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Investigating long-term potentiation (LTP) in disease models provides essential mechanistic insight into synaptic dysfunction and relevant behavioral changes in many neuropsychiatric and neurological diseases. Toxoplasma (T) gondii is an intracellular parasite causing bizarre changes in host's mind including losing inherent fear of life-threatening situations. We examined hippocampal-dependent behavior as well as in vivo short- and long-term synaptic plasticity (STP and LTP) in rats with latent toxoplasmosis. Rats were infected by T. gondii cysts. Existence of REP-529 genomic sequence of the parasite in the brain was detected by RT-qPCR. Four and eight weeks after infection, spatial, and inhibitory memories of rats were assessed by Morris water maze and shuttle box tests, respectively. Eight weeks after infection, STP was assessed in dentate gyrus (DG) and CA1 by double pulse stimulation of perforant pathway and Shaffer collaterals, respectively. High frequency stimulation (HFS) was applied to induce LTP in entorhinal cortex-DG (400 Hz), and CA3-CA1 (200 Hz) synapses. T. gondii infection retarded spatial learning and memory performance at eight weeks post-infection period, whereas inhibitory memory was not changed. Unlike uninfected rats that normally showed paired-pulse depression, the infected rats developed paired-pulse facilitation, indicating an inhibitory synaptic network disruption. T. gondii-infected rats displayed strengthened LTP of both CA1-pyramidal and DG-granule cell population spikes. These data indicate that T. gondii disrupts inhibition/excitation balance and causes bizarre changes to the post-synaptic neuronal excitability, which may ultimately contribute to the abnormal behavior of the infected host. [ABSTRACT FROM AUTHOR]

Epilepsy is one of the most common neurologic disorders. Underlying cause of epilepsy is unknown in 60 % of the patients. Toxoplasma gondii is an intracellular parasite which is capable of forming tissue cysts in brain of chronically infected hosts including humans. Some epidemiological studies suggested an association between toxoplasmosis and acquisition of epilepsy. In this study we determined seroprevalence of latent Toxoplasma infection in a population of Iranian epileptic patients. Participants were classified in three groups as Iranian epileptic patients (IEP, n = 414), non-epileptic patients who had other neurologic disorders (NEP, n = 150), and healthy people without any neurologic disorders (HP, n = 63). The presence of anti-Toxoplasma IgG antibodies and IgG titer in the sera were determined by ELISA method. Anti-T. gondii IgG seroprevalence obtained 35.3 %, 34.7 % and 38.1 % in IEP, NEP and HP, respectively. The seroprevalence rate was not significantly different among the three groups (P = 0.88). Anti-T. gondii IgG titer was 55.7 ± 78, 52.4 ± 74 and 69.7 ± 92 IU/ml in IEP, NEP and HP, respectively. There was not any statistically significant difference in the antibody titer between the study groups (P = 0.32). The rate of T. gondii infection in epileptic patients was not higher than non-epileptic patients and healthy people in the Iranian population. [ABSTRACT FROM AUTHOR]

Introduction: Although hippocampus is the most famous brain area involved in temporal lobe epilepsy, hippocampal kindling (HK) develops very slowly. Hence, rapid kindling is usually preferred to the traditional kindling and it is widely used. In this article we aimed at finding the optimal stimulus pattern, which yields the fastest HK rate. Methods: Stimulus patterns with different duration (2, 3, 5 and 10 s) and inter-train interval (ITI) (5, 10 and 30 min) as well as number of trains in 24 h (8 and 12) were exerted to rats' dorsal hippocampus. The stimuli were continued until appearance of 3 consecutive generalized seizures or maximum 7 days stimulations. Results: While the protocol with train duration of 10 seconds and ITI of 30 min caused the fastest kindling rate and the most growth of afterdischarges, the protocol with train duration of 5 seconds and ITI of 5 min was the most time-consuming protocol among protocols tested. Discussion: Rapid HK develops with a time course of days compared to weeks in traditional kindling. Train duration and inter-train interval are key factors for rapid HK. Among the patterns, 12 trains/24h of 50Hz monophasic square wave with 10 seconds duration and 30 min interval between trains, is the best stimulus pattern for eliciting rapid dorsal HK. [ABSTRACT FROM AUTHOR]

