411,642 results match your criteria: "Department of Clinical Pharmacology & DMPK[Affiliation]"

In recent years, with the experience of the COVID-19 pandemic, countries around the world have realized that improving patient access to new medicines can have a significant impact on public health and economic stability. The aim of this study was to identify new drugs that are urgently needed among those not yet available in South Korea from 2011 to 2020, and to develop strategies to improve access by analyzing the causes of delay. Through a 3-step screening process that included a literature review of new drugs, surveys of domestic clinicians and academics, and consideration of expedited review status by regulatory authorities, 34 out of 244 unreleased new drugs were prioritized for rapid introduction.

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Antibody-drug conjugates (ADCs) have advanced as a mainstay among the most promising cancer therapeutics, offering enhanced antigen targeting and encompassing wide diversity in their linker and payload components. Small-molecule inhibitors of tubulin polymerization have found success as payloads in FDA approved ADCs and represent further promise in next-generation, pre-clinical and developmental ADCs. Unique dual-mechanism payloads (previously designed and synthesized in our laboratories) function as both potent antiproliferative agents and promising vascular disrupting agents capable of imparting selective and effective damage to tumor-associated microvessels.

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Background: The increasing global prevalence of asthma necessitates effective disease management, with patients and their families playing a central role. Enhancing health literacy (HL) among caregivers is critical to improving asthma outcomes.

Purpose: This study aimed to validate the Arabic version of the Asthma Numeracy Questionnaire (Ar-ANQ) to address the gap in HL assessment tools for Arabic-speaking populations.

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Genomic characterization of Huntington's disease genetic modifiers informs drug target tractability.

Brain Commun

January 2025

Department of Pharmacology and Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaR3E 0T6.

Huntington's disease is caused by a CAG repeat in the gene. Repeat length correlates inversely with the age of onset but only explains part of the observed clinical variability. Genome-wide association studies highlight DNA repair genes in modifying disease onset, but further research is required to identify causal genes and evaluate their tractability as drug targets.

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Recent interest has been focused on extracellular matrix (ECM)-based scaffolds totreat critical-sized bone injuries. In this study, urea was used to decellularize and solubilize human placenta tissue. Then, different concentrations of ECM were composited with 8% alginate (Alg) and 12% silk fibroin (SF) for printing in order to produce a natural 3D construct that resembled bone tissue.

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The widespread adoption and commercialization of lateral flow assays (LFAs) for clinical diagnosis have been hindered by limitations in sensitivity, specificity, and the absence of quantitative data. To address these challenges, we developed aptamer-architectured gold nanoparticles as nanozymes that catalytically convert -phenylenediamine (PPD) into Bandrowski's base (BB), thereby amplifying signal strength and sensitivity. The physiochemical properties of the nanozymes were characterized and their specific binding efficiency was demonstrated using experimental studies.

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Opioid use disorder is heritable, yet its genetic etiology is largely unknown. C57BL/6J and C57BL/6NJ mouse substrains exhibit phenotypic diversity in the context of limited genetic diversity which together can facilitate genetic discovery. Here, we found C57BL/6NJ mice were less sensitive to oxycodone (OXY)-induced locomotor activation versus C57BL/6J mice in a conditioned place preference paradigm.

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C3/C3aR Bridges Spinal Astrocyte-Microglia Crosstalk and Accelerates Neuroinflammation in Morphine-Tolerant Rats.

CNS Neurosci Ther

January 2025

Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aims: Communication within glial cells acts as a pivotal intermediary factor in modulating neuroimmune pathology. Meanwhile, an increasing awareness has emerged regarding the detrimental role of glial cells and neuroinflammation in morphine tolerance (MT). This study investigated the influence of crosstalk between astrocyte and microglia on the evolution of morphine tolerance.

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Understanding tumor heterogeneity is a major challenge that was recognized as one of the first Cancer Grand Challenges, with a call to provide solutions to visualize tumor heterogeneity. The Rosetta team took on this challenge, exploiting advances in spatial-omics approaches centered around mass spectrometry imaging to map tumor heterogeneity at the cellular and molecular scales with different levels of resolution. See related article by Bressan et al.

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Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry.

Eur Heart J

January 2025

Department of Primary Care and Public Health, Imperial Centre for Cardiovascular Disease Prevention, School of Public Health, Imperial College London, White City Campus, 90 Wood Lane, London W12 0BZ, UK.

Background And Aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.

Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD.

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Background: Neurohormonal blocking drugs, like beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), are recommended for treating anthracycline-induced left ventricular dysfunction (AILVD). However, there is limited evidence supporting their benefit. Therefore, this study evaluated associations of neurohormonal blockers and other clinical factors with recovery of left ventricular ejection fraction (LVEF) in patients with AILVD.

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Lactulose Versus Naloxone for Opioid-Induced Constipation in Intensive Care.

Turk J Pharm Sci

January 2025

Shahid Beheshti University of Medical Sciences Faculty of Medicine, Toxicological Research Center, Excellence Center and Department of Clinical Toxicology, Tehran, Iran.

Objectives: Constipation caused by opioid-induced constipation (OIC) is prevalent among critically poisoned patients and can result in complications that prolong hospitalization and, in rare cases, cause bowel perforatio This research aimed to evaluate the safety and efficacy of lactulose and naloxone in the treatment of OIC in the intensive care unit for poisoning.

