Basic & Clinical Pharmacology & Toxicology

In many areas of medicine, gender equality has not yet been fully adopted despite recent developments. The inequality of gender in various areas of medicine is still debated. In this study, we analyzed the gender composition of the editorial boards of toxicology journals in the Science Citation Index-Expanded (SCI-E) databases and the factors affecting this composition. The genders of the participants were determined by the data obtained from the official websites of the journals in September 2023. We analyzed the journal metrics and publisher properties using Mann-Whitney U, Fisher exact, Chi-square tests, and Spearman correlation coefficient...

The bromodomain-containing protein 4 (BRD4) is highly expressed in oral squamous cell carcinoma (OSCC) and plays a crucial role in tumor progression. However, the impact of BRD4 on the efficacy of chemotherapy and radiotherapy by regulating the expression of programmed cell death-ligand 1 (PD-L1) in OSCC remains unclear. In this study, we found that the BRD4 inhibitor JQ1 effectively enhanced the inhibitory effects of cisplatin and radiotherapy on cell proliferation and promoted the apoptosis of OSCC cells by cisplatin and radiotherapy...

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterised by elevated pulmonary pressure, right ventricular failure (RVF) and ultimately death. Aggressive treatment of RVF is considered an important therapeutic strategy to treat PAH. Previous studies have indicated that betaine may be may a promising therapeutic approach for PAH-induced RVF. Therefore, in this study, betaine solution for injection was prepared and characterised using various techniques. The therapeutic efficacy of three different methods of administration (intragastric, nebulised inhalation, and intravenous injection) were comprehensively evaluated in terms of pharmacokinetics, tissue distribution, and pharmacodynamics...

Transient receptor potential vanilloid type-1 (TRPV1) channels play key roles in chronic pain conditions and are modulated by different inflammatory mediators to elicit heat sensitisation. Bradykinin is a 9-amino acid peptide chain that promotes inflammation. The aim of present study is to investigate how bradykinin and prostaglandin receptors (EP3 and EP4 ) modulate the sensitisation of TRPV1-mediated responses. Calcium imaging studies of rat dorsal root ganglion (DRG) neurons were employed to investigate the desensitizing responses of TRPV1 ion channels by capsaicin, and the re-sensitization of TRPV1 by bradykinin, then to explore the role EP3 and EP4 receptors in mediating these bradykinin-dependent effects...

In this study, we examined the pharmacokinetics of nifedipine and investigated the maternal and foetal background factors that prolong pregnancy in pregnant women undergoing long-term tocolysis. This prospective observational study included 38 pregnant women hospitalised for threatened preterm labour and treated with nifedipine extended-release tablets in combination with intravenous ritodrine infusion. Maternal plasma nifedipine concentrations were determined using high-performance liquid chromatography. All patients were administered 20 or 40 mg/dose of nifedipine every 6 h at the time of blood sampling...

Aberrant dopamine (DA) signaling has been implicated in various neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), schizophrenia, bipolar disorder (BPD) and addiction. The availability of extracellular DA is sculpted by exocytotic release of vesicular DA and subsequent transporter-mediated clearance, rendering the presynaptic DA transporter (DAT) a crucial regulator of DA neurotransmission. D2-type DA autoreceptors (D2ARs) regulate multiple aspects of DA homeostasis, including i) DA synthesis, ii) vesicular release, iii) DA neuron firing, and iv), the surface expression of DAT and DAT- mediated DA clearance...

No abstract text is available yet for this article.

Self-perceived learning outcomes of virtual academic detailing (AD) is poorly studied. We compared self-perceived learning outcomes of virtual and in-person AD among general practitioners (GPs). GPs from the Western region of Norway received a questionnaire before, and after, AD concerning rational pharmacotherapy of migraine in the autumn 2022. Five statements addressing specific knowledge and two statements addressing general knowledge and skills in pharmacotherapy of migraine were rated in both questionnaires...

Polycyclic aromatic hydrocarbons (PAHs) are organic pollutants and manufactured substances conferring toxicity to human health. The present study investigated whether pyrene, a type of PAH, harms rats. Our research provides an effective feature selection strategy for the animal dataset from Wenzhou Medical University's Experimental Animal Center to thoroughly examine the impacts of PAH toxicity on rat features. Initially, we devised a high-performance optimization method (SCBA) and added the Sobol sequence, vertical crossover, and horizontal crossover mechanisms to the bat algorithm (BA)...

No abstract text is available yet for this article.

The COVID-19 pandemic had a substantial impact on healthcare delivery, particularly in general practice. This study aimed to evaluate how dispensing of medications in primary care in Ireland changed following the COVID-19 pandemic's onset compared to expected trends. This interrupted time series study used data on medications prescribed in general practice 2016-2022 to patient eligible for state health cover, approximately one third of the population. Dispensing volumes for all therapeutic subgroups (ATC2 codes) and commonly dispensed medications were summarised...

