rad ima za cilj ispitivanje uloge vaspina i ometina-1 u NAFLD-patologiji, inflamaciji i povećanom krvnom pritisku.Ispitivanja su izvedena na 83 NAFLD pacijenta u Jahrom-u, Iran. Mereni su nivoi ometina-1, vaspina, hs-CRP i IL-6. Ispitivani su antropometrijski parametri, profil lipida, jetreni enzimi i abdominalna ultrasonografija.Delimičnom korelacijom između pola i starosti ukazala su na pozitivnu korelaciju između vaspina i nivoa glukoze u krvi (FBS), insulina, HOMA-IR i hs-CRP. Nađeno je da je ometin u negativnoj korelaciji sa nivoima glukoze. Međutim, marginalno značajna veza je nađena između nivoa ometina i sistolnog krvnog pritiska (SBP).Rezultati su pokazali da vaspin i ometion-1 su praćeni inflamacijom, insulinskom rezistencijom u nivoima glukoze u serumu kod pacijenata sa NAFLD.

Essential trace elements deficiency including zinc and copper are frequently reported in the literature, but the results are controversial. The aim of this study was to evaluate zinc and copper levels in thalassemia major (TM) patients who were on regular transfusion and iron chelation therapy. In a case-control cross-sectional study 43 TM patients and 43 age-matched and sex-matched healthy controls were examined. Patients were selected by convenience sampling method from TM patients who were registered in Thalassemia Clinic during 6 months. Serum zinc and copper levels were evaluated in all subjects. Zinc and copper dietary intake were also assessed. The median zinc level in the participants was significantly lower than the control group (35 [6.3 to 298] vs. 173 [3.1 to 584] μg/dL; P

Introduction Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease. Vaspin may modulate the inflammatory process, insulin resistance, and NAFLD. Omentin-1 is independently associated with hepatocyte ballooning. There is evidence of improvement in the adipokines level and histological hepatic steatosis following energy intake restriction and weight loss. The aim of the study was to evaluate the effects of Ramadan fasting on various circulating adipokines in NAFLD patients. Methods This study was conducted on 83 NAFLD patients, 42 cases who declared that they would fast during the month of Ramadan fasted and 41 controls who decided not to fast during Ramadan. Anthropometric parameters including weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and body fat percentage were measured before and after Ramadan. Dietary intake and physical activity levels were assessed by 24-h recall questionnaire and International physical activity questionnaire-short form (IPAQ-S), respectively. Serum adipokines including vaspin and omentin-1 were measured using commercial ELISA kit. Results Patients who fasted displayed a lower mean hip circumference and body mass index and considerable changes in serum vaspin and omentin-1 (p-value Conclusion There is a potential for fasting in improving several anthropometric indices in NAFLD patients. Additionally, fasting during Ramadan resulted in decreased levels of adipokines including vaspin and omentin-1. Studies with longer follow-up periods are required.

Abstract. Background: Nonalcoholic fatty liver disease (NAFLD) is a serious global health problem, thus the prevention and management of the disease is necessary. This study aimed to determine the effects of Ramadan Fasting (RF) on liver function, Visceral Adiposity Index (VAI) and Atherogenic Index of Plasma (AIP) in these patients. Methods: Eighty-three NAFLD patients (57 males and 26 females) were enrolled in the study, 42 patients who practiced RF, between Jun 18 through July 17, 2015 and 41 patients in non-fasting groups. Anthropometric parameters and Ultrasound grading were measured before and after Ramadan. The biochemical parameters including lipid profiles (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides), liver enzymes (Aspartate aminotransferase, SGOT and Alanine aminotransferase, SGPT) were evaluated before and after Ramadan. AIP and VAI were calculated based on formula. Results: The mean decreases in anthropometric indices were significantly different between groups. Similarly, the mean decrease in the total cholesterol values in the fasting group was remarkably greater than in the control group (p = 0.02). The values of AIP and VAI decreased at the end of the study in both group and the mean of changes showed no differences between groups (p = 0.79 and p = 0.65 for AIP and VAI, respectively). The changes in the concentrations of liver enzymes, as well as the severity of hepatic steatosis, showed remarkable differences between groups (p = 0.03, p = 0.05, and p = 0.02 for SGOT and SGPT, and Liver steatosis, respectively). Conclusion: RF improved liver steatosis in NAFLD patients and might be useful in the management of NAFLD.

