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Approach to Evaluating QT Prolongation of Quetiapine Fumarate in Late Stage of Clinical Development Using Concentration-QTc Modeling and Simulation in Japanese Patients With Bipolar Disorder.

PURPOSE: Quetiapine has been reported to prolong the QT interval, and has been used as a positive control in thorough QT studies. The objective of the present study was to evaluate, in the late stages of clinical development, the QT-prolongation effects of the extended-release (XR) formulation of quetiapine at the approved dose in Japanese patients with bipolar disorder, using concentration-QT modeling and simulation. METHODS: Plasma concentrations of quetiapine and 4 of its metabolites (M1, M2, M4, and M5), and the QT interval corrected using the Fridericia formula (QTcF), were used for the

Dimethyl fumarate protects cardiomyocytes against oxygen-glucose deprivation/reperfusion (OGD/R)-induced inflammatory response and damages via inhibition of Egr-1.

Acute myocardial infarction (AMI) is associated with high rates of morbidity and mortality. Atherosclerosis is among the leading causes of AMI. The rupture or erosion of atherosclerotic plaques can obstruct coronary arteries, thereby leading to an acute inflammatory reaction to ischemic injury and cardiomyocyte apoptosis. Dimethyl fumarate (DMF) is a fumaric acid diester which is used for the treatment of psoriasis and multiple sclerosis. DMF is most well-known for its modulatory actions on the Nrf2 and NF-κB cellular signaling pathways. In the present study, we employed an oxygen-glucose depr

Application of pharmacogenomics to investigate adverse drug reactions to the disease-modifying treatments for multiple sclerosis: a case-control study protocol for dimethyl fumarate-induced lymphopenia.

INTRODUCTION: Adverse drug reactions (ADRs) are a global public health issue. The potential for pharmacogenomic biomarkers has been demonstrated in several therapeutical areas, including HIV infection and oncology. Dimethyl fumarate (DMF) is a licensed disease-modifying therapy for the treatment of multiple sclerosis (MS). The use of DMF in MS has been associated with a severe reduction in lymphocyte counts and reports of progressive multifocal leukoencephalopathy. Here, we outline the protocol for a case-control study designed to discover genomic variants associated with DMF-induced lymphopen

Sino-implant (II)® continuation and effect of concomitant tenofovir disoproxil fumarate-emtricitabine use on plasma levonorgestrel concentrations among women in Bondo, Kenya.

OBJECTIVE: The objective was to assess associations between tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) exposure and levonorgestrel (LNG) concentrations among Kenyan HIV prevention trial participants using Sino-implant (II) LNG implants for contraception. METHODS: Women were offered implants among other contraceptive methods, were randomized to daily TDF-FTC or placebo, and followed monthly up to 56weeks. Associations between TDF-FTC exposure and mean LNG values were analyzed with linear mixed models. RESULTS: Of 739 women, 29 (3.9%) received implants with no incident pregnancies a

The extended-release formulation of quetiapine fumarate (quetiapine XR) adjunctive treatment in partially responsive generalized anxiety disorder (GAD): An open label naturalistic study.

AIMS: To assess the effect of adjunctive treatment with extended-release formulation of quetiapine fumarate (quetiapine XR) to other antidepressants in the treatment of partially responsive, poorly functioning patients with generalized anxiety disorder was assessed. MATERIALS AND METHODS: Twenty four consenting adult outpatients with confirmed DSM-IV diagnosis of generalized disorder were identified. All patients failed at least one 8-week treatment trial with SSRI or SNRI antidepressant. All were treated with quetiapine XR as an add on treatment to citalopram or vanlafaxine antidepressant fo

Antiviral effects of lamivudine, emtricitabine, adefovir dipivoxil, and tenofovir disoproxil fumarate administered orally alone and in combination to woodchucks with chronic woodchuck hepatitis virus infection.

Adefovir dipivoxil (ADV) and tenofovir disoproxil fumarate (TDF) are nucleotide analogs that inhibit the replication of wild-type hepatitis B virus (HBV) and lamivudine (3TC)-resistant virus in HBV-infected patients, including those who are coinfected with human immunodeficiency virus. The combination of ADV or TDF with other nucleoside analogs is a proposed strategy for managing antiviral drug resistance during the treatment of chronic HBV infection. The antiviral effect of oral ADV or TDF, alone or in combination with 3TC or emtricitabine (FTC), against chronic woodchuck hepatitis virus (WHV

Bioresorbable bone graft substitutes of different osteoconductivities: a histologic evaluation of osteointegration of poly(propylene glycol-co-fumaric acid)-based cement implants in rats.

