Amelioration of Pentylenetetrazole-Induced Seizures by Modulators of Sigma, N-Methyl-D-Aspartate, and Ryanodine Receptors in Mice.

BACKGROUND: Sigma receptors, N-methyl-D-aspartate (NMDA) antagonist, and modulators of intracellular calcium may be useful for seizure control. Therefore, we aimed to evaluate the antiepileptic effects of opipramol, a sigma receptor agonist, against pentylenetetrazole (PTZ)-induced seizures in mice and assess ketamine and caffeine interaction with the antiepileptic effects of opipramol. METHODS: PTZ (100 mg/kg) was used for the induction of seizure in 72 male albino Swiss strain of mice (n=8). Opipramole (10, 20, and 50 mg/kg), ketamine (50 mg/kg), caffeine (200 mg/kg), opipramole (20 mg/kg) plus ketamine (50 mg/kg), opipramole (20 mg/kg) plus caffeine (200 mg/kg), diazepam (5 mg/kg as a positive control), and the vehicle were administered interaperitoneally 30 minutes before the injection of PTZ. The latency was recorded for the clonic, tonic-clonic seizures, and death of animals after the injection of PTZ. Kruskal-Wallis test followed by Dunn's test was used for the analysis of data. Statistical analysis was performed with the SPSS software version 23.0 and P<0.05 was considered as the significant level. RESULTS: Opipramol (20 mg/kg) increased the latency for the PTZ-induced clonic (44%, P=0.021) and tonic-clonic (130.80%, P=0.043) seizures compared with the vehicle-treated group. Animals treated with opipramol (20 mg/kg) plus caffeine (200 mg/kg) had a significantly higher onset of PTZ-induced clonic and tonic-clonic seizures compared with the control (P=0.046 and <0.001, respectively). Ketamine combined with opipramol increased the onset of tonic-clonic seizure compared with the vehicle-treated groups (P<0.001). CONCLUSION: Opipramol attenuated the seizures induced by the PTZ. Ketamine and caffeine had no effect on the anticonvulsant activity of opipramol.

Glial cells as key elements in the pathophysiology and treatment of bipolar disorder.

OBJECTIVE: The exact pathophysiology of bipolar disorder (BD) is not yet fully understood, and there are many questions in this area which should be answered. This review aims to discuss the roles of glial cells in the pathophysiology of BD and their contribution to the mechanism of action of mood-stabilising drugs. METHODS: We critically reviewed the most recent advances regarding glial cell roles in the pathophysiology and treatment of BD and the neuroprotective and neurotrophic effects of these cells. RESULTS: Postmortem studies revealed a decrease in the glial cell number or density in the specific layers of prefrontal and anterior cingulate cortex in the patients with BD, whereas there was no difference in other brain regions, such as entorhinal cortex, amygdala and hippocampus. Astrocytes and oligodendrocytes were the most important glial types that were responsible for the glial reduction, but microglia activation rather than loss may be implicated in BD. The decreased number or density of glial cells may contribute to the pathological changes observed in neurons in the patients with BD. Alteration of specific neurotrophic factors such as glial cell line-derived neurotrophic factor and S100B may be an important feature of BD. Glial cells mediate the therapeutic effects of mood-stabilising agents in the treatment of BD. CONCLUSION: Recent studies provide important evidence on the impairment of glial cells in the pathophysiology and treatment of BD. However, future controlled studies are necessary to elucidate different aspects of glial cells contribution to BD, and the mechanism of action of mood-stabilising drugs.

