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Heliyon Mar 2024This study presents an efficient high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method for monitoring valproic acid (VPA) level in human...
This study presents an efficient high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method for monitoring valproic acid (VPA) level in human plasma. This method is distinguished by its simplicity, cost-effectiveness, and rapid execution, addressing the limitations associated with other advanced analytical techniques like liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), and immunoassays, which are generally complex and costly for routine application. A challenge in analyzing VPA is its non-linear protein binding profile and the absence of a chromophore in its structure, making direct detection difficult. To overcome this, the study developed an efficient HPLC-UV for VPA determination in human plasma, utilizing a simplified and rapid microwave-assisted derivatization process. Due to the lack of a chromophore in VPA structure, this work developed a microwave-assisted derivatization of VPA using phenylhydrazine hydrochloride (PH HCl). The process optimization was achieved at 450 W for 50 s, facilitating effective HPLC-UV detection. The derivatized product was characterized using H nuclear magnetic resonance (NMR) and Fourier transform infrared spectrometer (FT-IR). The derivative, identified as -phenyl-2-propylpentanehydrazonic acid, demonstrated specificity in plasma analysis with no detectable interference. The method exhibited a linear response for VPA concentrations ranging from 30 to 150 μg/mL, with a correlation coefficient exceeding 0.99. Recovery varied between 86.7% and 107%, with a maximum coefficient of variation (CV) of 10.0%. The findings suggest that the microwave-assisted derivatization technique substantially improves the feasibility and cost-effectiveness of HPLC-UV for the analysis of VPA in plasma. This method provides a viable alternative to conventional HPLC methodologies, offering a balance of efficiency and economic practicality for VPA quantification.
PubMed: 38545211
DOI: 10.1016/j.heliyon.2024.e27875 -
Medicina (Kaunas, Lithuania) Feb 2024Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed... (Review)
Review
Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed a narrative review to characterize further asterixis regarding nomenclature, historical aspects, etiology, pathophysiology, classification, diagnosis, and treatment. Asterixis has been classically used as a synonym for negative myoclonus across the literature and in previous articles. However, it is important to distinguish asterixis from other subtypes of negative myoclonus, for example, epileptic negative myoclonus, because management could change. Asterixis is not specific to any pathophysiological process, but it is more commonly reported in hepatic encephalopathy, renal and respiratory failure, cerebrovascular diseases, as well as associated with drugs that could potentially lead to hyperammonemia, such as valproic acid, carbamazepine, and phenytoin. Asterixis is usually asymptomatic and not spontaneously reported by patients. This highlights the importance of actively searching for this sign in the physical exam of encephalopathic patients because it could indicate an underlying toxic or metabolic cause. Asterixis is usually reversible upon treatment of the underlying cause.
Topics: Humans; Myoclonus; Tremor; Dyskinesias; Brain Diseases; Carbamazepine
PubMed: 38541088
DOI: 10.3390/medicina60030362 -
Biomolecules Mar 2024(1) Background: Valproic acid (VPA) is one of the frequently prescribed antiepileptic drugs and is generally considered well tolerated. However, VPA neurologic adverse...
