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Combinatorial Chemistry & High... 2023Currently, there are no effective differentiation-inducing agents for gliomas. Drug repositioning is a time-saving, low-risk, and low-cost drug development strategy. In...
BACKGROUND
Currently, there are no effective differentiation-inducing agents for gliomas. Drug repositioning is a time-saving, low-risk, and low-cost drug development strategy. In this study, drugs that could induce the differentiation of glioma cells were searched by using a drug repositioning strategy.
METHODS
Data mining was used to screen for differentially expressed genes (DEGs). The STRING 11.0 database was used for enrichment analysis. The Connectivity Map database was used for drug screening. The ChEMBL and STITCH databases were used to search for drug targets. The SwissDock database was used for molecular docking.
RESULTS
A total of 45 DEGs were identified. The biological processes in which the DEGs were enriched mainly involved nervous system development and the regulation of biological processes. The enriched molecular functions mainly involved transcription-related molecular binding. The enriched cellular components mainly involved membrane-bound organelles and cellular protrusions. The enriched local network clusters mainly involved autophagy, the retinoic acid signalling pathway, and DNA methylation. The drug screening results showed that the drug with the highest score was acenocoumarol. A total of 12 acenocoumarol targets were obtained, among which histone deacetylase 1 (HDAC1) was the target with the highest degree value; the lowest ΔG value for acenocoumarol docked with HDAC1 was -7.52 kcal/mol, which was between those of the HDAC1 inhibitors romidepsin and vorinostat.
CONCLUSION
Acenocoumarol may be a potential differentiation-inducing agent for glioma cells.
Topics: Humans; Molecular Docking Simulation; Drug Repositioning; Acenocoumarol; Glioma; Cell Differentiation
PubMed: 35538833
DOI: 10.2174/1386207325666220509194428 -
Journal of Physiology and Pharmacology... Aug 2023Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the...
Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be important therapeutic agents. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to determine whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 μg/kg) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of AP was assessed immediately after the last dose of cerulein, as well as at days 1, 2, 3, 5, and 10 after AP induction. Treatment with warfarin dose-dependently increased international normalized ratio (INR) and attenuated the severity of pancreatitis in histological examination and accelerated pancreatic recovery. These effects were accompanied with a faster reduction in the AP-evoked increase in serum activity of amylase and lipase, the serum concentration of pro-inflammatory interleukin-1β, and the plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight (an index of pancreatic edema) and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 μg/kg. We conclude that treatment with warfarin accelerated regeneration of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.
Topics: Rats; Male; Animals; Pancreatitis; Warfarin; Ceruletide; Rats, Wistar; Acenocoumarol; Acute Disease; Pancreas
PubMed: 37865961
DOI: 10.26402/jpp.2023.4.08 -
Molecules (Basel, Switzerland) Mar 2021Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some... (Comparative Study)
Comparative Study Observational Study
Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones ( < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin.
Topics: Acenocoumarol; Aged; Anticoagulants; Blood Coagulation; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Retrospective Studies; Venous Thromboembolism; Warfarin
PubMed: 33800767
DOI: 10.3390/molecules26051425 -
Medical Cannabis and Cannabinoids 2023Treatment with cannabis extracts for a variety of diseases has gained popularity. However, differences in herb-drug interaction potential of extracts from different...
INTRODUCTION
Treatment with cannabis extracts for a variety of diseases has gained popularity. However, differences in herb-drug interaction potential of extracts from different plant sources are poorly understood. In this study, we provide a characterization of cannabis extracts prepared from four cannabis chemotypes and an in vitro assessment of their Cytochrome P450 (CYP)-mediated herb-drug interaction profiles.
METHODS
Plant extracts were either commercially obtained or prepared using ethanol as solvent, followed by overnight decarboxylation in a reflux condenser system. The extracts were characterized for their cannabinoid content using NMR and HPLC-PDA-ELSD-ESIMS. CYP inhibition studies with the cannabis extracts and pure cannabinoids (tetrahydrocannabinol [THC] and cannabidiol [CBD]) were performed using pooled, mixed gender human liver microsomes. Tolbutamide and testosterone were used as specific substrates to assess the inhibitory potential of the extracts on CYP2C9 and CYP3A4, and the coumarinic oral anticoagulants warfarin, phenprocoumon, and acenocoumarol were studied as model compounds since in vivo herb-drug interactions have previously been reported for this compound class.
RESULTS
In accordance with the plant chemotypes, two extracts were rich in THC and CBD (at different proportions); one extract contained mostly CBD and the other mostly cannabigerol (CBG). Residual amounts of the corresponding acids were found in all extracts. The extracts with a single major cannabinoid (CBD or CBG) inhibited CYP2C9- and CYP3A4-mediated metabolism stronger than the extracts containing both major cannabinoids (THC and CBD). The inhibition of CYP3A4 and CYP2C9 by the extract containing mostly CBD was comparable to their inhibition by pure CBD. In contrast, the inhibitory potency of extracts containing both THC and CBD did not correspond to the combined inhibitory potency of pure THC and CBD. Although being structural analogs, the three coumarin derivatives displayed major differences in their herb-drug interaction profiles with the cannabis extracts and the pure cannabinoids.
