Journals Basic & Clinical Pharmacology ...

Basic & Clinical Pharmacology & Toxicology
Philip Ahle Erichsen, Kim Dalhoff, Michael Asger Andersen
N-acetylcysteine (NAC) is regarded as an effective treatment of paracetamol overdoses. However, in cases of "massive" paracetamol overdoses, recent studies indicate that patients may not be sufficiently treated with the standard dose of NAC (300 mg/kg over 20-21 h). The subject is further complicated because "massive overdoses" and "high-risk" are defined differently; some studies use the ingested amount (e.g., >40 g), and some studies use blood concentrations of paracetamol and transaminases...
July 14, 2024: Basic & Clinical Pharmacology & Toxicology
João Pedro da Silva Lopes, Joana Barbosa, Ricardo Jorge Dinis-Oliveira
Potassium iodide has demonstrated several therapeutic applications over time, being the choice for shielding the thyroid during radiation emergencies involving radioiodine release. Amidst the ongoing military conflict between Ukraine and Russia and the growing concern regarding the potential deployment of nuclear weapons, there has been a surge in the demand for potassium iodide across Europe. This work aimed to comprehensively review the current knowledge regarding the pharmacology, physiology, adverse effects, the protective role in reducing the risk of thyroid cancer and recommendations for potassium iodide use during radiation emergencies...
July 11, 2024: Basic & Clinical Pharmacology & Toxicology
Louise Westberg Strejby Christensen, Esben Iversen, Aino Leegaard Andersen, Anne Byriel Walls, Line Jee Hartmann Rasmussen, Ove Andersen, Thomas Kallemose, Morten Baltzer Houlind
Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation. Elevated suPAR levels are associated with adverse clinical outcomes, but a small subset of patients with low suPAR also experience poor outcomes. Therefore, we aimed to characterize patients presenting to the emergency department with low suPAR (<3 ng/mL) who died within 90 days after discharge in a registry-based study. Compared to patients with low suPAR who survived (n = 15 122), those who died within 90 days (n = 87) had higher age (75...
July 11, 2024: Basic & Clinical Pharmacology & Toxicology
Maartje M van de Meeberg, Janani Sundaresan, Marry Lin, Gerrit Jansen, Eduard A Struys, Herma H Fidder, Bas Oldenburg, Wout G N Mares, Nofel Mahmmod, Dirk P van Asseldonk, Svend T Rietdijk, Loes H C Nissen, Nanne K H de Boer, Gerd Bouma, Maja Bulatović Ćalasan, Robert de Jonge
BACKGROUND: Intracellular methotrexate polyglutamates (MTX-PGs) concentrations are measurable in red blood cells (RBCs) during MTX treatment. MTX-PG3 concentrations correlate with efficacy in patients with Crohn's disease (CD). Since RBCs are not involved in pathogenesis of CD and lack extended MTX metabolism, we determined MTX-PGs accumulation in peripheral blood mononuclear cells (PBMCs: effector cells) and intestinal mucosa (target cells) and compared those with RBCs as a potential more precise biomarker...
July 8, 2024: Basic & Clinical Pharmacology & Toxicology
Raimo K Tuominen, Juho-Matti Renko
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopamine neurons and aberrant deposits of alpha-synuclein (α-syn) in the brain. The symptomatic treatment is started after the onset of motor manifestations in a late stage of the disease. Preclinical studies with neurotrophic factors (NTFs) show promising results of disease-modifying neuroprotective or even neurorestorative effects. Four NTFs have entered phase I-II clinical trials with inconclusive outcomes...
July 8, 2024: Basic & Clinical Pharmacology & Toxicology
Tharwat El Zahran, Lina Hammoud, Rana Salam, Youssef Salam, Ziad Kazzi, Hani Tamim, Eveline Hitti
Poisoning poses a worldwide public health challenge and recent data from Lebanon in 2020 revealed that over half patients presenting with acute toxicological exposure intentionally poisoned themselves, primarily with suspected suicidal intent. This study aims to assess sex disparities in intentional toxicological exposures among patients presenting to the Emergency Department, at a tertiary care centre in Lebanon. This was a secondary analysis of an existing toxicological database, including patients aged 6 years and older admitted due to acute overdose from March 2015 to August 2022...
July 4, 2024: Basic & Clinical Pharmacology & Toxicology
(no author information available yet)
No abstract text is available yet for this article.