Introduction: Gap junctions are intercellular membrane channels that provide direct cytoplasmic continuity between adjacent cells. This communication can be affected by changes in expression of gap junctional subunits called Connexins (Cx). Changes in the expression and function of connexins are associated with number of brain neurodegenerative diseases. Neuroinflammation is a hallmark of various central nervous system (CNS) diseases, like multiple sclerosis, Alzheimer's disease and epilepsy. Neuroinflammation causes change in Connexins expression. Hippocampus, one of the main brain regions with a wide network of Gap junctions between different neural cell types, has particular vulnerability to damage and consequent inflammation. Cx32 - among Connexins- is expressed in hippocampal Olygodandrocytes and some neural subpopulations. Although multiple lines of evidence indicate that there is an association between neuroinflammation and the expression of connexin, the direct effect of neuroinflammation on the expression of connexins has not been well studied. In the present study, the effect of neuroinflammation induced by the Lipopolysaccharide (LPS) on Cx32 gene and protein expressions in rat hippocampus is evaluated. Methods: LPS (2.5µg/rat) was infused into the rat cerebral ventricles for 14 days. Cx32 mRNA and protein levels were measured by Real Time PCR and Western Blot after 1st, 7th and 14th injection of LPS in the hippocampus. Results: Signiicant increase in Cx32 mRNA expression was observed after 7th injection of LPS (P<0.001). However, no significant change was observed in Cx32 protein level. Conclusion: LPS seems to modify Cx32 GJ communication in the hippocampus at transcription level but not at translation or post-translation level. In order to have a full view concerning modification of Cx32 GJ communication, effect of LPS on Cx32 channel gating should also be determined. [ABSTRACT FROM AUTHOR]

The issue of medical errors is currently a global concern which places a heavy financial and emotional burden on communities. A clinical decision support system (CDSS) is an electronic system designed to support clinical decision making. Considering the increasing importance and use of Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), we developed SNOMED-CT to implement it more efficiently in making smart history taking, decisions to perform lab tests and imaging, diagnosis and recommendations. To evaluate these capabilities in real clinical problems, a new CDSS was compiled, aimed at supporting decisions on patients with a chief complaint of low back pain (LBP). A number of LBP differential diagnoses as well as some recommended indications and contraindications published by guidelines, were inputted to the database. Future software based on this model would help physicians to do necessary assessments and recommendations and might improve patients' safety. [ABSTRACT FROM AUTHOR]

Objective(s) Fabaceae is the third largest family of flowering plants. Lack of essential oils in the plants of this family can be considered as an advantage and can favor them in search for safe and antiepileptic medicines. The effects of Fabacea family plants including Ebenus stellata (E. stellata), Sophora alopecuroides and Caesalpinia gilliiesii were evaluated in pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure tests. Materials and Methods The hydroalcoholic extracts were obtained by percolation of 100 g aerial parts of each plant in 900 ml ethanol 80%. Acute toxicity of the extracts was assessed. Non-toxic doses of the extracts were injected to the mice intraperitoneally (i.p.) and occurrence of clonic seizures induced by PTZ (60 mg/kg, i.p.) or tonic seizures induced by MES (50 mA, 50 Hz, 1 sec), were monitored up to 30 min after each administration. The anticonvulsant extract was then fractionated by dichloromethane and water. Phytochemical screening of the effective extract was also carried out by thin layer chromatography to verify active constituents. Results Among the extracts used, only E. stellata had no toxicity and inhibited clonic seizures in a significant and dose-dependent (3-7 g/kg) manner with ED50 of 4 g/kg. Fractionation of the extract resulted in dosedependent (1-5 g/kg) anticonvulsant activity, which was observed in aqueous fraction with ED50 of 1.74 g/kg. Phytochemical screening revealed the presence of terpens/sterols, alkaloids, flavonoids, tannin and saponins in the extract. Conclusion The presence of anticonvulsant compounds in E. stellata suggests further activity-guided fractionation and analytical studies to find the potential of this plant as a source of anticonvulsant agents. [ABSTRACT FROM AUTHOR]

