Treatment Of Se Research Articles

Influence of valproate-induced hyperammonemia on treatment decision in an adult status epilepticus cohort

IntroductionStatus epilepticus (SE) is a neurological emergency in which immediate intervention is required to prevent permanent brain damage and death. Intravenous (IV) valproic acid (VPA) is often used for the treatment of SE. However, IV VPA frequently increases the blood ammonia level. In this study, we explore the impact of IV VPA-induced hyperammonemia (HA) on treatment management of SE and discuss the challenges related to this particular condition. MethodsWe used data from medical records of 31 adult patients (≥18 years) treated with IV VPA for SE at Oslo University Hospital between January 2006 and October 2019. Clinical and blood sample data and information about the influence of HA on treatment were collected. Correlations between ammonia levels and other continuous or categorical variables were tested using the Pearson's correlation coefficient. The Kruskal–Wallis H-test was used to analyze associations between different variables and treatment decisions. ResultsThirty of 31 patients had increased ammonia level during IV VPA treatment. In 16/30 patients, VPA was discontinued, and in 6/30 patients, the dose was reduced. We found a difference in the median peak ammonia level among the groups where VPA was discontinued (99 μmol/l), reduced (71 μmol/l), and continued (55.5 μmol/l) (P = 0.008). Also clinical status, measured by West Haven Criteria, varied among the groups where VPA was discontinued (3.5), reduced (2.5), and continued (2.0) (P = 0.01). Treatment decisions at peak ammonia were not associated with the level of liver enzymes and bilirubin. ConclusionHyperammonemia had a substantial impact on further management. To date, no recommendations exist on how to manage VPA-induced HA in SE. We call for systematic prospective studies and evidence-based guidelines.

Anti-NMDA receptor encephalitis presenting as new onset refractory status epilepticus in COVID-19

• Autoimmune encephalitis and status epilepticus in COVID-19 can be challenging. • Immunotherapy could be useful for anti-NMDAr encephalitis and SARS-Cov-2 infection. • Cytokines storm could play a role for NORSE presentation in NDMA-R encephalitis.

Efficacy of Immediate Perampanel Oral Loading in Convulsive Status Epilepticus: A Single-Center Experience of Consecutive 22 Patients

Convulsive Status epilepticus (CSE) is a relatively common neurological emergency with high morbidity and mortality and should be stopped as soon as possible to avoid cerebral damage. Despite novel anti-epileptic drugs, its control rate has not been changed sufficiently. Perampanel (PER) is an antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor which is identified as a potential therapeutic target for the treatment of SE. Data on the efficacy of PER in treatment of SE in humans are still insufficient due to lack of homogenous study with high doses and very early administration of the drug. We retrospectively analyzed treatment response, the outcome of all patients with CSE in our hospital who received 8mg of PER oral loading from January 2018 to June 2019. Twenty-two consecutive patients with CSE were included. The etiology and the seizure types were wide-ranging. Fifteen out of 22 patients suffering from CSE responded to PER oral loading (68%) and they became seizure-free within 24 hours. The responders’ outcome after 30 days was significantly better than that of non-responders. There were no severe side effects but minor somnolence which was acceptable for emergent cases. This should be applied to the standard treatment protocol of CSE.

The potential protective roles of zinc, selenium and glutathione on hypoxia-induced TRPM2 channel activation in transfected HEK293 cells