Involvement of PPARγ in the protective action of tropisetron in an experimental model of ulcerative colitis.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal (GI) tract. Tropisetron, a selective 5-HT3 receptor antagonist, is highly used to counteract chemotherapy-induced emesis. Previous studies revealed the anti-inflammatory properties of this drug. The aim of this study was to evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) receptor in the protective effect of tropisetron in an animal model of ulcerative colitis. Experimental colitis was induced by a single intra-colonic instillation of 4% (V/V) acetic acid in male rats. Tropisetron (3 mg/kg) and GW9662 (PPARγ antagonist) (5 mg/kg) were given twice daily for 2 days after colitis induction. Forty-eight hours after induction of colitis, colon was removed and macroscopic and microscopic features were given. Moreover, colonic concentrations of malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) levels, myeloperoxidase (MPO), and PPARγ activity were assessed. Both macroscopic and histopathological features of colonic injury were markedly ameliorated by tropisetron. Likewise, levels of NO, MDA, TNF-α, and IL-1ß diminished significantly (p < .05). GW9662 reversed the effect of tropisetron on these markers partially or completely. In addition, tropisetron increased the PPARγ and decreased the MPO activity (p < .05). Tropisetron exerts notable anti-inflammatory effects in acetic acid-induced colitis in rats, which is probably mediated through PPARγ receptors.

Anticonvulsant Effect of Guaifenesin against Pentylenetetrazol-Induced Seizure in Mice.

BACKGROUND: There have been some reports about the possible N-methyl-D-aspartate (NMDA) antagonist activity of Guaifenesin. As drugs with a similar structure to Guaifenesin (i.e. Felbamate) and those with NMDA antagonist activity have been clinically used as anticonvulsants, the aim of this study was to determine whether Guaifenesin has an anticonvulsant effect in an animal model of seizure. METHODS: Anticonvulsant effect of Guaifenesin was assessed via Pentylenetetrazol (PTZ)-induced convulsion. Male albino mice received Guaifenesin (100, 200, 300, or 400 mg/kg; n=8-10) or 0.25% Tween (vehicle) intraperitoneally 30 minutes before the injection of PTZ (95 mg/kg). Diazepam (3 mg/kg; n=8) was used as a reference drug. The latency time before the onset of myoclonic, clonic, and tonic-clonic convulsions, percentage of animals exhibiting convulsion, and percentage of mortality were recorded. In addition, the effect of Guaifenesin on neuromuscular coordination was assessed using the Rotarod. RESULTS: Guaifenesin at all the studied doses significantly increased the latency to myoclonic and clonic convulsions in a dose-dependent manner. In addition, Guaifenesin at the dose of 300 mg/kg increased the latency to tonic-clonic seizure. The ED50s of Guaifenesin for protection against PTZ-induced clonic and tonic-clonic seizures and death were 744.88 (360-1540), 256 (178-363), and 328 (262-411) mg/kg, respectively. Guaifenesin at all the investigated doses significantly reduced neuromuscular coordination, compared to the vehicle-treated group. CONCLUSION: These results suggest that Guaifenesin possesses muscle relaxant and anticonvulsant properties and may have a potential clinical use in absence seizure.

Increased bcl-2 Protein Levels in Rat Primary Astrocyte Culture Following Chronic Lithium Treatment.

BACKGROUND: B cell CLL/lymphoma 2 protein, bcl-2, is an important anti-apoptotic factor that has been implicated in lithium's neuroprotective effect. However, most studies have focused on assessing the effects of lithium in neurons, ignoring examination of bcl-2 in astrocytes, which also influence neuronal survival and are affected in bipolar disorder. The aim of this study was to evaluate whether chronic lithium treatment also elevates bcl-2 expression in astrocytes compared with neuronal and mixed neuron-astrocyte cultures. METHODS: Rat primary astrocyte, neuronal, and mixed neuron-astrocyte cultures were prepared from the cerebral cortices of 18-day embryos. The cell cultures were treated with lithium (1 mM) or vehicle for 24 h or 7 days. Thereafter, bcl-2 mRNA and protein levels were determined by RT-PCR and ELISA, respectively. RESULTS: Chronic, but not acute, lithium treatment significantly increased bcl-2 protein levels in the astrocyte cultures compared with the vehicle-treated cultures. While lithium treatment increased bcl-2 protein levels in both neuronal and mixed neuron-astrocyte cultures, the elevations fell short of statistical significance compared with the respective vehicle-treated cultures. However, neither acute nor chronic lithium treatment affected bcl-2 mRNA levels in any of the three cell types studied. CONCLUSION: Increased bcl-2 levels in rat primary astrocyte cultures following chronic lithium treatment suggest astrocytes are also a target of lithium's action. In light of the evidence showing decreased numbers of glial cells in the post-mortem brain of patients bipolar disorder with and increased glial numbers following lithium treatment, the findings of this study indicate that lithium's action on astrocytes may account, at least in part, for its therapeutic effects in bipolar disorder.

