Levodropropizine suppresses seizure activity in rats with pentylenetetrazol-induced epilepsy

WOS: 000461404200005PubMed ID: 30610970Background: Millions of individuals worldwide suffer from epilepsy, and up to 25% of patients have seizures that are resistant to currently available antiepileptic drugs. Hence, there continues to be a need for more seizure medications that are effective yet tolerable. Levodropropizine (LVDP) is an established antitussive drug that, based on preclinical data, may also have antiepileptic activity. Methods: We treated rats with either intraperitoneal (IP) LVDP at two different doses or placebo in randomized fashion and then exposed them to IP pentylenetetrazol (PTZ), a potent seizure-inducing compound. We measured the rats' subsequent seizure activity with electroencephalography (EEG), Racine's convulsion scale (RCS) and time to first myoclonic jerk (TFMJ) to determine whether LVDP has antiepileptic properties in our murine model for epilepsy. Results: When compared to placebo, LVDP at both doses significantly suppressed seizure activity. Mean EEG spike wave percentage score decreased from 76.8% (placebo) to 13.1% (lower dose) and 7.6% (higher dose, both p < 0.0001). RCS decreased from a mean of 5.8 (placebo) to 1.83 (lower dose) and 1.16 (higher dose, both p < 0.05). TFMJ had increased from a mean of 65.1 s (placebo), to 247.3 s (lower dose) and 295.5 s (higher dose, both p < 0.0001). Conclusions: Levodropropizine, a common antitussive drug, suppresses seizure activity in rats with PTZ-induced status epilepticus. Given the ongoing need to find effective therapies for refractory epilepsy, the possibility of using levodropropizine as an antiepilepticshould be further explored

Examination of patients admitted to the emergency department with blunt chest trauma

Blunt chest trauma is an important and common cause of morbidity and mortality. It constitutes an important part of the admissions to the emergency department. For this purpose, we evaluated the demographic characteristics, type of trauma, accompanying traumas, trauma scoring systems and results, duration of stay in the emergency department, and hospital outcomes of patients with chest trauma admitted to the emergency department of our hospital. In our study, patients who admitted to the emergency department of our hospital within one year with blunt chest trauma were evaluated retrospectively. Of the 156 patients examined, 114 (73%) were male and the mean age was 52.83±17.9 years. Pneumothorax (35%) and rib fracture (55%) were the most common thoracic injuries. When the duration of hospitalization was examined, the presence of lower extremity and abdomen pathologies, pneumothorax, hemothorax, and (>3) rib fracture prolonged the hospitalization period (p3) rib fracture and pneumomediastinum increased mortality (p<0.05). Patients with chest trauma can have life-threatening clinics. In the emergency department, it should be evaluated for possible life-threatening pathologies, especially in terms of multi-trauma, and thoracic pathologies and other organ injuries should be managed simultaneously in an efficient and rapid manner. The issues to be considered in the triage, stabilization and follow-up of the patients should be well known

Highly Selective SGLT2 Inhibitor Dapagliflozin Reduces Seizure Activity in Pentylenetetrazol-induced Murine Model of Epilepsy

Background: Worldwide, over 10 million individuals suffer from drug-resistant epilepsy. New therapeutic strategies are needed to address this debilitating disease. Inhibition of sodium-glucose linked transporters (SGLTs), which are variably expressed in the brain, has been demonstrated to reduce seizure activity in murine models of epilepsy. Here we investigated the effects of dapagliflozin, a highly competitive SGLT2 inhibitor currently used as a drug for diabetes mellitus, on seizure activity in rats with pentylenetetrazol (PTZ) induced seizures. Methods: Laboratory rats (n =&thinsp;48) were evenly randomized into two experiments, each with four study arms: (1) a vehicle-treated (placebo) arm infused with saline; (2) a control arm infused with PTZ; (3) a treatment arm with PTZ and dapagliflozin at 75 mg/kg, and (4) another treatment arm with PTZ and dapagliflozin at 150 mg/kg. Study subjects were assessed for seizures either via EEG as measured by spike wave percentage (SWP), or clinically via Racine’s scales scores (RSS) and time to first myoclonic jerk (TFMJ). Results: Rats treated with dapagliflozin had lower mean SWP on EEG (20.4% versus 75.3% for untreated rats). Behaviorally, treatment with dapagliflozin improved means RSS (2.33 versus 5.5) and mean TFMJ (68.3 versus 196.7 s). All of these findings were statistically significant with p-values of &lt;&thinsp;0.0001. There was a trend towards even better seizure control with the higher dose of dapagliflozin at 150 mg/kg, however this was not consistently statistically significant. Conclusions: Dapagliflozin decreased seizure activity in rats with PTZ–induced seizures. This may be explained by the anti-seizure effects of decreased glucose availability and a reduction in sodium transport across neuronal membranes which can confer a stabilizing effect against excitability and unwanted depolarization. The potential clinical role of dapagliflozin and other SGLT2 inhibitors as anti-seizure medications should be further explored