Hypoxia induces cell death through excessive production of reactive oxygen species (ROS) and calcium (Ca2+) influx in cells and TRPM2 cation channel is activated by oxidative stress. Zinc (Zn), selenium (Se), and glutathione (GSH) have antioxidant properties in several cells and hypoxia-induced TRPM2 channel activity, ROS and cell death may be inhibited by the Zn, Se, and GSH treatments. We investigated effects of Zn, Se, and GSH on lipid peroxidation (LPO), cell cytotoxicity and death through inhibition of TRPM2 channel activity in transfected HEK293 cells exposed to hypoxia defined as oxygen deficiency.We induced four groups as normoxia 30 and 60 min evaluated as control groups, hypoxia 30 and 60 min in the HEK293 cells. The cells were separately pre-incubated with extracellular Zn (100 µM), Se (150 nM) and GSH (5 mM). Cytotoxicity was evaluated by lactate dehydrogenase (LDH) release and the LDH and LPO levels were significantly higher in the hypoxia-30 and 60 min-exposed cells according to normoxia 30 and 60 min groups. Furthermore, we found that the LPO and LDH were decreased in the hypoxia-exposed cells after being treated with Zn, Se, and GSH according to the hypoxia groups. Compared to the normoxia groups, the current densities of TRPM2 channel were increased in the hypoxia-exposed cells by the hypoxia applications, while the same values were decreased in the treatment of Zn, Se, and GSH according to hypoxia group. In conclusion, hypoxia-induced TRPM2 channel activity, ROS and cell death were recovered by the Se, Zn and GSH treatments.

Zinc and selenium combination treatment protected diabetes-induced testicular and epididymal damage in rat

Diabetes increases the possibility of germ cell damage, hypogonadism, and male infertility. Diabetic condition negatively impacts zinc (Zn) and selenium (Se) levels in the body. Zn and Se are among the most important trace elements involved in the regulation of redox reaction, antioxidants enzymes activities, and DNA expression in a germ cell. The present study aimed to elucidate the combined effects of Zn and Se treatment on diabetes-induced germ cell damage in male Sprague Dawley rats. Type 1 diabetes was induced by the single intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg). Zn (3 mg/kg, i.p.) and Se (0.5 mg/kg, i.p.) were administered daily for 8 consecutive weeks. All the animals were provided with normal feed and water throughout the study. The effects on germ cell damage were evaluated by body weight, feed-water intake, organ weight, sperm count, motility, sperm head morphology, biochemical analysis, histology, immunohistochemistry, halo assay, germ cell comet assay, testes terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labeling (TUNEL) assay, sperm TUNEL assay, serum protein pattern analysis, and subcellular analysis using transmission electron microscopy. Further, the expressions of nuclear erythroid-derived related factor 2, catalase, glutathione peroxidase 4, and glutathione peroxidase 5 were carried out to ascertain the mechanism of protection. The present results demonstrated that 8 weeks combined treatment of Zn (3 mg/kg, i.p.) and Se (0.5 mg/kg, i.p.) reduced diabetes-induced germ cell damage. This study further highlighted that Zn and Se combination treatment might be a better strategy for the germ cell protection in diabetes and deserve further investigation.

Pharmacotherapy for Pediatric Convulsive Status Epilepticus.

Convulsive status epilepticus (CSE) is one of the most common pediatric neurological emergencies. Ongoing seizure activity is a dynamic process and may be associated with progressive impairment of gamma-aminobutyric acid (GABA)-mediated inhibition due to rapid internalization of GABAA receptors. Further hyperexcitability may be caused by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-d-aspartic acid) receptors moving from subsynaptic sites to the synaptic membrane. Receptor trafficking during prolonged seizures may contribute to difficulties treating seizures of longer duration and may provide some of the pathophysiological underpinnings of established and refractory SE (RSE). Simultaneously, a practice change toward more rapid initiation of first-line benzodiazepine (BZD) treatment and faster escalation to second-line non-BZD treatment for established SE is in progress. Early administration of the recommended BZD dose is suggested. For second-line treatment, non-BZD anti-seizure medications (ASMs) include valproate, fosphenytoin, or levetiracetam, among others, and at this point there is no clear evidence that any one of these options is better than the others. If seizures continue after second-line ASMs, RSE is manifested. RSE treatment consists of bolus doses and titration of continuous infusions under continuous electro-encephalography (EEG) guidance until electrographic seizure cessation or burst-suppression. Ultimately, etiological workup and related treatment of CSE, including broad spectrum immunotherapies as clinically indicated, is crucial. A potential therapeutic approach for future studies may entail consideration of interventions that may accelerate diagnosis and treatment of SE, as well as rational and early polytherapy based on synergism between ASMs by utilizing medications targeting different mechanisms of epileptogenesis and epileptogenicity.

