UNASSIGNED: Malignant hypertension is the most severe form of hypertension that may cause life-threatening manifestations. Carbamazepine is an antiepileptic drug primarily used for seizure disorders and trigeminal neuralgia. One of the rarely triggered adverse side effects of carbamazepine is drug-induced malignant hypertension. Here, we intend to present the first case report of carbamazepine-induced malignant hypertension from Nepal.
UNASSIGNED: Here, we aim to present a case report of a 26-year-old female with a history of generalized tonic-clonic seizure who had developed de-novo hypertension after initiation of carbamazepine with no decrease in blood pressure to normal levels despite several antihypertensive administrations which eventually resolved on the discontinuation of drug carbamazepine. The patient was subsequently managed at our institution, where levetiracetam was used as an alternative. The patient was in close follow-up monitoring blood pressure charting.
UNASSIGNED: Although rare, a variety of cardiovascular side effects, including hypertension led by the drug carbamazepine, have been reported. Carbamazepine acts by inducing cytochrome P450, which facilitates an early metabolism and clearance of several antihypertensive medications, causing a decrease in their role in hypertension. The exact etiology is still debatable. However, the removal of the drug carbamazepine may result in a remission of hypertension, as illustrated in several literatures.
UNASSIGNED: Malignant hypertension is caused in rare cases to the use of the drug carbamazepine. The hypertension can undergo remission by subsequent discontinuation of the carbamazepine therapy. Regular blood pressure monitoring and charting are crucial in such cases.

UNASSIGNED: Peripheral neurectomy(PN)is a minimally invasive procedure, for the management of trigeminal neuralgi (TN)consisting of surgical avulsion of terminal branches of the trigeminal nerve.
UNASSIGNED: To assess the efficacy of PN in the treatment of refractory TN and their recurrences in a follow up of 18 months.
UNASSIGNED: Retro-prospective and prospective study was conducted on randomly selected 30 TN patients irrespective of age, gender and socio-economic status. The branch of trigeminal nerve involved was identified according to the site of pain. Then the PN procedure was performed under local or general aesthesia. The follow up of each patient was done for next 18 months.
UNASSIGNED: Mean age of the TN patients 53.17 ± 13.84 years, with 66.7% of patients were within 60 years of age. Male to female ratio was 1:1.5. All patients showed unilateral TN. Mostly 26.7% trigger point was located in lower lip followed by 13.3% in upper lip. After 3,6 and 9 months follow-up, none of the TN patients treated with PN had pain and none had any effect on general activity. However, from 12 months till 18 months\' follow up, 2 (6.7%) patients reported of pain.
UNASSIGNED: PNs are viable treatment alternative for TN, although peripheral neurectomy has chances of reoccurrence but still offer better quality of life in patients for many years without relaps.

Iron(II)-based metal organic framework (Fe(II)-MOF) nanosheets have emerged as promising candidates for photo-Fenton catalysis. However, efficiently synthesizing Fe(II)-MOF nanosheets remains a significant challenge. Here, a bottom-up synthesis strategy is proposed to prepare two-dimensional Fe-MOF nanosheets (TFMN) with micrometer lateral dimensions and nanometer thickness, featuring Fe(II) as the metal nodes. The application of TFMN in the photo-Fenton degradation of carbamazepine (CBZ) demonstrates remarkable CBZ degradation performance and excellent efficiency across a wide range of pH values. The electron density and density of states are further calculated by density functional theory. Mechanism analysis identifies h+, •OH and •O2- as the predominant active species contributing to the catalytic oxidation process in the Vis/TFMN/H2O2 system.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening skin lesion triggered by hypersensitive drug reaction. They are characterized by extensive epidermal necrosis and skin exfoliation. Fulminant type 1 diabetes mellitus (FT1DM) is featured by a rapid-onset of hyperglycemia with ketoacidosis due to severely destroyed β-cell function. Fulminant type 1 diabetes mellitus as a sequela of SJS/TEN has rarely been reported.
METHODS: We present a 73-year-old female patient who developed SJS/TEN skin allergic reaction after taking carbamazepine and phenytoin for 35 days. Then, hyperglycemia and diabetic ketoacidosis occurred 20 days after discontinuation of antiepileptic drugs. A very low serum C-peptide level (8.79 pmol/l) and a near-normal glycosylated hemoglobin level met the diagnostic criteria for fulminant T1DM. Intravenous immunoglobulin (IVIG) and insulin were promptly administered, and the patient recovered finally.
CONCLUSIONS: This rare case indicates that monitoring blood glucose is necessary in SJS/TEN drug reaction, and comprehensive therapy with rehydration, insulin, antibiotics, and IVIG may improve the prognosis.