Context: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductiveage women. The hormonal and metabolic effects of coenzyme Q10 (CoQ10) and/or vitamin E in patients with PCOS have not been studied, to our knowledge. Objective: To evaluate the effects of CoQ10 and/or vitamin E on glucose homeostasis parameters and reproductive hormones in women with PCOS. Design, Setting, Participants: Randomized, double-blind, placebo-controlled clinical trial among 86 women with PCOS. Intervention: CoQ10 or vitamin E or combination for 8 weeks. Main Outcome Measures: Glucose homeostasis parameters and sex hormone concentrations. Results: After adjustment for potential confounders, supplementation with CoQ10 alone or in combination with vitamin E, compared with placebo, had significant effects on fasting blood sugar (FBS); vitamin E’s effect on FBS was not significant. A significant reduction in homeostasis model assessment of insulin resistance (HOMA-IR) was observed in the CoQ10 and combined groups. CoQ10, vitamin E, and cosupplementation led to decreased serum total testosterone levels (P , 0.001) compared with those of the placebo group. CoQ10 supplementation in combination with vitamin E significantly improved in sex hormone–binding globulin (SHBG) levels compared with other groups (P = 0.008). Linear regression analysis revealed that changes in FBS, insulin, and HOMAIR were predictors of change in free androgen index (P , 0.05). Conclusion: CoQ10 with or without vitamin E supplementation among women with PCOS had beneficial effects on serum FBS and insulin levels, as well as HOMA-IR and total testosterone levels. However, only cosupplementation affected SHBG concentrations.

For more than 60years, lithium has been the mainstay in the treatment of mental disorders as a mood stabilizer. In addition to the antimanic and antidepressant responses, lithium also shows some anticonvulsant properties. In spite of the ascertained neuroprotective effects of this alkali metal, the underlying mechanisms through which lithium regulates behavior are still poorly understood. Among different targets, some authors suggest neuromodulatory effects of lithium are the consequences of interaction of this agent with the brain neurotransmitters including adrenergic system. In order to study the involvement of α2-adrenergic system in anticonvulsant effect of lithium, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice. Injection of a single effective dose of lithium chloride (30mg/kg, i.p.) significantly increased the seizure threshold (p

Introduction White matter hyperintensity (WMH) volume on MRI is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer’s disease (AD). One potential explanation is that WMH, conventionally considered a marker of cerebrovascular disease, are a reflection of cerebral amyloid angiopathy (CAA) and that increased WMH in this population is a manifestation of this vascular form of primary AD pathology. We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between WMH and estimated symptom onset in individuals with and without autosomal dominant mutations for AD. Participants and methods Participants (n = 175, mean age = 41.1 years) included 112 with an AD mutation and 63 first-degree non-carrier controls. We calculated the estimated years from expected symptom onset (EYO) and analyzed baseline MRI data for WMH volume and presence of cerebral microbleeds. Mixed effects regression and tests of mediation were used to examine microbleed and WMH differences between carriers and non-carriers and to test the whether the association between WMH and mutation status is dependent on the presence of microbleeds. Results Mutation carriers were more likely to have microbleeds than non-carriers (p

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and is a serious global health problem. Regarding the increasing prevalence of NAFLD, finding various strategies to prevent and manage the disease is of great importance. The aim of this study was to determine the effects of caloric restriction during Ramadan fasting on anthropometric indices, fasting glucose, plasma insulin, insulin resistance, and inflammatory cytokines (C-reactive protein and interleukin 6) in patients with NAFLD.We conducted this study with 83 patients with NAFLD, 42 of whom decided to fast and 41 controls who decided not to fast for Ramadan, between June 18 and July 17, 2015. Anthropometric parameters were measured and a sample of venous blood was obtained for biochemical assays before and after Ramadan.There was a significant decrease in all anthropometric parameters as well as fasting glucose, plasma insulin, and insulin resistance. Relative to the nonfasting group, fasting significantly reduced circulating inflammatory, but changes in blood pressure after Ramadan were not significant.This study shows significant effects on parameters during Ramadan fasting such as anthropometric indices, fasting glucose, plasma insulin, and inflammatory cytokines in patients with NAFLD. The results of this study suggest that Ramadan fasting may be useful to improve NAFLD, so further studies are needed in this area.

