Metabotropic glutamate receptors(mGluRs)in epileptogenesis:an update on abnormal mGluRs signaling and its therapeutic implications

Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Metabotropic glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity.Dysregulated mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy.In this review,we first introduce the three groups of mGluRs and their associated signaling pathways.Then,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis.In addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized.We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.

Pharmacologic Effects of Cannabidiol and Its Molecular Mechanism

Cannabidiol(CBD)is the active constituent of Cannabis sativa and exhibits a diverse range of pharmacologic effects,including anticancer,antibacterial,anti-inflammatory,antioxidant,and antiepileptic properties.The pharmacologic effects of CBD and its molecular mechanisms are reviewed with the objective of proposing novel approaches for basic research and clinical applications of CBD and related pharmaceuticals.

Epileptic Seizures in Neonates Treated with Hypothermia for Hypoxo-Ischemic Encephalopathy in Brazzaville, Congo: Types and Evolution

Background: Moderate to severe hypoxic-ischemic encephalopathy (HIE) in neonates is often treated with hypothermia. However, some neonates may experience epileptic seizures during therapeutic hypothermia (TH). Data on the electrophysiologic and evolutionary aspects of these seizures are scarce in African countries. Objectives: To determine the types of epileptic seizures caused by HIE in neonates in Brazzaville;to describe the evolution of background EEG activities during TH and rewarming;to report the evolution of epileptic seizures. Methods: This was a cross-sectional, descriptive study conducted from January 2020 to July 2022. It took place in Brazzaville in the Neonatology Department of the Blanche Gomez Mother and Child Hospital. It focused on term neonates suffering from moderate or severe HIE. They were treated with hypothermia combined with phenobarbital for 72 hours. Results: Among 36 neonates meeting inclusion criteria, there were 18 boys and 18 girls. Thirty-one (86.1%) neonates had grade 2 and 5 (13.9%) grade 3 HIE. In our neonates, HIE had induced isolated electrographic seizures (n = 11;30.6%), electroclinical seizures (n = 25;69.4%), and 6 types of background EEG activity. During TH and rewarming, there were 52.8% of patients with improved background EEG activity, 41.7% of patients with unchanged background EEG activity, and 5.5% of patients with worsened background EEG activity. At the end of rewarming, only 9 (25%) patients still had seizures. Conclusion: Isolated electrographic and electroclinical seizures are the only pathological entities found in our studied population. In neonates with moderate HIE, the applied therapeutic strategy positively influences the evolution of both seizures and background EEG activity. On the other hand, in neonates with severe HIE, the same therapeutic strategy is ineffective. .

Hepatitis C virus treatment with glecaprevir and pibrentasvir in patients co-prescribed carbamazepine:Three case reports

BACKGROUND Highly effective and well-tolerated direct-acting antiviral(DAA)therapies have revolutionised the management of hepatitis C virus(HCV);however,niche populations face treatment barriers.DAAs co-prescribed with several firstgeneration anti-epileptic drugs(AEDs)are contraindicated due to drug-drug interactions.A common example is carbamazepine whereby steady-state carbamazepine reduces the maximum concentration and area under the curve of velpatasvir,glecaprevir and pibrentasvir due to potent cytochrome P450(CYP)3A4 induction.Carbamazepine also induces P-glycoprotein which reduces glecaprevir and pibrentasvir’s area under curve to infinite time.Sofosbuvirvelpatasvir and glecaprevir-pibrentasvir are contraindicated in patients who are co-prescribed carbamazepine due to the risk of reduced DAA therapeutic effect and consequently,virological treatment failure.This presents a challenge for patients in whom carbamazepine substitution is medically unfeasible,impractical or unacceptable.However,the properties of current generation DAA therapies,including high-potency non-structural protein 5A inhibitory effect,may be sufficient to overcome reduced bioavailability arising from carbamazepine related CYP 3A4 and P-glycoprotein induction.CASE SUMMARY We present a case series of three patients with non-cirrhotic,treatment-naïve,genotype 1a,1b,and 3a HCV who were treated with a 12 wk course of glecaprevir-pibrentasvir,while co-prescribed carbamazepine for seizure disorders.Glecaprevir-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated variants.DAA therapy was dose-separated from carbamazepine to maximise time to peak concentration,and taken with meals to improve absorption.Sustained virological response at 12 wk was achieved in each patient with no adverse outcomes.CONCLUSION DAA therapies,including glecaprevir-pibrentasvir,warrant consideration as a therapeutic agent in people with HCV who are co-prescribed carbamazepine,particularly if AED substitution is not feasible.

