Temperature-modulated morphological changes in MIL-88B(Fe)-derived iron-based materials triggering generation of the peroxymonosulfate nonradical pathway to degrade carbamazepine: The key role of iron nanoparticles and CN.

Temperature modulation of the synthesis process of MOF-derived composites is not well understood for changes in the peroxymonosulfate catalytic domain. This study synthesized a carbon-based nitrogen-doped (MN@C) MOF-derived composite catalyst derived from MIL-88B(Fe) (Materials Institute Lavoisier) by modulating temperature changes and calcination. Combined with density-functional theory calculations (DFT) analyses showed that changes in iron nanoparticles (FeNP) and CN content caused the alterations of the degradation pathways. MN@C-9 exhibited outstanding activation performance (100 % carbamazepine (CBZ) removal within 10 min). The system maintained efficient operation in different aqueous environments and a wide pH range and demonstrated efficient removal of many pollutants typical of pharmaceuticals and personal care products (PPCPs). After comprehensively analyzing the results of liquid chromatography mass spectrometry (LC-MS) and toxicity prediction, the possible degradation pathways were reasonably speculated, and the toxicity of the byproducts was greatly reduced. This study provides a potential and efficient catalyst preparation strategy for water purification.

Degradation of carbamazepine by the UVA-LED365/ClO2/NaClO process: Kinetics, mechanisms and DBPs yield.

A mixed oxidant of chlorine dioxide (ClO2) and NaClO was often used in water treatment. A novel UVA-LED (365 nm)-activated mixed ClO2/NaClO process was proposed for the degradation of micropollutants in this study. Carbamazepine (CBZ) was selected as the target pollutant. Compared with the UVA365/ClO2 process, the UVA365/ClO2/NaClO process can improve the degradation of CBZ, with the rate constant increasing from 2.11×10-4 sec-1 to 2.74×10-4 sec-1. In addition, the consumption of oxidants in the UVA365/ClO2/NaClO process (73.67%) can also be lower than that of UVA365/NaClO (86.42%). When the NaClO ratio increased, both the degradation efficiency of CBZ and the consumption of oxidants can increase in the UVA365/ClO2/NaClO process. The solution pH can affect the contribution of NaClO in the total oxidant ratio. When the pH range of 6.0-8.0, the combination process can generate more active species to promote the degradation of CBZ. The change of active species with oxidant molar ratio was investigated in the UVA365/ClO2/NaClO process. When ClO2 acted as the main oxidant, HO• and Cl• were the main active species, while when NaClO was the main oxidant, ClO• played a role in the system. Both chloride ion (Cl-), bicarbonate ion (HCO3-), and nitrate ion (NO3-) can promote the reaction system. As the concentration of NaClO in the reaction solution increased, the generation of chlorates will decrease. The UVA365/ClO2/NaClO process can effectively control the formation of volatile disinfection by-products (DBPs), and with the increase of ClO2 dosage, the formation of DBPs can also decrease.

The protective effect of carbamazepine on acute lung injury induced by hemorrhagic shock and resuscitation in rats.

Hemorrhagic shock and resuscitation (HSR) enhances the risk of acute lung injury (ALI). This study investigated the protective effect of carbamazepine (CBZ) on HSR-induced ALI in rats. Male Sprague-Dawley rats were allocated into five distinct groups through randomization: control (SHAM), saline + HSR (HSR), CBZ + HSR (CBZ/HSR), dimethyl sulfoxide (DMSO) + HSR (DMSO/HSR), and CBZ + chloroquine (CQ) + HSR (CBZ/CQ/HSR). Subsequently, HSR models were established. To detect tissue damage, we measured lung histological changes, lung injury scores, and wet/dry weight ratios. We measured neutrophil counts as well as assessed the expression of inflammatory factors using RT-PCR to determine the inflammatory response. We detected autophagy-related proteins LC3II/LC3I, P62, Beclin-1, and Atg12-Atg5 using western blotting. Pretreatment with CBZ improved histopathological changes in the lungs and reduced lung injury scores. The CBZ pretreatment group exhibited significantly reduced lung wet/dry weight ratio, neutrophil aggregation and number, and inflammation factor (TNF-α and iNOS) expression. CBZ changed the expression levels of autophagy-related proteins (LC3II/LC3I, beclin-1, Atg12-Atg5, and P62), suggesting autophagy activation. However, after injecting CQ, an autophagy inhibitor, the beneficial effects of CBZ were reversed. Taken together, CBZ pretreatment improved HSR-induced ALI by suppressing inflammation, at least in part, through activating autophagy. Thus, our study offers a novel perspective for treating HSR-induced ALI.