Background: With approximately 386,000 deaths per year, esophageal cancer is the 6th most common cause of death due to cancer in the world. This cancer, like any other cancer, is the outcome of genetic alterations or environmental factors such as tobacco smoke and gastro-esophageal reflux. Tobacco smoking is a major etiologic factor for esophageal squamous cell carcinoma in western countries, and it increases the risk by approximately 3 to 5 folds. Chronic gastro-esophageal reflux usually leads to the replacement of squamous mucosa by intestinal-type Barrett's metaplastic mucosa which is considered the most important factor causing esophageal adenocarcinoma. In contrast to esophageal adenocarcinoma, different risk factors and mechanisms, such as mutations in oncogenes and tumor suppressor genes, play an important role in causing esophageal squamous cell carcinoma. Molecular studies on esophageal cancers have revealed frequent genetic abnormalities in esophageal squamous cell carcinoma and adenocarcinoma, including altered expression of p53, p16, cyclin D1, EGFR, E-cadherin, COX-2, iNOS, RARs, Rb, hTERT, p21, APC, c-MYC, VEGF, TGT-α and NF-κB. Many studies have focused on the role of different polymorphisms such as aldehyde dehydrogenase 2 and alcohol dehydrogenase 2 in causing esophageal cancer. Different agents including bestatin, curcumin, black raspberries, 5-lipoxygenase (LOX) and COX- 2 inhibitors have been found to play a role in inhibiting esophageal carcinogenesis. Different gene therapy approaches including p53 and p21WAF1 replacement gene therapies and therapy by suicide genes have also been experimented. Moreover, efforts have been made to use nanotechnology and aptamer technology in this regard. [ABSTRACT FROM AUTHOR]

A review of the publications in traditional medicine indicates that the root of Glycyrrhiza glabra L., Fabaceae, is recommended for treatment of epilepsy. As a renewable source, the leaves of G. glabra var. glandulifera growing in Iran were examined for possible anticonvulsant activity. The anticonvulsant activity of the leaves' ethanol extract and dichloromethane, f1, n-Hexane, f1A, and methanol, f1B, fractions were evaluated intraperitoneally in mice using maximal electroshock (MES) and pentylenetetrazol (PTZ) seizure tests. Acute toxicity of the extract and the fractions were also assessed. Phytochemical screening of the extract and the fractions for their active constituents was also carried out by thin layer chromatography and various chemical reagents. The extract and the fractions showed anticonvulsant effect in PTZ test. The ED50 value of 2.11 g/Kg and 1.30 g/Kg was obtained for the crude extract and f1 fraction, respectively. The LD50 value of 3.0 g/Kg was found for the extract. Triterpenes/sterols, alkaloids, flavonoids, anthraquinones and tannins were present in the extract and fractions. Triterpenes and anthraquinones were the highest in the extract, while triterpenes and tannins were prevailing in f1 fraction. The anticonvulsant activity of the extract and f1 fraction could be mainly attributed to the compounds of triterpenes/sterols class present in the leaves of the plant. The therapeutic index of the leaves' extract was narrow and in this regard it has low anticonvulsant potential. Evaluation of the possible anticonvulsant activity of the leaves of the other varieties of G. glabra grown in Iran (e.g., var. violacea) is suggested. [ABSTRACT FROM AUTHOR]

Background: Contribution of neuroinflammation and epilepsy in the mature brain has elicited contradictory results with either excitatory or inhibitory effects. The amygdala is one of the main parts of the limbic system susceptible to insults that lead to neuroinflammation and epilepsy. This study evaluates the effect of chronic inflammation of the rat amygdala induced by lipopolysaccharide (LPS) on kindling epilep- togenesis. Methods: LPS (5µg/rat) was infused once daily into the basolateral amygdala (BLA) of adult rats. Daily electrical stimulation (150 - 300 µA, 100 Hz, monophasic square wave stimulus of 1 msec per wave, 2 sec duration) was delivered into BLA 30 min after LPS injections until the animals became fully kindled. Results: LPS had no significant effect on the development of focal and generalized seizures. Conclusion: The type of neural system exposed to LPS and its specific electrophysiological properties seems to ascertain the final excitatory or inhibitory outcome. [ABSTRACT FROM AUTHOR]