The Effect of Spironolactone on ß-amyloid-Induced Memory Impairment in Male Rats: The Role of Microglial Inhibition.

Purpose: Neuroinflammation was indicated in the pathophysiology of Alzheimer's disease (AD). Previous reports have also signified that spironolactone has anti-inflammatory effects. Therefore, the aim of this study was to assess the modulatory effects of spironolactone on neuroinflammation and memory loss in a rat model of AD. Methods: The ß-amyloid protein fragment 25-35 (Aß) was injected in the dorsal hippocampus (5 µg/2.5 µL each side) of male Sprague-Dawley rats for four consecutive days to induce memory impairment. Animals have intraperitoneally received spironolactone (10, 25, or 50 mg/kg, N = 6/ group) or vehicle for 14 days. The passive inhibitory avoidance and the novel recognition tests were used for memory evaluation. Neuroinflammation was assessed by measuring the level of Iba1 protein, a marker of microglial activation, using western immunoblotting. Results: Different doses of spironolactone showed no significant changes in latency times and discriminations ratios in passive inhibitory avoidance and novel recognition tests, respectively, as compared to vehicle. However, spironolactone-treated groups showed significantly lower Iba1 protein levels in comparison to the vehicle-treated group (P < 0.01). Conclusion: Spironolactone had a modulatory effect on neuroinflammation through a repressive effect on microglial activation with no valuable effect on memory improvement in a rat model of AD. The findings of this study suggest that Aß-induced memory loss may not be directly linked to microglial activation. Spironolactone may be a potential candidate to be examined in other neuroinflammatory disorders.

Persian version of the work design questionnaire: measurement of its psychometric characteristics.

BACKGROUND: Work design questionnaire (WDQ), as a comprehensive and integrative tool, is one of the most important instruments frequently used to assess work characteristics. The aim of this study was to measure the psychometric characteristics of the Persian version of WDQ. METHODS: Translation and cross-cultural adaptation procedures were applied in translating the original WDQ into Persian. A total of 270 participants participated in this study. The validity of the questionnaire were measured using face validity, content validity, convergent validity, and construct validity based on confirmatory factor analysis (CFA). Reliability was assessed through internal consistency. RESULTS: Mean content validity index was 0.95. The CFA results indicated support for a 21-factor solution. There were significant correlations between dimensions of WDQ and both job satisfaction and perceived stress. Cronbach's alpha of all items was 0.87. CONCLUSION: Results indicated that the WDQ exhibited very good psychometric properties and can be applied as a useful tool to assess work characteristics among Iranian employees. Accordingly, the authors recommend its administration in future studies. The work characteristics was significantly associated with job satisfaction and job stress. Therefore, improved work design would reduce negative consequences, such as job stress, and increase positive behaviors, such as job satisfaction.

Preserving effect of Loboob (a traditional multi-herbal formulation) on sperm parameters of male rats with busulfan-induced subfertility.