Association of HLA-B*1502 and*1511 Allele with Antiepileptic Drug-induced Stevens-Johnson Syndrome in Central China

Previous studies have demonstrated a strong association between carbamazepine（CBZ）-induced Stevens-Johnson syndrome（SJS） and HLA-B 1502 in Han Chinese. Here, we extended the study of HLA-B 1502 susceptibility to two different antiepileptic drugs, oxcarbazepine（OXC） and phenobabital（PB）. In addition, we genotyped HLA-B 1511 in a case of CBZ-induced SJS with genotype negative for HLA-B 1502. The presence of HLA-B 1502 was determined using polymerase chain reaction with sequence-specific primers（PCR-SSP）. Moreover, we genotyped HLA-B 1502 in 17 cases of antiepileptic drugs（AEDs）-induced cutaneous adverse drug reactions（cADRs）, in comparison with AEDs-tolerant（n=32） and normal controls（n=38） in the central region of China. The data showed that HLA-B 1502 was positive in 5 of 6 cases of AEDs-induced SJS（4 CBZ, 1 OXC and 1 PB）, which was significantly more frequent than AEDs-tolerant（2/32, 18 CBZ, 6 PB and 8 OXC） and normal controls（3/38）. Compared with AEDs-tolerant and normal controls, the OR for patients carrying the HLA-B 1502 with AEDs-induced SJS was 6.25（95% CI： 1.06–36.74） and 4.86（95% CI： 1.01–23.47）. The sensitivity and specificity of HLA-B 1502 for prediction of AEDs-induced SJS were 71.4%. The sensitivity and specificity of HLA-B 1502 for prediction of CBZ-induced SJS were 60% and 94%. HLA-B 1502 was not found in 11 children with maculopapular exanthema（MPE）（n=9） and hypersensitivity syndrome（HSS）（n=2）. However, we also found one case of CBZ-induced SJS who was negative for HLA-B 1502 but carried HLA-B 1511. It was suggested that the association between the CBZ-induced SJS and HLA-B 1502 allele in Han Chinese children can extend to other aromatic AEDs including OXC and PB related SJS. HLA-B 1511 may be a risk factor for some patients with CBZ-induced SJS negative for HLA-B 1502.

Low-velocity simultaneous bilateral femoral neck fracture following long-term antiepileptic therapy:A case report

BACKGROUND Simultaneous bilateral femoral neck fractures are relatively rare injuries.They are usually associated with underlying metabolic bone disorders or systemic diseases.Long-term use of narcotics and bisphosphonates can also result in similar fracture patterns;however,association of this fracture type with longterm use of antiepileptic drugs is not very common.Only one such case has been reported in the literature.This article describes the second.CASE REPORT We report a case of simultaneous displaced bilateral femoral neck fractures in a 50-year-old epileptic patient,who had taken phenytoin for the past 3 years.The fractures were a result of low-velocity injury following a fall from the bed.The fractures were managed with a bilateral hemi-replacement arthroplasty.Oral bisphosphonates were given to improve the bone quality in the post-operative period.The patient had a good post-operative outcome,that was sustained throughout the entire follow-up period of 1 year.CONCLUSION Antiepileptic drugs should be supplemented with bisphosphonates and vitamin D to improve bone quality and prevent fractures in epileptic patients.