Bioresorbable bone graft substitutes may significantly reduce the disadvantages associated with autografts, allografts and other synthetic materials currently used in bone graft procedures. We investigated the biocompatibility and osteointegration of a bioresorbable bone graft substitute made from the unsaturated polyester poly(propylene-glycol-co-fumaric acid), or simply poly(propylene fumarate), PPF, which is crosslinked in the presence of soluble and insoluble calcium filler salts. Four sets of animals each having three groups of 8 were evaluated by grouting bone graft substitutes of varyin

Деэскалация болезней, изменяющих методы лечения: ретроспективное исследование с использованием одного центра наблюдения.

ЦЕЛЬ: Из-за риска продолжительного воздействия более эффективной терапии не ясно, как долго нужно лечить людей с склерозами. Имеется мало данных о деэскалации лечения, что может восполнить разрыв между более эффективной терапией и прекращением лечения. Цель этого исследования заключается в определении результатов деэскалации ДМТ. МЕТОДЫ: Данные были получены ретроспективно из медицинской документации. Ежегодный коэффициент рецидива (ARR) оценивался с использованием общих моделей линейного смешанного воздействия Poisson (GLMM), а активность MRI и инвалидность оценивались с использованием логист

Совпадение в аннотации оригинала
PURPOSE: Due to risks of prolonged higher efficacy therapy exposure, it is unclear how long to treat people with MS. There is little data on … Freedom from both relapses and MRI activity were higher on those de-escalating from ocrelizumab or fumarates compared to natalizumab or s1p modulators. Non-inferiority for de-escalation was not demonstrated in either cohort. CONCLUSIONS: Our study provides real world evidence on de-escalation strategies. De-escalation from ocrelizumab and fumarates appear …

Real-World Outcomes across Baseline Risk Profiles in Patients with COPD Initiating Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate in Spain: Insights from the ORESTES Study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by persistent symptoms such as dyspnea and cough, as well as exacerbations. Triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) is recommended for patients not adequately controlled by dual therapy. Key clinical parameters guide COPD management. METHODS: The observational, retrospective ORESTES study included adults ≥ 40 years with COPD initiating BGF in routine practice. In this analysis, patients were grouped according to exacerbation history, airflow obstruc

Efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler in patients with tuberculosis-associated chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Clinical trials have shown that glycopyrrolate/formoterol fumarate improves lung function in patients with chronic obstructive pulmonary disease (COPD) caused by tobacco exposure. Although tuberculosis-associated COPD has worse respiratory health outcomes than smoking-associated COPD, no clinical trials have determined whether pharmacological intervention is effective. We designed a clinical trial to evaluate the safety and efficacy of glycopyrrolate/formoterol fumarate for the treatment of tuberculosis-associated COPD. METHODS: We report the protocol for a prospective, multicentr

Intravascular propagation of adenomyosis within the blood vessels of the myometrium and uterine leiomyoma in a patient harboring germline mutation in the fumarate hydratase gene - a rare finding simulating malignancy.

BACKGROUND: Hereditary leiomyomatosis and renal cell carcinoma is a rare genetic disorder characterized by a predisposition to the development of multiple cutaneous and uterinne leiomyomas with a potential for malignant transformation and a risk of renal carcinoma. CASE: A 39-year-old woman suffered from this disease underwent hysterectomy due to uterus myomatosus. Histologically, some tumors showed typical appearance of fumarate hydratase-deficient leiomyomas. There were foci of adenomyosis in the myometrium. As an incidental finding, multiple thin-walled blood vessels filled with conglomera

The blocking efficacy and safety of tenofovir disoproxil fumarate tablets on mother-to-child transmission in pregnant women with high serum HBV DNA load: a retrospective cohort study.

OBJECTIVE: We aimed to evaluate the efficacy and safety of using/not using the antiviral drug tenofovir disoproxil fumarate (TDF) in preventing mother-to-child transmission (MTCT) of hepatitis B virus (HBV) among pregnant women with high serum HBV DNA viral loads. METHODS: This retrospective study included 512 pregnant women with HBV infection and a high serum HBV DNA load (> 2 × 105 IU/mL) diagnosed and treated at our hospital between January 2018 and April 2023. Based on the treatment received, 314 women were identified as the TDF-treated group, while the remaining 198 comprised the TDF-une

Mitochondrial Disorders After 12 Months of Human Immunodeficiency Virus Type 1 Preexposure Prophylaxis Based on Tenofovir Disoproxil Fumarate Plus Emtricitabine in Healthy Adults.

