Valproic acid

A 60-year-old man treated with valproic acid (VPA) for epilepsy developed atelectasis and respiratory failure after an accidentally aspirated VPA tablet-induced mucus hypersecretion. Following bronchoscopic removal of the aspirated tablet, his respiratory status improved and massive sputum production did not recur. We hypothesized that the aspirated VPA tablet increased the expression of mucin-related genes, thereby increasing mucus production. Our in vitro experiments using a human respiratory epithelial cell line revealed that VPA directly upregulates the airway mucin-related genes...

Abdominal migraine (AM) is a prevalent pediatric condition that rarely affects adults. Multiple diagnostic criteria have been established, but in general, AM is characterized by unprovoked episodes of acute central abdominal pain with migrainous characteristics and periods of respite. Recurrent stomach pain is a prevalent symptom globally, with a significant portion of cases falling under the category of functional gastrointestinal disorders (FGIDs) due to the absence of identified biological causes. There is a notable prevalence of migraines among individuals with a family history of the condition, indicating a genetic predisposition...

Oral squamous cell carcinoma (OSCC) is a frequent human malignancy that demonstrates a range of genetic and epigenetic alterations. Histone deacetylases (HDACs) are key epigenetic regulators of cell-cycle progression, differentiation and apoptosis and their dysregulation is implicated in cancer development. HDACs are promising targets for anticancer therapy through the utilisation of HDAC inhibitors (HDACis). OSCC cells have been shown to have low levels of histone acetylation, suggesting that HDACis may produce beneficial effects in patients with OSCC...

BACKGROUND: Valproic acid has been widely used as an antiepileptic drug for several decades. Long-term valproic acid treatment is usually accompanied by liver injury. Although both men and women are susceptible to valproic acid-associated liver injury, hepatotoxicity differs between the sexes. However, the mechanisms underlying sex differences in valproic acid-associated liver injury remain unclear. METHODS: To explore potential risk factors for the susceptibility to valproic acid-associated liver injury, 231 pediatric patients with epilepsy (119 males, 112 females) were enrolled for laboratory and genetic analysis...

BACKGROUND: Several different formulations of valproic acid derivatives are available in the United States. Although these formulations have different absorption characteristics, they are believed to be interchangeable, with the exception of the extended-release product. CASE REPORT: A 31-year-old African American man with schizoaffective disorder was started on fluphenazine concentrate and valproate oral solution on admission to an inpatient unit. A 12-hour steady-state concentration, drawn on 1000 mg/day, resulted in 40...

BACKGROUND: Drug resistance is one of the most critical problems in gastric cancer therapy. This study was performed to investigate the valproic acid effects on the proliferation of sensitive and resistant cell lines of human gastric cancer, and to explore the mechanism of the agent on multi drug resistance and apoptosis genes. METHODS: The cytotoxicity effect of valproic acid on the EPG85.257 and EPG85.257RDB cells was assessed by the MTT assay, and the IC50 concentration was evaluated...

Selecting appropriate antiseizure medications (ASMs) for combination therapy in patients with drug-resistant epilepsy (DRE) is a complex task that requires an empirical approach, especially in patients receiving polytherapy. We aimed to analyze the effectiveness of various three-drug combinations in a group of patients with DRE under real-world conditions. This single-center, longitudinal observational study investigated patients with drug-resistant focal epilepsy who received three-drug regimens in the outpatient clinic of Tongji Hospital from September 2019 to December 2022...

N-Arylenaminones are highly versatile compounds which can be synthesized in relatively simple ways. In this work we explored the synthesis of the four monosubstituted N-(4-R-phenyl)enaminones 3a (R = NO2), 3b (R = F), 3c (R = H), and 3d (R = OMe) with the goal of determining the influence of the substituents' electronic effects on tautomer stability and biological activity. These compounds were analyzed by means of Density Functional Theory calculations (DFT), to evaluate the relative stability of the possible tautomers...

INTRODUCTION: The relationship between epilepsy and psychiatric disorders has been highlighted for a long time. Idiopathic epilepsy is known to have a benign course in most cases. However, the association of psychiatric disturbances could worsen the disease outcome. AIM: To study the frequency of psychiatric symptoms in patients with idiopathic epilepsy, and to assess the determinant factors in the patient group with these manifestations. METHODS: In one-year prospective study, consecutive patients diagnosed with idiopathic epilepsy were included...

In recent years, exposures to organophosphate pesticide have been highlighted as a possible cause or aggravating factor of autism spectrum disorder (ASD). The present study examined if Wistar rats prenatally exposed to chlorpyrifos (CPF) at a dose of 1 mg/kg in GD 12.5-15.5 could express similar behaviors to those exposed to valproic acid (VPA, 400 mg/kg) during the same administration window, which is an accepted animal model of autism. The 3-chambered test was employed to evaluate sociability and reaction to social novelty in two experiments, the first in adolescence and the second in adulthood...