Comparison of efficacy of folic acid and silymarin in the management of antiepileptic drug induced liver injury:a randomized clinical trial

BACKGROUND： Liver injury associated with antiepileptic drugs accounts for a large proportion of drug-induced liver injuries （DILI） in children. Although withdrawal of the causative agent is the only proved treatment for DILI, in some dinical situations it is not possible. Recent studies have reported promising results of using hepatoprotective drugs with antioxidant actions for the management of DILl. This study aimed to evaluate the efficacy of folic acid versus silymarin treatment in relation to decreasing liver enzymes in patients with DILI due to antiepileptic therapy. METHODS： This randomized, open-label, clinical trial evalu- ated 55 children with epilepsy who were on antiepileptic treat- ment and experienced DILL The children were randomized to receive either silymarin （5 mg/kg per day） or folic acid （1 mg per day） for one month and were followed up for three months. RESULTS： Liver enzymes significantly decreased in both groups. The decrease trend in alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were stronger in the folic acid group compared to silymarin group （P=0.04 and P=0.007, respectively）. At the end of the study patients in the folic acid group had significantly lower ALT （P=0.04）, AST （P=0.02）, and gamma-glntamyl transferase （GGT） （P〈0.001） levels and also higher percentage of normal ALT （30.7% vs 3.4%, P=0.009） and AST （42.3% vs 0%, P〈0.001）, and GGT （23.1% vs 0%, P=0.008） values compared to the patients in the silymarin group. No rebound elevations in ALT, AST and GGT levels or adverse reactions were noted in neither of the study groups.CONCLUSION： Although both treatments were safe and effective in decreasing liver enzymes, folic acid seems to be superior to silymarin in the management of DILl.

Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study

AIM To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug(AED) treatment.METHODS The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category(lamotrigine or levetiracetam, n=16), an "intermediate risk" category(carbamazepine, oxcarbazepine, phenytoin, or valproate, n=34) and a "high risk" category(topiramate, n=5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment. RESULTS Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant(P < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category(P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient(ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient(linear regression analysis, P > 0.15) were observed. CONCLUSION Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.

Tall gastrodis tuber combined with antiepileptic drugs repairs abnormal perfusion foci in focal epilepsy

One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 （34% of 86）; the total number of abnormal perfusion foci decreased by 52 （36%） and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.

Short-term use of antiepileptic drugs is neurotoxic to the immature brain

Previous studies have shown that the long-term use of antiepileptic drugs can cause nervous system damage. However, short-term antiepileptic drug treatment is frequently given to in-fants, especially neonates, to control seizure. Whether the short-term use of antiepileptic drugs is neurotoxic remains unclear. In the present study, immature rats, 3–21 days of age, were intraperitoneally injected with phenobarbital and/or topiramate for 3 consecutive days. Hema-toxylin-eosin and immunohistochemical staining revealed that phenobarbital and topiramate, individually or in combination, were cytotoxic to hippocampal CA1 neurons and inhibited the expression of GluR1 and NR2B, excitatory glutamate receptor subunits. Furthermore, the com-bination of the two drugs caused greater damage than either drug alone. The results demonstrate that the short-term use of antiepileptic drugs damages neurons in the immature brain and that the combined use of antiepileptic drugs exacerbates damage. Our ifndings suggest that clinicians should consider the potential neurotoxic risk associated with the combined use of antiepileptic drugs in the treatment of seizure.

Topiramate induced peripheral neuropathy:A case report and review of literature

Drug-induced peripheral neuropathy had been rarely reported as an adverse effect of some antiepileptic drugs(AEDs) at high cumulative doses or even within the therapeutic drug doses or levels.We describe clinical and diagnostic features of a patient with peripheral neuropathy as an adverse effect of chronic topiramate(TPM) therapy.A 37-year-old woman was presented for the control of active epilepsy(2010).She was resistant to some AEDs as mono-or combined therapies(carbamazepine,sodium valproate,levetiracetam,oxcarbazepine and lamotrigine).She has the diagnosis of frontal lobe epilepsy with secondary generalization and has a brother,sister and son with active epilepsies.She became seizure free on TPM(2013-2017) but is complaining of persistent distal lower extremities paresthesia in a stocking distribution.Neurological examination revealed presence of diminished Achilles tendon reflexes,stocking hypesthesia and delayed distal latencies,reduced conduction velocities and amplitudes of action potentials of posterior tibial and sural nerves,indicating demyelinating and axonal peripheral neuropathy of the lower extremities.After exclusion of the possible causes of peripheral neuropathy,chronic TPM therapy is suggested as the most probable cause of patient's neuropathy.This is the first case report of topiramate induced peripheral neuropathy in the literature.

