PTZ Group Research Articles

212. Effectiveness of Empirical Piperacillin/tazobactam Compared to Cefepime for Bloodstream Infection Caused by Gram-Negative Bacilli

Abstract Background Piperacillin/tazobactam (PTZ) and cefepime (CFP) are commonly used antibiotics for healthcare-associated infections and immunocompromised patients. However, few studies have compared the clinical effectiveness of these two antibiotics. Thus, we compared the effectiveness of empirical PTZ and CFP in patients with monomicrobial blood-stream infection (BSI) caused by gram-negative bacilli. Methods We conducted a retrospective cohort study of consecutive, non-duplicate monomicrobial BSIs caused by 1 of 4 taxa (Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and Acinetobacter species) identified from a nationwide, prospective surveillance (Korean Antimicrobial Resistance Surveillance Network [KARS-Net]). Patients who were treated with PTZ or CFP as the only active empirical antibiotic were included. The primary outcome was all-cause, in-hospital 30-day mortality. Logistic regression with backward selection was used to adjust for imbalance in baseline characteristics. Results A total of 120 cases were included, among which 87 (72.5%) were treated with PTZ and 33 (27.5%) with CFP. Underlying renal disease was more common in the PTZ group whereas malignancy, septic shock, and neutropenia were more common in the CFP group. (Table 1). All-cause 30-day in-hospital mortality was comparable between the two groups (16.1% vs 12.1%, p=0.777; table 2), as well as attributable mortality. However, the early clinical response at 72 hr was significantly more common in the patients treated with CFP (25.3% vs 57.6%, p=0.001) The choice of empirical antibiotics was not significantly associated with mortality in a multivariable logistic regression model (Table 3). Older age (≥65 years; adjusted OR. 16.24; 95% CI, 2.21-119.60), lower ECOG (aOR, 2.91 per 1 point, 95% CI, 1.35-6.25), high PITT score (aOR, 1.68; 95% CI, 1.17-6.25) and chronic liver disease (aOR, 39.70; 95% CI, 2.56-615.13) were significant independent risk factors for 30-day in-hospital mortality. Conclusion In patients with BSI caused by gram-negative bacilli, empirical use of either PTZ or CFP was associated with comparable clinical outcomes. Disclosures All Authors: No reported disclosures

Optimization of the Zebrafish Larvae Pentylenetetrazol-Induced Seizure Model for the Study of Caffeine and Topiramate Interactions.

Epilepsy is a common neurological disorder characterized by seizures that cause neurobiological and behavioral impairment. Caffeine (CAF), which is the most widely consumed stimulant in the world, is reported to influence epileptic seizures and antiepileptic drugs, especially topiramate (TPM). The aim of the study was to optimize the zebrafish larvae pentylenetetrazol-induced seizure model for the study of CAF and TPM interactions, which include the determination of dose space, and the delivery of an analytical method for monitoring CAF, TPM, and CAF metabolite paraxanthine (PAR) in Zebrafish larvae. Methods: The zebrafish larvae, 4 days post-fertilization, were incubated for 18 h with CAF, TPM, or CAF + TPM, with subsequent locomotor activity assessment. Seizures were evoked by adding PTZ solution to obtain a final concentration of 20 mM. Subsequently, the liquid chromatography-mass spectrometry (LC-MS/MS) analytical method was used to simultaneously assess the levels of both CAF and TPM in the larvae. CAF (50 mg/L) and TPM (75 μM) given separately decreased the average larvae locomotor activity compared to the PTZ group but, however, were not able to lower it to the control level. Co-administration of 25 mg/L CAF and 50 μM TPM suppressed the activity to the same level. Adding 25 μM TPM to 50 mg/L CAF decrease the measured CAF level in the larvae. Until proven otherwise, CAF consumption should be regarded as a potential determinant in the modulation of TPM's efficacy in the management of epileptic seizures. The optimized model will contribute to the standardization of studying CAF and TPM interactions and building the understanding of the molecular bases of the interaction.

Notopterygium incisum Root Extract (NRE) Alleviates Epileptiform Symptoms in PTZ-Induced Acute Seizure Mice.