Reactive Oxygen Species Generated in Situ During Carbamazepine Photodegradation at 222 nm Far-UVC: Unexpected Role of H2O Molecules.

When 222 nm far-UVC is used to drive AOPs, photolysis emerges as a critical pathway for the degradation of numerous organic micropollutants (OMPs). However, the photodegradation mechanisms of the asymmetrically polarized OMPs at 222 nm remain unclear, potentially posing a knowledge barrier to the applications of far-UVC. This study selected carbamazepine (CBZ), a prevalent aquatic antiepileptic drug that degrades negligibly at 254 nm, to investigate its photodegradation mechanisms at 222 nm. Accelerated CBZ treatment by 222 nm far-UVC was mainly attributed to in situ ROS generation via self-sensitized photodegradation of CBZ. By quenching experiments and EPR tests, •OH radicals were identified as the major contributor to the CBZ photodegradation, whereas O2•- played a minor role. By deoxygenation and solvent exchange experiments, the H2O molecules were demonstrated to play a crucial role in deactivating the excited singlet state of CBZ (1CBZ*) at 222 nm: generating •OH radicals via electron transfer interactions with 1CBZ*. In addition, 1CBZ* could also undergo a photoionization process. The transformation products and pathways of CBZ at 222 nm were proposed, and the toxicities of CBZ's products were predicted. These findings provide valuable insights into OMPs' photolysis with 222 nm far-UVC, revealing more mechanistic details for far-UVC-driven systems.

Polymorphism and Pharmacological Assessment of Carbamazepine.

This work provides insight into carbamazepine polymorphs (Forms I, II, III, IV, and V), with reports on the cytoprotective, exploratory, motor, CNS-depressant, and anticonvulsant properties of carbamazepine (CBZ), carbamazepine formulation (CBZ-F), topiramate (TOP), oxcarbazepine (OXC), and diazepam (DZP) in mice. Structural analysis highlighted the significant difference in molecular conformations, which directly influence the physicochemical properties; and density functional theory description provided indications about CBZ reactivity and stability. In addition to neuron viability assessment in vitro, animals were treated orally with vehicle 10 mL/kg, as well as CBZ, CBZ-F, TOP, OXC, and DZP at the dose of 5 mg/kg and exposed to open-field, rotarod, barbiturate sleep induction and pentylenetetrazol (PTZ 70 mg/kg)-induced seizure. The involvement of GABAergic mechanisms in the activity of these drugs was evaluated with the intraperitoneal pretreatment of flumazenil (2 mg/kg). The CBZ, CBZ-F, and TOP mildly preserved neuronal viability. The CBZ-F and the reference AEDs potentiated barbiturate sleep, altered motor activities, and attenuated PTZ-induced convulsion. However, flumazenil pretreatment blocked these effects. Additional preclinical assessments could further establish the promising utility of CBZ-F in clinical settings while expanding the scope of AED formulations and designs.

Stevens-Johnson syndrome and toxic epidermal necrolysis: Updates in pathophysiology and management.

ABSTRACT: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions characterized by extensive detachment of the epidermis and mucous membranes. These severe disorders carry a high mortality rate, and their pathogenesis remains largely unclear. Furthermore, optimal therapeutic strategies for SJS/TEN remain a subject of ongoing debate. Early diagnosis of SJS/TEN is challenging, and reliable biomarkers for diagnosis or severity prediction have not been firmly established. Certain drugs, such as carbamazepine and allopurinol, have shown a strong association with specific human leukocyte antigen (HLA) types. Recently, the potential benefits of HLA screening prior to administering these drugs to reduce the incidence of SJS/TEN have been explored. Epidermal cell death in SJS/TEN lesions is caused by extensive apoptosis, primarily through the Fas-Fas ligand (FasL) and perforin/granzyme pathways. Our findings suggest that necroptosis, a form of programmed necrosis, also contributes to epidermal cell death. Annexin A1, released from monocytes, interacts with the formyl peptide receptor 1 to induce necroptosis. Several biomarkers, such as CC chemokine ligand (CCL)-27, interleukin-15, galectin-7, receptor-interacting protein kinases 3 (RIP3), and lipocalin-2, have been identified for diagnostic and prognostic purposes in SJS/TEN. Supportive care is recommended for treating SJS/TEN, but the efficacy of various therapeutic options-including systemic corticosteroids, intravenous immunoglobulin, cyclosporine, and tumor necrosis factor-α antagonists-remains controversial. Recent studies have investigated the potential benefits of tumor necrosis factor-α antagonists. In this review, we discuss recent advances in the understanding and management of SJS/TEN.

