-
Clinical Medicine (London, England) Jul 2023
Topics: Humans; Valproic Acid; Hyperammonemia; Anticonvulsants; Epilepsy; Amino Acid Metabolism, Inborn Errors; Carnitine
PubMed: 37524421
DOI: 10.7861/clinmed.Let.23.4.1 -
Arquivos de Neuro-psiquiatria Dec 2023Migraine is one of the most prevalent and disabling diseases in the world. Migraine attack treatments and prophylactic treatments of this disease are essential to lessen... (Review)
Review
Migraine is one of the most prevalent and disabling diseases in the world. Migraine attack treatments and prophylactic treatments of this disease are essential to lessen its individual, social, and economic impact. This is a narrative review of the main drugs used for treating migraine, as well as the experimental models and the theoretical frameworks that led to their development. Ergot derivatives, triptans, non-steroid anti-inflammatory drugs, tricyclic antidepressants, beta-blockers,: flunarizine,: valproic acid,: topiramate, onabotulinumtoxin A, ditans, monoclonal antibodies against CGRP and its receptor, and gepants are discussed. Possible therapeutic targets for the development of new drugs that are under development are also addressed. Many of the drugs currently in use for treating migraine were developed for the treatment of other diseases, but have proven effective for the treatment of migraine, expanding knowledge about the disease. With a better understanding of the pathophysiology of migraine, new drugs have been and continue to be developed specifically for the treatment of this disease.
Topics: Humans; Migraine Disorders; Tryptamines; Calcitonin Gene-Related Peptide Receptor Antagonists; Valproic Acid; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38157876
DOI: 10.1055/s-0043-1777723 -
International Journal of Molecular... Feb 2024Hepatocellular carcinoma (HCC) is among the main causes of death by cancer worldwide, representing about 80-90% of all liver cancers. Treatments available for advanced... (Review)
Review
Hepatocellular carcinoma (HCC) is among the main causes of death by cancer worldwide, representing about 80-90% of all liver cancers. Treatments available for advanced HCC include atezolizumab, bevacizumab, sorafenib, among others. Atezolizumab and bevacizumab are immunological options recently incorporated into first-line treatments, along with sorafenib, for which great treatment achievements have been reached. However, sorafenib resistance is developed in most patients, and therapeutical combinations targeting cancer hallmark mechanisms and intracellular signaling have been proposed. In this review, we compiled evidence of the mechanisms of cell death caused by sorafenib administered alone or in combination with valproic acid and metformin and discussed them from a molecular perspective.
Topics: Humans; Carcinoma, Hepatocellular; Sorafenib; Liver Neoplasms; Valproic Acid; Bevacizumab; Metformin; Cell Death
PubMed: 38339037
DOI: 10.3390/ijms25031760 -
Acta Psychiatrica Scandinavica Nov 2023No study has investigated the impact of smoking habits and concomitant valproic acid (VPA) use on clinical outcomes in maintenance treatment with clozapine. Thus, we...
Effect of smoking habits and concomitant valproic acid use on relapse in patients with treatment-resistant schizophrenia receiving clozapine: A 1-year retrospective cohort study.
INTRODUCTION
No study has investigated the impact of smoking habits and concomitant valproic acid (VPA) use on clinical outcomes in maintenance treatment with clozapine. Thus, we aimed to examine the effect of smoking habits and concomitant VPA use on relapse during the first year after discharge in patients with treatment-resistant schizophrenia (TRS) receiving clozapine.
METHODS
This retrospective cohort study included patients with TRS who were initiated on clozapine during hospitalization and discharged between April 2012 and January 2021 in two tertiary psychiatric hospitals in Japan. Relapse was defined as rehospitalization due to psychiatric exacerbation during the first year after discharge. A multivariable Cox proportional hazards regression analysis was performed to analyze the effect of smoking habits and concomitant VPA use on relapse. Subgroup analyses were also conducted to examine potential interactions between smoking habits and concomitant VPA use.
RESULTS
Among the included 192 patients, 69 (35.9%) met the criteria of relapse. While smoking habits (adjusted hazard ratio [aHR], 2.27; 95% confidence interval [CI], 1.28-4.01; p < 0.01) independently increased the risk of relapse, a significant interaction for relapse risk was found between smoking habits and concomitant VPA use (p-interaction = 0.015). Concomitant VPA use may be an effective modifier of the increased relapse risk associated with smoking habits. Among patients who smoked, those using VPA concomitantly exhibited a higher risk of relapse (aHR, 5.32; 95% CI, 1.68-16.9; p < 0.01) than those not using VPA (aHR, 1.41; 95% CI, 0.73-2.70; p = 0.30).
CONCLUSION
The findings suggest that the combination of smoking habits and concomitant VPA use may increase the risk of relapse after discharge. Future studies are required to elucidate the mechanisms underlying these findings, such as a decrease in clozapine blood levels.