BACKGROUND: Lamotrigine (LTG) is an antiepileptic drug that has been used in pediatric epilepsy as a combination therapy or monotherapy after stabilization in recent years. However, there are significant drug-drug interactions (DDI) between LTG and combined drugs such as carbamazepine (CBZ) and valproic acid (VPA). It is particularly important to consider the risk of DDI in combination therapy for intractable epilepsy in pediatric patients. Therefore, it is necessary to adjust the dosage of LTG accordingly. The aim of this study was to establish and validate a pediatric physiologically based pharmacokinetic (PBPK) model for predicting LTG exposure. The model is designed to explore the potential for quantifying pharmacokinetic (PK) DDI of LTG when administered concurrently with CBZ or VPA in pediatric patients.
METHODS: Adult and pediatric PBPK models for LTG and VPA were developed using PK-Sim® software in combination with physiological information and drug-specific parameters, and a DDI model was developed in combination with the published CBZ model. The models were validated against available PK data.
RESULTS: Predictive and observational results in adults, children, and the DDI model were in good agreement. The recommended doses of LTG for preschool children (2-6 years) and school-aged children (6-12 years) in the absence of drug interactions were 1.47 and 1.2 times higher than those for adults, respectively; 3.1 and 2.6 times higher than those for adults in combination with CBZ; and 0.67 and 0.57 times lower than those for adults in combination with VPA. In addition, plasma exposures in adolescents (12-18 years) were similar to those in adults at the same doses.
CONCLUSIONS: We have successfully developed PBPK models and DDI models for LTG in adults and children, which provide a reference for rational drug use in the pediatric population.

Background and Objectives: Oxidative stress resulting from a disturbance of the endogenous redox system is suspected in numerous diseases of the central nervous system, including epilepsy. In addition, antiseizure medications (ASMs), especially those of the old generation, may further increase oxidative stress. To evaluate the effects of ASM generation on oxidative stress, we conducted a cross-sectional study in patients with epilepsy treated with old, new, and polytherapy. Materials and Methods: The antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, as well as the concentrations of malondialdehyde, protein carbonyl, nitrate, nitrite, and glutathione in reduced and oxidized forms, were measured in 49 patients with epilepsy and 14 healthy controls. In addition, the plasma concentrations of ASMs and metabolites of carbamazepine and valproic acid were measured in the patients. Results: Patients with epilepsy showed increased activities of superoxide dismutase and catalase (p < 0.001), concentrations of glutathione disulfide and markers of nitric oxide metabolism (p < 0.001), and decreased activities of glutathione peroxidase, glutathione reductase, glutathione, and nitrite concentrations (p ≤ 0.005) compared to healthy controls. A comparison of ASM generations revealed increased levels of superoxide dismutase and catalase (p ≤ 0.007) and decreased levels of glutathione peroxidase and glutathione reductase (p ≤ 0.01) in patients treated with old ASMs compared to those treated with new generation ASMs. In addition, an increase in protein carbonyl and nitric oxide metabolites (p ≤ 0.002) was observed in patients treated with old generation ASMs compared to those treated with new generation ASMs. Most oxidative stress parameters in patients receiving polytherapy with ASMs were intermediate between the results of patients treated with the old and new generations of ASMs. Conclusions: An increase in oxidative stress markers and modulation of antioxidant enzyme activities was observed in patients with epilepsy compared to controls. The results of our study showed significantly higher oxidative stress in patients treated with old ASMs compared to those treated with new generation ASMs.