The Adverse Effects of Commonly Prescribed Antiseizure Medications in Adults With Newly Diagnosed Focal Epilepsy.

BACKGROUND AND OBJECTIVES: Systematic screening can help identify antiseizure medication (ASM)-associated adverse events (AEs) that may preclude patients from reaching effective doses or completing adequate trial periods. The Adverse Event Profile (AEP) is a self-completed instrument to identify the frequency of common AEs associated with ASM use. This study aimed to compare the AE profile of commonly used ASMs in adults with newly diagnosed focal epilepsy. METHODS: The Human Epilepsy Project is a prospective, international, observational study investigating markers of treatment response in newly diagnosed focal epilepsy. Participants were enrolled within 4 months of treatment initiation. Adult participants on levetiracetam, lamotrigine, carbamazepine, or oxcarbazepine monotherapy who completed the AEP and Mini International Neuropsychiatric Interview at enrollment were included. Multivariable generalized linear and penalized logistic regression models assessed differences in total and itemized marginal AEP scores and dichotomized responses ("never/rarely" vs "sometimes/always"). RESULTS: A total of 225 adults initiated on levetiracetam (n = 132, 59%), lamotrigine (n = 55, 24%), carbamazepine (n = 19, 8.4%), or oxcarbazepine (n = 19, 8.4%) were included. There were no significant differences in AEP total scores between ASMs. Patients with depression (adjusted marginal score ratio [aMSR] 1.23, 95% CI 1.09-1.39, p = 0.001) and anxiety (aMSR 1.15, 95% CI 1.04-1.26, p = 0.007) had worse AEP total scores than those without. After adjusting for depression and anxiety, levetiracetam users were >3 times more likely to report feelings of aggression (adjusted odds ratio [aOR] 3.38, 95% CI 1.07-10.7, p = 0.038) and almost half as likely to experience unsteadiness (aOR 0.45, 95% CI 0.21-0.99, p = 0.047) than lamotrigine users. Carbamazepine and oxcarbazepine had the highest rates of discontinuation (42.1%, each), followed by levetiracetam (34.8%) and lamotrigine (16.4%). Levetiracetam users had the highest proportion of discontinuations because of AEs alone (18%), and lamotrigine had the lowest (5%). DISCUSSION: Systematic screening for AEs in adults with newly diagnosed focal epilepsy on ASM monotherapy showed that those with comorbid psychiatric conditions report greater AEs overall, irrespective of ASM. Levetiracetam was associated with >3-fold risk of psychiatric AEs and half the risk of experiencing unsteadiness than lamotrigine. Levetiracetam had the highest proportion of discontinuations because of AEs alone, while lamotrigine had the lowest.

Experimental investigation of dynamic drying in single pharmaceutical granules containing acetaminophen or carbamazepine using synchrotron X-ray micro computed tomography.

Drying time, velocity, and temperature are important aspects of the drying process for pharmaceutical granules observed during tablet manufacturing. However, the drying mechanism of single granules is often limited to modelling and simulation, with the internal and physical changes difficult to quantify at an experimental level. In this study, in-situ synchrotron-based X-ray imaging techniques were used for the first time to investigate the dynamic drying of single pharmaceutical granules, quantifying internal changes occurring over the drying time. Two commonly used excipients (lactose monohydrate (LMH) and microcrystalline cellulose (MCC)) were used as pure components and binary mixtures with one of either two active pharmaceutical ingredients of differing hydrophilicity/hydrophobicity (acetaminophen (APAP) and carbamazepine (CBZ)). Water was used as a liquid binder to generate single granules of 25 % to 30 % moisture content. Results showed that for most samples, the drying time and composition significantly influences the pore volume evolution and the moisture ratio, with the velocity and temperature of the drying air possessing mixed significance on increasing the rate of pore connectivity and moisture removal depending on the sample composition. Effects of active ingredient loading resulted in minimal influence on the drying of CBZ and generated binary mixtures, with APAP and its respective mixtures' drying behaviour dominated by the material's hydrophilic nature.