Effect of Second-generation Antiepileptic Drugs on Diplopia:A Metaanalysis of Placebo-controlled Studies

Different antiepileptic drugs(AEDs) may cause similar adverse effects,one of which is diplopia.However,the AEDs causing diplopia and the dose-response effect of each drug remains uncertain.In this study,we compared several second-generation AEDs to find out whether they would contribute to the risk of diplopia and their effect-causing dose.A meta-analysis was performed on 19 studies in agreement with our inclusion criteria.The results showed that eight commonly used second-generation AEDs(gabapentin,levetiracetam,oxcarbazepine,lamotrigine,pregabalin,topiramate,vigabatrin and zonisamide) could cause diplopia.The reported odds ratios(ORs) ranged from 1.406 to 7.996.Ranking risks from the highest to the lowest ORs of the eight AEDs of any dose resulted in the following order:use of oxcarbazepine(7.996),levetiracetam(7.472),lamotrigine(5.258),vigabatrin(3.562),pregabalin(3.048),topiramate(2.660),gabapentin(1.966),zonisamide(1.406).Taking into account the ORs above,we can conclude that second-generation AEDs of any dose may cause diplopia.However,the levetiracetam-caused diplopia needs to be further studied according to the data(OR,7.472;95% confidence interval,0.375-148.772).These findings ask for better concerns about patients’ quality of life when giving antiepileptic treatments.

Potent Anticonvulsant 1H-Imidazol-5(4H)-One Derivatives with Low Neurotoxicity

We report here the synthesis and in vivo anticonvulsant/neurotoxicity activities of a series of compounds belonging to 2-aryl-4-arylidene-1-phenyl-1H-imidazol-5(4H)-one. The scaffold is based on the commonality of 5-membered lactam ring structures as successful anticonvulsant agents. The present compounds exhibited a range of anticonvulsant activity in pentylenetetrazole (PTZ)-induced seizure test. In particular, the protection was excellent by compounds bearing furylmethylidene on C4, possibly due to good pharmacokinetic properties. It was found that high lipophilicity and/or electron deficient aryl ring substitution at C4 compromised the anticonvulsant activities. For example, chloro analogues were found much less active than unsubstituted phenyl or furyl derivatives. Regarding side effects, active compounds exerted no observable neurotoxic effect at their therapeutic doses in Chimney test.

Low-dose clozapine-related seizure: A case report and literature review

BACKGROUND Treatment-resistant schizophrenia is a severe form of schizophrenia characterized by poor response to at least two antipsychotic drugs and is typically treated with clozapine.However,clozapine lowers the epileptic threshold,leading to seizures,which are severe side effects of antipsychotics that result in multiple complications.Clozapine-related seizures are generally considered to be dose-dependent and especially rare in the low-dose(150-300 mg/d)clozapine treated population.Due to clinical rarity,little is known about its clinical characteristics and treatment.CASE SUMMARY A 62-year-old Chinese man with a 40-year history of treatment-resistant schizophrenia presented to the Emergency Department with symptoms of myoclonus,consciousness disturbance and vomiting after taking 125 mg clozapine.Upon admission,the patient had a suddenly generalized tonic-clonic seizure lasting for about half a minute with persistent disturbance of consciousness,fever,cough and bloody sputum,which was considered to be low-dose clozapine-related seizure.After antiepileptic and multiple anti-infection treatments,the patient was discharged without epileptic or psychotic symptoms.CONCLUSION Our aim is to highlight the early prevention and optimal treatment of clozapine related seizure through case analysis and literature review.