(1) Background: Valproic acid (VPA) is one of the frequently prescribed antiepileptic drugs and is generally considered well tolerated. However, VPA neurologic adverse effects in the absence of liver failure are fairly common, suggesting that in the mechanism for the development of VPA-induced encephalopathy, much more is involved than merely the exposure to hyperammonemia (HA) caused by liver insufficiency to perform detoxification. Taking into account the importance of the relationship between an impaired brain energy metabolism and elevated ammonia production, and based on the ability of VPA to interfere with neuronal oxidative pathways, the current study intended to investigate a potential regional ammoniagenic effect of VPA on rats' brains by determining activities of the enzymes responsible for ammonia production and neutralization. (2) Methods: Rats received a single intraperitoneal injection of VPA (50, 100, 250, 500 mg/kg). Plasma, the neocortex, the cerebellum, and the hippocampus were collected at 30 min after injection. The levels of ammonia, urea, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in blood plasma. The activities of glutaminase and glutamate dehydrogenase (GDH) in mitochondria and the activities of AMP deaminase (AMPD), adenosine deaminase (ADA), and glutamine synthetase (GS) in cytosolic fractions isolated from rat brain regions were measured. Ammonia, ALT, and AST values were determined in the mitochondrial and cytosolic fractions. (3) Results: Multi-dose VPA treatment did not significantly affect the plasma levels of ammonia and urea or the ALT and AST liver enzymes. Significant dose-independent increases in the accumulation of ammonia were found only in the cytosol from the cerebellum and there was a strong correlation between the ammonia level and the ADA activity in this brain structure. A significant decrease in the AMPD and AST activities was observed, while the ALT activity was unaffected. Only the highest VPA dose (500 mg/kg) was associated with significantly less activity of GS compared to the control in all studied brain structures. In the mitochondria of all studied brain structures, VPA caused a dose-independent increases in ammonia levels, a high concentration of which was strongly and positively correlated with the increased GDH and ALT activity, while glutaminase activity remained unchanged, and AST activity significantly decreased compared to the control in all studied brain structures. (4) Conclusions: This study highlights the rat brain region-specific ammoniagenic effects of VPA, which may manifest themselves in the absence of hyperammonemia. Further research should analyze how the responsiveness of the different brain regions may vary in VPA-treated animals that exhibit compromised energy metabolism, leading to increased ammoniagenesis.
Topics: Rats; Animals; Valproic Acid; Glutaminase; Hyperammonemia; Ammonia; Urea
PubMed: 38540788
DOI: 10.3390/biom14030370 -
The Journal of Clinical Psychiatry Mar 2024
Topics: Humans; Valproic Acid; Weight Gain
PubMed: 38535508
DOI: 10.4088/JCP.23com15213 -
Case Reports in Pulmonology 2024A 60-year-old man treated with valproic acid (VPA) for epilepsy developed atelectasis and respiratory failure after an accidentally aspirated VPA tablet-induced mucus...
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 experiments using a human respiratory epithelial cell line revealed that VPA directly upregulates the airway mucin-related genes. We believe that this is the first case report of aspirated VPA-induced severe atelectasis and respiratory failure, which were successfully treated with the bronchoscopic removal of the VPA tablet.
PubMed: 38529055
DOI: 10.1155/2024/6650141 -
Clinical Case Reports Mar 2024Abdominal migraine (AM) is a prevalent pediatric condition that rarely affects adults. Multiple diagnostic criteria have been established, but in general, AM is...
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. A descriptive report has been prepared on the participant who had AM associated with acute watery diarrhea (AWD) on January 2023. The patient's parents had given written informed consent for publishing this case report. In this case report, we present the clinical scenario of a 12-year-old male child who experienced AM symptoms alongside a history of absence seizures. The child presented with episodes of abdominal pain and AWD. Despite extensive investigation and treatment, there was no improvement in abdominal pain. However, after 1 week of oral valproic acid administration, the patient remained symptom-free during the follow-up period. Dehydration, along with other factors, has been identified as a triggering factor for AM. Acute watery diarrhea has the potential to disrupt the normal functioning of the gastrointestinal system, and dehydration may lead to subsequent abdominal symptoms.
PubMed: 38523821
DOI: 10.1002/ccr3.8703 -
Oncology Letters May 2024Oral squamous cell carcinoma (OSCC) is a frequent human malignancy that demonstrates a range of genetic and epigenetic alterations. Histone deacetylases (HDACs) are key... (Review)
Review
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. Valproic acid (VPA) is a class I and IIa HDACi and, therefore, may be useful in anticancer therapy. VPA has been reported as a chemo-preventive epigenetic agent in individuals with high-risk oral dysplasia (OD) and thus associated with a reduced risk of HNSCC. It is hypothesised that HDAC inhibition by VPA triggers a change in the expression levels of different HDAC family gene-members. The present review summarises the current literature on HDAC expression changes in response to VPA in oral cancer patients and studies in an effort to better understand the potential epigenetic impact of VPA treatment. The present review outlined the need for exploring supportive evidence of the chemo-preventive role played by VPA-based epigenetic modification in treating oral pre-cancerous lesions and, thus, providing a novel tolerable chemotherapeutic strategy for patients with oral cancer.