Cognitive outcomes after fetal exposure to carbamazepine, lamotrigine, valproate or levetiracetam monotherapy: Data from the EURAP neurocognitive extension protocol.

PURPOSE: Prenatal exposure to antiseizure medications (ASMs) has been associated with an increased risk of major malformations and neurodevelopmental disorders, with the latter being mainly associated with valproate (VPA). Our aim was to compare neurocognitive outcome at age 6-7 years in children exposed prenatally to lamotrigine (LTG), carbamazepine (CBZ), valproate (VPA) or levetiracetam (LEV) monotherapy. METHODS: Eligible mother-child pairs were identified from the observational prospective multinational EURAP cohort study. Assessor-blinded testing was conducted at age 6-7 years using WISC-III and NEPSY-II. Verbal IQ (VIQ), performance IQ (PIQ), full scale IQ (FSIQ) and performance in neuropsychological tasks were compared across ASM groups by ANOVA. Scores were adjusted for maternal IQ, paternal education, maternal epilepsy type and child sex. RESULTS: Of 169 children enrolled in the study, 162 (LTG n = 80, CBZ n = 37, VPA n = 27, LEV n = 18) had sufficient data from WISC-III, NEPSY-II or both, and were included in the analyses. Observed (unadjusted) PIQ and FSIQ did not differ across exposure groups, but a difference was identified for VIQ (P<0.05), with children exposed to VPA having lower scores than children exposed to LEV (P<0.05) and children from all groups combined (P<0.01). Adjusted VIQ, PIQ and FSIQ scores did not differ significantly across groups, but VPA-exposed children had borderline significantly lower adjusted VIQ scores than children from all groups combined (P=0.051). VPA-exposed children had lower scores in comprehension of instructions before and after adjustment for confounding variables than children exposed to LTG (P<0.001), LEV (P<0.01) or children from all groups combined (p < 0.001). The VPA-exposed group also had lower scores in immediate and delayed memory for faces compared to children exposed to CBZ (P<0.05 and P<0.001, respectively) and LTG (P<0.05 and P<0.02, respectively), and children from all groups combined (P<0.02 and P<0.001, respectively). LEV-exposed children had lower scores in delayed memory for names than children exposed to LTG (P<0.001), CBZ (P<0.001), VPA (P<0.05) and children from all groups combined (P<0.001). CONCLUSIONS: Consistent with previous reports, our results provide evidence for an adverse effect of prenatal exposure to valproate on verbal development. Our finding of relatively weaker performance of VPA-exposed children compared to other ASM exposures in both comprehension of instructions and face memory also suggest that children of mothers treated with VPA are at increased risk for compromised memory functions or altered processing of socially relevant information.

Intravenous Lidocaine Response as a Predictor for Oral Oxcarbazepine Efficacy in Neuropathic Pain Syndrome: A Prospective Cohort Study.

BACKGROUND Providing pain relief for patients with neuropathic pain syndrome (NPS) is difficult, as sodium-channel blockers pose serious adverse events (AEs). Intravenous (i.v.) lidocaine infusion responses may identify patients likely to benefit from oral sodium channel blockers. We evaluated i.v. lidocaine responses to predict oral oxcarbazepine (OXC) efficacy in patients with NPS. MATERIAL AND METHODS This prospective cohort study administered one-time 3 mg/kg i.v. lidocaine infusion to patients with NPS. Numeric rating scale (NRS) pain scores and AEs were observed. Next, OXC 150 mg was prescribed; dosages were increased by 150 mg every 3 days until ≥50% pain reduction or the maximum tolerable dose or 1800 mg/day was reached. NRS, rescue drug requirements, and AEs were evaluated by phone at 1, 3, and 5 weeks and clinic visits at 2, 4, and 6 weeks. Depression, Anxiety & Stress Scales 21 (DASS-21), and EuroQol-Five Dimensions-Five Levels (EQ-5D-5L) questionnaires were assessed at baseline and in week 6. RESULTS Of 46 patients, 14 discontinued due to intolerable AEs, and 32 were in the final analysis. Average post-intervention NRS significantly decreased from 6.8±1.7 (baseline) to 3.8±2.0 (lidocaine) and 4.1±2.3 (OXC); P<0.001. Negative and positive predictive values for OXC efficacy were 76.2% (95% CI: 61.6-86.5%) and 54.5% (95% CI: 32-75.4%), respectively. Six weeks after OXC treatment, 20 and 11 patients achieved ≥30% pain reduction and ≥50% pain relief, respectively. EQ-5D-5L (P=0.018) and DASS-21 stress dimension (P<0.001) significantly improved. CONCLUSIONS Negative responses to i.v. lidocaine predicted a lack of oral OXC response. AEs of OXC may have obscured an analgesic effect.