July 1, 2024: Basic & Clinical Pharmacology & Toxicology
Sonja Buratovic, Gaetan Philippot, Bo Stenerlöw, Per-Arne Lönnqvist
BACKGROUND: The local anaesthetic lidocaine is widely used in the neonatal intensive unit to treat seizures in premature babies. However, other antiepileptics administered during early development in various animal models have shown negative long-term behavioural effects. Since no long-term behavioural data so far exist regarding lidocaine exposure at an early age, we decided to perform this extended follow-up study using a sensitive behavioural test. METHODS: Neonatal mice received a subcutaneous administration of saline or one dose of lidocaine (0...
June 19, 2024: Basic & Clinical Pharmacology & Toxicology
Adamczuk Piotr, Jamka Konrad, Bojar Hubert, Łukawski Krzysztof, Raszewski Grzegorz
Exogenous, well-established antioxidant N-acetylcysteine can reduce or prevent the deleterious effects of pesticides. In this study, utilizing a mouse model of daily single dose of N-acetylcysteine administration, we investigated the impact of this adjuvant on the treatment with atropine and/or obidoxime as well as oxidative stress response in pyrimiphos-methyl-induced toxicity. We found that N-acetylcysteine significantly reduces the oxidative stress generated by pyrimiphos-methyl. The therapy consisting of atropine and/or obidoxime routinely used in organophosphorous insecticide poisonings, including pyrimiphos-methyl, had no effect on the antioxidant properties of N-acetylcysteine...
June 19, 2024: Basic & Clinical Pharmacology & Toxicology
Guofang Bi, Fengting Liang, Ting Wu, Peng Wang, Xiaowen Jiang, Shuang Hu, Chenghua Wu, Wenhong Zhou, Jiayin Guo, Xiao Yang, Jian-Hong Fang, Wenying Chen, Huichang Bi
Human pregnane X receptor (PXR) is critical for regulating the expression of key drug-metabolizing enzymes such as CYP3A and CYP2C. Our recent study revealed that treatment with rodent-specific PXR agonist pregnenolone-16α-carbonitrile (PCN) significantly induced hepatomegaly and promoted liver regeneration after two-thirds partial hepatectomy (PHx) in mice. However, it remains unclear whether PXR activation induces hepatomegaly and liver regeneration and simultaneously promotes metabolic function of the liver...
June 17, 2024: Basic & Clinical Pharmacology & Toxicology
Shi-Kang Lin, Shi-Ting Chen, Ying Zhan, Xin-Yue Guo, Wen-Tao Wu, Yi-Ting Lin, Chang-Xi Yu, Jian Yang
The aim of this study was to validate the preventive effects of koumine (KM), a monoterpene indole alkaloid, on gouty arthritis (GA) and to explore its possible mechanisms. C57BL/6 mice were intraperitoneally administered KM (0.8, 2.4 or 7.2 mg/kg), colchicine (3.0 mg/kg) or sterile saline. One hour later, a monosodium urate (MSU) suspension was injected into the right hind paws of the mice to establish an acute gout model. Inflammation symptoms were evaluated at 0, 3, 6, 12 and 24 h, and the mechanical withdrawal threshold was evaluated at 0, 6 and 24 h...
June 3, 2024: Basic & Clinical Pharmacology & Toxicology
Steffen Jørgensen, Thorsten Brodersen, Ole Birger Vesterager Pedersen, Niels Westergaard
No abstract text is available yet for this article.
May 30, 2024: Basic & Clinical Pharmacology & Toxicology
Yuxi Wang, Lan Long, Qian Luo, Xinyi Huang, Ying Zhang, Xiao Meng, Dayi Chen
Aflatoxin B1 (AFB1) is extremely harmful to both humans and animals. Mitophagy is a selective process of self-elimination and has an important role in controlling mitochondrial quality. The present study aimed to investigate the effect of reactive oxygen species (ROS) accumulation on AFB1-induced mitophagy in HepG2 cells to provide a new perspective from which to design novel therapeutic strategies to treat AFB1 poisoning. ROS release was induced in HepG2 cells with AFB1 (10 μmol/L). Cell autophagy activity, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) levels, Parkin translocation and both the transcription and expression of mitophagy-related proteins were measured when N-acetyl-L-cysteine (NAC) partially decreased the ROS level, while the knockdown of nuclear factor erythroid 2-related factor 2 (Nrf2) resulted in a large accumulation of ROS...