Epilepsy is a common neurological disorder affecting more than 70 million people worldwide. Despite numerous efforts on new antiepileptic drugs, approximately one-third of epilepsy patients suffer from uncontrolled seizures. It leads to serious psychosocial consequences, cognitive problems, and decreased quality of life. Our previous studies have shown that N. incisum root extract (NRE) can improve cognitive dysfunction in Alzheimer's disease (AD) mice. In addition, our research shows that AD and epilepsy have pathological mechanisms overlapping. Therefore, we tried to investigate whether NRE can ameliorate the seizures of epileptic mice in this study. NRE-treated mice group was given an oral administration with 1 g/kg/d for 7 days. On the 8th day, mice were exposed to PTZ (i.p. injection) to induce epilepsy. Then the cognitive tests of mice in the water maze were carried out, and the biochemical indexes and pathological tests were carried out after the mice were sacrificed. SOD level in the NRE group was significantly higher than that in the PTZ group, while MDA, TNF-α, and IL-1β levels were decreased. The cognitive ability of NRE-treated mice was significantly improved compared with the PTZ group. Immunohistochemistry (IHC) results showed that the activation of microglia and astrocytes in the hippocampus and cortex of NRE mice were inhibited. This study suggests that NRE can alleviate epilepsy and improve cognitive function in mice with epilepsy, and its mechanism may be through reducing inflammation and enhancing antioxidant defense.

Ceftriaxone and selenium mitigate seizures and neuronal injury in pentylenetetrazole-kindled rats: Oxidative stress and inflammatory pathway

Epilepsy is one of the most serious worldwide neurological disorders that lead to the cognitive-psychosocial insults in recurrent seizures. About one third of the patients are drug-resistant, so innovative drugs are needed to manage seizures to improve the quality of life. Ceftriaxone is a cephalosporin antibiotic that increases the expression of glutamate transporters-1 and improves the neurobehavioral effects caused by increased glutamate level in the CNS. Selenium is well known antioxidant. The present study aimed to investigate ceftriaxone and selenium therapeutic effects against epilepsy in rats. Epilepsy was induced by PTZ given at a dose (50 mg/kg I.P) on alternative days for 13 days. Eighty rats were randomly divided into 8 groups: Group1-2; normal and vehicle control, Group 3; PTZ group, Group 4–8; kindled rats received selenium, ceftriaxone100, ceftriaxone200, selenium + ceftriaxone100 and selenium + ceftriaxone200 mg/kg/day respectively for a week. At the end of the study, behavioral tests were performed. Oxidative stress, inflammatory markers, neurotransmitters and GLT-1 were measured in brain tissue homogenate. Brain histopathological investigation was also done. PTZ-kindled rats exhibited increased Racine score, besides behavioral tests and histopathological changes, significant elevation in oxidative stress and inflammatory markers, with decrease in serotonin, dopamine, GABA levels and GLT-1 expressions. Selenium and Ceftriaxone alone or combined treatment decreased Racine score with remarkable improvement in behavioral and histopathological changes. The antioxidant enzymes, neurotransmitters and GLT-1 expressions were increased, along with reduced TNF-α, IL-1 levels. Current study showed that selenium + ceftriaxone100 group represents a possible approach to improve epilepsy particularly through inhibiting oxidative stress and inflammation.

Anticonvulsant like Activity of Silybin Correlates Blood Glucose Levels in PTZ induced Chemo-convulsive Rats