Hybrid packed bed bioreactor using combined biodegradation and ozonation to enhance nitrogen and micropollutants removal from landfill leachate.

Landfill leachate contains ammonium and micropollutants. Ammonium can be biologically removed but bio-recalcitrant micropollutants removal requires post-treatment like ozonation. This study developed an expanded clay aggregates packed biofilm column (EBC) and demonstrated its feasibility of coupling biodegradation and ozonation (CBAO) to simultaneously remove nitrogen and bio-recalcitrant micropollutants. The first 60 days only had biodegradation process to start the bioreactor. 51 % nitrogen was biologically removed but the removal of micropollutant carbamazepine (CBZ) was only 30 %. From 61 d to 150 d, both biodegradation and ozonation were performed in the EBC. After 48 h-biodegradation, ozone gas was introduced and bubbling through EBC for 30 min to further remove residual micropollutants. At 0.4 gO3/gCOD, CBZ were completely removed. The average nitrogen removal efficiency (85 %) was increased by 34 % because the increased abundance of nitrifying and denitrifying bacteria in EBC. This study confirmed the promising potential of the CBAO process for treating landfill leachte.

Anelosimuseximius bioinspired ZnO nano cobwebs for environmental remediation of drugs and endocrine disruptors from water.

The pollution of wastewater with pharmaceuticals and endocrine-disrupting chemicals (EDCs) in populated areas poses a growing threat to humans and ecosystems. To address this serious problem, various one-dimensional (1D) hierarchical ZnO-based nanostructures inspired by Anelosimus eximius cobwebs were developed and successfully grown on a glass substrate through simple hydrothermal synthesis. The nanorods (nr) obtained during primary growth were chemically etched with KOH (ZnOnr-KOH), followed by the secondary growth of nano cobweb-like (ncw) structures using polyethyleneimine (ZnOnr/ncw). These structures were further decorated by the photoreduction of Ag nanoparticles (ZnOnr/ncw/Ag). The feasibility of ZnO-based 1D nanostructures to remove pollutants was demonstrated by degrading commonly prescribed pharmaceutical drugs (diclofenac and carbamazepine) in a miniature cuvette reactor. The photocatalytic activities for drug degradation generally decreased in the order ZnOnr/ncw/Ag > ZnOnr/ncw > ZnOnr-KOH. Additionally, the suitability of the samples for scaling up and practical application was demonstrated by photocatalytic degradation of the hormone estriol (E3) in a flow-through photoreactor. The photocatalytic degradation efficiency of E3 followed the same trend observed for drug degradation, with the complete elimination of the endocrine disruptor achieved by the best-performing ZnOnr/ncw/Ag within 4 h, due to optimized charge transfer and separation at the heterostructure interface.

Fe-MOFs nanosheets for photo-Fenton degradation of carbamazepine.

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.

Stevens-Johnson Syndrome/Toxic epidermal necrolysis complicated with fulminant type 1 diabetes mellitus: a case report and literature review.

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 ß-cell function. Fulminant type 1 diabetes mellitus as a sequela of SJS/TEN has rarely been reported. CASE PRESENTATION: 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.

Levetiracetam versus carbamazepine monotherapy in the management of pediatric focal epilepsy: A systematic review and meta-analysis of randomized controlled trials.

