The Anti-Seizure Effect of Liraglutide on Ptz-Induced Convulsions Through its Anti-Oxidant and Anti-Inflammatory Properties.

Epilepsy is a prevalent and frequently devastating neurological disorder defined by recurring spontaneous seizures caused by aberrant electrical activity in the brain. Over ten million people worldwide suffer from drug-resistant epilepsy. This severe condition requires novel treatment approaches. Both oxidative and nitrosative stress are thought to have a role in the etiology of epilepsy. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that is used to treat type-2 diabetes mellitus. According to recent studies, Liraglutide also shows neuroprotective properties, improving memory retention and total hippocampus pyramidal neuronal population in mice. The purpose of this investigation was to determine the anti-seizure and anti-oxidative effects of liraglutide in a pentylenetetrazole (PTZ)-induced rat model of epilepsy. 48 rats were randomly assigned to two groups: those who had electroencephalography (EEG) recordings and those who underwent behavioral assessment. Rats received either intraperitoneal (IP) liraglutide at two different dosages (3-6 mg/kg) or a placebo, followed by pentylenetetrazole (IP). To determine if liraglutide has anti-seizure characteristics, we examined seizure activity in rats using EEG, the Racine convulsion scale (RCS), the time of first myoclonic jerk (FMJ), and MDA, SOD, TNF-α, IL-1ß and GAD-67 levels. The mean EEG spike wave percentage score was reduced from 75.8% (placebo) to 59.4% (lower-dose) and 41.5% (higher-dose). FMJ had increased from a mean of 70.6 s (placebo) to 181.2 s (lower-dose) and 205.2 s (higher-dose). RCS was reduced from a mean of 5.5 (placebo) to 2.7 (lower-dose) and 2.4 (higher-dose). Liraglutide (3 and 6 mg/kg i.p.) successfully decreased the spike percentages and RCS associated with PTZ induced epilepsy, as well as considerably decreased MDA, TNF-α, IL-1ß and elevated SOD, GAD-67 levels in rat brain. Liraglutide significantly decreased seizure activity at both dosages when compared to control, most likely due to its anti-oxidant and anti-inflammatory properties. The potential clinical role of liraglutide as an anti-seizure medication should be further explored.

Effects of Diclofenac Sodium on Seizure Activity in Rats with Pentylenetetrazole-Induced Convulsions.

Epilepsy is a disease which affects between 1 and 2% of the population, and a large proportion of these people do not react to currently available anticonvulsant medications, indicating the need for further research into novel pharmacological therapies. Numerous studies have demonstrated that oxidative stress and inflammation occur during epilepsy and may contribute to its development and progression, indicating higher levels of oxidative and inflammatory parameters in experimental models and clinical patients. This research aimed to assess the impact of diclofenac sodium, a nonsteroidal anti-inflammatory medicine, on seizure and levels of oxidative stress and inflammatory biomarkers in a rat model of epilepsy triggered by pentylenetetrazole (PTZ). 60 rats were randomly allocated to one of two groups: electroencephalography (EEG) recordings or behavioral evaluation. Rats received diclofenac sodium at three various doses (25, 50, and 75 mg/kg) intraperitoneally (IP) or a placebo, followed by intraperitoneal (IP) pentylenetetrazole, a powerful seizure-inducing medication. To investigate if diclofenac sodium had antiseizure properties, seizure activity in rats was evaluated using EEG recordings, the Racine convulsion scale (RCS) behaviour score, the duration of the first myoclonic jerk (FMJ), and the levels of MDA, TNF-α, and SOD. The average percentage of EEG spike waves decreased from 76.8% (placebo) to 64.1% (25 mg/kg diclofenac), 55.9% (50 mg/kg diclofenac), and 37.8% (75 mg/kg diclofenac). FMJ had increased from a mean of 58.8 s (placebo), to 93.6 s (25 mg/kg diclofenac), 185.8 s (50 mg/kg diclofenac) and 231.7 s (75 mg/kg diclofenac). RCS scores decreased from a mean score of 5.6 (placebo), to 3.75 (25 mg/kg diclofenac), 2.8 (50 mg/kg diclofenac) and 1.75 (75 mg/kg diclofenac). MDA levels reduced from 14.2 ng/gr (placebo) to 9.6 ng/gr (25 mg/kg diclofenac), 8.4 ng/gr (50 mg/kg diclofenac) and 5.1 ng/gr (75 mg/kg diclofenac). Likely, TNF-α levels decreased from 67.9 ng/gr (placebo) to 48.1 ng/gr (25 mg/kg diclofenac), 33.5 ng/gr (50 mg/kg diclofenac) and 21.3 ng/gr (75 mg/kg diclofenac). SOD levels, however, enhanced from 0.048 U/mg (placebo) to 0.055 U/mg (25 mg/kg diclofenac), 0.14 U/mg (50 mg/kg diclofenac), and 0.18 U/mg (75 mg/kg diclofenac). Diclofenac sodium (25, 50, and 75 mg/kg i.p.) effectively lowered the spike percentages and RCS scores linked with PTZ-induced epilepsy in rats, as well as significantly decreased MDA, TNF-α, IL-1ß, PGE2 and increased SOD levels. Probably as a result of its anti-oxidative and anti-inflammatory effects, diclofenac sodium dramatically lowered seizure activity at both doses compared to placebo control. Each of these results were significant, with p-values of < 0.01, < 0.05. Therefore, the therapeutic application diclofenac sodium as a potential anticonvulsant should be investigated further.