BACKGROUND: New nucleos(t)ide reverse transcriptase inhibitors are considerably less toxic than their predecessors, but they may not be entirely devoid of toxicity. However, their effect in healthy adults remains unknown. We aimed to analyze the impact of tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC)-based preexposure prophylaxis (PrEP) on mitochondria of subjects at high risk of human immunodeficiency virus type 1 infection. METHODS: This was an observational, prospective study of 59 healthy adults enrolled in the PrEP program at Virgen del Rocío University Hospital. Mitochondri

Luteolin rescues myelin integrity and cognitive-motor function via Nrf2 pathway activation: a natural candidate vs. dimethyl fumarate in cuprizone-induced multiple sclerosis.

Objective: Targeting the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway represents a promising therapeutic strategy for multiple sclerosis (MS). However, approved drugs like dimethyl fumarate (DMF) often induce severe side effects. This study investigated the natural flavonoid luteolin (LUT) as a potential dietary supplement alternative to DMF in a cuprizone (CPZ)-induced demyelination mouse model of MS.Methods: Mice were randomly assigned to five groups: control, CPZ model, CPZ+DMF (15 mg/kg), CPZ+LUT (25 mg/kg), and CPZ+LUT (50 mg/kg). Motor coordination and spatial memory were a

Benefits of budesonide/glycopyrronium/formoterol fumarate dihydrate on lung function and exacerbations of COPD: a post-hoc analysis of the KRONOS study by blood eosinophil level and exacerbation history.

BACKGROUND: Japanese guidelines recommend triple inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) and no concurrent asthma diagnosis who experience frequent exacerbations and have blood eosinophil (EOS) count ≥ 300 cells/mm3, and in patients with COPD and asthma with continuing/worsening symptoms despite receiving dual ICS/LABA therapy. These post-hoc analyses of the KRONOS study in patients with COPD and without an asthma diagnosis, examine the effects of fixed-dose triple

Blood immune cells from people with HIV on antiviral regimens that contain tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) have differential metabolic signatures.

BACKGROUND: Mitochondria regulate immune and organ function. It is unknown whether higher intracellular drug levels observed in peripheral blood mononuclear cells (PBMCs) treated with tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) may alter mitochondrial function and energy production in immune cells in HIV(+) patients. METHODS: Cellular bioenergetics were determined in PBMCs from HIV-1(-) participants exposed to TAF versus TDF in vitro, at a comparable concentration to a clinically relevant plasma exposure. A decrease in cellular oxygen consumption rate (OCR) at

Metabolic-Related Outcomes After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Adults With Human Immunodeficiency Virus (HIV): A Multicenter Prospective Cohort Study.

BACKGROUND: Tenofovir alafenamide (TAF) has replaced tenofovir disoproxil fumarate (TDF) in many clinical settings. However, concerns remain about potential metabolic complications of TAF. We aimed to evaluate changes in weight, laboratory markers, and metabolic-related clinical events after replacing TDF with TAF. METHODS: Multicenter prospective cohort study in the Spanish CoRIS cohort. We included virologically suppressed adults with human immunodeficiency virus (HIV) receiving TDF for more than 12 months who either switched to TAF or maintained TDF, with no changes in the core agent. Part

Dimethyl fumarate improves cognitive deficits in chronic cerebral hypoperfusion rats by alleviating inflammation, oxidative stress, and ferroptosis via NRF2/ARE/NF-κB signal pathway.

Cerebrovascular disease and its risk factors cause persistent decrease of cerebral blood flow, chronic cerebral hypoperfusion (CCH) is the major foundation of vascular cognitive impairment (VCI). The hippocampus is extremely vulnerable to cerebral ischemia and hypoxia. Oxidative stress and neuroinflammation injury are important pathophysiological mechanisms of this process, which is closely related to hippocampal neurons damage and loss. Dimethyl fumarate (DMF), an FDA-approved therapeutic for multiple sclerosis (MS), plays a protective role in multiple neurological disorders. Studies have sho

Comparison of 3- and 6-Month Outcomes of Combined Oral L-Carnitine Fumarate and Acetyl-L-Carnitine Therapy, Included in an Antioxidant Formulation, in Patients with Idiopathic Infertility.

The male factor is responsible for infertility in about 35-40% of all cases. Idiopathic oligo- and/or astheno- and/or therato-zoospermia is one of the most common male fertility disorders and remains a significant therapeutic challenge. The primary cause of idiopathic male infertility remains unknown but seems to be associated with oxidative stress. Objective: The use of antioxidative formulation to improve qualitative and quantitative deficiencies in the male gametes.In total, 78 subjects were treated with a combination of 1,725 mg L-carnitine fumarate, 500 mg acetyl-L-carnitine, 90 mg vitami