PubMed: 38516679
DOI: 10.3892/ol.2024.14330 -
The Mental Health Clinician Jun 2023Several different formulations of valproic acid derivatives are available in the United States. Although these formulations have different absorption characteristics,...
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 40.8 mg/L, and the dose continued to be titrated. Despite increasing doses, confirmed medication adherence, and accurate lab sampling, his concentrations remained low: 60.3 and 60.1 mg/L on 1500 mg/day, and 65.6 mg/L on 1750 mg/day. He was switched to divalproex delayed-release tablets, and his dose was increased to 2000 mg/day. Follow-up 12-hour steady-state concentrations were significantly higher, at 126.6 and 113.8 mg/L. It is theorized that the formulation of divalproex/valproic acid is what contributed to these differences in concentrations.
DISCUSSION
Valproic acid formulations are considered to be interchangeable, and several studies have demonstrated that chronic psychiatric inpatients stabilized on delayed-release divalproex may be safely switched to valproate oral solution without changes in psychiatric stability. This case demonstrates a significant difference in serum drug concentrations when switching from valproate oral solution to divalproex delayed-release tablets.
PubMed: 38500509
DOI: 10.9740/mhc.2023.06.152 -
Cell and Tissue Research Jun 2024Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy...
Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy and the death of neurons. Overloading of intracellular iron ions has recently been identified as the cause of a newly recognized form of controlled cell death called ferroptosis. Inhibiting ferroptosis has shown promise as a treatment for epilepsy, according to recent studies. So, the current study aimed to assess the possible antiepileptic impact of CoQ10 either alone or with the standard antiepileptic drug sodium valproate (SVP) and to evaluate the targeted effect of COQ10 on hippocampal oxidative stress and ferroptosis in a SE rat model. Using a lithium-pilocarpine rat model of epilepsy, we evaluated the effect of SVP, CoQ10, or both on seizure severity, histological, and immunohistochemical of the hippocampus. Furthermore, due to the essential role of oxidative stress and lipid peroxidation in inducing ferroptosis, we evaluated malonaldehyde (MDA), reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferritin in tissue homogenate. Our work illustrated that ferroptosis occurs in murine models of lithium-pilocarpine-induced seizures (epileptic group). Nissl staining revealed significant neurodegeneration. A significant increase in the number of astrocytes stained with an astrocyte-specific marker was observed in the hippocampus. Effective seizure relief can be achieved in the seizure model by administering CoQ10 alone compared to SVP. This was accomplished by lowering ferritin levels and increasing GPX4, reducing MDA, and increasing GSH in the hippocampus tissue homogenate. In addition, the benefits of SVP therapy for regulating iron stores, GPX4, and oxidative stress markers were amplified by incorporating CoQ10 as compared to SVP alone. It was concluded that CoQ10 alone has a more beneficial effect than SVP alone in restoring histological structures and has a targeted effect on hippocampal oxidative stress and ferroptosis. In addition, COQ10 could be useful as an adjuvant to SVP in protecting against oxidative damage and ferroptosis-related damage that result from epileptic seizures.
Topics: Animals; Ferroptosis; Status Epilepticus; Ubiquinone; Hippocampus; Disease Models, Animal; Rats; Male; Oxidative Stress; Pilocarpine; Rats, Sprague-Dawley; Valproic Acid; Lipid Peroxidation
PubMed: 38499882
DOI: 10.1007/s00441-024-03880-z