OBJECTIVE: Male infertility secondary to exposure to gonadotoxic agents during reproductive age is a concerning issue. The aim of this experimental study was to determine the effect of Loboob on sperm parameters. METHODS: 55 healthy rats were selected, weighted and divided into five groups consisting of 11 rats each. The control group received no medication. Rats in Treatment Group 1 received 10mg/kg Busulfan and rats in Treatment Groups 2, 3, and 4 received 35,70 and 140 mg/kg Loboob respectively in addition to 10mg/kg Busulfan. Finally, the sperm parameters and weights of the rats were compared using the Kolmogorov-Smirnov, non-parametric Kruskal-Wallis, and Dunn-Bonferroni tests. RESULTS: All sperm parameters and weights were significantly decreased among rats receiving Busulfan. All dosages of Loboob were effective to enhance the motility of slow spermatozoa, while only in the rats given 70 and 140 mg/kg of Loboob saw improvements in progressively motile sperm percentages (0.024 and 0.01, respectively). Loboob at a dosage of 140mg/kg improved sperm viability. It did not improve normal morphology sperm or decrease immotile sperm counts. Loboob did not affect mean rat weight. CONCLUSIONS: Loboob offered a dose-dependent protective effect on several sperm parameters in rats with busulfan-induced subfertility.

Contribution of Lysosome and Sigma Receptors to Neuroprotective Effects of Memantine Against Beta-Amyloid in the SH-SY5Y Cells.

Purpose: Memantine is an approved drug for the treatment of Alzheimer's disease (AD). Autophagy, lysosome dysfunction, and sigma receptors have possible roles in the pathophysiology of AD. Therefore, we aimed to investigate the contribution of sigma receptors and lysosome inhibition to the neuroprotective effects of memantine against amyloid-beta (Aß)-induced neurotoxicity in SH-SY5Y cells. Methods: We determined the neuroprotective effects of memantine (2.5 µM), dizocilpine (MK801, as a selective N-methyl-D-aspartate (NMDA) receptor antagonist) (5 µM) against Aß25- 35 (2 µg/µL)-induced neurotoxicity. We used chloroquine (10, 20, and 40 µM) as a lysosome inhibitor and BD-1063 (1, 10, and 30 µM) as a selective sigma receptor antagonist. The MTT assay was used to measure the neurotoxicity in the SH-SY5Y cells. Data were analyzed using the one-way ANOVA. Results: Memantine (2.5 µM), dizocilpine (5 µM), chloroquine (10 and 20 µM) and BD-1063 (1, 10 and 30 µM) decreased the neurotoxic effects of Aß on the SH-SY5Y cells. However, chloroquine (40 µM) increased the neurotoxic effects of Aß. Cell viability in the cells treated with memantine + Aß + chloroquine (10, 20, and 40 µM) was significantly lower than the memantine + Aß-treated group. Moreover, cell viability in the memantine + Aß group was higher than the memantine + Aß + BD-1063 (10 and 30 µM) groups. Conclusion: The lysosomal and sigma receptors may contribute to the neuroprotective mechanism of memantine and other NMDA receptor antagonists. Moreover, the restoration of lysosomes function and the modulation of sigma receptors are potential targets in the treatment of AD.

Interaction of sigma-1 receptor modulators with seizure development in pentylenetetrazole-induced kindled mice.

This study aimed to investigate the effects of sigma receptor modulators, opipramol and BD-1063, on epileptogenesis in pentylenetetrazole (PTZ)-kindling model of epilepsy. Mice (n = 6/group) were received PTZ (30 mg/kg), PTZ plus opipramol (5 or 10 mg/kg), PTZ plus opipramol (5 mg/kg) plus BD-1063 (5 mg/kg, a selective sigma-1 receptor antagonist), and PTZ plus BD-1063 on alternate days for 15 days. Opipramol (5 and 10 mg/kg) + PTZ groups became fully kindled and had higher seizure scores compared to the PTZ group. In contrast, the PTZ plus BD-1063 and the PTZ plus opipramol (5 mg/kg) plus BD-1063 group did not show full kindling. These findings indicate that opipramol has a pro-convulsant effect, which is possibly mediated through activation of sigma-1 receptors.

The neuroprotective mechanism of cinnamaldehyde against amyloid-ß in neuronal SHSY5Y cell line: The role of N-methyl-D-aspartate, ryanodine, and adenosine receptors and glycogen synthase kinase-3ß.