The objective of this study is to observe the impact of Silybin (SIB) on the link between blood glucose and seizure prevention in chemo-convulsive rats. To produce seizures, adult male rats were administered with pentylenetetrazol (PTZ-105 mg/kg i.p.) at the CD97 dose. SIB (100 mg/kg.p.o.) was administered for two weeks. The animals were subjected to chemo convulsions on the 14th day, and the effectiveness of SIB to reduce clonus-type chemo convulsions (CC) was recorded, as well as blood glucose levels measured with a one-touch glucometer.Morphometric analysis and chimney tests were evaluated to know the neurotoxic profile of SIB, while actophotometer, rota rod, and hole board tests were used for behavioural analysis.Pre-treatment with SIB (100 mg/kg p.o) resulted in a significant delay in the onset of CC (*p<0.05) and a significant reduction in the duration of CC (**p<0.01) as compared to controls. The acute dose of SIB significantly reduced blood glucose levels. In addition, acute administration of SIB considerably lowered blood glucose levels and promoted body weight of animals whereas chimney tests, indicating that, non-neurotoxic profile of silybin to animals. Additionally, behavioural tests revealed that no significant alterations in muscular coordination, locomotion, or anxious behaviour were noticed in animals. In summary; results reveal that the NDH + PTZ groups had considerably greater hyperglycemia levels, which is reflected in the early onset and longer duration of chemo convulsions in rat. SIB treatment, However, there was a significant reduction in elevated glucose levels, as well as a considerable delay in the onset and duration of seizures, demonstrating the relationship between blood glucose and Anticonvulsant like activity against chemo convulsive episodes. Keywords: Silybin, Hyperglycaemia, Pentylenetetrazol, chemo convulsions, seizure protection

Deep brain stimulation of the anterior thalamus attenuates PTZ kindling with concomitant reduction of adenosine kinase expression in rats

BackgroundDeep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an emerging therapy to provide seizure control in patients with refractory epilepsy, although its therapeutic mechanisms remain elusive. ObjectiveWe tested the hypothesis that ANT-DBS might interfere with the kindling process using three experimental groups: PTZ, DBS-ON and DBS-OFF. Methods79 male rats were used in two experiments and exposed to chemical kindling with pentylenetetrazole (PTZ, 30 mg/kg i.p.), delivered three times a week for a total of 18 kindling days (KD). These animals were divided into two sets of three groups: PTZ (n = 26), DBS-ON (n = 28) and DBS-OFF (n = 25). ANT-DBS (130 Hz, 90 μs, and 200 μA) was paired with PTZ injections, while DBS-OFF group, although implanted remained unstimulated. After KD 18, the first set of PTZ-treated animals and an additional group of 11 naïve rats were euthanized for brain extraction to study adenosine kinase (ADK) expression. To observe possible long-lasting effects of ANT stimulation, the second set of animals underwent a 1-week treatment and stimulation-free period after KD 18 before a final PTZ challenge. ResultsANT-DBS markedly attenuated kindling progression in the DBS-ON group, which developed seizure scores of 2.4 on KD 13, whereas equivalent seizure scores were reached in the DBS-OFF and PTZ groups as early as KD5 and KD6, respectively. The incidence of animals with generalized seizures following 3 consecutive PTZ injections was 94%, 74% and 21% in PTZ, DBS-OFF and DBS-ON groups, respectively. Seizure scores triggered by a PTZ challenge one week after cessation of stimulation revealed lasting suppression of seizure scores in the DBS-ON group (2.7 ± 0.2) compared to scores of 4.5 ± 0.1 for the PTZ group and 4.3 ± 0.1 for the DBS-OFF group (P = 0.0001). While ANT-DBS protected hippocampal cells, the expression of ADK was decreased in the DBS-ON group compared to both PTZ (P < 0.01) and naïve animals (P < 0.01). ConclusionsOur study demonstrates that ANT-DBS interferes with the kindling process and reduced seizure activity was maintained after a stimulation free period of one week. Our findings suggest that ANT-DBS might have additional therapeutic benefits to attenuate seizure progression in epilepsy.

Anticonvulsant Activity of trans-Anethole in Mice.

