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1.
Molecules ; 29(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38893448

RESUMO

Epilepsy is a prevalent neurological disorder characterized by recurrent seizures. Validamycin A (VA) is an antibiotic fungicide that inhibits trehalase activity and is widely used for crop protection in agriculture. In this study, we identified a novel function of VA as a potential anti-seizure medication in a zebrafish epilepsy model. Electroencephalogram (EEG) analysis demonstrated that VA reduced pentylenetetrazol (PTZ)-induced seizures in the brains of larval and adult zebrafish. Moreover, VA reduced PTZ-induced irregular movement in a behavioral assessment of adult zebrafish. The developmental toxicity test showed no observable anatomical alteration when the zebrafish larvae were treated with VA up to 10 µM within the effective range. The median lethal dose of VA in adult zebrafish was > 14,000 mg/kg. These results imply that VA does not demonstrate observable toxicity in zebrafish at concentrations effective for generating anti-seizure activity in the EEG and alleviating abnormal behavior in the PTZ-induced epileptic model. Furthermore, the effectiveness of VA was comparable to that of valproic acid. These results indicate that VA may have a potentially safer anti-seizure profile than valproic acid, thus offering promising prospects for its application in agriculture and medicine.


Assuntos
Anticonvulsivantes , Modelos Animais de Doenças , Epilepsia , Pentilenotetrazol , Peixe-Zebra , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Pentilenotetrazol/efeitos adversos , Epilepsia/tratamento farmacológico , Epilepsia/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamente , Eletroencefalografia , Ácido Valproico/farmacologia , Larva/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Inositol/análogos & derivados
2.
Clin Transl Sci ; 17(6): e13867, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38894615

RESUMO

Genetic screening for HLA-B*15:02 before prescribing carbamazepine is standard practice to prevent severe cutaneous adverse reactions in Asian populations. These reactions are associated not only with this allele but also with closely related HLA-B75 serotype markers-HLA-B*15:11 and HLA-B*15:21-which are prevalent in several Asian countries. However, a reliable method for identifying HLA-B75 serotype markers is still not available. We developed an in-house quantitative PCR (qPCR) for HLA-B75 screening and validated it using 303 anonymized DNA samples. Due to inadequate quality control, the qPCR results for 11 samples were excluded. We analyzed the sensitivity and specificity of the test using 93 HLA-typed samples. The concordance between the qPCR method and an established screening method was assessed using 199 HLA-screened samples tested for HLA-B*15:02 at Songklanagarind Hospital, Songkhla, Thailand. All discordant results were confirmed by Sanger sequencing. The qPCR method demonstrated a sensitivity of 100% (95% confidence interval = 83.16%-100.00%) and a specificity of 100% (95% confidence interval = 95.07%-100.00%). Concordance analysis revealed a 96.5% agreement between methods (192/199; 44 positive and 148 negative results). All discordant results were due to HLA-B75 markers not being HLA-B*15:02 (two samples with HLA-B*15:11 and five samples with HLA-B*15:21). In conclusion, this qPCR method could be useful for identifying HLA-B75 carriers at risk of carbamazepine-induced reactions in Asian populations where carriers of HLA-B*15:02, HLA-B*15:11, or HLA-B*15:21 are common.


Assuntos
Carbamazepina , Antígeno HLA-B15 , Humanos , Carbamazepina/efeitos adversos , Antígeno HLA-B15/genética , Antígeno HLA-B15/imunologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Tailândia , Anticonvulsivantes/efeitos adversos , Povo Asiático/genética , Farmacogenética , Sorogrupo , Sensibilidade e Especificidade , Alelos
3.
Actas Esp Psiquiatr ; 52(3): 375-377, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38863053

RESUMO

A case of Kloos syndrome is presented, a rare psychopathological manifestation in psychiatry characterized by the experience of "time paralysis" related to an epileptic focus in the left temporoparietal areas. This syndrome was identified through a detailed psychopathological analysis and detected by an electroencephalographic record. The patient's symptoms disappeared after receiving antiepileptic treatment with Carbamazepine. In this case report we highlight the detailed phenomenological and clinical analysis, as well as the importance of carrying out complementary tests when we are faced with unusual or sudden-onset symptoms without any trigger, as took place in the case exposed.