OBJECTIVE: Cinnamaldehyde may be responsible for some health benefits of cinnamon such as its neuroprotective effects. We aimed to investigate the cinnamaldehyde neuroprotective effects against amyloid beta (Aß) in neuronal SHSY5Y cells and evaluate the contribution of N-methyl-D-aspartate (NMDA), ryanodine, and adenosine receptors and glycogen synthase kinase (GSK)-3ß, to its neuroprotective effects. MATERIALS AND METHODS: After seeding the cells in 96-well plates, adenosine (20, 40, 80, and 120 µM), NMDA (20, 40, 80, and 120 µM), and dantrolene (as a ryanodine receptor antagonist; 2, 4, 6, 8, and 16 µM) were added to the medium containing Aß25-35 and/or cinnamaldehyde. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide method was used to assess neurotoxicity and western blot to measure the GSK-3ß protein level. RESULTS: Cinnamaldehyde (15, 20, 23, and 25 µM) significantly reversed Aß-induced toxicity in SHSY5Y neuronal cells. Adenosine (20, 40, 80 and 120 µM) inhibited the neuroprotective effects of cinnamaldehyde (15 µM). NMDA (20, 40, 80, and 120 µM) reduced cinnamaldehyde (15 and 23 µM) neuroprotective effects against Aß neurotoxicity. Dantrolene (2, 4, 8, and 16 µM) significantly reduced cinnamaldehyde (15 µM) neuroprotective effects. Cinnamaldehyde (15 and 23 µM) suppressed the Aß-induced increment of GSK-3ß protein level. CONCLUSION: NMDA and adenosine receptors suppression together with ryanodine receptors stimulation may be relevant to cinnamaldehyde neuroprotective effects against Aß neurotoxicity. Moreover, the inhibition of GSK-3ß may contribute to the cinnamaldehyde neuroprotection.

The contribution of S100B to the glioprotective effects of valproic and arundic acids.

OBJECTIVES: Valproic and arundic acids are astrocytes-modulating agents with potential effects in the treatment of Alzheimer's disease (AD). S100B is an astrocytic cytokine with a possible role in the pathogenesis of AD. In this study, we aimed to assess the glioprotective effects of valproic and arundic acids against amyloid-ß-peptide (Aß)-induced glial death and contribution of S100B to the glioprotective effects of these agents in an astrocytic culture. MATERIALS AND METHODS: We used Aß25-35 at a concentration of 200 µM in 1321N1 astrocyte cells. We treated the cells with valproic acid (0.5 and 1 mM) and/or arundic acid 50 µM for 24 hr. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) test was used to measure cell viability. The intracellular and extracellular S100B levels were measured using an ELISA kit. The data were analyzed using one-way analysis of variance followed by the Tukey's test. RESULTS: Aß (200 µM) decreased the cell viability compared to the control group (P<0.001). Valproic acid (0.5 and 1 mM) and arundic acid (50 µM) ameliorated the gliotoxic effects of Aß (P<0.05). The Aß-treated group had higher S100B levels (both intracellular and extracellular) compared to the negative control groups (P<0.001). Arundic and valproic acids (0.5 and 1 mM) decreased both the intracellular and extracellular S100B levels compared to the Aß-treated group (P<0.001). CONCLUSION: By considering homeostatic and neuroprotective functions of astrocyte, the astroprotective effects and the attenuation of S100B level may be responsible, at least in part, for the beneficial effects of valproic and arundic acids in AD.

CYP2A6 allele frequencies in an Iranian population.