Epilepsy is a chronic neurological disorder affecting 1-2% of world population, and one-third of patients are refractory to pharmacological treatment. This fact has stimulated research for new antiepileptic drugs and natural products have been an important source. trans-Anethole (TAN) is a phenylpropanoid, component of some essential oils, extracted from plants, and its effects have been little studied. Therefore, this study is aimed at investigating the TAN effect in classic seizure models and evaluate the electroencephalographic (EEG) profile of animals treated with this substance. For this, Swiss male mice (Mus musculus) were used, and the lethal dose was evaluated and subsequently submitted to the test maximal electroshock (MES), the pentylenetetrazole- (PTZ) induced seizure test, and the EEG profile. Initially, the LD50 for TAN was estimated in 1000 mg/kg (i.p.) dose and there was no sign of acute toxicity or death. In the MES test, TAN 300, i.p. (12.00 ± 2.9 s) and 400 mg/kg, i.p. (9.00 ± 4.4 s) doses was able to decrease tonic seizures duration induced by electric discharge (0.5 mA, 150 pulses/s, for 0.5 s). In the PTZ test (75 mg/kg, i.p.), TAN 400 mg/kg, i.p. increased the latency to myoclonic jerks (80.0 (56.0–134.0)), the latency totonic-clonic seizures (900.0 (861.0–900.0) and decrease seizure duration (0.0 (0.0–10.0)). No deaths were found in this groups compared to vehicle. EEG analysis showed an amplitude decrease of waves (ratio of baseline) in TAN 300 (1.82 ± 0.23) and 400 mg/kg (1.06 ± 0.16) groups. In this way, TAN at 400 mg/kg was able to inhibit and/or attenuate seizures by increasing the time for the onset of spasms and convulsions, as reducing the duration of seizures. The EEG profile corroborate with this results showing a reduction in the amplitude of waves compared to the PTZ group. Thus, TAN showed an anticonvulsant effect in all experimental models performed, behavioral and electroencephalographic.

Anticonvulsant activity of oxaprozin in a rat model of pentylenetetrazole-induced seizure by targeting oxidative stress and SIRT1/PGC1α signaling.

The effect of oxaprozin (OXP) on an experimental model of seizures in rats was investigated in this study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg). The anticonvulsant effect of OXP (100, 200, and 400 mg/kg, intraperitoneally) was evaluated in a seizure model. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for antioxidant assays (nitric oxide (NO) and glutathione (GSH)). The animals' brains were also isolated to gauge the relative expression of genes in the oxidative stress pathway (sirtuin 1 (Sirt1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α)). Intraperitoneal injection of OXP increased the mean latency of myoclonic jerks and generalized tonic-clonic seizure (GTCS) and decreased the number of myoclonic jerks and GTCS duration compared with the PTZ group. Biochemical tests showed that pretreatment with OXP was able to restore GSH serum levels and reverse the augmented NO serum levels caused by PTZ induction to the normal level. The quantitative polymerase chain reaction results also revealed that OXP counteracts the negative effects of PTZ by affecting the expression of the Sirt1 and Pgc1α genes. Overall, this study suggests the potential neuroprotective effects of the nonsteroidal, anti-inflammatory OXP drug in a model of neural impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

Pentylenetetrazole-induced kindling rat model: miR-182 and miR-27b-3p mediated neuroprotective effect of thymoquinone in the hippocampus

ABSTRACT Objectives: Epilepsy is a neurological disease that pathologically affects brain functions. The epileptic hippocampus has modified microRNA(miRNA) levels. Therefore, we aimed to evaluate the neuroprotective effect of thymoquinone (TQ) in PTZ-induced epilepsy and to demonstrate the overlap between miRNA and mRNA expression profiles. Methods: Male adult Wistar albino rats (200–230 g, n = 20) were divided into three groups as control (n = 6), PTZ (n = 7), and TQ + PTZ (n = 7). The PTZ kindling model was created by injecting PTZ in sub convulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, and 24 of the study into animals. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the TQ+PTZ group were treated by oral gavage with a 20 mg/kg TQ 2 h before each PTZ injection. The rats in the control group were treated with 0.5 ml saline. Seizure severity was evaluated with the Racine scale. The genes and signaling pathways targeted by miRNAs were determined by bioinformatics analysis. Results: In the rat hippocampus, mature 728 miRNAs were analyzed by microarray and the nine miRNA were verified by quantitative Real-Time PCR. rno-miR-182 and rno-miR-27b-3p were up-regulated in the PTZ group and down-regulated in the TQ + PTZ group. Discussion: In the PTZ kindling epilepsy model, the expression of these two miRNAs was regulated by TQ and exerted a neuroprotective effect by controlling the activities of target genes.