Assuntos
Eletroencefalografia , Humanos , Síndrome , Masculino , Carbamazepina/uso terapêutico , Adulto , Anticonvulsivantes/uso terapêutico
4.
Neurology ; 103(2): e209500, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38870473

RESUMO

BACKGROUND AND OBJECTIVES: Few studies evaluate physicians' choice of antiseizure medication (ASM) to treat patients with newly diagnosed epilepsy. The objective of this study was to analyze the choice of ASM and its use by age, sex, psychiatric comorbidities, and concurrent treatment with other drugs (antidepressant medications and contraceptives) in patients who initiated epilepsy treatment using monotherapy. METHODS: Included in this study were persons (any age) with an incident hospital diagnosis of epilepsy during 2010-2022 in the Swedish Patient Register (SPR), preceding a first dispensing of any ASM (as reported in the Swedish Prescribed Drug Register, SPDR) for the period 2010-2022. Incident patients were identified using retrospective information during 2000-2009 in the SPR. Primary outcome was first dispensed ASM by age, sex, comorbidity, and comedication with antidepressants or contraceptives (SPDR). Secondary outcomes were time to ASM switch or termination assessed by survival analyses. RESULTS: Of 67,984 patients included (mean age 46; 46% female), 66,441 initiated ASM treatment using monotherapy. Relative risk (RR) for initiating treatment using monotherapy did not differ between age groups, sex, or patients with concurrent treatment with antidepressants, contraceptives, or psychiatric illness (RR and 95% CI did include 1.0). The share initiating treatment using levetiracetam increased from 10% in 2010 to 55% in 2022; valproic acid: 10%-5%. The likelihood of initiating treatment using 1 of the 5 most frequent ASMs differed between all compared groups (0.3 < RR < 1; 95% CI < 1; 1 < RR < 15; 1 <95% CI). Seven percent of female patients of childbearing age initiated treatment with valproic acid, levetiracetam was the most frequent initial ASM in patients with psychiatric comorbidity (40.2%), and lamotrigine the most prescribed initial ASM to women on contraceptives (50.4%). Highest likelihoods of treatment termination were found among children (1.72 < RR < 3.07; 1 <95% CI) and among patients with psychiatric comorbidity (initiated on carbamazepine, RR 1.38; 1 <95% CI or lamotrigine, RR 1.31; 1 <95% CI). Thirty-one percent to 47% of patients switched from an initial monotherapy to a new monotherapy within 5 years. Twenty percent to 42% terminated ASM treatment within 5 years. DISCUSSION: Levetiracetam and lamotrigine were the most frequently dispensed initial ASMs, also among patients with comorbidities or comedications complicating the use of these ASMs, highlighting the need for improved education of prescribers concerning ASM selection in relation to individual patient characteristics. Use of ASMs in hospital is not captured in the SPDR.


Assuntos
Anticonvulsivantes , Epilepsia , Humanos , Feminino , Masculino , Anticonvulsivantes/uso terapêutico , Adulto , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Pessoa de Meia-Idade , Suécia/epidemiologia , Adulto Jovem , Adolescente , Estudos Retrospectivos , Idoso , Criança , Sistema de Registros , Pré-Escolar , Antidepressivos/uso terapêutico , Levetiracetam/uso terapêutico , Lactente , Substituição de Medicamentos/tendências , Ácido Valproico/uso terapêutico
7.
Sci Rep ; 14(1): 13001, 2024 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844500