Objectives: Iminoral is the generic microemulsion of cyclosporine. We performed a randomized double-blind multicenter trial to evaluate its efficacy and safety compared with the innovator medication Neoral for preventing acute rejection episodes in adult patients during the first year after renal transplant., Materials and Methods: We used 221 de novo renal transplant recipients from 6 transplant centers in Iran enrolled between April 2008, and January 2010. They were randomized to receive either Iminoral or Neoral as the calcineurin inhibitor component of the immunosuppressive regimen in addition to mycophenolate mofetil and oral corticosteroids. They were followed-up for 1 year. The primary endpoint was the rate of acute allograft rejection. Secondary endpoints consisted of 1-year graft survival rates, daily dosages of cyclosporine, trough and C2 cyclosporine blood level, serum creatinine levels, patient death rates, discontinuing the study drug, tolerability, and adverse events., Results: The risk of acute rejection episode during the first month after transplant was 9% for Iminoral and 10% for Neoral; these declined to 4% and 2% during next 11 months. One-year graft survival rate was 0.86 for both groups. Renal function stabilized during the first month. Declination of the creatinine levels was similar between the 2 groups and reached a stable value of 114.9 μmol/L five months after the transplant. The frequency of clinical complications was similar between the groups., Conclusions: Iminoral is safe and effective when used in de novo kidney transplant patients as an immunosuppressive medication.

There are abundant studies indicating that blocking gap junctions (GJs) containing connexin 36 (Cx36) inhibit seizures. However, recent evidences demonstrate proconvulsant effect of such intervention. Electrical coupling between GABAergic interneurons in CA1 region of hippocampus is mediated through Cx36 GJs. We investigated effect of quinine, a specific blocker of Cx36, on the seizure severity and epileptogenesis in amygala kindling model of epilepsy in rats. Quinine (1, 50, 100, 500 and 2000 µM/rat) was injected directly into the CA1 and kindled seizure parameters including behavioral seizure stage, duration of evoked afterdischarges, and duration of generalized seizures behavior were recorded 10 min afterward. Moreover, quinine (1, 30, and 100 µM/rat) was injected intra CA1 once daily during kindling development. At the doses used, quinine had no significant effect on amygdala-kindled seizures. However, quinine 100 µM significantly accelerated kindling rate. Blockade of Cx36 GJs coupling and consequent disruption of inhibitory transmission in GABAergic interneurons in CA1 area seems to be responsible for the antiepileptogenic effect of quinine.

Background: One third of epileptic patients are resistant to several anti-epileptic drugs (AED). P-glycoprotein (P-gp) is an efflux transporter encoded by ATP-binding cassette subfamily B member 1 (ABCB1) gene that excludes drugs from the cells and plays a significant role in AEDs resistance. Over-expression of P-gp could be a result of polymorphisms in ABCB1 gene. We studied the association of T129C and T1236C single-nucleotide polymorphisms (SNP) of ABCB1 gene with drug-resistant epilepsy in Iranian epileptics., Methods: DNA samples were obtained from 200 healthy controls and 332 epileptic patients, of whom 200 were drug responsive and 132 drug resistant. The frequencies of the genotypes of the two SNP were determined by polymerase chain reaction followed by restriction fragment length polymorphism., Results: No significant association was found between T129C and T1236C genotypes and drug-resistant epilepsy neither in adults nor in children. However, the risk of drug resistance was higher in female patients with 1236CC (P = 0.02) or CT (P = 0.008) genotype than in those with TT genotype. The risk of drug resistance was also higher in patients with symptomatic epilepsies with 1236CC (P = 0.02) or CT (P = 0.004) genotype than in those with TT genotype. The risk of drug resistance was lower in patients with idiopathic epilepsies with 129TT genotype (P = 0.001) than in those with CT genotype., Conclusion: Our results indicate that T1236C polymorphism is associated with drug resistance in Iranian female epileptic patients. Replication studies with large sample sizes are needed to confirm our results.