Investigation of efficacy of asenapine on passive avoidance learning and memory and oxidative stress in animal model of seizure-induced with pentylenetetrazole

Asenapine (ASE) has been used for treatment of bipolar disorder. There is also evidence that it may be useful in the treatment of neurodegenerative disorders. In this regard, the efficacy of ASE in an experimental model of seizure and memory impairment caused by seizures in rats has been investigated in the present study. Seizures in male Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)), and the anticonvulsant effect of ASE (0.5 and 1 mg/kg, i.p.) was evaluated. The effect on memory was assessed using passive avoidance (PA) test in a shuttle box apparatus. After behavioral tests, the animals underwent deep anesthesia and were euthanized painlessly. Serum was isolated for oxidative stress assays (nitric oxide (NO), and glutathione (GSH)). Intraperitoneal injection of ASE decreased the mean number of myoclonic jerks and duration of generalized tonic clonic seizures (GTCS) and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, ASE caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that ASE was able to significantly increase GSH serum levels and significantly reduce NO serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of ASE in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

Investigation of efficacy of asenapine on passive avoidance learning and memory and oxidative stress in animal model of seizure-induced with pentylenetetrazole

Asenapine (ASE) has been used for treatment of bipolar disorder. There is also evidence that it may be useful in the treatment of neurodegenerative disorders. In this regard, the efficacy of ASE in an experimental model of seizure and memory impairment caused by seizures in rats has been investigated in the present study. Seizures in male Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)), and the anticonvulsant effect of ASE (0.5 and 1 mg/kg, i.p.) was evaluated. The effect on memory was assessed using passive avoidance (PA) test in a shuttle box apparatus. After behavioral tests, the animals underwent deep anesthesia and were euthanized painlessly. Serum was isolated for oxidative stress assays (nitric oxide (NO), and glutathione (GSH)). Intraperitoneal injection of ASE decreased the mean number of myoclonic jerks and duration of generalized tonic clonic seizures (GTCS) and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, ASE caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that ASE was able to significantly increase GSH serum levels and significantly reduce NO serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of ASE in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

Nonsteroidal Anti-inflammatory Drug Oxaprozin is Beneficial Against Seizure-induced Memory Impairment in an Experimental Model of Seizures in Rats: Impact On Oxidative Stress and Nrf2/HO-1 Signaling Pathway.

There is substantial evidence that anti-inflammatory agents and antioxidants have neuroprotective properties and may be useful in the treatment of neurodegenerative disorders. In this regard, the effects of oxaprozin (OXP) (a nonsteroidal anti-inflammatory drug) on the experimental model of seizure and memory impairment caused by seizures in rats were investigated in the present study. Seizures in male Wistar rats (200-250g, 8weeks) were induced by pentylenetetrazol (PTZ, 60mg/kg). The anticonvulsant effects of OXP (100, 200, and 400mg/kg, administered intraperitoneally) were evaluated in the seizure model. The effect on memory was assessed using the passive avoidance (PA) test. After behavioral tests, the animals underwent deep anesthesia and were euthanized painlessly. Animal serum was isolated for antioxidant assays (MDA and GPx). The animals' brains (hippocampus) were also isolated to gauge the relative expression of genes in the oxidative stress pathway (Nrf2/HO-1). Intraperitoneal injection of OXP decreased the mean score on the Racine scale compared to the PTZ group. Moreover, in the PA test, OXP caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that OXP was able to significantly increase GPx serum levels and significantly reduce MDA serum levels compared to the PTZ group. Quantitative polymerase chain reaction (qPCR) results also revealed that OXP counteracted the negative effects of PTZ by significantly increasing the expression of the Nrf2 and Hmox1 genes. Overall, this study suggests the potential neuroprotective effects of the nonsteroidal anti-inflammatory drug OXP in a model of memory impairment caused by seizures via inhibition of the oxidative stress pathway.

The Effect of Coenzyme Q10 on Liver Injury Induced by Valproic Acid and Its Antiepileptic Activity in Rats.