May 28, 2024: Basic & Clinical Pharmacology & Toxicology
Mustafa Sengul, Baris Karadas, Selin Acar-Sahan, Ozan Ozturk, Huseyin Yılmaz, Fatma Simsek, Tijen Kaya-Temiz
INTRODUCTION: To investigate the in vitro effect of diclofenac on tubal smooth muscle as an alternative to hyoscine-N-butyl bromide, which is used for premedication before hysterosalpingography (HSG). MATERIAL AND METHODS: Fallopian tubes were retrieved from seven healthy women after bilateral tubal ligation and in vitro contractility and histological studies were conducted using tissue bath and immunohistochemistry. RESULTS: Diclofenac sodium and hyoscine-N-butyl bromide did not significantly change the basal mean tension; however, they decreased the contractions induced by potassium chloride (KCl)...
May 27, 2024: Basic & Clinical Pharmacology & Toxicology
Shokouh Arjmand, Mehran Ilaghi, Ali Karimi Sisakht, Matti Bock Guldager, Gregers Wegener, Anne M Landau, Albert Gjedde
Alzheimer's disease (AD) is a neurodegenerative disorder that primarily manifests itself by progressive memory loss and cognitive decline, thus significantly affecting memory functions and quality of life. In this review, we proceed from the understanding that the canonical amyloid-β hypothesis, while significant, has faced setbacks, highlighting the need to adopt a broader perspective considering the intricate interplay of diverse pathological pathways for effective AD treatments. Sex differences in AD offer valuable insights into a better understanding of its pathophysiology...
May 27, 2024: Basic & Clinical Pharmacology & Toxicology
Jodie L Morris, Hayley L Letson, Geoffrey P Dobson
Adenosine, lidocaine and Mg2+ (ALM) solution is an emerging therapy that reduces secondary injury after intravenous administration in experimental models of traumatic brain injury (TBI). Intranasal delivery of ALM may offer an alternative route for rapid, point-of-care management of TBI. As a preliminary safety screen, we evaluated whether ALM exerts cytotoxic or inflammatory effects on primary human nasal epithelial cells (pHNEC) in vitro. Submerged monolayers and air-liquid interface cultures of pHNEC were exposed to media only, normal saline only, therapeutic ALM or supratherapeutic ALM for 15 or 60 min...
May 24, 2024: Basic & Clinical Pharmacology & Toxicology
Han-Xiao Song, Yu-Han Xie, Yuan-Yuan Fang, Jun-Jie Lin, Lei-Lei Wang, Cui-Liu Gan, Michael Aschner, Yue-Ming Jiang
We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para-aminosalicylate (PAS-Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage...
May 23, 2024: Basic & Clinical Pharmacology & Toxicology
Qiao Liu, Qingman Luo, Bin Zhong, Yingxin Xiong, Xueling Chen, Xiaohui Li
There is a lack of effective therapeutic drugs for pulmonary arterial hypertension. Previous studies have demonstrated the positive cardiovascular system protective effects of the new peptide ACTY116. However, its stability in ordinary aqueous solution injections is poor and its half-life in the body is short, which has hindered the development of preparations. This study aimed to prepare in situ forming implants (ISFIs) of the peptide ACTY116 and investigate its impact on pulmonary arterial hypertension. We prepared ISFIs using NMP/TA as a solvent and PLGA as a polymer...
May 20, 2024: Basic & Clinical Pharmacology & Toxicology
(no author information available yet)
No abstract text is available yet for this article.
May 16, 2024: Basic & Clinical Pharmacology & Toxicology
Zeena A Hussein, Ahmed R Abu-Raghif, Hayder Adnan Fawzi
This study investigated the therapeutic benefits of para-hydroxycinnamic acid in mice with bleomycin-induced lung fibrosis. Forty male BALB/c mice were randomly assigned to four groups: normal, which received 0.9% normal saline; induced, which received a single dose of bleomycin (5 mg/kg) by oropharyngeal challenge; pirfenidone-treated; and para-hydroxycinnamic acid-treated, which challenged with bleomycin and received a daily oral dose of 300 and 50 mg/kg, respectively, from day 7 to day 21. Tissue pro-fibrotic and inflammatory cytokines, oxidative indicators, pulmonary histopathology, immunohistochemistry of fibrotic proteins and the assessment of gene expression by RT-qPCR were evaluated on day 22 after euthanizing animals...
May 14, 2024: Basic & Clinical Pharmacology & Toxicology
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