BACKGROUND: Genetic polymorphism of CYP2A6 gene is a major causal factor in the large interindividual differences in nicotine metabolism. It may have an impact on smoking behavior and smoke-related cancer susceptibility. Until now, there are no reports of CYP2A6 allele frequencies in Iranian population. METHODS: In the present study, we investigated the frequencies of CYP2A6 alleles in 250 male Iranians. CYP2A6*2, CYP2A6*4, CYP2A6*9, and CYP2A6*12 were determined by allele-specific polymerase chain reaction. RESULTS: Frequencies of *2, *4, *9, and *12 alleles were 2.2%, 0.95%, 12.4%, and 1.34%, respectively. CONCLUSION: These results showed that the distribution of CYP2A6 alleles in Iranian population was different from those reported previously for other ethnic groups. This highlights the importance of conducting further studies to investigate the implications on smoking dependence and cancer in Iranians.

Anti-diabetic effects of Sargassum oligocystum on Streptozotocin-induced diabetic rat.

OBJECTIVES: Diabetes is a metabolic syndrome which is associated with the worldwide major public health problems. There are many natural compounds from the sea-market, as a valuable aquatic source, along with the variety of health and therapeutic benefits. In the present research, with respect to the traditional and ethnic uses of Sargassum oligocystum algae for healing of some diseases which have similar metabolic mechanism to the diabetes, its anti-diabetic effects in animal model was proposed. MATERIALS AND METHODS: The animals (rat) were divided into the normal control, diabetic control, positive control and, the test groups. The test groups were gavaged with oral doses of 150 and 300 mg/kg of algae hydroalcoholic extracts. After 30 days of intervention the serum glucose, cholesterol, triglyceride, HDLC, LDLC, insulin, insulin resistance, ß-cells function and, the histopathology of pancreatic tissue were evaluated. RESULTS: In animals that were fed with algae extracts a significant decrease in the fasting blood glucose, triglyceride and HOMA-IR and an increase in the HOMA-B with no significant impacts on the insulin, cholesterol and HDL were observed. Also, the histopathology evaluations in the groups which were treated with algae extract revealed the regeneration and reconstitution of damaged pancreatic ß-cells. CONCLUSION: The results give evidence that, the S. oligocystum algae extract has a healing effect on diabetes which can be considered as a new research prospect for the natural therapy of diabetes.

Caffeine Neuroprotective Mechanism Against ß-Amyloid Neurotoxicity in SHSY5Y Cell Line: Involvement of Adenosine, Ryanodine, and N-Methyl-D-Aspartate Receptors.

Purpose: Some reports have shown neuroprotective effects of caffeine in several neurodegenerative disorders. However, its mechanism of action is not completely clear. Therefore, the aim of this study was to explore the interference of ryanodine, N-methyl-D-aspartate (NMDA) and adenosine modulators with the neuroprotective effects of caffeine against ß-amyloid (Aß) neurotoxicity in the SHSY5Y cells. Methods: The SHSY5Y cells were treated with Aß23-35 (20µM) and/or caffeine (0.6 and 1mM), or both for 24 hours. Adenosine (20, 40, 60, 80, 100µM), NMDA (20, 50, 70, 90µM), dantrolene (2, 4, 6, 8, 10µM) were also added to the medium and incubated for 24 hours. The cell viability was measured via the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) method. The data were analyzed using one-way ANOVA followed by Bonferroni test. Results: Caffeine at all the used concentrations (0.6, 0.8, 0.9, 1, and 3mM) significantly protected neuronal cells against Aß neurotoxicity. Adenosine at the concentrations of 20, 40, 80 and 100µM diminished the neuroprotective effects of caffeine (0.6 and 1mM) against Aß neurotoxicity. NMDA at the concentrations of 20, 50, 70 and 90µM blocked caffeine (0.6 and 1mM) neuroprotective effects. Dantrolene at the concentration of 2, 4, 6, 8 and 10µM diminished the neuroprotective effects of caffeine (0.6mM) and at the concentrations of 2 and 10µM impede caffeine (1mM) neuroprotection against Aß neurotoxicity. Conclusion: Caffeine produced neuroprotective effect against Aß neurotoxicity. Blockade of adenosine and NMDA receptors, as well as the activation of ryanodine receptors, may contribute to the neuroprotective effects of caffeine.