Valproic acid (VPA) has toxic metabolites that can elevate oxidative stress markers, and the hepatotoxicity of VPA has been reported. Coenzyme Q10 (CoQ10) is one of the most widely used antioxidants. The effect of CoQ10 on epileptogenesis and VPA hepatotoxicity were examined. Rats were randomly divided into five groups: the control group received 0.5% methylcellulose by oral gavages daily and saline by intraperitoneal injection three times weekly. The PTZ group received 1% methylcellulose by gavages daily and 30 mg/kg PTZ by intraperitoneal injection three times weekly. The valproic acid group received 500 mg/kg valproic acid by gavage and 30 mg/kg PTZ, as above. The CoQ10 group received 200 mg/kg CoQ10 by gavages daily and 30 mg/kg PTZ, as above. The Valproic acid + CoQ10 group received valproic acid and CoQ10, as above. Results: CoQ10 exhibited anticonvulsant activity and potentiated the anticonvulsant effect of VPA. CoQ10 combined with VPA induced a more significant reduction in oxidative stress and improved the histopathological changes in the brain and liver compared to VPA treatment. In addition, CoQ10 reduced the level of toxic VPA metabolites. These findings suggest that the co-administration of CoQ10 with VPA in epilepsy might have therapeutic potential by increasing antiepileptic activity and reducing the hepatotoxicity of VPA.

Anti-seizure effect of zinc on PTZ-induced epilepsy in rat model.

Epilepsy is a widespread and mainly severe neurological condition portrayed by recurring spontaneous seizures caused by the brain's abnormal electrical activity. According to new research, inflammation may be both a result and the cause of epileptic seizures. The highest zinc levels in the brain have been found in the hippocampus which is one of the most studied regions of the brain regarding epilepsy. Zinc may have an anti-inflammatory potential as zinc co-factors affect numerous biochemical and physiological reactions. In this study, we evaluated the effects of intraperitoneal zinc administration on seizure activity in murine PTZ model. Rats received either intraperitoneal (IP) zinc sulfate at two different dosages (50-100 mg/kg) or a placebo followed by pentylenetetrazole (IP), a strong seizure-inducing drug. The spike percentages were considerably lower in the PTZ (35 mg/kg) and 50 or 100 mg/kg zinc-treated groups (A3 and A4) than in the PTZ (35 mg/kg) and saline-treated group (A2; p may be used as an adjuvant therapy in combination with other antiepileptic drugs in the future (Tab. 3, Fig. 1, Ref. 27) Keywords: anti-seizure effect of zinc, epilepsy, abnormal electrical activity, antiepileptic drugs, rat model.

Vitamin E Exerts Neuroprotective Effects in Pentylenetetrazole Kindling Epilepsy via Suppression of Ferroptosis.

Epilepsy is one of the most common chronic neurological diseases. There is increasing evidence for ferroptosis playing an important role in the occurrence and development of epilepsy. Vitamin E is a common fat-soluble antioxidant that can regulate ferroptosis. The aim of this study was to investigate the effects of vitamin E on ferroptosis of hippocampal neurons in epileptic rats. Sixty-four male Sprague-Dawley (SD) rats were randomly divided into control, pentylenetetrazol (PTZ; 35mg/kg), vitamin E (200mg/kg) + PTZ, and Ferrostatin-1 (Fer-1; 2.5μmol/kg) + PTZ groups, with drugs administered intraperitoneally 15 times every other day for 29days. The behavioral manifestations (epileptic score, latency, and number of seizures in 30min) and EEG changes were observed and recorded. Nissl staining and electrophysiological recording were used to assess neuronal damage and excitability in the hippocampal CA1 region, respectively. The levels of iron, glutathione (GSH), and malondialdehyde (MDA) in the hippocampus were assessed by spectrophotometry. Immunofluorescence staining was used to detect lipoxygenase 15 (15-LOX) expression. Western blot was used to determine glutathione peroxidase 4 (GPX4) and 15-LOX protein levels. Vitamin E treatment was associated with decreased epileptic grade, seizure latency, and number of seizures in the PTZ-kindled epileptic model. Vitamin E treatment also decreased 15-LOX expression, inhibited MDA and iron accumulation, and increased GPX4 and GSH expression. In conclusion, vitamin E can reduce neuronal ferroptosis and seizures by inhibiting 15-LOX expression.