Status epilepticus as an initial manifestation of hepatic encephalopathy:A case report

BACKGROUND Status epilepticus in patients with hepatic encephalopathy (HE) is a rare butserious condition that is refractory to antiepileptic drugs, and current treatmentplans are vague. Diagnosis may be difficult without a clear history of cirrhosis.Liver transplantation (LT) is effective to alleviate symptoms, however, there arefew reports about LT in the treatment of status epilepticus with HE. To ourknowledge, this is the first report of status epilepticus present as initialmanifestation of HE.CASE SUMMARY A 59-year-old woman with a 20-year history of heavy drinking was hospitalizedfor generalized tonic-clonic seizures. She reported no history of episodes of HE,stroke, spontaneous bacterial peritonitis, ascites or gastrointestinal bleeding.Neurological examination revealed a comatose patient, without papilledema.Laboratory examination suggested liver cirrhosis. Plasma ammonia levels uponadmission were five times normal. Brain computed tomography (CT) was normal,while abdominal CT and ultrasound revealed mild ascites, liver cirrhosis andsplenomegaly. Electroencephalography (EEG)showed diffuse slow waves rhythm,consistent with HE, and sharp waves during ictal EEG corresponding to clinicalsemiology of focal tonic seizures. The symptoms were reversed by continuousantiepileptic treatment and lactulose. She was given oral levetiracetam, and focalaware seizures occasionally affected her 10 mo after LT.CONCLUSION Status epilepticus could be an initial manifestation of HE. Antiepileptic drugs combined with lactulose are essential for treatment of status epilepticus with HE,and LT is effective to prevent the relapse.

The efficacy and tolerability of lamotrigine adjunctive/monotherapy in patients with partial seizures refractory to poly-AEDs

Objective： This study was designed as an open-label trial to assess the effects of changing the antiepileptic drugs （AEDs） regimen to lamotrigine （LTG） as adjunctive/monotherapy in patients with partial seizures who were dissatisfied with their drug regimen because of intractable seizures. Methods： The patients were recruited from mulficenters using the following criteria： age≥ 18 years; at least 3 seizures per month during the last 16 weeks; previous use of at least 3 AEDs. The study involved a baseline phase and 2 experimental phases： LTG was first added to the regimen, and then patients could gradually change to LTG monotherapy if their seizures were reduced by at least 50 percent/month. Tolerability, the primary end point, was assessed using the Liverpool Adverse Experience Profile （LAEP）. Secondary end points included quality of life, as measured with the Quality of Life in Epilepsy-31 inventory. Reductions in seizures from baseline throughout each phase were also analyzed. Results： One hundred and fourteen patients aged between 18 and 52 years （age 27.8___ 13.2 years; 71 men and 43 women） were enrolled. After adding LTG, 105 patients （92.11%） Completed adjunctive therapy. Upon completion of the adjunctive phase, mean improvement from baseline was 2.6 points on the LAEP （p=0.037）. The overall score on the QOLIE-31 improved by 8.49 points from baseline （p=0.023）. At the end of the trial, 26 （22.81%） of patients completed LTG monotherapy, and 65 patients （57.02%） experienced at least 50% reduction in seizure frequency compared to baseline, The mean improvement from baseline was 5.1 points on the LAEP （p=0.0059）, and the overall score on the QOLIE-31 score improved by 12,72 points from baseline（p=0,0071）. Twenty-two （19.30%） patients reported adverse effects and 9 patients discontinued participation in the trial because of adverse effects. Conclusion： For patients with partial seizures who were dissatisfied with their AED regimen because of intractable seizures, adding LTG to the drug regimen was well tolerated and effective in improving the quality of life and controlling seizures. Furthermore, switching to LTG monotherapy was associated with further improvement.