Materials And Methods: This was a randomized, double-blind, clinical trial of patients with opioid poisoning who experienced constipation for 14 months. Patients were divided into two groups: one receiving lactulose (30 cc daily) and the other receiving naloxone (8 mg three times a day).

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Enterococcus species, natural inhabitants of the human gut, have become major causes of life-threatening bloodstream infections (BSIs) and the third most frequent cause of hospital-acquired bacteremia. The rise of high-level gentamicin resistance (HLGR) in enterococcal isolates complicates treatment and revives bacteriophage therapy. This study isolated and identified forty E.

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Objectives: This study aimed to assess the general population's knowledge, attitudes, and practices regarding hair dye (HD) usage and its adverse effects in the Northern Emirates of the United Arab Emirates.

Materials And Methods: A cross-sectional study was conducted over 3 months in the general population of Ras Al Khaimah. Information was collected by administering a pre-validated self-administered questionnaire related to HDs.

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Background And Aims: To investigate the treatment of ofatumumab in autoimmune nodopathy (AN).

Methods: An open-label, prospective, observational study was conducted in patients with AN. The regimen was 20 mg ofatumumab subcutaneously on day 0, 7, 14, 28, and subsequently every 4 weeks in a total of 24 weeks.

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Molecular Identification and Antifungal Susceptibility of Fusarium spp. Clinical Isolates.

Mycoses

January 2025

Clinical Microbiology Laboratory, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Background: Accurate identification of Fusarium species requires molecular identification. Treating fusariosis is challenging due to widespread antifungal resistance, high rates of treatment failure, and insufficient information relating antifungal susceptibility to the clinical outcome. Despite recent outbreaks in Mexico, there is limited information on epidemiology and antifungal susceptibility testing (AST).

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Background: Colorectal cancer (CRC) is a major public health concern. Animal models play a crucial role in understanding the disease pathology and development of effective treatment strategies. Chemically induced CRC represents a cornerstone in animal model development; however, due to the presence of different animal species with different genetic backgrounds, it becomes mandatory to study the susceptibility of different mice species to CRC induction by different chemical entities such as 1,2-dimethylhydrazine (DMH).

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Background: Preceding studies of environmental and occupational risk factors of sarcoidosis yielded inconsistent findings.

Aims: We aimed to ascertain the occupational risk factors for sarcoidosis in a case-control study.

Methods: A total of 237 sarcoidosis patients with a histologically confirmed diagnosis were matched with 474 controls for sex and age (median 49, interquartile range 37; 60 years) recruited from the university hospitals and outpatient centres in Belarus, Kazakhstan and the Russian Federation.

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Recent evidence indicates that endocrine resistance in estrogen receptor-positive (ER+) breast cancer is closely correlated with phenotypic characteristics of epithelial-to-mesenchymal transition (EMT). Nonetheless, identifying tumor tissues with a mesenchymal phenotype remains challenging in clinical practice. In this study, we validated the correlation between EMT status and resistance to endocrine therapy in ER+ breast cancer from a transcriptomic perspective.

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Cell cycle dysregulation and the corresponding metabolic reprogramming play significant roles in tumor development and progression. CDK9, a kinase that regulates gene transcription and cell cycle, also induces oncogene transcription and abnormal cell cycle in AML cells. The function of CDK9 for gene regulation in AML cells requires further exploration.

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Mitophagy that disrupt mitochondrial membrane potential (MMP), represents a critical focus in pharmacology. However, the discovery and evaluation of MMP-disrupting drugs are often hampered using commercially available marker molecules that target similar or identical zones. These markers can significantly interfere with, obscure, or amplify the functional effects of MMP-targeting drugs, frequently leading to clinical failures.

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Background: Chemical derivatization is a common technique in liquid chromatography-mass spectrometry (LC-MS) metabolomics used to improve the ionizability and chromatographic properties of metabolites in complex biological samples. This process facilitates better detection and separation of a wide array of compounds. The reagent 2-(4-boronobenzyl) isoquinolin-2-ium bromide (BBII), developed as a glucose labeling reagent for matrix-assisted laser desorption/ionization MS, enhances ionization for glucose and other hydroxyl metabolites.

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With the rapid development of epidermal growth factor receptor (EGFR) gene testing of lung adenocarcinoma patients has been routinely carried out, EGFR mutations are also possible for some small samples of non-smoking female lung squamous cell carcinoma patients. This increases the opportunity for targeted therapy for this group of patients. However, drug resistance in patients with lung squamous cell carcinoma during targeted therapy is an important factor affecting subsequent treatment.

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Dietary supplementation and the role of phytochemicals against the Alzheimer's disease: Focus on polyphenolic compounds.

J Prev Alzheimers Dis

January 2025

Indian Scientific Education and Technology Foundation, Lucknow, 226002, India. Electronic address:

Alzheimer's disease is a complicated, multifaceted, neurodegenerative illness that places an increasing strain on healthcare systems. Due to increasing malfunction and death of nerve cells, the person suffering from Alzheimer's disease (AD) slowly and steadily loses their memories, cognitive functions and even their personality. Although medications may temporarily enhance memory, there are currently no permanent therapies that can halt or cure this irreversible neurodegenerative process.

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