Intravenous Brivaracetam in the treatment of status epilepticus: a systematic review

Background: Brivaracetam (BRV) is a high-affinity synaptic vesicle glycoprotein 2A (SV2A) ligand. Although structurally related to levetiracetam, BRV has higher brain permeability, faster brain SV2A occupancy, and more rapid onset of action. These properties make BRV potentially an ideal compound in the emergency setting. The aim of our study was to systematically review the evidence about the clinical efficacy and tolerability of BRV in the treatment of SE.

Electrophysiological and Neurochemical Assessment of Selenium Alone or Combined with Carbamazepine in an Animal Model of Epilepsy

The present study aims to evaluate the efficacy of selenium (Se) alone or combined with carbamazepine (CBZ) against the adverse effects induced by the chemoconvulsant pentylenetetrazole (PTZ) in the cortex of adult male rats. Electrocorticogram (ECoG) and oxidative stress markers were implemented to evaluate the differences between treated and untreated animals. Animals were divided into five groups: control group that received i.p. saline injection, PTZ-treated group that received a single i.p. injection of PTZ (60mg/kg) for induction of seizures followed by a daily i.p. injection of saline, Se-treated group that received an i.p. injection of sodium selenite (0.3mg/kg/day) after PTZ administration, CBZ-treated group that received orally CBZ (80mg/kg/day) after PTZ administration, and combination (Se plus CBZ)-treated group that received an oral administration of CBZ (80mg/kg/day) followed by an i.p. injection of sodium selenite (0.3mg/kg/day) after PTZ administration. Quantitative analyses of the ECoG indices and the neurochemical parameters revealed that Se and CBZ have mitigated the adverse effects induced by PTZ. The main results were decrease in the number of epileptic spikes, restoring the normal distribution of slow and fast ECoG frequencies and attenuation of most of the oxidative stress markers. However, there was an increase in lipid perioxidation marker in combined treatment of CBZ and Se. The electrophysiological and neurochemical data proved the potential of these techniques in evaluating the treatment's efficiency and suggest that supplementation of Se with antiepileptic drugs (AEDs) may be beneficial in ameliorating most of the alterations induced in the brain as a result of seizure insults and could be recommended as an adjunct therapy with AEDs.

Identification of Risk Factors for Refractory Status Epilepticus.

Objective: The objective of this study is to identify risk factors for the development of refractory status epilepticus (RSE). Methods: This was an IRB-approved, retrospective case control study that included patients admitted with status epilepticus between August 1, 2014, and July 31, 2017. Cases were defined as those with RSE, and controls were those who did not develop RSE. A bivariate analysis was conducted comparing those with RSE and those without RSE. A stepwise logistic regression model was constructed predicting for progression to RSE. Risk factors for progression to RSE were extrapolated from this model. Results: A total of 184 patients met inclusion criteria for the study (99 controls and 49 cases). After adjusting for covariates in the logistic regression, patients with convulsive seizures had a lower odds of developing RSE (odds ratio [OR] = 0.375; 95% CI = 0.148 to 0.951; P = 0.0388). Treatment with benzodiazepines plus levetiracetam had a higher odds of developing RSE (OR = 3.804; 95% CI = 1.523 to 9.499; P = 0.0042). Conclusion and Relevance: This study found that patients with convulsive seizures had a lower odds of developing RSE. In addition, patients treated with benzodiazepines and levetiracetam had a higher odds of developing RSE. This information can be used to potentially identify patients at higher risk of developing RSE, so that treatment can be modified to reduce morbidity and mortality. These results may warrant further investigation into the effectiveness of levetiracetam as a first-line agent for the treatment of SE.

