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Indian Pediatrics Aug 2023
Topics: Child; Humans; Levetiracetam; Anticonvulsants; Status Epilepticus; Phenytoin
PubMed: 37209049
DOI: No ID Found -
CNS Neuroscience & Therapeutics May 2024Synaptic vesicle protein 2A (SV2A) is a unique therapeutic target for pharmacoresistant epilepsy (PRE). As seizure-induced neuronal programmed death, parthanatos was...
AIMS
Synaptic vesicle protein 2A (SV2A) is a unique therapeutic target for pharmacoresistant epilepsy (PRE). As seizure-induced neuronal programmed death, parthanatos was rarely reported in PRE. Apoptosis-inducing factor (AIF), which has been implicated in parthanatos, shares a common cytoprotective function with SV2A. We aimed to investigate whether parthanatos participates in PRE and is mitigated by SV2A via AIF.
METHODS
An intraperitoneal injection of lithium chloride-pilocarpine was used to establish an epileptic rat model, and phenytoin and phenobarbital sodium were utilized to select PRE and pharmacosensitive rats. The expression of SV2A was manipulated via lentivirus delivery into the hippocampus. Video surveillance was used to assess epileptic ethology. Biochemical tests were employed to test hippocampal tissues following a successful SV2A infection. Molecular dynamic calculations were used to simulate the interaction between SV2A and AIF.
RESULTS
Parthanatos core index, PARP1, PAR, nuclear AIF and MIF, γ-H2AX, and TUNEL staining were all increased in PRE. SV2A is bound to AIF to form a stable complex, successfully inhibiting AIF and MIF nuclear translocation and parthanatos and consequently mitigating spontaneous recurrent seizures in PRE. Moreover, parthanatos deteriorated after the SV2A reduction.
SIGNIFICANCE
SV2A protected hippocampal neurons and mitigated epileptic seizures by inhibiting parthanatos via binding to AIF in PRE.
Topics: Animals; Rats; Apoptosis Inducing Factor; Male; Nerve Tissue Proteins; Disease Models, Animal; Rats, Sprague-Dawley; Drug Resistant Epilepsy; Membrane Glycoproteins; Hippocampus; Anticonvulsants
PubMed: 38801174
DOI: 10.1111/cns.14778 -
Epilepsy & Behavior Reports 2024Traumatic brain injury (TBI) patients are recommended to receive anti-seizure medication (ASM) as posttraumatic seizure (PTS) prophylaxis. However, the utilization of...
Traumatic brain injury (TBI) patients are recommended to receive anti-seizure medication (ASM) as posttraumatic seizure (PTS) prophylaxis. However, the utilization of ASM, including the prescription patterns and associated clinical characteristics, is limited in Taiwan. Thus, this study aimed to investigate the ASM trends and clinical characteristics. This retrospective cohort study enrolled TBI patients who received levetiracetam, phenytoin, and valproic acid during hospitalization using the National Health Insurance Research Database between 2012 and 2019. The primary outcome was the trend of the ASMs based on the index year. The duration of levetiracetam prescription was categorized as short-term (seven days or less) or long-term (more than seven days). Logistic regression identified the factors associated with long-term usage. A total of 64,461 TBI patients were included. Levetiracetam usage increased yearly, while phenytoin declined. Among the levetiracetam users, 5681 (30.38%) were short-term users, and 13,016 (69.62%) were long-term users. Diagnoses of contusions, intracranial hemorrhage, other intracranial injuries, receiving operations, and a history of cerebrovascular disease were significantly associated with longer duration. Conclusions This study revealed the rising trend of levetiracetam usage, indicating its potential as an alternative to phenytoin. TBI patients with more severe conditions were more likely to receive longer prescriptions.
PubMed: 38590545
DOI: 10.1016/j.ebr.2024.100662 -
Heliyon Jan 2024This study investigates the novel application of Phenyl Boronic Acid Functionalized-Quercetin nanoparticles (PBA-Qt NPs) in the context of antibacterial and diabetic...