BACKGROUND: Methods for safety signal detection in electronic healthcare data analyzing data sequentially are being developed to meet the limitations of spontaneous reporting systems. OBJECTIVES: To provide an overview of the literature on sequential analysis of electronic healthcare data and describe the development and testing of a novel epidemiological surveillance system. METHODS: We searched Medline, Embase, PubMed, Scopus, Web of Science, and the Cochrane Library applying similar in- and exclusion criteria as those of a previous systematic review...

Duloxetine is metabolized by cytochrome P450 (CYP)1A2 and CYP2D6. The aim of this study was to investigate the effect of CYP2D6 genotype on duloxetine serum concentration adjusting for age and sex. Patients were included retrospectively from a therapeutic drug monitoring service. Multiple linear regression analysis was used to investigate the effect of CYP2D6 genotype, age and sex on duloxetine concentration-to-dose (C/D) ratio. In total, 269 patients were included and assigned to the following genotype-predicted phenotype subgroups: CYP2D6 poor metabolizers (PMs, n = 23), intermediate metabolizers (IMs, n = 121), normal metabolizers (NMs, n = 120), and ultrarapid metabolizers (UMs, n = 5)...

No therapeutic ranges linking drug concentrations of apixaban and rivaroxaban to clinical outcomes have been defined. We investigated whether direct oral anticoagulant (DOAC) concentrations among patients admitted to hospital with symptoms of stroke differed between those later verified to suffer an ischemic cerebrovascular event (stroke or transient ischemic attack) and those having other diagnoses (control group). Serum concentrations in 102 patients on DOAC for atrial fibrillation (84%) and thromboembolic disease (16%) were measured within 24 hours of the acute event, employing ultra-high performance liquid chromatography with tandem mass spectrometry...

The incidence of fatal adverse drug reactions (ADRs) in hospitals varies widely and ADRs are often underreported. The impact of medical safety processes is not easily evaluated and although medical practice changes constantly, little is known about ADR trends. This study concentrated on the current incidence and properties of fatal ADRs occurring in a university hospital and compared the results with two previous studies performed in the same hospital. We investigated retrospectively all 1236 deaths that occurred during 2019 in the Helsinki University Hospital...

Understanding the patient perspective is a significant part of the deprescribing process. This study aimed to explore the attitudes of older patients with psychiatric disorders towards deprescribing. A total of 72 of psychiatric outpatients (68% women; median age 76 years) completed the validated Danish version of the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. Patients used a median of 8 medications (interquartile range 6-12), with 88%, 49% and 24% using antidepressants, antipsychotics and anxiolytics, respectively...

Deprescribing is the planned and supervised reduction or discontinuation of medications that may be causing harm or are no longer benefiting a patient. The need for deprescribing to be a routine part of patient care is essential with an aging population and rising prevalence of polypharmacy, which has been associated with increased adverse outcomes, such as falls, hospitalizations, and mortality. Deprescribing is a complex intervention, which requires collaboration between the patient, caregivers, and healthcare providers to adequately support all involved, as well as to ensure medications are not restarted in error...

Per- and polyfluoroalkyl substances (PFAS) are a group of persistent and widespread environmental pollutants that represent a high concern for human health. They have been shown to be associated with several important physiological processes such as lipid metabolism and the immune system. Consequently, PFAS are suspected to play a role in cardiometabolic disease development. However, the evidence regarding associations between PFAS and overt cardiovascular disease and type 2 diabetes remains limited and inconsistent...

Data on drug transfer into human breast milk is sparse. This study aimed to quantify concentrations of cetirizine and levocetirizine in breast milk and to estimate drug exposure to infants. Breastfeeding women at least eight weeks postpartum and using cetirizine or its pure (R)-enantiomer levocetirizine were eligible to participate. Breast milk samples were collected at six predefined times during a dose interval (0, 2, 4, 8, 12 and 24 hours after drug intake) at steady state. Infant drug exposure was estimated by calculating the absolute infant dose (AID) and the weight-adjusted relative infant dose (RID)...

Berberine acts via multiple pathways to alleviate fibrosis in various tissues and shows renoprotective effects. However, its role and underlying mechanisms in renal fibrosis remains unclear. Herein, we aimed to investigate the protective effects and molecular mechanisms of Berberine against unilateral ureteric obstruction-induced renal fibrosis. The results indicated that Berberine treatment (50 mg/kg/d) markedly alleviated histopathological alterations, collagen deposition, and inflammatory cell infiltration in kidney tissue; and restored mouse renal function...