RESUMO

Achieving favorable seizure outcomes is challenging in patients with seizures resulting from hypothalamic hamartoma. Although minimally invasive and non-invasive surgical procedures are used to treat this population, these procedures have limitations. Therefore, we analyzed the outcomes of patients with hypothalamic hamartoma following direct resection. We included 159 patients with hypothalamic hamartoma who underwent direct resection using the transcallosal interforniceal approach between 2011 and 2018. The relationships between clinical parameters and seizure outcomes were analyzed. In total, 55.3% achieved gross total resection and 25.2% underwent near-total resection. Of all patients, 79.2% were overall seizure-free at one year, but this number dropped to 77.0% at more than five years. Moreover, 88.4% (129/146) reached gelastic seizure (GS)-free status at one year and this number increased to 89.0% (97/109) at more than five years. Seventy-one patients took antiseizure medication (ASM) long-term, 68 took it for one year, and 11 took it for one-half year. The duration of ASM consumption (p < 0.001) and extent of hypothalamic hamartoma resection (p = 0.016) were significant independent predictors of long-term overall seizure-free survival, while the duration of ASM consumption (p = 0.011) and extent of hypothalamic hamartoma resection (p = 0.026) were significant independent predictors of long-term GS-free survival. Most patients' behavior, school performance, and intelligence were not affected after surgery. Direct resection is effective and safe strategy for patients with hypothalamic hamartomas. Hypothalamic hamartomas should be removed as completely as possible, and patients should take ASM long-term following surgery to reach long-term overall seizure-free or GS-free status.


Assuntos
Hamartoma , Doenças Hipotalâmicas , Convulsões , Humanos , Hamartoma/cirurgia , Hamartoma/complicações , Doenças Hipotalâmicas/cirurgia , Doenças Hipotalâmicas/complicações , Feminino , Masculino , Convulsões/cirurgia , Criança , Pré-Escolar , Resultado do Tratamento , Adolescente , Lactente , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/efeitos adversos , Estudos Retrospectivos , Adulto , Adulto Jovem , Anticonvulsivantes/uso terapêutico
8.
JAMA Netw Open ; 7(6): e2414709, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38833248

RESUMO

Importance: Concerns exist about teratogenic and long-term neurodevelopmental outcomes of paternal use of valproate during spermatogenesis. Objective: To evaluate the association between paternal use of valproate during spermatogenesis and offspring risk of congenital malformations and neurodevelopmental disorders. Design, Setting, and Participants: This nationwide cohort study included 1 235 353 singletons born in Denmark between January 1, 1997, and December 31, 2017, identified in the Medical Birth Register; 1336 children had fathers who had filled prescriptions for valproate during spermatogenesis. Congenital malformations were identified in the first year of life and neurodevelopmental disorders were identified from 1 year of age until December 31, 2018. Statistical analysis was performed March 2024. Exposures: Paternal valproate exposure was defined as fathers who filled 1 or more prescriptions for valproate immediately before or during the time of spermatogenesis (ie, 3 months prior to conception). Main Outcomes and Measures: Children with major congenital malformations in the first year of life and with neurodevelopmental disorders before death or end of follow-up were identified in Danish health registers. Log-binomial regression was used to estimate adjusted relative risks (ARRs) of congenital malformations, and Cox proportional hazards regression was used to estimate adjusted hazards ratios (AHRs) of neurodevelopmental disorders, adjusted for relevant confounders. Results: Among 1 235 353 live births (634 415 boys [51.4%] and 600 938 girls [48.6%]), 1336 children (0.1%) had fathers who filled prescriptions for valproate during spermatogenesis. The median follow-up was 10.1 years (IQR, 5.1-14.8 years) for valproate-exposed children and 10.3 years (IQR, 5.2-15.6 years) for valproate-unexposed children. A total of 43 903 children (3.6%) received a diagnosis of major congenital malformations in the first year of life, and 51 633 children (4.2%) received a diagnosis of neurodevelopmental disorders during follow-up. When comparing the risk among valproate-exposed children with that among unexposed children, the ARR of major congenital malformations was 0.89 (95% CI, 0.67-1.18), the AHR of neurodevelopmental disorders was 1.10 (95% CI, 0.88-1.37), and the AHR of autism spectrum disorder was 0.92 (95% CI, 0.65-1.30). In analyses addressing the robustness of the findings (ie, dose-response analyses, sibling analyses, analyses restricted to children of fathers with epilepsy, analyses that used children with paternal lamotrigine exposure as active comparator, and analyses that used children with paternal exposure to valproate only before spermatogenesis as a negative control exposure), there still was no increased risk of any of the included end points. Conclusions and Relevance: In all analyses based on this large Danish cohort study, results suggest that exposure to valproate during spermatogenesis was not associated with offspring risk of congenital malformations or neurodevelopmental disorders, including autism spectrum disorder.