Topics: Humans; Clozapine; Valproic Acid; Schizophrenia; Smoking; Retrospective Studies; Schizophrenia, Treatment-Resistant; Habits; Antipsychotic Agents
PubMed: 37681448
DOI: 10.1111/acps.13612 -
Experimental & Molecular Medicine Aug 2023Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social behavior and communication, repetitive behaviors, and restricted...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social behavior and communication, repetitive behaviors, and restricted interests. In addition to genetic factors, environmental factors such as prenatal drug exposure contribute to the development of ASD. However, how those prenatal factors induce behavioral deficits in the adult stage is not clear. To elucidate ASD pathogenesis at the molecular level, we performed a high-resolution mass spectrometry-based quantitative proteomic analysis on the prefrontal cortex (PFC) of mice exposed to valproic acid (VPA) in utero, a widely used animal model of ASD. Differentially expressed proteins (DEPs) in VPA-exposed mice showed significant overlap with ASD risk genes, including differentially expressed genes from the postmortem cortex of ASD patients. Functional annotations of the DEPs revealed significant enrichment in the Wnt/β-catenin signaling pathway, which is dysregulated by the upregulation of Rnf146 in VPA-exposed mice. Consistently, overexpressing Rnf146 in the PFC impaired social behaviors and altered the Wnt signaling pathway in adult mice. Furthermore, Rnf146-overexpressing PFC neurons showed increased excitatory synaptic transmission, which may underlie impaired social behavior. These results demonstrate that Rnf146 is critical for social behavior and that dysregulation of Rnf146 underlies social deficits in VPA-exposed mice.
Topics: Animals; Female; Mice; Pregnancy; Autism Spectrum Disorder; Disease Models, Animal; Proteomics; Ubiquitin-Protein Ligases; Up-Regulation; Valproic Acid; Wnt Signaling Pathway
PubMed: 37524878
DOI: 10.1038/s12276-023-01065-2 -
Current Pain and Headache Reports Oct 2023Although the association between CGRP and migraine disease is well-known and studied, therapies can target other pathways to minimize migraine symptoms. It is important... (Review)
Review
PURPOSE OF REVIEW
Although the association between CGRP and migraine disease is well-known and studied, therapies can target other pathways to minimize migraine symptoms. It is important to understand the role of these medications as options for migraine treatment and the varied mechanisms by which symptoms can be addressed. In the present investigation, the role of non-CGRP antagonist/non-triptan options for migraine disease therapy is reviewed, including NSAIDs, ß-blockers, calcium channel blockers, antidepressants, and antiepileptics. Pharmacologic therapies for both acute symptoms and prophylaxis are evaluated, and their adverse effects are compared.
RECENT FINDINGS
At present, the Food and Drug Association has approved the beta-blockers propranolol and timolol and the anti-epileptic drugs topiramate and divalproex sodium for migraine prevention. Clinicians have other options for evidence-based treatment of episodic migraine attacks. Treatment decisions should consider contraindications, the effectiveness of alternatives, and potential side effects. NSAIDs are effective for the acute treatment of migraine exacerbations with caution for adverse effects such as gastrointestinal upset and renal symptoms. Beta-blockers are effective for migraine attack prophylaxis but are associated with dizziness and fatigue and are contraindicated in patients with certain co-morbidities, including asthma, congestive heart failure, and abnormal cardiac rhythms. Calcium channel blockers do not show enough evidence to be recommended as migraine attack prophylactic therapy. The anti-epileptic drugs topiramate and divalproex sodium and antidepressants venlafaxine and amitriptyline are effective for migraine exacerbation prophylaxis but have associated side effects. The decision for pharmacologic management should ultimately be made following consideration of risk vs. benefit and discussion between patient and physician.
Topics: Humans; Topiramate; Valproic Acid; Tryptamines; Migraine Disorders; Propranolol; Calcium Channel Blockers; Antidepressive Agents; Anti-Inflammatory Agents, Non-Steroidal; Serotonin 5-HT1 Receptor Agonists; Drug-Related Side Effects and Adverse Reactions
PubMed: 37584847
DOI: 10.1007/s11916-023-01151-0 -
Journal of Investigative Medicine : the... Jan 2024Dysregulated cholesterol metabolism represents an increasingly recognized feature of autism spectrum disorder (ASD). Children with fetal valproate syndrome caused by...