CONCLUSION
Despite the fact that cannabinoids are the major components in ethanolic, decarboxylated cannabis extracts, it is difficult to foresee their herb-drug interaction profiles. Our in vitro data and the literature-based evidence on in vivo interactions indicate that cannabis extracts should be used cautiously when co-administered with drugs exhibiting a narrow therapeutic window, such as coumarinic anticoagulants, regardless of the cannabis chemotype used for extract preparation.
PubMed: 36814687
DOI: 10.1159/000528465 -
Journal of Population Therapeutics and... Apr 2020Intracerebral hemorrhage (ICH)1 is characterized by the pathological accumulation of blood within the brain parenchyma, most commonly associated with hypertension,... (Review)
Review
BACKGROUND
Intracerebral hemorrhage (ICH)1 is characterized by the pathological accumulation of blood within the brain parenchyma, most commonly associated with hypertension, arteriovenous malformations, or trauma. However, it can also present in patients receiving antithrombotic drugs, either anticoagulants such as acenocoumarol/warfarin-novel oral anticoagulants or antiplatelets, for the prevention and treatment of thromboembolic disease.
OBJECTIVE
The purpose of this review is to present current bibliographic data regarding ICH irrespective of the cause, as well as post-hemorrhage use of antithrombotic agents. Moreover, this review attempts to provide guidelines concerning the termination, inversion, and of course resumption of antithrombotic therapy.
METHODS AND MATERIALS
We reviewed the most recently presented available data for patients who dealt with intracerebral hemorrhagic events while on antithrombotic agents (due to atrial fibrillation, prosthetic mechanical valves or recent/recurrent deep vein thrombosis). Furthermore, we examined and compared the thromboembolic risk, the bleeding risk, as well as the re-bleeding risk in two groups: patients receiving antithrombotic therapy versus patients not on antithrombotic therapy.
CONCLUSION
Antithrombotic therapy is of great importance when indicated, though it does not come without crucial side-effects, such as ICH. Optimal timing of withdrawal, reversal, and resumption of antithrombotic treatment should be determined by a multidisciplinary team consisting of a stroke specialist, a cardiologist, and a neurosurgeon, who will individually approach the needs and risks of each patient.
Topics: Anticoagulants; Antidotes; Cerebral Hemorrhage; Fibrinolytic Agents; Humans; Patient Care Team; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Thromboembolism
PubMed: 32320168
DOI: 10.15586/jptcp.v27i2.660 -
BMC Public Health Jul 2021Assessment health literacy in people with cardiovascular health problems would facilitate the development of appropriate health strategies for the care and reduction of...
BACKGROUND
Assessment health literacy in people with cardiovascular health problems would facilitate the development of appropriate health strategies for the care and reduction of complications associated with oral anticoagulation therapy.
AIM
To evaluate the relationship between health literacy and health and treatment outcomes (concordance with oral anticoagulants, Normalized Ratio control and occurrence of complications) in patients with cardiovascular pathology.
METHODS
Observational, analytic and cross-sectional study carried out on 252 patients with cardiovascular pathology (atrial fibrillation, flutter or valve prosthesis), aged 50-85 years, accessing primary care services in Valencia (Spain) in 2018-2019. Variables referring to anticoagulant treatment with vitamin K antagonists (years of treatment, adequate control, polypharmacy and occurrence of complications, among others) and health literacy (Health Literacy Questionnaire) were analysed.
RESULTS
All dimensions of health literacy were significantly related to the level of education (p < 0.02), social class (p < 0.02), an adequate control of acenocoumarol (p < 0.001), frequentation of health services (p < 0.001), information by patients to health professionals about anticoagulant treatment (p < 0.03), emergency care visits (p < 0.001) and unscheduled hospital admissions (p < 0.001).
CONCLUSION
Health literacy has a relevant influence on the adequate self-management of anticoagulation treatment and the frequency of complications. The different dimensions that comprise health literacy play an important role, but the "social health support" dimension seems to be essential for such optimal self-management.
TRIAL REGISTRATION
ACC-ACE-2016-01. Registration date: December 2015.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Health Literacy; Humans; Social Determinants of Health; Spain; Treatment Outcome
PubMed: 34243749
DOI: 10.1186/s12889-021-11259-w -
Journal of Clinical Pharmacology Jun 2022The therapeutic efficacy of clopidogrel as an antiplatelet drug varies among individuals, being the mainstream hypothesis that its bioavailability depends on the...