Background. Obesity is considered as a low grade inflammation condition. The aim of this study was to investigate the effect of nutritional education on diet quality and biomarkers of inflammation in Iranian obese women.Method. Sixty obese women voluntarily participated in this randomized clinical trial and were randomly assigned to intervention or control group(n=30). Intervention group was instructed to attend nutrition education sessions (1 hr/wk, for 3 months) in small groups. Diet quality scores were measured by Healthy Eating Index (HEI). Anthropometric indices and serum concentration of hs-CRP, TNF-α, and adiponectin were measured at the baseline and end of the intervention.Results. There were no significant differences in anthropometric indices of participants between the two groups at the end of intervention(P>0.05). However, the total HEI score was significantly higher in the educated group compared to the control group after intervention(P<0.05). The educated group also showed significant lower concentration of TNF-αand hs-CRP and higher levels of adiponectin than the control group at the end of study(P<0.05).Conclusions. Our results provide limited evidence that higher dietary quality contributes to reduced inflammation in obese women. This effect could be independent of the weight loss.

Delayed neuronal destruction after acute spinal injury is attributed to excitotoxicity mediated by hyperactivation of poly(ADP-ribose) polymerase-1 (PARP-1) that induces ‘parthanatos’, namely a non-apoptotic cell death mechanism. With an in vitro model of excitotoxicity, we have previously observed parthanatos of rat spinal cord locomotor networks to be decreased by a broad spectrum PARP-1 inhibitor. The present study investigated whether the selective PARP-1 inhibitor N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino)acetamide.HCl (PJ-34) not only protected networks from kainate-evoked excitotoxicity, but also prevented loss of locomotor patterns recorded as fictive locomotion from lumbar (L) ventral roots (VRs) 24 h later. PJ-34 (60 μm) blocked PARP-1 activation and preserved dorsal, central and ventral gray matter with maintained reflex activity even after a large dose of kainate. Fictive locomotion could not, however, be restored by either electrical stimulation or bath-applied neurochemicals (N-methyl-D-aspartate plus 5-hydroxytryptamine). A low kainate concentration induced less histological damage that was widely prevented by PJ-34. Nonetheless, fictive locomotion was observed in just over 50% of preparations whose histological profile did not differ (except for the dorsal horn) from those lacking such a rhythm. Our data show that inhibition of PARP-1 could amply preserve spinal network histology after excitotoxicity, with return of locomotor patterns only when the excitotoxic stimulus was moderate. These results demonstrated divergence between histological and functional outcome, implying a narrow borderline between loss of fictive locomotion and neuronal preservation. Our data suggest that either damage of a few unidentified neurons or functional network inhibition was critical for ensuring locomotor cycles.

Lithium is still the mainstay in the treatment of affective disorders as a mood stabilizer. Lithium also shows some anticonvulsant properties. While the underlying mechanisms of action of lithium are not yet exactly understood, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of lithium is mediated via NO-cGMP pathway. Injection of a single effective dose of lithium chloride (25 mg/kg) intraperitoneally (i.p.) increased significantly the seizure threshold (P0.01). The anticonvulsant properties of the effective dose of lithium were prevented by pre-treatment with the per se non-effective doses of L-ARG [the substrate for nitric oxide synthase; NOS] (30 and 50 mg/kg) or sildenafil [a phosphodiesterase 5 inhibitor] (10 and 20 mg/kg). L-NAME [a non-specific NOS inhibitor] (5, 15 and 30 mg/kg), 7-NI [a specific neural NOS inhibitor] (30 and 60 mg/kg) or MB [a guanylyl cyclase inhibitor] (0.5 and 1 mg/kg) augmented the anticonvulsant effect of a sub-effective dose of lithium (10 mg/kg, i.p.). Whereas several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of lithium. Our findings demonstrated that nitric oxide-cyclic GMP pathway could be involved in the anticonvulsant properties of the lithium chloride. In addition, the role of constitutive NOS versus inducible NOS is prominent in this phenomenon.