EFFECT OF SPRAYING WASHINGTON NAVEL ORANGE TREES WITH SELENIUM ON VEGETATIVE GROWTH, PRODUCTIVITY AND FRUIT QUALITY

ve seasons, 2012 and 2013 in a private orchard in Barshom vallage located at El-Kalubia Governorate Egypt. Washington Navel Orange trees (Citrus Sinensis) budded on sour orange rootstock (Citrus aurantium, L.) were 7- years- old and planted at 5 x 5 meters under basin irrigation system. This investigation aimed to study the effect of selenium (Se) levels (0, 20, 40, 80 and 160 ppm) as foliar spray on growth, yield, fruit quality, leaf mineral content and enzymes activity of Washington Navel orange trees. The obtained data showed that, selenium had a significant promotive effect on growth, yield, fruit quality, leaf mineral content and enzymes activity of Washington Navel orange trees. Results indicated that treatment of Se at 40 ppm gave the highest significant results, whereas, treatment 160 ppm gave the highest fruit selenium content.

Latency to treatment of status epilepticus is associated with mortality and functional status

IntroductionStatus epilepticus (SE) is a life-threatening neurologic emergency. Despite advances in management, in-hospital mortality remains unchanged. This is partly due to the pharmacoresistance which develops the longer that seizures persist. Therefore, rapid antiseizure medication (ASM) administration may represent a beneficial treatment option. The purpose of this study was to determine: 1) whether in-hospital mortality is reduced with shorter latencies to initial treatment of SE with an ASM (LTSE); and 2) the critical time frame during which LTSE is associated with reduced in-hospital mortality. Materials and methodsThis was a retrospective, single-center study of adults diagnosed with SE between 1/1/2005 and 10/31/2012. Demographic characteristics included seizure history, etiology, semiology, and duration. Subjects were assigned to LTSE groups at the time frames of 5, 10, 30 and 60min. The primary outcome was in-hospital mortality, with poor functional status (mRS 3–6) as a secondary measure. Pearson's chi-square, Mann-Whitney-U, two-sample-t-tests, and binary logistic regression analysis were used as appropriate, with p<0.05. ResultsIn unadjusted analysis, LTSE>30min demonstrated increased risk of mortality (OR 2.06, CI 1.01–4.17, p=0.046) and poor functional status (OR 2.48, CI 1.05–5.85, p=0.038) compared to LTSE≤30min. Increased mortality risk remained after adjusting for SE duration (OR 2.07, CI 1.01–4.26, p=0.047) and nonconvulsive seizures (OR 2.28, CI 1.08–4.80, p=0.03). Compared to subjects treated within 60min, those treated after 60min were at increased risk of poor functional status, regardless of the presence of nonconvulsive seizures (OR 2.96, CI 1.14–7.73, p=0.026). In addition, when acute symptomatic SE was stratified by cardiac versus non-cardiac etiologies, subjects with non-cardiac acute symptomatic SE demonstrated worse functional outcome when treated after 60min (OR 7.20, CI 1.13–46.07, p=0.037). ConclusionsTreatment of SE within 30min of onset is associated with reduced risk of in-hospital mortality and poor functional status, although this may be attenuated by acute symptomatic seizures related to cardiac arrest. This represents a therapeutic option which has the potential to benefit patient outcomes.