Levetiracetam (LEV) and carbamazepine (CBZ) are effective monotherapies for focal epilepsy in children. However, the best drug remains controversial. Therefore, we performed a systematic review and meta-analysis comparing LEV and CBZ monotherapy in the management of pediatric focal epilepsy (PFE). We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) published until February 2024 comparing LEV and CBZ monotherapy in PFE. Statistical analysis was performed using R version 4.2.2, heterogeneity was assessed using I2 statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered significant. The outcomes of interest were seizure freedom, any adverse events, adverse events leading to treatment discontinuation, dermatologic adverse events, and the frequency of at least one seizure, defined as the proportion of patients experiencing one or more seizures during the treatment period. Four RCTs comprising 381 children with a mean age of 7.32 to 9.28 years were included, of whom 186 (48.8%) received LEV monotherapy. There was no significant difference between groups (RR: 1.15; 95% CI 0.88-1.50; p = 0.31; I2 = 90%) regarding seizure freedom. The frequency of at least one seizure (RR: 0.71; 95% CI 0.52-0.97; p = 0.03; I2 = 8%) and dermatologic adverse events (RR: 0.24; 95% CI 0.09-0.64; p < 0.01; I2 = 0%) were both significantly lower in the LEV group. There were no significant differences in the presence of any adverse events (RR: 0.58; 95% CI 0.33-1.01; p = 0.05; I2 = 36%) or adverse events leading to treatment discontinuation (RR: 0.67; 95% CI 0.13-3.42; p = 0.63; I2 = 30%).Conclusion: In monotherapy, LEV was more advantageous than CBZ for PFE, with a lower frequency of seizures and fewer dermatological adverse events. However, both drugs are equally effective in achieving seizure freedom, adverse events without specification, and those that lead to treatment discontinuation. Our findings have important implications for clinical practice and decision-making in this condition.

Association of glutamine synthetase polymorphisms rs2296521, rs10911021 and rs12136955 with plasma ammonia concentration in valproic acid-treated Egyptian epilepsy patients.

INTRODUCTION: The use of valproic acid (VPA) in the treatment of some psychiatric and neurological disorders such as bipolar disorder, migraines, and epilepsy is associated with hyperammonemia. However, the mechanism of this negative effect of VPA is unclear. In this study, we investigate gene glutamate-ammonia ligase (GLUL) polymorphisms for the glutamine synthetase (GS) enzyme, a key enzyme that catalyzes the removal of ammonia by incorporating it with glutamate to form glutamine, and we investigate whether it has a relationship with the emergence of hyperammonemia during VPA-based therapy. PATIENTS AND METHODS: We enrolled 180 Egyptian epilepsy patients in this study. Patient history, general and neurological examination and blood samples from arm veins were taken. Real time TaqMan PCR polymorphism for three polymorphism SNPs (rs2296521, rs10911021 and rs12136955) of GLUL was done. We assessed the relationship between the patient features, including three GLUL polymorphisms, and the development of hyperammonemia during VPA-based therapy. RESULTS: We found that the ammonia levels showed a positive correlation with VPA treatment duration (p = 0.015) and a negative correlation with carbamazepine total dose per day (p = 0.027) and with WBCs count (p = 0.026). Also, female patients having rs2296521 SNPs with the A allele and patients having rs10911021 SNPs with the C allele were at high risk for elevated plasma ammonia levels. Moreover, patients having rs12136955 SNPs with the A allele or associated hypertension as a co-morbidity were at high risk for elevated plasma ammonia levels. CONCLUSION: Female patients who have rs2296521 with the A allele, rs10911021 with the C allele, or rs12136955 with the A allele, are independent risk factors for elevated plasma ammonia levels during VPA-based therapy. Moreover, carbamazepine combined therapy may protect against the development of hyperammonemia in VPA-treated patients.

Cardioneuroablation can be an effective strategy to treat glossopharyngeal neuralgia-related sinus bradycardia and pauses.

INTRODUCTION: Cardioneuroablation (CNA) has proven effectiveness in addressing hypervagotonia symptoms, such as neurocardiogenic syncope. METHODS AND RESULTS: In this case, we present the first-time application of CNA in a case of vago-glossopharyngeal neuralgia (VGPN). A 59-year-old female with near-syncope, sinus bradycardia, and sinus pauses triggered by recurrent right-sided neck pain was diagnosed with VGPN. The patient underwent successful treatment with carbamazepine and CNA. Subsequent follow-up revealed the sustained absence of sinus bradycardia or pauses, even upon neck pain resurgence after discontinuing carbamazepine. CONCLUSION: In this patient, CNA successfully prevented pauses associated with VGPN, avoiding permanent pacemaker implantation.

Excipient-Induced Lattice Disorder in Active Pharmaceutical Ingredient: Implications on Drug Product Continuous Manufacturing.