This study investigates the novel application of Phenyl Boronic Acid Functionalized-Quercetin nanoparticles (PBA-Qt NPs) in the context of antibacterial and diabetic wound healing. The research reveals a multifaceted approach, encompassing physicochemical characterization, antioxidant activity, antibacterial potential, and wound healing efficacy. The purpose of the study was to improve wound healing and antibacterial effects of quercetin and its esterified nanoparticles with phenyl boronic acid (PBA-Qt) compared with phenytoin streptozotocin-induced diabetic rats as a model. PBA-Qt NPs were confirmed using TLC, SEM, and FTIR. They exhibited superior DPPH scavenging (84.2 ± 0.12 %) compared to PBA (59.00 ± 0.18 %) and quercetin (79.02 ± 0.17 %). PBA-Qt showed significant antimicrobial properties with ZOI against Gram-negative (30.34 ± 0.02) and Gram-positive bacteria (25.40 ± 0.03). The MIC for was 1.41 ± 0.03 μg/100 μL, and for , it was 8.25 ± 0.02 μg/100 μL. The MBC against was 4.33 ± 0.02 μg/100 μL, and for , it was 8.25 ± 0.02 μg/100 μL. PBA-Qt NPs reduced MIC for both Gram-positive and Gram-negative bacteria compared to quercetin. They enhanced wound healing by 60-99 % in infected diabetic rats, outperforming phenytoin. PBA-Qt NPs stimulated angiogenesis, tissue repair, and regeneration, improving wound closure. In diabetic and non-diabetic wounds, PBA-Qt NPs demonstrated superior wound contraction and granulation tissue formation. In conclusion, PBA-Qt nanoparticles are promising for treating diabetic chronic wounds due to reduced irritation and enhanced antibacterial and wound-healing properties.
PubMed: 38169972
DOI: 10.1016/j.heliyon.2023.e23452 -
Radiology Case Reports Jan 2024This case serves as a reminder of the infrequent, yet consequential occurrence of cerebellar degeneration linked to phenytoin usage. Whilst emphasizes the importance of...
This case serves as a reminder of the infrequent, yet consequential occurrence of cerebellar degeneration linked to phenytoin usage. Whilst emphasizes the importance of monitoring patients on long-term phenytoin therapy, and it further suggests considering employing bedside imaging tools such as Ultrasound fusion imaging for follow-up of patients at risk of this type of disorder. We present a case study involving a 23-year-old woman who experienced significant neurological impairment resulting in severe cerebellar atrophy while undergoing phenytoin treatment. On cessation of phenytoin, the patient exhibited improvement with enhanced cerebellar function.
PubMed: 38033670
DOI: 10.1016/j.radcr.2023.10.064 -
Scientific Reports May 2024A growing body of evidence suggests that adverse drug reactions (ADRs) are a major cause of morbidity and mortality in the healthcare system. Fifteen to twenty-five... (Observational Study)
Observational Study
A growing body of evidence suggests that adverse drug reactions (ADRs) are a major cause of morbidity and mortality in the healthcare system. Fifteen to twenty-five percent of patients with epilepsy discontinued antiseizure drugs (ASDs) within 6 months of therapy owing to intolerable adverse drug reactions. In Ethiopia, the prevalence of antiseizure adverse drug reactions and associated factors was not extensively conducted in advanced settings like Jimma Medical Centers. Hence, the objective of this study is to assess patterns of adverse drug reactions and associated factors among ambulatory epileptic patients at tertiary hospitals in Ethiopia. A hospital-based prospective observational study was spanned for 1 year. Two hundred ninety patients were consecutively recruited into the study from all epileptic patients attending the ambulatory clinic. Relevant data were collected through patient interviews and medical chart reviews. The causality assessment was done by using the Naranjo Probability Scale. Epi-Data manager version 4.6.0.4 was used for data entry and statistical analysis was performed by Statistical Package for Social Science version 25.0 (SPSS). Stepwise backward logistic regression analysis was done to identify factors that increase the risk