Short-term protective effect of octreotide on the lungs of rats with experimentally induced sepsis.

BACKGROUND: Acute respiratory distress syndrome is a devastating complication of severe sepsis. Preclinical models suggest that direct lung injury begins with attack to the lung epithelium, but indirect lung injury results from systemic endothelial damage due to inflammatory mediators. The aim of the present study was to explore the effect of octreotide on lungs in a surgically induced sepsis model in rats. METHODS: We used 32 male Sprague Dawley rats and divided into four groups. Group 1: Normal (non-operative and orally fed control, n=8); Group 2: Sham operated (n=8); Group 3: Cecal ligation and puncture (CLP) (untreated group, n=8); and Group 4: CLP and 100 µg/kg octreotide i.p. (n=8). For sepsis, CLP procedure was performed on 16 rats to induce a sepsis model. All groups were analyzed, their blood was taken for arterial blood gas analysis. For histological examination, lung tissues were removed and sections were prepared. RESULTS: In histological examination, if we compare CLP + Octreotide with only CLP group in CLP + Octreotide group decreased inflammatory cell infiltration in alveolar and interstitial area as well as edema, bleeding, when CLP group was compared with octreotide group, all histopathological parameters improved significantly and the severity index decreased from 3 to 1. For arterial blood gas, when CLP and octreotide groups were compared with CLP group, it was observed that there was a significant change in favor of healing and that they almost came up to controls and sham group. CONCLUSION: It could be hypothesized that it would be beneficial to administer octreotide for ameliorate lung injury state in sepsis patients.

Evaluation of the prognostic role of NLR, LMR, PLR, and LCR ratio in COVID-19 patients.

We aimed to find the most useful biomarker by examining the prognostic effect of neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and lymphocyte-C reactive protein ratio (LCR) in patients with coronavirus disease 2019 (COVID-19). Three hundred and four patients diagnosed with COVID-19 infection in our hospital within 5 months (April-August 2020) were examined. Laboratory values and demographic findings of the patients were analyzed retrospectively. Thirty-six patients were diagnosed with severe cases. The ratio of NLR, LMR, PLR, and LCR of patients with severe and those with nonsevere clinical symptoms were statistically analyzed. The NLR and PLR ratios of those with severe clinical symptoms were significantly higher (p < 0.001), the LCR rate was significantly lower (p < 0.001), and there was no significant difference in the LMR rate (p = 0.199). When we examined other peripheral blood parameters, we found that CRP was high, lymphocyte and monocyte were low (p < 0.001), but neutrophil (p = 0.416) and platelet (p = 0.998) were not statistically different between the groups. According to the results, routine blood values are abnormal in patients with COVID-19. NLR, PLR, and LCR ratios can be used as more significant biomarkers than other values in predicting the prognosis of patients.

Effects of the Calcium Channel Blocker Otilonium Bromide on Seizure Activity in Rats With Pentylenetetrazole-Induced Convulsions.

Millions of people suffer from drug-resistant epilepsy. New therapeutic approaches for removing this life-affecting disease are required. The activation of T-type calcium channels (TTCC) is one of the epileptogenesis mechanisms that cause epilepsy. So, we researched the effects of Otilonium bromide (OB), an antisposmolytic drug that inhibits TTCC, on seizure activity in rats with pentylenetetrazol (PTZ) induced convulsion. Randomly, 48 rats were divided into two groups; for electroencephalography (EEG) recordings and for behavioral assesment. Rats were treated with either intraperitoneal (IP) OB at two separate doses (25 mg/kg and 50 mg/kg) or placebo, and then pentylenetetrazole (IP), a potent seizure-inducing chemical administered to them. In our model we have measured rat seizure activity with EEG, the convulsion scala of Racine (RCS), the time of first myoclonic jerk (FMJ) and MDA levels to assess if OB has antiepileptic properties. The mean EEG spike wave percentage score reduced from 79.5% (placebo) to 59.2% (lower-dose) and 35.2% (higher-dose). FMJ had increased from a mean of 67.2 s (placebo), to 105.2 (lower-dose), 150.6 (higher-dose). RCS reduced from a mean of 5.12 (placebo) to 4.4 (lower-dose), 3.8 (higher-dose). MDA leves reduced from 84.5 nmol/gr to 51.09 nmol/gr (lower-dose), 33.2 nmol/gr (higher-dose). Compared to placebo, OB reduced significantly seizure activity at both doses, probably through blocking T-type calcium channels. All these results were statistically significant with < 0.0001 p-values. Otilonium bromide reduced seizure activity in rats with PTZ-induced convulsion. Therefore, the clinical role of OB and other TTCC inhibitors as potential anti-seizure drugs should be further investigated.

Levodropropizine suppresses seizure activity in rats with pentylenetetrazol-induced epilepsy.

BACKGROUND: 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, bothp < 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.

Aorto-caval fistula resulting from an abdominal aortic aneurysm: A case report from the Emergency Department of Izmir Bozyaka Training and Research Hospital, Turkey.

The rupture of an abdominal aortic aneurysm into the inferior vena cava with fistula formation is a rare condition but is associated with high mortality. Classical symptoms and findings vary in a wide range, and early diagnosis and intervention can be life-saving. In this study, we present a case of abdominal aortic aneurysm associated with aorto-caval fistula formation accompanied by mortality.

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 = 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 < 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.