Abstract 1187: Discovery of new AML and MDS patient subsets sensitive to the highly selective RARα agonist SY-1425 (tamibarotene) through super-enhancer analysis

Abstract Super-enhancers (SEs) are large, highly active chromatin regions that regulate key cell identity genes including oncogenes in malignant cells. Using our gene control platform, we identified SEs genome-wide in 60 primary AML patient samples to enable the discovery of novel tumor vulnerabilities. One of the SEs that showed a highly asymmetric distribution amongst patient samples was associated with the gene encoding the retinoic acid receptor alpha (RARα). We have discovered that the presence of a RARA SE is predictive for response of non- APL AML cell lines to the highly selective RARα agonist SY-1425. SY-1425 is a clinical stage RARα agonist with improved PK, potency, and selectivity over existing pan-retinoic acid agonists. SY-1425 has sub-nanomolar potency on RARα, with 200-2000 fold selectivity over other RAR family members. SY-1425 treatment of AML cell lines containing a RARA SE results in 0.2-2 nanomolar EC50 anti-proliferative effects, whereas proliferation of cell lines without SEs are not affected. The RARA enhancer level (as measured by H3K27ac ChIP-seq) is well correlated with mRNA levels for RARα. Two patient derived xenograft models with high RARα mRNA show prolonged survival and tumor cell differentiation response to SY-1425, whereas two models with low RARα mRNA do not show a treatment effect. In contrast, treatment with the non-selective agonist ATRA fails to show a survival benefit in a RARα mRNA high model, presumably due to its lower agonist activity and its inferior PK. RARα is a nuclear hormone receptor that acts as a transcriptional repressor when unliganded and as a transcriptional activator when bound by an agonist. SY-1425 treatment of SE containing AML cells shows a transcriptional response very similar to retinoid treatment of APL cells. Analysis of ex vivo treated primary AML cells as well as analysis of bone marrow and blood samples from SY-1425 treated patient derived xenograft models support an anti-proliferative and differentiation induction effect in cells containing the RARA SE but not in cells lacking the RARA SE. In addition to AML, a sub-population of MDS patient samples also contain elevated RARα mRNA levels, suggesting the potential utility of SY-1425 in this closely related indication. In summary, using our gene control platform, we have identified subsets of non-APL AML and MDS who may respond to the selective RARa agonist, SY-1425. A phase 2 clinical study with SY-1425 is being planned in patients identified with a novel biomarker based on these findings. Citation Format: Michael R. McKeown, Emily Lee, Chris Fiore, Matthew L. Eaton, Jeremy Lopez, Ryan Corces-Zimmerman, Ravindra Majeti, Christian Fritz, Eric Olson. Discovery of new AML and MDS patient subsets sensitive to the highly selective RARα agonist SY-1425 (tamibarotene) through super-enhancer analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1187.

Intensive care management of status epilepticus

AbstractStatus epilepticus (SE) is a life-threatening neurological emergency that requires prompt diagnosis and treatment. SE may be classified into convulsive and non-convulsive types, based on the presence of rhythmic jerking of the extremities. Clinically, tonic-clonic convulsive SE (CSE) is divided into four subsequent stages: Early, established, refractory and super-refractory. Initial elements of resuscitation include airway protection, haemodynamic resuscitation and seizure control. Further treatment should then be guided by the diagnostic workup. Rapid treatment of early SE is achieved with intravenous (IV) lorazepam or intramuscular midazolam. In established SE, IV antiepileptic drugs (AEDs) (phenytoin/fosphenytoin, valproate, levetiracetam, phenobarbital) are most commonly used, but there is no Class I evidence for choosing one over the other. Considered overall, cumulative data from the literature are consistent with valproate and levetiracetam, being a safe and effective therapeutic alternative to phenobarbital and phenytoin for treatment of established SE. Refractory SE (RSE) and super-RSE are treated with anaesthetic medications (propofol, midazolam, thiopental/pentobarbital, ketamine), non-anaesthetic drugs (lidocaine, magnesium, pyridoxine), AEDs (levetiracetam, lacosamide, topiramate, lacosamide, pregabalin, gabapentin) and other cause-directed treatments with low success rates. Potential non-pharmacologic interventions to be considered in super-RSE include hypothermia, electroconvulsive therapy, ketogenic diet, immunomodulatory treatments, emergency resective epilepsy surgery, cerebrospinal fluid drainage and vagal nerve or deep brain stimulation or transcranial magnetic stimulation. Diagnosis of non-CSE requires continuous electroencephalography and involves a high index of suspicion in all patients with an altered mental status of unclear cause or with a prolonged postictal state. Treatment options include addressing underlying causes and aggressive pharmacologic interventions with a benzodiazepine, phenytoin and valproate.