Our previous work (Mol Pharm, 20 (2023) 3427) showed that crystalline excipients, specifically anhydrous dibasic calcium phosphate (DCPA), facilitated the dehydration of carbamazepine dihydrate (CBZDH) and the formation of an amorphous product phase during the mixing stage of continuous tablet manufacturing. Understanding the mechanism of this excipient-induced effect was the object of this study. Blending with DCPA for 15 min caused pronounced lattice disorder in CBZDH. This was evident from the 190% increase in the apparent lattice strain determined by the Williamson-Hall plot. The rapid dehydration was attributed to the increased reactivity of CBZDH caused by this lattice disorder. Lattice disorder in CBZDH was induced by a second method, cryomilling it with DCPA. The dehydration was accelerated in the milled sample. Annealing the cryomilled sample reversed the effect, thus confirming the effect of lattice disorder on the dehydration kinetics. The hardness of DCPA appeared to be responsible for the disordering effect. DCPA exhibited a similar effect in other hydrates, thereby revealing that the effect was not unique to CBZDH. However, its magnitude varied on a case-by-case basis. The high shear powder mixing was necessary for rapid and efficient powder mixing during continuous drug product manufacturing. The mechanical stress imposed on the CBZDH, and exacerbated by DCPA, caused this unexpected destabilization.

Effective peroxymonosulfate activation by lithium cobaltite recovered from spent lithium-ion batteries for enhanced carbamazepine degradation in a wide pH range.

Considering the high cost and complicated recycling process of spent lithium-ion batteries (SLIBs), transforming SLIBs into environment functional materials may be a wise approach. Herein, lithium cobaltite (LCO) cathode powders recovered from SLIBs were used to activate peroxymonosulfate (PMS) for removing carbamazepine (CBZ). The recovered LCO enables a 98.2% removal efficiency of CBZ (2.5 mg/L) within 10 min, which was effective at a broader pH range (pH = 5.0-11.0). The influence of key factors (initial pH, PMS, and catalyst dosage) and coexisting substances (SO42-, H2PO4-, NO3-, Cl-, HCO3-, and HA) on CBZ degradation were examined in detail. The primary radical species during the degradation of CBZ were proved to be 1O2, SO4-, and.OH that generated from PMS activation initiated by the valence change of Co in recovered LCO. The recovered LCO displayed excellent reusability with about 80.0% removal of CBZ after six cycles. Homogeneous activation of PMS mainly contributed to CBZ degradation in the first run, but the recovered LCO catalyst dominated the heterogeneous activation of PMS for the degradation of CBZ in the second to sixth run. Finally, the CBZ degradation pathways were presented based on the identified intermediates. This research has offered a new strategy of "treating wastes with wastes" to maximize the recycling of electronic wastes to remove emerging pollutants.

CuFeS2/GAC particle combined with electrochemical activation of persulfates for efficient degradation of carbamazepine.

Electrochemically activated persulfate is a potential advanced oxidation process due to its advantages of environmental friendliness, high efficiency, and convenient operation. An Fe-Cu-S granular activated carbon (CuFeS2/GAC, abbreviated as FCSG) particles electrode was developed and applied to degrade carbamazepine (CBZ) combined with electrochemical activation of persulfate (E-PDS-FCSG) in this work. Compared to two-dimensional electrochemical process (E-PDS), the three-dimensional (3D) E-PDS-FCSG process exhibited higher removal efficiency of CBZ and lower energy consumption. The removal efficiency of CBZ and power consumption increased by 96% and reduced by 67%, respectively. Over 98% of CBZ removal rate was reached within 25 min. Apart from the same free radicals in two-dimensional electrochemical process, both Fe2+ and Cu+ on the surface of three-dimensional particle electrodes can directly activate PDS to produce SO4•-, and the existence of S2- strengthens the circulation of Fe3+/Fe2+ and Cu2+/Cu+. Furthermore, FCSG particle electrode can not only directly enhance the activation of PDS, but also accelerate the electron transfer, and then effectively promoting reactive species generation. LC-MS analysis showed that the main degradation pathways of CBZ involved decarbonylation, deamination, dealkylation, ring opening and mineralization. Moreover, after five cycle experiments, over 80% of CBZ removal rate could be achieved, demonstrating that the E-PDS-FCSG system had excellent electrocatalytic performance and good stability. These findings indicate that FCSG is a promising material and could be used as a particle electrode for removing organic pollutants from water.