Therapeutic Drug Monitoring of Direct Oral Anticoagulants in Patients with Extremely Low and High Body Weight-Pilot Study.

Phase III clinical trials for individual direct oral anticoagulants (DOACs) contained a limited representation of subjects with abnormal body weight, which were mostly limited to a BMI > 40 kg/m2, or body weight > 120 kg for obese subjects, and <50 kg for underweight subjects. Although low or high body weight is not a contraindication to DOACs therapy, it can significantly affect the safety and effectiveness of treatment. Due to the limited amount of clinical data on the use of DOACs in extremely abnormal weight ranges, optimal pharmacotherapy in this group of patients is a matter of controversy. The objective of this study was to evaluate the pharmacokinetics of DOAC properties in patients with abnormal body weight beyond the established cut-off points in the phase III studies for rivaroxaban, apixaban, and dabigatran. In total, 38 patients took DOACs for at least 12 months for non-valvular atrial fibrillation in 2019-2021. Blood samples were collected before the planned intake of the drug and 4 h after its administration. The determined concentrations of DOACs were statistically analyzed in relation to body weight, age, and eGFR (estimated Glomerular Filtration Rate). Among subjects taking apixaban, rivaroxaban, and dabigatran, the smallest representation of patients who achieved therapeutic concentrations were those treated with dabigatran. The population of people with abnormal body weight is a potential risk group of patients, in which some of them do not reach the therapeutic range of DOACs.

All That Glitters Is Not Gold: Assessment of Bee Pollen Supplementation Effects on Gastric Mucosa.

The aim of this study was to assess the influence of bee pollen supplementation on the levels of enzymes important for gastric mucosal homeostasis, namely cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and a biomarker-asymmetric dimethylarginine (ADMA)-in the gastric mucosa of Wistar rats. The experimental phase divided the rats into four groups: two control groups, sedentary and active, both not supplemented, and two experimental groups, sedentary and active, supplemented with bee pollen. The results indicated that bee pollen supplementation reduced the levels of COX-1 and elevated iNOS levels, while showing no significant impact on COX-2 levels. These findings do not conclusively support the gastroprotective and anti-inflammatory effects of bee pollen on gastric mucosa. However, the supplementation could have resulted in reduced ADMA levels in the physically active supplemented group. Our study does not unequivocally demonstrate the positive effects of bee pollen supplementation on the gastric mucosa, which may be attributed to the specific metabolism and bioavailability of substances within unprocessed, dried bee pollen. Further research should explore the topic of potential therapeutic applications of bee pollen in gastrointestinal health and its interactions with ADMA signaling pathways.

11ß-HSD as a New Target in Pharmacotherapy of Metabolic Diseases.

Glucocorticoids (GCs), which are secreted by the adrenal cortex, are important regulators in the metabolism of carbohydrates, lipids, and proteins. For the proper functioning of the body, strict control of their release is necessary, as increased GCs levels may contribute to the development of obesity, type 2 diabetes mellitus, hypertension, cardiovascular diseases, and other pathological conditions contributing to the development of metabolic syndrome. 11ß-hydroxysteroid dehydrogenase type I (11ß-HSD1) locally controls the availability of the active glucocorticoid, namely cortisol and corticosterone, for the glucocorticoid receptor. Therefore, the participation of 11ß-HSD1 in the development of metabolic diseases makes both this enzyme and its inhibitors attractive targets in the pharmacotherapy of the above-mentioned diseases.

The Analysis of Oxidative Stress Markers May Increase the Accuracy of the Differential Diagnosis of Alzheimer's Disease with and without Depression.

INTRODUCTION: The aim of work is to assess the usefulness of oxidative stress parameters in the differential diagnosis of dementia of the Alzheimer's type and dementia of the Alzheimer's type with coexisting depression. METHODS: The study involved three groups of people: patients with Alzheimer's disease (AD) (AD; N=27), patients with Alzheimer's disease and depression (D) (AD+D; N=30), and a control group that consisted of people without dementia and without depression (C; N=24). The assessment of cognitive functioning was carried out using among alia, Auditory Verbal Learning Test and Verbal Fluency Test. Furthermore, we determined the activity of superoxide dismutase (SOD-1) and superoxide anion radical. RESULTS: Multiple models with different combinations of independent variables showed that SOD together with Rey delayed recall were the best significant predictors of AD with the area under curve (AUC) of 0.893 (p = 0.001) and superoxide anion radical (O2•-) together with verbal fluency - sharp objects were the best significant predictors of AD +D diagnosis with the AUC of 0.689 (p = 0.034). CONCLUSION: This study confirmed the value of neuropsychological diagnosis and analysis of oxidative stress markers in the diagnosis of AD and major depressive disorder (MDD) in the course of AD. The combination of the use of biochemical markers and neuropsychological tests seems particularly important for differential diagnosis.

Immunocytochemical examinations of hippocampal nerve cells after experimental administration of dexamethasone.

The purpose of this research was an assessment of MAP2 immunoreactivity in hippocampal neurons after administration of toxic doses of dexamethasone. Experiments were led on Albino-Swiss mouse males. The obtained results indicate that dexamethasone causes significant decrease of MAP2 immunoreactivity in hippocampal nerve cells of the CA3 region. Our results show damage of neuronal cytoskeleton in this area of the brain.