of antiseizure adverse drug reactions. The mean (± SD) age of the participants were 29.91(± 11.26) years. The overall prevalence of ADR was 33.8% (95% CI 29.2-39.9%). A total of 110 adverse drug reactions were identified among 98 patients with an average of 1.12 per patient. ADRs were frequently reported with phenobarbital (52.04%) and phenytoin (34.70%). The commonly identified adverse drug reactions were epigastric pain (27.55%) and central nervous system drowsiness (23.46%). Comorbidity (AOR = 5.91, 95% CI (2.14-16.32), seizure-free period of fewer than 2 years (AOR = 1.94, 95% CI (1.18-3.19), and polytherapy (AOR = 1.35, 95% CI (1.80-2.26) were significantly associated with adverse drug reactions. This trial had a comparatively high percentage of adverse medication reactions. Adverse medication reactions were more common in patients with polytherapy, comorbidities, and seizure-free durations less than two years. Therefore, medical practitioners should advise patients who exhibit these traits on how to reduce or avoid bad drug responses or provide comfort in the event of small incidents.
Topics: Humans; Female; Male; Anticonvulsants; Epilepsy; Adult; Prospective Studies; Ethiopia; Drug-Related Side Effects and Adverse Reactions; Adolescent; Young Adult; Middle Aged; Risk Factors; Prevalence
PubMed: 38773234
DOI: 10.1038/s41598-024-61393-9 -
Clinical Case Reports Oct 2023Drug-induced gingival overgrowth can occur as a side effect of specific drugs and lead to poor oral function. Appropriate dental management of the overgrowth may improve...
Drug-induced gingival overgrowth can occur as a side effect of specific drugs and lead to poor oral function. Appropriate dental management of the overgrowth may improve oral function and improve cognitive deficits after cerebrovascular accidents.
PubMed: 37881202
DOI: 10.1002/ccr3.8093 -
Cureus Dec 2023Sepsis is a life-threatening emergency that arises owing to a dysregulated host response to infection, leading to existence organ dysfunction. Vitamin C administration...
Sepsis is a life-threatening emergency that arises owing to a dysregulated host response to infection, leading to existence organ dysfunction. Vitamin C administration has led to a lower mortality rate in sepsis. N-acetylcysteine (NAC) treatment during sepsis improves hepatic function and enhances tissue oxygenation. The objective of this case report is to investigate the synergistic effect of the combination of vitamin C, thiamine, and NAC in delaying sepsis cascade and prolongation of survival time. In this case report, an oral dose of vitamin C 500 mg three times daily in combination with IV thiamine 100 mg three times daily, IV NAC, and hydrocortisone stress dose resulted in 12 days of survival of an immunocompromised patient with ventilator-associated pneumonia on single anti-pseudomonas beta-lactam antibiotic. The patient was a 60-year-old Malay female with previous bone marrow transplantation surgery and a medical history of ischemic stroke on phenytoin and valproate therapy. The patient was transferred to a medical ward in Penang General Hospital, Malaysia, due to community-acquired pneumonia. She was on ceftriaxone for five days, then sedated and ventilated in the ICU, with a shift to cefepime for three days, which was then changed to meropenem for nine days until the last day of life. Total anti-pseudomonas coverage was 12 days. The patient had multiple comorbidities from phenytoin-induced hepatic encephalopathy, acute kidney injury, and three sessions of hemodialysis. IV vitamin C was not available, so an oral dose was administered with potential efficacy in delaying the sepsis inflammatory cascade, leading to the use of a single (not double) anti-pseudomonas antibiotic for 12 days. Prolonged survival duration may be expected in the case of normal bone marrow patients with ventilator-associated pneumonia sepsis. In conclusion, Vitamin C, thiamine, and NAC combination resulted in delayed sepsis progression for 12 days and the survival of the immunocompromised patient on a single anti-pseudomonas beta-lactam antibiotic.