Assuntos
Transtornos do Neurodesenvolvimento , Espermatogênese , Ácido Valproico , Humanos , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêutico , Masculino , Dinamarca/epidemiologia , Espermatogênese/efeitos dos fármacos , Feminino , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/induzido quimicamente , Lactente , Adulto , Estudos de Coortes , Pré-Escolar , Criança , Exposição Paterna/efeitos adversos , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Sistema de Registros , Recém-Nascido , Anormalidades Induzidas por Medicamentos/epidemiologia , Fatores de Risco , Anormalidades Congênitas/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
9.
Top Curr Chem (Cham) ; 382(2): 20, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829467

RESUMO

Cannabis sativa has long been used for neurological and psychological healing. Recently, cannabidiol (CBD) extracted from cannabis sativa has gained prominence in the medical field due to its non-psychotropic therapeutic effects on the central and peripheral nervous systems. CBD, also acting as a potent antioxidant, displays diverse clinical properties such as anticancer, antiinflammatory, antidepressant, antioxidant, antiemetic, anxiolytic, antiepileptic, and antipsychotic effects. In this review, we summarized the structural activity relationship of CBD with different receptors by both experimental and computational techniques and investigated the mechanism of interaction between related receptors and CBD. The discovery of structural activity relationship between CBD and target receptors would provide a direction to optimize the scaffold of CBD and its derivatives, which would give potential medical applications on CBD-based therapies in various illnesses.


Assuntos
Canabidiol , Canabidiol/química , Canabidiol/farmacologia , Canabidiol/metabolismo , Humanos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Cannabis/química , Relação Estrutura-Atividade , Receptores de Canabinoides/metabolismo , Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antidepressivos/química , Antidepressivos/farmacologia
10.
Continuum (Minneap Minn) ; 30(3): 682-720, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38830068

RESUMO

OBJECTIVE: Status epilepticus is a neurologic emergency that can be life- threatening. The key to effective management is recognition and prompt initiation of treatment. Management of status epilepticus requires a patient-specific-approach framework, consisting of four axes: (1) semiology, (2) etiology, (3) EEG correlate, and (4) age. This article provides a comprehensive overview of status epilepticus, highlighting the current treatment approaches and strategies for management and control. LATEST DEVELOPMENTS: Administering appropriate doses of antiseizure medication in a timely manner is vital for halting seizure activity. Benzodiazepines are the first-line treatment, as demonstrated by three randomized controlled trials in the hospital and prehospital settings. Benzodiazepines can be administered through IV, intramuscular, rectal, or intranasal routes. If seizures persist, second-line treatments such as phenytoin and fosphenytoin, valproate, or levetiracetam are warranted. The recently published Established Status Epilepticus Treatment Trial found that all three of these drugs are similarly effective in achieving seizure cessation in approximately half of patients. For cases of refractory and super-refractory status epilepticus, IV anesthetics, including ketamine and γ-aminobutyric acid-mediated (GABA-ergic) medications, are necessary. There is an increasing body of evidence supporting the use of ketamine, not only in the early phases of stage 3 status epilepticus but also as a second-line treatment option. ESSENTIAL POINTS: As with other neurologic emergencies, "time is brain" when treating status epilepticus. Antiseizure medication should be initiated quickly to achieve seizure cessation. There is a need to explore newer generations of antiseizure medications and nonpharmacologic modalities to treat status epilepticus.