Comparative Prevalence of Acute Kidney Injury in Chinese Patients Receiving Vancomycin with Concurrent β-Lactam Antibiotics: A Retrospective Cohort Study

PurposeThe combination of vancomycin and piperacillin/tazobactam (VAN + PTZ) provides a broad spectrum of activity against multiple pathogens. However, a major issue in previous research concerned significant nephrotoxicity associated with this drug combination, and most studies have been conducted in American and European countries, with no similar data available from China. Therefore, this study evaluated the nephrotoxic effects of VAN + PTZ in a large-scale Chinese cohort to determine the prevalence of acute kidney injury (AKI) in this population by comparing PTZ and vancomycin monotherapies and the combined use of vancomycin and β-lactam antibiotics. MethodsThis retrospective cohort study identified adult patients who received vancomycin either as monotherapy or in combination with PTZ or carbapenem (VAN + CAR) for at least 48 hours at Jiangsu Province Hospital from January 1, 2017, to December 31, 2018. Patients were also evaluated for the development of AKI, defined according to the Kidney Disease Improving Global Outcome criteria. Duration of vancomycin exposure, steady-state trough vancomycin concentrations, and other risk factors for AKI were assessed. A Bayesian network meta-analysis was conducted to validate our results and comparatively evaluate the nephrotoxicity of β-lactam antibiotics in combination with vancomycin. FindingsIn all, 752 patients were included in the present study. The prevalence of AKI was higher in the VAN + PTZ group than in the VAN and VAN + CAR groups (15.2% vs 4.0% and 6.0%, respectively). After adjustment for confounding factors, VAN + PTZ was still related to AKI (odds ratio [OR] = 4.37; 95% CI, 1.65–11.59; P = 0.003). The network meta-analysis indicated that VAN + PTZ was associated with a significantly higher risk for AKI than was VAN (OR = 3.23; 95% CI, 2.50–4.35), PTZ (OR = 2.86; 95% CI, 1.92–4.12), VAN + cefepime (FEP) (OR = 2.37; 95% CI, 1.80–3.19), or VAN + CAR (OR = 2.28; 95% CI, 1.64–3.21). However, there was no significant difference with respect to AKI prevalence among the VAN, PTZ, VAN + FEP, and VAN + CAR groups. ImplicationsThe prevalence of AKI was higher with VAN + PTZ therapy than with VAN or PTZ monotherapy or with the concurrent use of VAN and FEP or CAR in our study. Clinicians should adequately assess renal function and consider this differential risk for nephrotoxicity when choosing empiric antibiotics in hospitalized patients to minimize the rates of AKI.

PREVENTIVE EFFECT OF PHASEOLUS VULGARIS SEED COATS ON PENTYLENETETRAZOLE (PTZ) INDUCED KINDLING AND BEHAVIORAL COMORBIDITIES

Introduction: To investigate the preventive effect of Phaseolus vulgaris seed coats on pentylenetetrazole-induced kindling and behavioral comorbidities. Material and Methods: Thirty Wistar albino rats were categorized into five groups. The first group received regular saline (0.9 % w/v NaCl) p.o.; the second group received PTZ (35 mg/kg b.w.) i.p.; the third group received valproic acid (200 mg/kg b.w.) p.o.; the fourth group received P. vulgaris extract (100 mg/kg b.w.) p.o.; the fifth group received P. vulgaris extract (200 mg/kg b.w.) p.o. on an alternate day for 21 days. PTZ improved lipid peroxidase levels, decreased Glutathione level, decreased superoxide dismutase activity, increased Nitric Oxide level. Result: This study revealed that P. vulgaris (Hydroalcoholic extract) increased the anti-oxidant level of both 100 mg/kg and 200 mg/kg compared to the PTZ category. Histopathological findings revealed that the hippocampal section of the brain of rats receiving P. vulgaris extract had improved relative to the receiving PTZ group. Conclusion: Based on the result, it is proposed that Phaseolus vulgaris has anti-oxidant properties. This is useful for the treatment of epilepsy.