Supplementation with Selenium yeast on the prooxidant–antioxidant activities and anti-tumor effects in breast tumor xenograft-bearing mice

Selenium (Se) is essential for antioxidant activity involved in immune function and anti-carcinogenic action, whereas at higher concentrations, Se may have pro-oxidant properties. The present study was aimed at determining the effects of Se supplementation, as Se yeast, on oxidative stress in non-tumor/tumor tissues, as well as regulation of the apoptotic process, and immune responses in mice-bearing breast tumor xenografts. Female BALB/cByJNarl mice were divided into control (CNL and CNL-con), Se-supplemented control (CNL-HS, given as a single oral dose of 912 ng Se daily), breast tumor-bearing (TB and TB-con), TB-LS (228 ng Se), TB-MS (456 ng Se) and TB-HS (912 ng Se) groups. All mice were treated with/without Se for 14 days. A number of variables were further measured. Compared with the TB groups, tumor bearing mice with Se supplement had increased plasma Se concentrations, reduced erythrocyte Se-dependent glutathione peroxidase (GPx) activity and malondialdehyde (MDA) products and inhibited tumor growth. They have also higher Se concentrations in non-tumor and tumor tissues. Significantly elevated concentrations of MDA and reduced GPx activities, as well as increased anti-apoptotic bcl-2 and tumor suppressor p53 concentrations in tumor tissues were observed as Se accumulated in tumor, whereas lower MDA products were found in various non-tumor tissues than did the corresponding values. Further, there were elevated concentrations of Th1-derived cytokines and decreased Th2-type interleukin (IL)-4 in tumor-bearing mice with the treatment of Se. In conclusion, accumulation of Se in tumors may induce oxidative stress and p53-dependent pro-oxidative apoptosis, thus inhibiting the growth of breast tumor.

The Antagonistic Effect of Selenium on Lead Toxicity Is Related to the Ion Profile in Chicken Liver.

The interactions between the essential element selenium (Se) and the toxic element lead (Pb) have been reported extensively; however, limited data are available regarding the effects of Se on Pb and the ion profile in chicken liver. Whether the change in the ion profile was involved in the protective process of Se and the toxic effect of Pb is unknown. In the present study, we detected 26 ion profiles (including those of Na, Mg, K, Ca, B, Si, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Se, Mo, Sb, Ba, Tl, Li, Al, As, Cd, Sn, Hg, and Pb) in chicken liver following treatment with Se or Pb and with the compound treatment of Se and Pb. The results showed that Se supplementation decreased the content of B and Cr and increased that of Zn and Ba (P<0.05); however, Pb exposure decreased Cr, Mn, Cu, Se, Mo, and Hg and increased V, Fe, Cd, and Sn (P<0.05). The results showed that Se and Pb primarily influenced essential microelements and toxic microelements in the chicken liver. In this process, Se alleviated the increased Cd and Pb induced by Pb exposure but aggravated the decreased Cu and Mn. The results also indicated that there existed both synergistic and antagonistic interactions between different ions, further verifying the principal component analysis. Thus, the results showed that prolonged exposure to Se and Pb influences the ion profiles in chicken liver. The protective role of Se and toxic effect of Pb may be related to these changing ion profiles in chicken liver.

Forehead EEG electrode set versus full-head scalp EEG in 100 patients with altered mental state.