Assuntos
Anticonvulsivantes , Estado Epiléptico , Humanos , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/terapia , Estado Epiléptico/diagnóstico , Estado Epiléptico/fisiopatologia , Anticonvulsivantes/administração & dosagem , Masculino , Feminino , Gerenciamento Clínico , Eletroencefalografia
11.
Int J Mol Sci ; 25(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38891938

RESUMO

Neurological disorders present a wide range of symptoms and challenges in diagnosis and treatment. Cannabis sativa, with its diverse chemical composition, offers potential therapeutic benefits due to its anticonvulsive, analgesic, anti-inflammatory, and neuroprotective properties. Beyond cannabinoids, cannabis contains terpenes and polyphenols, which synergistically enhance its pharmacological effects. Various administration routes, including vaporization, oral ingestion, sublingual, and rectal, provide flexibility in treatment delivery. This review shows the therapeutic efficacy of cannabis in managing neurological disorders such as epilepsy, neurodegenerative diseases, neurodevelopmental disorders, psychiatric disorders, and painful pathologies. Drawing from surveys, patient studies, and clinical trials, it highlights the potential of cannabis in alleviating symptoms, slowing disease progression, and improving overall quality of life for patients. Understanding the diverse therapeutic mechanisms of cannabis can open up possibilities for using this plant for individual patient needs.


Assuntos
Cannabis , Epilepsia , Doenças Neurodegenerativas , Humanos , Cannabis/química , Doenças Neurodegenerativas/tratamento farmacológico , Epilepsia/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Animais , Dor/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Canabinoides/uso terapêutico , Canabinoides/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Analgésicos/uso terapêutico , Analgésicos/química , Analgésicos/farmacologia
12.
Int J Mol Sci ; 25(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38892264

RESUMO

Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy.


Assuntos
Anticonvulsivantes , Descoberta de Drogas , Epilepsia , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Humanos , Animais , Descoberta de Drogas/métodos , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Inflamassomos/metabolismo , Inflamassomos/antagonistas & inibidores , Desenvolvimento de Medicamentos
13.
BMJ Open ; 14(6): e080126, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844392

RESUMO

OBJECTIVES: We aimed to develop a new data-driven method to predict the therapeutic indication of redeemed prescriptions in secondary data sources using antiepileptic drugs among individuals aged ≥65 identified in Danish registries. DESIGN: This was an incident new-user register-based cohort study using Danish registers. SETTING: The study setting was Denmark and the study period was 2005-2017. PARTICIPANTS: Participants included antiepileptic drug users in Denmark aged ≥65 with a confirmed diagnosis of epilepsy. PRIMARY AND SECONDARY OUTCOME MEASURES: Sensitivity served as the performance measure of the algorithm. RESULTS: The study population comprised 8609 incident new users of antiepileptic drugs. The sensitivity of the algorithm in correctly predicting the therapeutic indication of antiepileptic drugs in the study population was 65.3% (95% CI 64.4 to 66.2). CONCLUSIONS: The algorithm demonstrated promising properties in terms of overall sensitivity for predicting the therapeutic indication of redeemed antiepileptic drugs by older individuals with epilepsy, correctly identifying the therapeutic indication for 6 out of 10 individuals using antiepileptic drugs for epilepsy.


Assuntos
Algoritmos , Anticonvulsivantes , Epilepsia , Sistema de Registros , Humanos , Anticonvulsivantes/uso terapêutico , Dinamarca , Idoso , Feminino , Epilepsia/tratamento farmacológico , Masculino , Idoso de 80 Anos ou mais , Prescrições de Medicamentos/estatística & dados numéricos , Estudos de Coortes , Fonte de Informação
14.
Curr Neuropharmacol ; 22(13): e240524230306, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38847378

RESUMO

Epilepsy is a neurological disease with no defined cause, characterized by recurrent epileptic seizures. These occur due to the dysregulation of excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Psychopharmaceuticals have undesirable side effects; many patients require more than one pharmacotherapy to control crises. With this in mind, this work emphasizes the discovery of new substances from natural products that can combat epileptic seizures. Using in silico techniques, this review aims to evaluate the antiepileptic and multi-target activity of phenylpropanoid derivatives. Initially, ligand-based virtual screening models (LBVS) were performed with 468 phenylpropanoid compounds to predict biological activities. The LBVS were developed for the targets alpha- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), voltage-gated calcium channel Ttype (CaV), gamma-aminobutyric acid A (GABAA), gamma-aminobutyric acid transporter type 1 (GAT-1), voltage-gated potassium channel of the Q family (KCNQ), voltage-gated sodium channel (NaV), and N-methyl D-aspartate (NMDA). The compounds that had good results in the LBVS were analyzed for the absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and later, the best molecules were evaluated in the molecular docking consensus. The TR430 compound showed the best results in pharmacokinetic parameters; its oral absorption was 99.03%, it did not violate any Lipinski rule, it showed good bioavailability, and no cytotoxicity was observed either from the molecule or from the metabolites in the evaluated parameters. TR430 was able to bind with GABAA (activation) and AMPA (inhibition) targets and demonstrated good binding energy and significant interactions with both targets. The studied compound showed to be a promising molecule with a possible multi-target activity in both fundamental pharmacological targets for the treatment of epilepsy.