Cannabinoid system plays a pivotal role in the seizure threshold modulation which is mainly mediated through activation of the cannabinoid CB(1) receptor. There is also several evidence of interaction between cannabinoid system and other neurotransmitters including nitric oxide (NO) system. Using model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice, we investigated whether NO is involved in the effects of cannabinoids on the seizure threshold. Injection of the selective cannabinoid CB(1) agonist ACEA (2mg/kg, i.p.) significantly (P0.01) increased the seizure threshold which was prevented (P0.001) by pretreatment with the selective CB(1) antagonist AM251 (1mg/kg, i.p.). The NO precursor l-arginine (50 and 100mg/kg, i.p.) potentiated the anticonvulsant effects of the sub-effective dose of ACEA (1mg/kg, i.p.). Pretreatment with non-effective doses of the non-specific NOS inhibitor l-NAME (15 and 30mg/kg, i.p.) and the specific neuronal NOS inhibitor 7-NI (40 and 80mg/kg, i.p.) but not the inducible NOS inhibitor aminoguanidine (10, 50 and 100mg/kg, i.p.) prevented the anticonvulsant effect of ACEA (2mg/kg, i.p.). Co-administration of non-effective dose of AM251 (0.5mg/kg) with both low and per se non-effective doses of l-NAME (1mg/kg, i.p.) and 7-NI (10mg/kg, i.p.) had significant (P0.01) effect in preventing the anticonvulsant effect of ACEA (2mg/kg, i.p.). Our findings demonstrated that central NO system could be involved in the anticonvulsant properties of the specific cannabinoid CB(1) agonist ACEA, emphasizing on the interaction between two systems in the seizure modulation.

Cannabinoid compounds are anticonvulsant since they have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to G(i/o) proteins. Surprisingly, both the analgesic and anticonvulsant effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist naltrexone and as opioid and cannabinoid systems interact, it has been shown that ultra-low dose naltrexone also enhances cannabinoid-induced antinociception. Thus, concerning the seizure modulating properties of both classes of receptors this study investigated whether the ultra-low dose opioid antagonist naltrexone influences cannabinoid anticonvulsant effects. The clonic seizure threshold was tested in separate groups of male NMRI mice following injection of vehicle, the cannabinoid selective agonist arachidonyl-2-chloroethylamide (ACEA) and ultra-low doses of the opioid receptor antagonist naltrexone and a combination of ACEA and naltrexone doses in a model of clonic seizure induced by pentylenetetrazole (PTZ). Systemic injection of ultra-low doses of naltrexone (1pg/kg to 1ng/kg, i.p.) significantly potentiated the anticonvulsant effect of ACEA (1mg/kg, i.p.). Moreover, the very low dose of naltrexone (500pg/kg) unmasked a strong anticonvulsant effect for very low doses of ACEA (10 and 100microg/kg). A similar potentiation by naltrexone (500pg/kg) of anticonvulsant effects of non-effective dose of ACEA (1mg/kg) was also observed in the generalized tonic-clonic model of seizure. The present data indicate that the interaction between opioid and cannabinoid systems extends to ultra-low dose levels and ultra-low doses of opioid receptor antagonist in conjunction with very low doses of cannabinoids may provide a potent strategy to modulate seizure susceptibility.

Oxidative stress and generation of reactive oxygen species are strongly implicated in a number of neuronal and neuromuscular disorders, including epilepsy. The functions of selenium as an antioxidant trace element are believed to be carried out by selenoproteins that possess antioxidant activities and the ability to promote neuronal cell survival. Because of this protective role of selenium against oxidative damage, a case-control study was designed to compare its serum level between intractable epileptic patients and normal subjects. Eighty patients who met the criteria of intractable epilepsy were compared with a normal control group of the same age, socioeconomic level, and place of living. Serum selenium level was measured with an atomic absorption spectrophotometer. The mean (+/- S.D.) of serum selenium were 68.88 (+/-17.58) ng/mL and 85.93 (+/-13.93) ng/mL in the patient and control groups respectively. Independent sample t test with P0.05 indicated a significant lower mean of serum selenium in the patient group compared with that of the normal control group. However, there was no association between serum selenium and some suggested predictive factors of intractable seizures, including age at the onset of seizures, neonatal seizure, neurologic impairment, and etiology of epilepsy. Measurement of serum selenium in patients with intractable epilepsy should be considered.