Acute EEG is vastly underutilized in acute neurological settings. The most common reason for this is simply the fact that acute EEG is not available when needed or getting EEG is delayed as it requires trained technicians and equipment to be properly recorded. We have recently described a handy disposable forehead EEG electrode set that is suitable for acute emergency EEG recordings. The specific objective in this study was to assess the forehead electrode's utility when the clinical demand was to exclude SE. One hundred consecutive acute neurological patients (53 women, 47 men, age: 18-90 years) with unexplained altered mental state were studied with acute emergency EEG to rule out SE. Electroencephalographic recordings were obtained simultaneously with forehead EEG electrode and routine 10-20 system full-head scalp electrodes to clarify the clinical usefulness of forehead EEG electrode in this setting. Electroencephalographic recordings were interpreted blindly by three experienced clinical neurophysiologists first only based on forehead EEG and then by full-head EEG. Ninety-six out of the 100 patients did not show EEG evidence of SE. There was 100% agreement with forehead and routine EEG. Four out of the 100 patients showed EEG evidence of SE in routine EEG, with 50% agreement between different electrode types. The forehead EEG missed two cases because the EEG findings supporting SE were restricted to the posterior parts of the brain. With a forehead EEG set, the sensitivity of detecting NCSE was 50%. There were no false positive cases yielding a specificity of 100%. Patients with AMS can benefit from forehead EEG recording in prehospital, hospital, and ICU settings. Since EEG recording can be started within a few minutes with the forehead EEG set, it will significantly reduce the delay in treatment of SE. This article is part of a Special Issue entitled "Status Epilepticus".

Single versus combinatorial therapies in status epilepticus: Novel data from preclinical models

Drug-refractory status epilepticus (RSE) is a major medical emergency with a mortality of up to 40% and the risk of severe long-term consequences. The mechanisms involved in RSE are incompletely understood. Animal models are important in developing treatment strategies for more effective termination of SE and prevention of its long-term outcomes. The pilocarpine and lithium-pilocarpine rat models are widely used in this respect. In these models, resistance to diazepam and other antiseizure drugs (ASDs) develops during SE so that an SE that is longer than 30 min is difficult to suppress. Furthermore, because all ASDs used in SE treatment are much more rapidly eliminated by rodents than by humans, SE recurs several hours after ASD treatment. Long-term consequences include hippocampal damage, behavioral alterations, and epilepsy with spontaneous recurrent seizures. In this review, different rational polytherapies for SE, which are more effective than monotherapies, are discussed, including a novel polytherapy recently developed by our group. Based on data from diverse seizure models, we hypothesized that cholinergic mechanisms are involved in the mechanisms underlying ASD resistance of SE. We, therefore, developed an intravenous drug cocktail, consisting of diazepam, phenobarbital, and the anticholinergic scopolamine. This drug combination irreversibly terminated SE when administered 60, 90, or 120 min after SE onset. The efficacy of this cocktail in terminating SE was comparable with the previously reported efficacy of polytherapies with the glutamate receptor antagonist ketamine. Furthermore, when injected 60 min after SE onset, the scopolamine-containing cocktail prevented development of epilepsy and hippocampal neurodegeneration, which was not observed with high doses of diazepam or a combination of phenobarbital and diazepam. Our data add to the existing preclinical evidence that rational polytherapy can be more effective than monotherapy in the treatment of SE and that combinatorial therapy may offer a clinically useful option for the treatment of RSE. This article is part of a Special Issue entitled "Status Epilepticus".