INSTRUCTIONS TO AUTHORS

AIM:To characterize the relationship between depression and epilepsy-related seizures,treatment,hormonal and biological variables.METHODS:Included were 200 Egyptian adults(male=100,female=100)with epilepsy(mean age:30.87±7.88 years;duration of illness:13.89±7.64 years)and 100 healthy matched subjects for comparison.Psychiatric interview,Beck Depression Inventory(BDIII)and Hamilton Anxiety Rating Scale(HAM-A)were used to assess depression and anxiety.Blood levels of free testosterone,sex hormone binding globulin,prolactin,free thyroxin and thyroid stimulating hormone,serotonin,noradrenaline and adrenaline neurotransmitters were measured to assess endocrine and biological states.RESULTS:Patients had higher rates of depressive disorder(25.5%or 51/200),mostly intermixed with anxiety(47.06%),psychotic features(19.61%),aggression(40%)and suicide(55%).Compared to controls,higher scores on the BDI-II were observed with right-sided epileptic foci(P=0.011),polytherapy(P=0.001)and lack of control on antiepileptic drugs(AEDs)(P=0.0001).Patients had lower levels of serotonin(P=0.001)[marked with depression(P=0.012)]and adrenaline(P=0.0001),while noradrenaline was lower with temporal lobe epilepsy(P=0.039),left-sided foci(P=0.047)and lack of control on AEDs(P=0.017).Negative correlations were observed between levels of serotonin and BDI-II(P=0.048)and HAM-A(P=0.009)scores,but not with AEDs dose or drug level.CONCLUSION:Comorbid depressive disorder with epilepsy appears to be closely related to seizure type,focus,side,intractability to medications and neurotransmitter changes.Thus,optimizing seizure control and early recognition and management of depression is necessary to improve patients’quality of life.

Renal transplant recipient seizure practical management

Seizures are not uncommon in renal transplant patients.The common aetiologies are metabolic disturbance associated with renal failure,immunosuppression and associated complications and infections.Their management can be challenging because of altered pharmacokinetics of antiepileptic drugs(AEDs)and their removal by dialysis.A practical approach to the management of seizure in renal transplant patients is discussed.This review highlights the guidelines for use of various AEDs in renal transplants.

Antiepileptic activity of lobeline isolated from the leaf of Lobelia nicotianaefolia and its effect on brain GABA level in mice

Objective:To investigate the anticonvulsant activity of the lobeline isolated from the Lobelia nicotianaefolia in chemoconvulsant-induced seizures and its biochemical mechanism by investigating relationship between seizure activities and altered gamma amino butyric acid(GABA)in brain of mice in Pentylenetetrazol(PTZ) seizure models.Methods:The anticonvulsant activity of the isolated lobelinc(5,10,20 and 30 mg/kg.i.p.) was investigated in PTZ and strychnine induced seizures in mice and the effect of isolated lolieline on brain GABA level in seizures induced by PTZ.Diazepam was used as reference anticonvulsant drugs for comparison.Results:Isolated lobeliue(10,20 and 30 nig/kg.up.) significautly delayed and antagonized(P < 0.050-0.001)the onset of PTZ-induced seizures.It also antagonized strychnine induced seizures.The mortality was also prevented in the test group of animals.In biochemical evaluation,isolated lolieline(5,10and 20 mg/kg,i.p.) significantly increased the brain GABA level.And at dose of 30 mg/kg GABA level showed slight decrease in PTZ model.Conclusions:In our findings,isolated lolieline(20mg/kg) exhibited potent anticonvulsant activity against PTZ induced seizures.Also a biochemical evaluation suggested significant increase in harain GABA level at 20 nig/kg up.of isolated lolieline.Hence,we may propose that lolieline reduces epileptic seizures by enhancing the GABA release supporting the GABAergic mechanism.

Emergency treatment of proximal femural fracture within 48h: The Umbria Region experience

Objective: To study the main aspects of osteoporotic emergency fracture of the hip in the Umbria Region in the years 2006-2011. Methods: The study was conducted from January 1 of 2006 to December 31 of 2011, and included only patients over 49 years of age. Patients who did not habitually reside in the region were excluded. They were collected in each based on the following data: age, sex, place of residence (urban or rural), time of the year, fractured side, type of trauma, history of fracture contralateral and perioperative mortality. Results: From 2006 to 2011, a progressive increase in the number of femoral fracture admissions in regional hospitals was observed, equal to 4.73% per annum. The incidence went from 6.8 to 8.1 for 1.000 ultra-65th residents. The most affected age groups are those between 75-84 years and 85-94 years. Conclusions: The epidemiology of osteoporotic hip fracture in the Umbria Region follows a pattern similar to that of other Italian regions. The in-hospital mortality of these patients is partly determined by age and number of complications they suffer during admission. The impact of economic resources on patients who break the osteoporotic hip justifies the implementation of programs for the prevention of osteoporosis and fractures.