Valproic acid (VPA) has been widely used as an antiepileptic drug for decades. Although VPA is effective and well-tolerated, long-term VPA treatment is usually associated with hepatotoxicity. However, the underlying mechanisms of VPA-caused hepatotoxicity remain unclear. In this study, a total of 157 pediatric patients with epilepsy were recruited and divided into normal liver function (NLF, 112 subjects) group and abnormal liver function (ABLF, 45 subjects) group. We observed that MTHFR A1298C and MTHFR C677T variants may be linked to VPA-induced liver dysfunction ( p = 0...

Certain environmental factors can impact fertility and reproductive parameters such as the number and quality of sperm and eggs. One possible mechanism is the perturbation of epigenetic landscapes in the germline. To explore this possibility, we conducted a CRISPRi screen of epigenetic-related genes to identify those that specifically perturb the differentiation of embryonic stem cells (ESCs) into primordial germ cell-like cells (PGCLCs), exploiting a highly scalable cytokine-free platform. Of the 701 genes screened, inhibition of 53 decreased the efficiency of PGCLC formation...

INTRODUCTION AND IMPORTANCE: Acute psychosis is a common brief psychiatric emergency period of delusions, hallucinations, disorganized thoughts and/or speech with or without psychomotor elements, which is not commonly induced by isotretinoin therapy. Dermatologists should counsel the patient before starting the treatment with all new, uncommon side effects, especially neuropsychiatric manifestations before starting this medication. CASE PRESENTATION: A 23-year-old male smoker with a known case of acne vulgaris recently started on isotretinoin for 2 weeks after which he developed abnormal hyperactive psychomotor activity...

Autism spectrum disorder (ASD) has increased in incidence over the past several decades, and is associated with a range of co-morbidities including gastrointestinal (GI) dysfunctions including gastroesophageal reflux, abdominal pain, bloating, constipation and/or diarrhea. Several animal models have been used that replicate several aspects of ASD but no single model has been able to replicate the entire disease pathophysiology. In humans, prenatal exposure to valproic acid (VPA) has been identified as a significant risk factor and rodent models have shown that in utero VPA exposure leads to behavioral deficits in offspring...

BACKGROUND: Although antiseizure medications play a crucial role in the management of epilepsy, their benefit can be compromised due to drug-related problems. Drug therapy problems can lead to poor seizure control, reduced quality of life, and increased morbidity and mortality in patients with epilepsy. However, in our setting, there is limited knowledge about drug therapy problems and the factors that contribute to them. OBJECTIVE: The aim of this study was to investigate the prevalence and contributing factors of drug-therapy problems among patients with epilepsy...

STUDY DESIGN: A Systematic Review OBJECTIVES: To determine the therapeutic efficacy of in vivo reprogramming of astrocytes into neuronal-like cells in animal models of spinal cord injury (SCI). METHODS: PRISMA 2020 guidelines were utilized, and search engines Medline, Web of Science, Scopus, and Embase until June 2023 were used. Studies that examined the effects of converting astrocytes into neuron-like cells with any vector in all animal models were included, while conversion from other cells except for spinal astrocytes, chemical mechanisms to provide SCI models, brain injury population, and conversion without in-vivo experience were excluded...

Podocytes play a critical role in the formation and maintenance of the glomerular filtration barrier and injury to these cells can lead to a breakdown of the glomerular barrier causing permanent damage leading to progressive chronic kidney disease. Matured podocytes have little proliferative potential, which makes them critical cells from a health perspective, but also challenging cells to maintain in vitro. Differentiating podocyte-like cells from induced pluripotent stem cells (iPSC) cells provides a novel and continuous source of cells...

BACKGROUND: High self-renewal capacity and most permissive nature of umbilical cord blood (CB) results with successful transplant outcomes but low hematopoietic stem and progenitor cell (HSPC) counts limits wider use. In order to overcome this problem ex vivo expansion with small molecules such as Valproic acid (VPA) or Nicotinamide (NAM) have been shown to be effective. To the best of our knowledge, the combinatory effects of VPA and NAM on HSPC expansion has not been studied earlier...

BACKGROUND: Seizures are an important palliative symptom, the management of which can be complicated by patients' capacity to swallow oral medications. In this setting, and the wish to avoid intravenous access, subcutaneous infusions may be employed. Options for antiseizure medications that can be provided subcutaneously may be limited. Subcutaneous sodium valproate may be an additional management strategy. AIM: To evaluate the published experience of subcutaneous valproate use in palliative care, namely with respect to effectiveness and tolerability...

Stiripentol (Diacomit® ) (STP) is an orally active antiseizure medication (ASM) indicated as adjunctive therapy, for the treatment of seizures associated with Dravet syndrome (DS), a severe form of childhood epilepsy, in conjunction with clobazam and, in some regions valproic acid. Since the discovery of STP, several mechanisms of action (MoA) have been described that may explain its specific effect on seizures associated with DS. STP is mainly considered as a potentiator of gamma-aminobutyric acid (GABA) neurotransmission: (i) via uptake blockade, (ii) inhibition of degradation, but also (iii) as a positive allosteric modulator of GABAA receptors, especially those containing α3 and δ subunits...