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Zebrafish embryo-based assays are a promising alternative for animal testing to screen new compounds for developmental toxicity. However, recent studies in zebrafish embryos showed an immature intrinsic cytochrome P450 (CYP)-mediated biotransformation capacity, as most CYPs were only active at the end of the organogenesis period. Data on other phase I enzymes involved in the biotransformation of xenobiotics in zebrafish embryos is limited. This information is pivotal for proteratogens needing bioactivation to exert their teratogenic potential. Therefore, this study aimed to investigate whether carbamazepine (CBZ) and levetiracetam (LTC), two anti-epileptic drugs that require bioactivation to exert their teratogenic potential, are biotransformed into non-CYP mediated metabolites in the zebrafish embryo and whether one or more of these metabolites cause developmental toxicity in this species. In the first step, zebrafish embryos were exposed to LTC and CBZ and their non-CYP mediated human metabolites, etiracetam carboxylic acid (ECA) and 9-acridine carboxaldehyde (9ACA), acridine (AI), and acridone (AO), respectively, from 5.25 to 120 hpf and morphologically evaluated. Next, the uptake of all compounds and the formation of the metabolites were assessed using LC-MS methods. As LTC and ECA were, respectively, poorly or not taken up by zebrafish larvae during the exposure experiments, we could not determine if LTC and ECA are teratogenic. However, biotransformation of LTC into ECA was observed at 24 hpf and 120 hpf, which indicates that the special type of B-esterase is already active at 24 hpf. CBZ and its three metabolites were teratogenic, as a significant increase in malformed embryos was observed for all of them. All three metabolites were more potent teratogens than CBZ, with AI being the most potent, followed by 9ACA and AO. The myeloperoxidase (MPO) homologue is already active at 24 hpf, as CBZ was biotransformed into 9ACA and AO in 24 hpf zebrafish embryos, and into 9ACA in 120 hpf larvae. Moreover, 9ACA was also found to be biotransformed into AI and AO, and AI into AO. As such, one or more of these metabolites probably contribute to the teratogenic effects observed in zebrafish larvae after exposure to CBZ.

Introduction: Pharmacotherapy with antiseizure medications (ASMs) has been a cornerstone for achieving long-term remissions in persons with epilepsy (PWEs). This study aims to determine the prescription patterns and treatment gaps (TGs) among PWEs. Methods: Accordingly, a descriptive cross-sectional study was conducted with 940 PWEs aged ≥18 years having clinically confirmed diagnosis of epilepsy based on the International League Against Epilepsy (ILAE) criteria. At a scheduled interview with each participant, a previously established questionnaire was used to obtain clinical information relating to epilepsy in terms of the age of onset, etiology, duration of epilepsy, frequency, types, and number of ASMs used. Results: There were fewer male participants [445 (47.4%) vs. 495 (53.6%)] than females, with a higher mean age of onset [(35.19 ± 21.10 vs. 31.58 ± 20.82 years; p = 0.009]. The medication characteristics showed that 336 (35.7%) of the 940 PWEs recruited were not on any ASMs, whereas the remaining 604 (64.3%) patients were on ASMs, with 504 (83.4%) on monotherapy vs. 100 (16.6%) on polytherapy. The PWEs on ASM monotherapy had a higher mean age [40.92 ± 19.40 vs. 33.61 ± 16.51 years; p < 0.001] and higher mean age of onset [34.47 ± 21.80 vs. 25.39 ± 19.78 years; p < 0.001] than those on polytherapy. Furthermore, there were more persons on ASM monotherapy among the participants with seizure duration < 2 years [251 (87.5%) vs. 36 (12.5%)] and seizure duration > 2 years [253 (79.8%) vs 64 (20.2%)]. Conclusion: The majority of the participants receiving ASMs were on monotherapy, with carbamazepine being the most frequently prescribed medication. Furthermore, about a third of the participants had TGs; therefore, healthcare providers should focus on alleviating the TGs among PWEs.

The antiepileptic drug carbamazepine (CBZ) has been widely detected in freshwater, yet its toxic actions in fish at multiple endpoints and the subsequent recovery patterns of the impacted are less discussed. This study investigated the bioaccumulation, physiological and behavioral changes of crucian carp (Carassius carassius) following CBZ exposure (G1 = 6.15 μg/L, G2 = 61.5 μg/L, G3 = 615 μg/L, G4 = 6150 μg/L) and subsequent recovery. Our results showed that CBZ was more likely to accumulate in the liver and brain than in the gills. A concentration-dependent phenomenon was observed; however, the residual CBZ decreased to similar levels after recovery. The behavioral indicators (i.e. feeding, social and spontaneous swimming) were significantly inhibited after 7-days of CBZ exposure, and only recovered at low concentration treatment (G1) after 7-days recovery in CBZ-free water. The acetylcholinesterase (AChE) activity in the brain and superoxide dismutase (SOD) activity in the liver and gills were induced after CBZ exposure and returned to normal levels after 7-days of recovery. In contrast, the inhibition of catalase (CAT) activity caused by CBZ exposure persisted in the high concentration treatment (G4) after recovery. Furthermore, correlation analysis indicated that changes in feeding behavior were closely related to the variation of CBZ concentrations in tissues, and the persistence of abnormal swimming and social behavior was closely related to gill CAT activity. These findings contribute to explore the toxic mechanisms of CBZ and highlight the recovery process and connections between various endpoints.