Dysregulated cholesterol metabolism represents an increasingly recognized feature of autism spectrum disorder (ASD). Children with fetal valproate syndrome caused by prenatal exposure to valproic acid (VPA), an anti-epileptic and mood-stabilizing drug, have a higher incidence of developing ASD. However, the role of VPA in cholesterol homeostasis in neurons and microglial cells remains unclear. Therefore, we examined the effect of VPA exposure on regulation of cholesterol homeostasis in the human microglial clone 3 (HMC3) cell line and the human neuroblastoma cell line SH-SY5Y. HMC3 and SH-SY5Y cells were each incubated in increasing concentrations of VPA, followed by quantification of mRNA and protein expression of cholesterol transporters and cholesterol metabolizing enzymes. Cholesterol efflux was evaluated using colorimetric assays. We found that VPA treatment in HMC3 cells significantly reduced ABCA1 mRNA, but increased ABCG1 and CD36 mRNA levels in a dose-dependent manner. However, ABCA1 and ABCG1 protein levels were reduced by VPA in HMC3. Furthermore, similar experiments in SH-SY5Y cells showed increased mRNA levels for ABCA1, ABCG1, CD36, and 27-hydroxylase with VPA treatment. VPA exposure significantly reduced protein levels of ABCA1 in a dose-dependent manner, but increased the ABCG1 protein level at the highest dose in SH-SY5Y cells. In addition, VPA treatment significantly increased cholesterol efflux in SH-SY5Y, but had no impact on efflux in HMC3. VPA differentially controls the expression of ABCA1 and ABCG1, but regulation at the transcriptional and translational levels are not consistent and changes in the expression of these genes do not correlate with cholesterol efflux in vitro.
Topics: Pregnancy; Female; Child; Humans; Valproic Acid; ATP Binding Cassette Transporter, Subfamily G, Member 1; Autistic Disorder; Autism Spectrum Disorder; Neuroblastoma; Cholesterol; CD36 Antigens; RNA, Messenger
PubMed: 37864505
DOI: 10.1177/10815589231210521 -
Neurology May 2024
Topics: Humans; Valproic Acid; Anticonvulsants; Epilepsy
PubMed: 38569129
DOI: 10.1212/WNL.0000000000209325 -
La Tunisie Medicale Nov 2023The 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....
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. Those with a known psychiatric follow-up or with post ictal psychiatric disturbances were excluded. Psychiatric symptoms were evaluated with the Neurological Disorders Depression Inventory for Epilepsy, the Generalized Anxiety Disorder - 7 and the Neuropsychiatric Inventory Scale. Demographic and clinical data were collected and analyzed.
RESULTS
Among 101 consecutive patients with idiopathic epilepsy, psychiatric symptoms were diagnosed in 61% of them. Anxiety (36.6%), psychotic features (21%) and depression (15.8 %) were the most commonly found psychiatric manifestations. Female gender (p < 10-3) and longer duration of epilepsy (p = 0.046) were significantly associated with occurrence of psychiatric disturbances. Patients under Carbamazepine and Valproic acid showed a lower frequency of depression (respectively p = 0.018 and p = 0.003).
CONCLUSIONS
Occurrence of psychiatric disturbances was frequent in idiopathic epilepsy, with psychotic manifestations and anxiety being the most common of them. Female gender and long disease course were the main determining factors of psychiatric manifestations and should be considered in management of idiopathic epilepsy.
Topics: Humans; Female; Prospective Studies; Epilepsy; Anxiety Disorders; Anxiety
PubMed: 38468585
DOI: No ID Found -
European Journal of Pharmacology Nov 2023Parkinson's Disease (PD) is the most rapidly growing neurological disorder globally in terms of disability and mortality. While symptomatic treatment is available for...
Parkinson's Disease (PD) is the most rapidly growing neurological disorder globally in terms of disability and mortality. While symptomatic treatment is available for PD, there is a critical unmet need for effective disease-modifying therapies. Recently, histone deacetylase inhibitors (HDACi), an important class of epigenetic modulators grabbed significant attention as drug targets for neurodegenerative diseases including PD. In this regard, novel pan-HDACi, cinnamyl sulphonamide hydroxamate derivatives (NMJ-2 and NMJ-3), synthesized and characterized in our laboratory, were screened for neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rat model of PD. Twenty-four hours after the bilateral intranigral injection of MPTP, rats were administered orally with NMJ-2 or NMJ-3 (150 mg/kg) daily for 30 days. MPTP administration resulted in a marked rise in lipid peroxidation, and interleukin-1β concentration accompanied by reduced tyrosine hydroxylase and dopamine levels in the striatum compared to the sham group. These biochemical changes were associated with functional motor and non-motor deficits as revealed by loss of motor coordination (rota rod test), impaired grip strength (beam walk test), enhanced rigidity (catalepsy scores), loss of memory (novel object recognition test) and depressive-like behaviour (forced swim test). However, oral treatment with NMJ-2 or NMJ-3, or valproic acid for 30 days significantly attenuated the PD-induced adverse changes in motor and non-motor functions by ameliorating the oxidative stress as well as inflammation, and restoring the dopamine levels in the striatum comparable to the valproic acid group. These results suggest that targeting HDACi could be a rational therapeutic strategy for the development of disease-modifying therapies for PD.
Topics: Rats; Animals; Mice; Parkinson Disease; Dopamine; Histone Deacetylase Inhibitors; Neuroprotection; Valproic Acid; Neuroprotective Agents; Disease Models, Animal; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Mice, Inbred C57BL
PubMed: 37751833
DOI: 10.1016/j.ejphar.2023.176067