Effects of selenium on lead-induced alterations in Aβ production and Bcl-2 family proteins

Previous studies in humans and animals have suggested that lead (Pb) may increase the expression of amyloid precursor protein (APP) and accumulation of amyloid β protein (Aβ). Our previous studies have revealed that selenium (Se) can partially improve memory deficits induced by Pb exposure. In this study we sought to investigate the effect of Pb and Se on the endogenous expression of APP, Aβ40 and Bcl-2 family proteins. In vitro, the protein levels of APP and Aβ significantly decreased in SH-SY5Y and PC12 cells co-incubated with Pb-acetate and selenomethionine (SeMet) for 48h, compared with cells treated with Pb-acetate alone. Furthermore, these reductions induced by Se appeared to be concentration-dependent. In Wistar rats, we observed that the mRNA and protein levels of APP, the protein level of Bax, and the ratio of Bax/Bcl-2 protein significantly increased after Pb treatment at embryonic stage and in neonates. These increases were significantly reversed by the treatment of Se. Taken together, our results suggest that Se can attenuate the alterations in APP expression and Aβ production as well as Bcl-2 family proteins induced by lead exposure in cells and in animals.

Status epilepticus in adults: A study from Nigeria

BackgroundStatus epilepticus (SE) is a common neurologic emergency. Immediate treatment to stop seizure activity and prompt diagnostic evaluation to recognize potentially treatable causes are paramount in the management of SE. Thus, increased awareness of presentation, etiologies, and treatment of status epilepticus SE is central in the practice of critical care medicine. However, there is a paucity of information on SE from Nigeria. ObjectiveWe evaluated the clinical profile and predictors of one-month outcome in a group of Nigerian patients with SE. MethodologyPatients with SE were recruited from the medical, high dependency unit, intensive care unit and accident and emergency departments of a tertiary hospital from 2008 to 2013. The outcome was assessed using Glasgow Outcome Score (GOS). The outcome, which was categorized into dead (GOS = 1) or alive was analyzed in a multivariate logistic regression model. ResultA total of 76 patients was studied. The four most common underlying etiologies were stroke, antiepileptic drug (AED) non-compliance, CNS infections and metabolic derangement. Fifty-nine (77.6%) patients survived. Duration of seizure, delay in initiation of treatment (Odd ratio (OR) = 4.4, 95% CI = 1.17–16.56), refractory status epilepticus (OR = 87.1, 95% CI = 12.94–781.1) were significantly associated with death. On multivariate analysis, however, refractory status epilepticus remained an independent predictor of death. ConclusionOur study showed that the most common underlying etiologies in SE were stroke, antiepileptic drug non-compliance CNS infections and metabolic derangement. Duration of seizure, delay in treatment and refractory the SE were significantly associated with death, but refractory seizure was an independent predictor of death in SE.

The effect of selenium and polysaccharide of Atractylodes macrocephala Koidz. (PAMK) on immune response in chicken spleen under heat stress.

The aim of the present study was to investigate the effect of selenium (Se), polysaccharide of Atractylodes macrocephala Koidz. (PAMK), and the combination of Se and PAMK on the immune response, heat shock protein (HSP) levels under heat stress (HS) condition in chicken spleen. Two hundred chickens were randomly divided into two groups, the HS group and the control (Con) group. Then these chickens were treated with Se (0.3 mg/kg), PAMK (200 mg/kg) alone, and the combination of Se (0.3 mg/kg) and PAMK (200 mg/kg). The antioxidative enzymes, cytokines contents, and expression levels of HSP27 and HSP70 were examined in chicken spleen. The results indicated that HS induced higher levels of TNF-α, IL-4, HSP27, HSP70, and MDA levels but lower level of IFN-γ, IL-2, Gpx, and SOD in spleen (P < 0.05). These responses were ameliorated by the treatment of Se, PAMK alone, and the combination of Se and PAMK (P < 0.05 or not) The results showed that under common condition, Se and PAMK could improve the immune response by enhancing the levels of some cytokines to proper levels; however, under HS condition, Se and PAMK could change the abnormal levels of cytokines and oxidative damages to ameliorate the injury induced by HS. In addition, there existed synergistic effect on the modulation of these biomarkers in chicken spleen between Se and PAMK. So both Se and PAMK play important roles in regulating the immune function in chicken. Considering the synergistic effect on immune regulation of PAMK, this herb deserves further investigation to evaluate its role in improving the effect of traditional immune regulators.