Assuntos
Anticonvulsivantes , Epilepsia , Humanos , Epilepsia/tratamento farmacológico , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/química , Simulação de Acoplamento Molecular
15.
Iran J Allergy Asthma Immunol ; 23(2): 139-148, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38822509

RESUMO

BACKGROUND: There are limited data on severe cutaneous adverse reactions (SCARs) associated with antiepileptic medications. The current study aims to investigate the clinical and epidemiological characteristics of antiepileptic medication-induced SCARs in hospitalized children. MATERIALS AND METHODS: The current five-year retrospective study was conducted at Isfahan University of Medical Sciences, Iran. This study included all children with a definite diagnosis of SCARs secondary to the use of antiepileptic medications based on the world health organization (WHO) definition. In our study SCARs were categorized into three fields: Hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). RESULTS: Among 259 children with SCARs induced by antiepileptic medications, 199 (76.83%), 42 (16.22%), and 18 (6.95%) had hypersensitivity syndrome, DRESS, and SJS/TEN, respectively. Phenobarbital was the most common offending drug in all types of SCARs. The multinomial logistic regression model revealed that lymphadenopathy increased the occurrence of DRESS by 35 times compared to hypersensitivity syndrome (P < 0.001). Girls were at risk of SJS/TEN approximately 6 times more than boys (P = 0.027). Age (P = 0.021), weight (P = 0.036), and mucosal involvement (P < 0.001) affected the hospitalization duration in children with SCARs related to antiepileptic medication. CONCLUSION: There are some similarities and differences in the clinical and epidemiological features of Iranian children suffering from antiepileptic medication-induced SCARs.


Assuntos
Anticonvulsivantes , Síndrome de Stevens-Johnson , Humanos , Anticonvulsivantes/efeitos adversos , Feminino , Masculino , Criança , Estudos Retrospectivos , Pré-Escolar , Irã (Geográfico)/epidemiologia , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia , Síndrome de Hipersensibilidade a Medicamentos/epidemiologia , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Adolescente , Lactente , Criança Hospitalizada , Hospitalização/estatística & dados numéricos , Fatores de Risco
16.
Mikrochim Acta ; 191(7): 400, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879615

RESUMO

Ultrathin molecularly imprinted polymer (MIP) films were deposited on the surfaces of ZnO nanorods (ZNRs) and nanosheets (ZNSs) by electropolymerization to afford extended-gate field-effect transistor sensors for detecting phenytoin (PHT) in plasma. Molecular imprinting efficiency was optimized by controlling the contents of functional monomers and the template in the precursor solution. PHT sensing was performed in plasma solutions with various concentrations by monitoring the drain current as a function of drain voltage under an applied gate voltage of 1.5 V. The reliability and reproducibility of the fabricated sensors were evaluated through a solution treatment process for complete PHT removal and PHT adsorption-removal cycling, while selectivity was examined by analyzing responses to chemicals with structures analogous to that of PHT. Compared with the ZNS/extracted-MIP sensor and sensors with non-imprinted polymer (NIP) films, the ZNR/extracted-MIP sensor showed superior responses to PHT-containing plasma due to selective PHT adsorption, achieving an imprinting factor of 4.23, detection limit of 12.9 ng/mL, quantitation limit of 53.0 ng/mL, and selectivity coefficients of 3-4 (against tramadol) and ~ 5 (against diphenhydramine). Therefore, we believe that the MIP-based ZNR sensing platform is promising for the practical detection of PHT and other drugs and evaluation of their proper dosages.