Comparison of the Prevalence of Psychiatric Disorders in Performance-Enhancing Drug Users and Nonuser Bodybuilders.

Objective: The present study aimed at comparing the prevalence of major psychiatric disorders including major depressive disorder, bipolar disorder, schizophrenia, and generalized anxiety disorder between performance-enhancing drug users and nonuser bodybuilders. Moreover, the prevalence of major psychiatric disorders in bodybuilders was also reported. Method: In this study, 453 athletes were recruited from Bushehr bodybuilding gyms from February to May 2015. A structured questionnaire was used to collect the participants' information, including demographic characteristics, sports' status and performance-enhancing drug use. According to the condition of performance-enhancing drug use, the participants were divided into current users, non-current users, and nonusers. The psychiatric status of the participants was evaluated using DSM-IV diagnostic criteria for major depressive disorder, bipolar disorder, generalized anxiety disorder, and schizophrenia. We also asked about the acute psychotic disturbances after using performance-enhancing drugs, alcohol use, and history of aggressive behavior in bodybuilders. Data were analyzed using one-way analysis of variance and chi-square tests. Results: Prevalence of major depressive disorder, bipolar disorder, schizophrenia, generalized anxiety disorder, and the overall prevalence of psychiatric disorders in the bodybuilders was 19.7%, 3.8%, 1.5%, 16.6%, and 26.7%, respectively. After using performance-enhancing drugs, 33% of the bodybuilders had experienced acute psychological disturbances. There were no significant differences between current, non-current, and nonuser bodybuilding athletes in the measured psychiatric disorders. Conclusion: Prevalence of psychiatric disorders was not significantly different in performance-enhancing drug users and nonusers. Thus, it can be concluded that performance-enhancing drugs do not increase the risk of psychiatric disorders in bodybuilders.

Protective effects of tropisetron on cerulein-induced acute pancreatitis in mice.

Acute pancreatitis (AP) causes morbidity and mortality. The aim of the present study was to investigate the protective effect of tropisetron against AP induced by cerulein. Cerulein (50µg/kg, 5 doses) was used to induce AP in mice. Six hours after final cerulein injection, animals were decapitated. Hepatic/pancreatic enzymes in the serum, pancreatic content of malondialdehyde (MDA), pro-inflammatory cytokines and myeloperoxidase (MPO) activity were measured. Tropisetron significantly attenuated pancreatic injury markers and decreased the amount of elevated serum amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), MPO activities and pro-inflammatory cytokines levels caused by AP in mice. Tropisetron didn't affect the pancreatic levels of MDA. Our results suggest that tropisetron could attenuate cerulein-induced AP by combating inflammatory signaling. Further clinical studies are needed to confirm its efficacy in patients with AP.

Dantrolene: A Selective Ryanodine Receptor Antagonist, Protects Against Pentylenetetrazole-Induced Seizure in Mice.

Ryanodine receptor abnormalities has implicated in the generation and maintenance of seizure. Dantrolene, a selective ryanodine receptor antagonist, may be a potential drug for the prevention of seizure. Therefore, we aimed to clarify the protective effects of dantrolene against pentylenetetrazole seizure in mice. Male albino mice were received an intra-peritoneal injection of pentylenetetrazole (80 mg/kg) in seven separate groups (n=8). We used dantrolene (10,20 and 40 mg/kg), caffeine (200 mg/kg), dantrolene (40 mg/kg) + caffeine (200 mg/kg), diazepam (5 mg/kg as a positive control) and vehicle 30 minutes before the injection of pentylenetetrazole. Then, we registered the latency time of the first seizure, the severity of seizures and the incidence of seizure and death. Kruskal-Wallis test followed by Mann-Whitney and Fisher's exact test were used to analyze the data. Dantrolene (10,20 and 40 mg/kg) significantly increased the latency time for the first seizure. Furthermore, dantrolene (20 and 40 mg/kg, but not 10 mg/kg) attenuated the severity of seizures in comparison to the vehicle group. Moreover, dantrolene only at the dose of 40 mg/kg prevented from tonic-clonic seizure and death in comparison to the vehicle group. In contrast, the addition of caffeine abolished the protective effects of dantrolene on the tonic-clonic seizure/death and inhibited the beneficial effects of dantrolene on the severity of pentylenetetrazol seizures. The acute dantrolene administration produced an anticonvulsant effect in the pentylenetetrazole-induced seizure. Moreover, caffeine prevented from dantrolene anticonvulsant effects. These results may imply about ryanodine receptors and intracellular calcium roles in the generation and control of pentylenetetrazole seizure.