The therapeutic efficacy of clopidogrel as an antiplatelet drug varies among individuals, being the mainstream hypothesis that its bioavailability depends on the individual genetic background and/or interactions with other drugs. A total of 477 patients receiving double antiaggregation therapy with aspirin and clopidogrel, after suffering a first event, were followed for 1 year to record relapse, as a surrogate end point to measure their therapeutic response, as defined by presenting with an acute coronary event (unstable angina, ST-segment-elevation myocardial infarction, or non-ST-segment-elevation myocardial infarction), stent thrombosis/restenosis, or cardiac mortality. Anthropometric, clinical, and pharmacological variables along with CYP2C19 genotypes were analyzed for their association with the disease relapse phenotype. Only 75 patients (15%) suffered a relapse, which occurred during the first 6 months of therapy, with a peak at 4.5 months. An initial univariate analysis identified that patients in the relapse group were significantly older (67.4 ± 11.0 vs 61.6 ± 12.3 years old) and presented with diffuse coronary disease, insulin-dependent type 2 diabetes mellitus dyslipidemia, and arterial hypertension. A poor clinical response to the platelet antiaggregation regime also occurred more frequently among patients taking acenocoumarol and calcium channel blockers, along with aspirin and clopidogrel, while no association was found according to CYP2C19 genotypes. A retrospective multivariate analysis indicated that patients belonging to the nonresponder phenotype to treatment with aspirin and clopidogrel were older, presented with diffuse coronary disease, a group largely overlapping with type 2 insulin-dependent diabetes mellitus, and were taking dihidropyrimidinic calcium channel blockers.
Topics: Acute Coronary Syndrome; Aspirin; Calcium Channel Blockers; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Diabetes Mellitus, Type 2; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Recurrence; Retrospective Studies; Ticlopidine; Treatment Outcome
PubMed: 34958683
DOI: 10.1002/jcph.2016 -
Oral Diseases Apr 2023The aim of this study was to evaluate the risk factors associated with xerostomia and hyposalivation in a group of hypertensive patients.
OBJECTIVE
The aim of this study was to evaluate the risk factors associated with xerostomia and hyposalivation in a group of hypertensive patients.
SUBJECTS AND METHODS
A cross-sectional study was conducted. Hypertensive patients belonged to two healthcare centers were included. Xerostomia was assessed by asking a question and using the Xerostomia Inventory. Unstimulated salivary flow was collected. Different epidemiological variables were analyzed such as age, sex, habits, diseases, drugs, and blood pressure.
RESULTS
221 individuals were included. Xerostomia was reported in 51.13% of patients. Patients with xerostomia suffered more from osteoarthritis and diaphragmatic hernia. These patients took more anticoagulants (acenocoumarol), antiarrhythmics (amiodarone), analgesics (paracetamol) and epilepsy drugs (pregabalin) and less platelet aggregation inhibitors and angiotensin II receptor blockers (losartan). Unstimulated flow was reduced in 37.56% of patients. Patients suffering hyposalivation presented more diseases such as anxiety, infectious or parasitic diseases, hepatitis C, diaphragmatic hernia, and osteoarthritis. These patients took more repaglinide, thiazides, anti-inflammatories, anti-rheumatics, glucosamine, diazepam, and selective beta-2-adrenoreceptor agonists and less combinations of candesartan and diuretics.
CONCLUSIONS
Xerostomia and hyposalivation are frequent in hypertensive patients. It is advisable to take into consideration the comorbidities and the drugs they receive, since they can increase the risk of these salivary disorders.
Topics: Humans; Saliva; Cross-Sectional Studies; Xerostomia; Risk Factors; Hernia, Diaphragmatic
PubMed: 34839577
DOI: 10.1111/odi.14090 -
Journal of Comparative Effectiveness... Oct 2019To compare the risk of stroke, systemic thromboembolism and bleeding, in patients initiating apixaban or acenocoumarol for the treatment of nonvalvular atrial... (Observational Study)
Observational Study
Patient characteristics and stroke and bleeding events in nonvalvular atrial fibrillation patients treated with apixaban and vitamin K antagonists: a Spanish real-world study.
To compare the risk of stroke, systemic thromboembolism and bleeding, in patients initiating apixaban or acenocoumarol for the treatment of nonvalvular atrial fibrillation. An observational, retrospective study was performed using medical records of patients who initiated apixaban or acenocoumarol between 2015 and 2017. Propensity score matching was used to match patients; stroke, systemic thromboembolism, major and minor bleeding events were compared between the matched patients. Patients who were prescribed apixaban had a lower rate of systemic embolism/stroke (hazard ratio [HR] = 0.54; 95% CI: 0.38-0.78; p = 0.001), minor bleeding (HR = 0.64; 95% CI: 0.52-0.79; p < 0.001) and major bleeding (HR = 0.51; 95% CI: 0.37-0.72; p < 0.001). Patients prescribed apixaban for the treatment of nonvalvular atrial fibrillation had lower rates of thromboembolic events and minor/major bleeding than patients on acenocoumarol.
Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Stroke; Vitamin K
PubMed: 31333045
DOI: 10.2217/cer-2019-0079 -
EXCLI Journal 2019
PubMed: 31611751
DOI: 10.17179/excli2019-1714