Assuntos
Anticonvulsivantes , Limite de Detecção , Polímeros Molecularmente Impressos , Fenitoína , Transistores Eletrônicos , Óxido de Zinco , Anticonvulsivantes/sangue , Anticonvulsivantes/análise , Polímeros Molecularmente Impressos/química , Óxido de Zinco/química , Fenitoína/sangue , Fenitoína/análise , Fenitoína/química , Humanos , Impressão Molecular , Nanotubos/química , Adsorção , Reprodutibilidade dos Testes , Polímeros/química
17.
Int J Biol Macromol ; 272(Pt 1): 132739, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38825290

RESUMO

A stable Madhuca indica oil-in-water nanoemulsion (99-210 nm, zeta potential: > - 30 mV) was produced employing Tween 20 (surfactant) and Transcutol P (co-surfactant) (3:1). The nanoemulsion (oil: Smix = 3:7, 5:5, and 7:3) were subsequently incorporated into oxcarbazepine-loaded carboxymethylxanthan gum (DS = 1.23) dispersion. The hydrogel microspheres were formed using the ionic gelation process. Higher oil concentration had a considerable impact on particle size, drug entrapment efficiency, and buoyancy. The maximum 92 % drug entrapment efficiency was achieved with the microspheres having oil: Smix ratio 5:5. FESEM study revealed that the microspheres were spherical in shape and had an orange peel-like surface roughness. FTIR analysis revealed a hydrogen bonding interaction between drug and polymer. Thermal and x-ray examinations revealed the transformation of crystalline oxcarbazepine into an amorphous form. The microspheres had a buoyancy period of 7.5 h with corresponding release of around 83 % drug in 8 h in simulated stomach fluid, governed by supercase-II transport mechanism. In vivo neurobehavioral studies on PTZ-induced rats demonstrated that the microspheres outperformed drug suspension in terms of rotarod retention, number of crossings, and rearing activity in open field. Thus, Madhuca indica oil-in-water nanoemulsion-entrapped carboxymethyl xanthan gum microspheres appeared to be useful for monitoring oxcarbazepine release and managing epileptic seizures.


Assuntos
Mananas , Microesferas , Animais , Ratos , Mananas/química , Hidrogéis/química , Tamanho da Partícula , Epilepsia/tratamento farmacológico , Masculino , Portadores de Fármacos/química , Emulsões , Convulsões/tratamento farmacológico , Liberação Controlada de Fármacos , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Galactose/análogos & derivados
18.
J Clin Psychiatry ; 85(2)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836866

RESUMO

The age-standardized global prevalence of epilepsy is about 0.3% in women. Seizures are associated with morbidity and mortality risks; so, women with epilepsy (WWE) are usually advised antiepileptic drug (AED) treatment even during pregnancy. Women may also knowingly or unknowingly be exposed during pregnancy to AEDs advised for other on- or off-label indications. In this context, a meta-analysis of 35 adverse gestational outcomes examined in 76 observational studies found that WWE were at increased risk of most of the adverse outcomes, regardless of gestational exposure to AEDs. AEDs, especially in polytherapy, further increased at least a few of the gestational risks, including risks of congenital conditions, neonatal intensive care unit admission, small for gestational age, low birth weight, and neonatal/infant death (it is unclear whether the lack of statistical significance for the remaining risks was because AED exposure was truly limited to these risks or whether the nonsignificant analyses were underpowered). Reassuringly, the increases in risk were mostly in the small to modest range. This meta-analysis pooled unadjusted risks (which would probably be larger than adjusted risks), so readers are informed about expected findings in the population but not about cause-effect relationships that may be cautiously hypothesized from adjusted analyses. A take-home message is that, because of the wide range of outcomes for which risk is increased, WWE should be closely monitored and followed all through pregnancy, regardless of treatment with AEDs. This article also provides readers with suggestions on how to critically interpret literature with regard to 8 matters: confounding by indication and confounding by severity of indication, as specific to the indication for AED prescription; unadjusted and adjusted analyses; the base rate of an outcome in the population; the examination of multiple outcomes; the uniform direction of findings; the sample numbers; the timing of AED exposure; and self-fulfilling prophecies.