The Prevalence and Characteristics of Performance-Enhancing Drug Use Among Bodybuilding Athletes in the South of Iran, Bushehr.

BACKGROUND: Several reports have implied progressive increase of performance-enhancing drug (PED) use among Iranian athletes. More importantly, most of the previous research in the Iranian population had mainly focused on the anabolic steroid abuse, and ignored other agents. OBJECTIVES: The aim of this study was to investigate the prevalence and characteristics of PED use among bodybuilding athletes in Bushehr, south of Iran. METHODS: Four hundred and fifty three male bodybuilding athletes were recruited from Bushehr gyms between February and May of 2015. Men were eligible to participate in the survey if they had regularly participated in the strength-training exercise (minimum of 1 year and 4 hour/week). Data were collected via a face-to-face interview. The survey consisted of three separate parts including demographic data, exercise pattern and PED use. RESULTS: According to this study, 234 (51.7%) of bodybuilding athletes had used PEDs. The PED users reported an average of 3.80 ± 4.52 agents' use in their programs and they had used PEDs for the average of 3.24 ± 3.99 years. The most prevalent agents which had been abused by the athletes were anabolic steroids (used by 185 athletes (79.4% of athletes). Furthermore, 110 (47%) of athletes reported stimulant agents' use during their routines. The most prevalent motivation for using PEDs was increasing muscle mass that was reported by 164 (70.1%) of PED users. In addition, sexual and dermatologic effects were the most prevalent adverse effects reported by the PED user athletes (114 (49.4%) and 103 (44.2%), respectively). CONCLUSIONS: This study showed the high rate of PED use among recreational and professional Iranian bodybuilding athletes that can expose them to the serious side effects of these agents.

Chronic lithium treatment increased intracellular S100ß levels in rat primary neuronal culture.

S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenesis of bipolar disorder. Thus, lithium may exert its neuroprotective effects to some extent through S100ß. Furthermore, the possible effects of lithium on astrocytes as well as on interactions between neurons and astrocytes as a part of its mechanisms of actions are unknown. This study was undertaken to determine the effect of lithium on S100ß in neurons, astrocytes and a mixture of neurons and astrocytes. Rat primary astrocyte, neuronal and mixed neuro-astroglia cultures were prepared from cortices of 18-day's embryos. Cell cultures were exposed to lithium (1mM) or vehicle for 1day (acute) or 7 days (chronic). RT-PCR and ELISA determined S100ß mRNA and intra- and extracellular protein levels. Chronic lithium treatment significantly increased intracellular S100ß in neuronal and neuro-astroglia cultures in comparison to control cultures (P<0.05). Acute and chronic lithium treatments exerted no significant effects on intracellular S100ß protein levels in astrocytes, and extracellular S100ß protein levels in three studied cultures as compared to control cultures. Acute and chronic lithium treatments did not significantly alter S100ß mRNA levels in three studied cultures, compared to control cultures. Chronic lithium treatment increased intracellular S100ß protein levels in a cell-type specific manner which may favor its neuroprotective action. The findings of this study suggest that lithium may exert its neuroprotective action, at least partly, by increasing neuronal S100ß level, with no effect on astrocytes or interaction between neurons and astrocytes.