PubMed: 38169912
DOI: 10.7759/cureus.49868 -
Molecules (Basel, Switzerland) Nov 2023The objective of the present report was to develop and validate a simple, selective, and reproducible high-performance liquid chromatography method with UV detection...
The objective of the present report was to develop and validate a simple, selective, and reproducible high-performance liquid chromatography method with UV detection suitable for routine therapeutic drug monitoring of the most commonly used antiepileptic drugs and some of their metabolites. Simple precipitation of plasma proteins with acetonitrile was used for sample preparation. 10,11-dihydrocarbamazepine was used as an internal standard. Chromatographic separation of the analytes was achieved by gradient elution on a Phenyl-Hexyl column at 40 °C, using methanol and potassium phosphate buffer (25 mM; pH 5.1) as a mobile phase. The method was validated according to the FDA guidelines for bioanalytical method validation. It showed to be selective, accurate, precise, and linear over the concentration ranges of 1-50 mg/L for phenobarbital, phenytoin, levetiracetam, rufinamide, zonisamide, and lacosamide; 0.5-50 mg/L for lamotrigine, primidone, carbamazepine and 10-monohydroxycarbazepine; 0.2-10 mg/L for carbamazepine metabolites: 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine and carbamazepine-10,11-epoxide; 0.1-10 mg/L for oxcarbazepine; 2-100 mg/L for felbamate and 3-150 mg/L for ethosuximide. The suitability of the validated method for routine therapeutic drug monitoring was confirmed by quantification of the analytes in plasma samples from patients with epilepsy on combination antiepileptic therapy.
Topics: Humans; Anticonvulsants; Chromatography, High Pressure Liquid; Drug Monitoring; Carbamazepine; Oxcarbazepine
PubMed: 38067559
DOI: 10.3390/molecules28237830 -
Pharmaceuticals (Basel, Switzerland) Jun 2024The discovery of new peptides and their derivatives is an outcome of ongoing efforts to identify a peptide with significant biological activity for effective usage as a...
The discovery of new peptides and their derivatives is an outcome of ongoing efforts to identify a peptide with significant biological activity for effective usage as a possible therapeutic agent. Spinorphin peptides have been documented to exhibit numerous applications and features. In this study, biologically active peptide derivatives based on novel peptide analogues of spinorphin conjugated with 5,5'-dimethyl (Dm) and 5,5'-diphenyl (Ph) hydantoin derivatives have been successfully synthesized and characterized. Scanning electron microscopy (SEM) and spectral methods such as UV-Vis, FT-IR (Fourier Transform Infrared Spectroscopy), CD (Circular Dichroism), and fluorimetry were used to characterize the microstructure of the resulting compounds. The results revealed changes in peptide morphology as a result of the restructuring of the aminoacidic sequences and aromatic bonds, which is related to the formation of intermolecular hydrogen bonds between tyrosyl groups and the hydantoin moiety. Electrochemical and fluorescence approaches were used to determine some physicochemical parameters related to the biological behavior of the compounds. The biological properties of the spinorphin derivatives were evaluated in vivo for anticonvulsant activity against the psychomotor seizures at different doses of the studied peptides. Both spinorphin analog peptides with Ph and Dm groups showed activity against all three phases of the seizure in the intravenous Pentylenetetrazole Seizure (ivPTZ) test. This suggests that hydantoin residues do not play a crucial role in the structure of spinorphin compounds and in determining the potency to raise the seizure threshold. On the other hand, analogs with a phenytoin residue are active against the drug-resistant epilepsy test (6-Hz test). In addition, bioactivity analyses revealed that the new peptide analogues have the potential to be used as antimicrobial and antioxidant compounds. These findings suggest promising avenues for further research that may lead to the development of alternative medicines or applications in various fields beyond epilepsy treatment.
PubMed: 38931437
DOI: 10.3390/ph17060770