Assuntos
Anticonvulsivantes , Epilepsia , Complicações na Gravidez , Resultado da Gravidez , Feminino , Humanos , Recém-Nascido , Gravidez , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
19.
PLoS One ; 19(6): e0304869, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38837984

RESUMO

OBJECTIVE: Epilepsy patients exhibit considerable differences in their response to sodium valproate (VPA) therapy, a phenomenon that might be attributed to individual genetic variances. The role of genetic variations, specifically in sodium channels encoded by SCN1A and SCN2A genes, in influencing the effectiveness of VPA in treating epilepsy is still debated. This research focuses on examining the impact of these genetic polymorphisms on the efficacy of VPA therapy among pediatric epilepsy patients in China. METHODS: Five single nucleotide polymorphisms (SNPs), including SCN1A (rs10188577, rs2298771, rs3812718) and SCN2A (rs2304016, rs17183814), were genotyped in 233 epilepsy patients undergoing VPA therapy. The associations between genotypes and the antiepileptic effects of VPA were assessed, with 128 patients categorized as VPA responders and 105 as VPA non-responders. RESULTS: In the context of VPA monotherapy, SCN1A rs2298771 and SCN2A rs17183814 were found to be significantly associated with VPA response (P< 0.05). CONCLUSION: Our study suggests the findings of this investigation indicate that the polymorphisms SCN1A rs2298771 and SCN2A rs17183814 could potentially act as predictive biomarkers for the responsiveness to VPA among Chinese epilepsy patients.


Assuntos
Anticonvulsivantes , Epilepsia , Canal de Sódio Disparado por Voltagem NAV1.1 , Canal de Sódio Disparado por Voltagem NAV1.2 , Polimorfismo de Nucleotídeo Único , Ácido Valproico , Humanos , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Ácido Valproico/uso terapêutico , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Criança , Masculino , Feminino , Epilepsia/tratamento farmacológico , Epilepsia/genética , Anticonvulsivantes/uso terapêutico , Pré-Escolar , China , Povo Asiático/genética , Adolescente , Resultado do Tratamento , Genótipo , Lactente , População do Leste Asiático
20.
Neurologia (Engl Ed) ; 39(5): 426-431, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38830721

RESUMO

INTRODUCTION: Status epilepticus is an important cause of pediatric neurological emergency. Immediate treatment is essential to prevent definitive neurological damage. Several antiepileptic drugs are available for the management of status epilepticus. METHODS: Retrospective study of patients admitted at the emergency department of a tertiary hospital for 5 years (2014-2019). We analyzed the compliance to the treatment guidelines for pediatric status epilepticus. RESULTS: One hundred and seventeen admissions were identified, 23.9% of these were febrile status epilepticus. Among the other cases, the most frequent cause was genetic (22.2%). The majority were convulsive status epilepticus (93.1%), 58.7% of which were generalized tonic-clonic seizures. Benzodiazepines were the most used first and second line drug (98.2% and 94.8%). The most frequent third drug used was diazepam (56.4%) followed by phenytoin (18.2%). An infra-therapeutic antiepileptic drug dose was given in 48.7% of cases. 49.6% presented with a prolonged status epilepticus and 6.8% needed intensive care. Incorrect sequence of drugs and infra-therapeutic doses were associated with prolonged status (p<0.001 and p<0.05) and an increased number of antiepileptic drugs used (p<0.001 and p<0.05). CONCLUSIONS: Benzodiazepines were the most frequently first and second line drugs used for status epilepticus management. Surprisingly, the most frequently third line drugs used were also benzodiazepines. These findings were partially explained by the misuse of infra-therapeutic doses of these drugs. Noncompliance with the implemented guidelines was associated with unfavorable outcomes.


Assuntos
Anticonvulsivantes , Serviço Hospitalar de Emergência , Estado Epiléptico , Humanos , Estado Epiléptico/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Estudos Retrospectivos , Feminino , Masculino , Criança , Pré-Escolar , Lactente , Benzodiazepinas/uso terapêutico , Fidelidade a Diretrizes , Adolescente , Diazepam/uso terapêutico
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