Effects of Tanacetum polycephalum on passive avoidance learning and oxidative stress in epileptic model of memory impairment in the male Wistar rats

In the present study, the medicinal plant Tanacetum polycephalum, was used to evaluate its effect on oxidative stress and memory deficit caused by PTZ in the rats. Twenty-four rats were randomly categorized into four groups: control negative under treatment with PTZ (sub-threshold dose 35 mg kg−1 for 1 month), control positive under treatment with phenobarbital (PB 30 mg kg−1), and two PTZ groups under treatment with T. polycephalum extract (TPE 300, and 600 mg kg−1). Standard passive avoidance test was used to evaluate memory and learning. After behavioral evaluation, the rats were anesthetized and their brains were removed; following the preparation of brain homogenates, oxidative stress parameters were evaluated using specified methods. It was found that step-through latency in passive avoidance test in PTZ group receiving TPE was greater than that of PTZ group. In addition, brain lipid peroxidation (malondialdehyde) and nitric oxide level in TPE-treated group was significantly lower and glutathione activity and superoxide dismutase level were significantly greater in comparison to PTZ group. Our results showed that TPE could prevent memory deficit and ameliorate hippocampal oxidative stress in PTZ-kindled rats.

Curcumin offsets PTZ-induced epilepsy: involving inhibition of apoptosis, wnt/β-catenin, and autophagy pathways

ABSTRACT Curcumin is a natural antioxidant isolated from Curcuma longa that proved to protect against experimentally induced epilepsy in animals. In the current work, we aimed to explore the possible molecular mechanisms of curcumin neuroprotective effect on PTZ-induced epilepsy in rats. Thirty male Sprague Dawley rats were subdivided into three groups: (a) normal control group, (b) PTZ group: rats received PTZ (50 mg/kg i.p. every other day) for 14 days, (c) curcumin + PTZ group: received PTZ as in PTZ group in addition to curcumin (200 mg/kg per oral daily) for 14 days. After each PTZ injection, the seizure stage, time to the first seizure and the duration of seizures were recorded. Also, at the end of experiment, oxidative stress markers, the expression of splitted caspase-3, β-catenin, LC3 (marker of autophagy), and alpha synuclein proteins were measured in brain tissues. treatment with curcumin caused significant reduction in seizure score, increased time to the first seizure and shortened seizure duration. Also, curcumin caused a significant reduction in oxidative stress (decreased MDA level and increased GSH level) and a significant reduction in the expression of splitted caspase-3, β-catenin, LC3 and alpha synuclein proteins. These results suggest that curcumin has a neuroprotective effect that is not attributed only to its antioxidant activity, but it involves also suppression of PTZ-induced apoptosis, Wnt/β-catenin and autophagy pathways.

Investigation of anti-epileptic mechanisms of 5HT1A receptor with pentylenetetrazole induced epilepsy model in rats

Objective: According to current neurophysiological evidence, the role of 5-hydroxytryptamine (5-HT) receptors in epileptic seizure formation is still not fully elucidated. The aim of this study was to investigate the effects of 5-HT 1A receptor on epileptic seizure with pentylenetetrazole induced epilepsy in rats. Method: In this study, 28 male Wistar Albino rats weighing 240-260 g were used. Pentylenetetrazole (PTZ, 35 mg/kg, i.p.) was injected to the rats to induce epilepsy and seizure stages were determined according to the Racine scale. Electrodes were placed in the skulls of the animals under stereotaxis for ECoG recording. All the experimental animals were sacrificed by decapitation after ECoG and video recordings. GABA level was measured using the Elisa kit from brain tissues, and c-Fos expression was shown immunohistochemically. Results: According to the results, it was shown that 8-OH-DPAT increased the time of initial myoclonic jerk (FMJ (p<0.05). However, the number of epileptic spikes was reduced by 8-OH-DPAT (p<0.05). GABA levels decreased in PTZ group (p<0.05). 8-OH-DPAT and WAY-100135 decreased c-Fos expression in all hippocampal areas (p<0.05). Conclusions: In conclusion, 5-HT 1A receptor agonist 8-OH-DPAT, showed an anti-epileptic effect. The anti-epileptic effects of 5-HT 1A receptor were found to be inconsistent with changes in GABA level. c-Fos expression is a marker of neuronal activation and may be related to the anti-convulsive effect of 5-HT 1A receptor.