Searching for Old and New Small-Molecule Protein Kinase Inhibitors as Effective Treatments in Pulmonary Hypertension-A Systematic Review.

Treatment options for pulmonary arterial hypertension (PAH) have improved substantially in the last 30 years, but there is still a need for novel molecules that can regulate the excessive accumulation of pulmonary artery smooth muscle cells (PASMCs) and consequent vascular remodeling. One set of possible candidates are protein kinases. The study provides an overview of existing preclinical and clinical data regarding small-molecule protein kinase inhibitors in PAH.

Innovative Approaches to Enhance and Measure Medication Adherence in Chronic Disease Management: A Review.

Medication non-adherence is a problem that affects up to 50% of patients with chronic diseases. The result is a failure to achieve therapeutic goals and an increased burden on the healthcare system. It is, therefore, highly appropriate to develop models to assess patient adherence to prescribed therapy.

Improving the treatment of bacterial infections caused by multidrug-resistant bacteria through drug repositioning.

Drug repurposing (repositioning) is a dynamically-developing area in the search for effective therapy of infectious diseases. Repositioning existing drugs with a well-known pharmacological and toxicological profile is an attractive method for quickly discovering new therapeutic indications. The off-label use of drugs for infectious diseases requires much less capital and time, and can hasten progress in the development of new antimicrobial drugs, including antibiotics.

An evaluation of written materials for supporting hypertensive patient education and counselling when performing a new medicine service in Poland.

Background: The New Medicine Service (NMS) was developed in England more than ten years ago, as a three-stage consultation led by community pharmacists to support patients taking new medication for a chronic disease. In Poland, the scheme was officially introduced in January 2023. However, its implementation into common practice has been presented with various obstacles, including the need to develop relationships with general practitioners, resolve the payment structure, and provide training with adequate supporting materials.

An updated review of experimental rodent models of pulmonary hypertension and left heart disease.

Left heart disease (LHD) is the leading cause of pulmonary hypertension (PH). Its recent growth has not been matched by the design of therapeutic agents directly targeting the disease. Effective therapies approved for pulmonary arterial hypertension (PAH) have been shown to be inefficient in patients with PH-LHD.

The current state of preclinical modeling of human diabetic cardiomyopathy using rodents.

The prevalence of diabetic cardiomyopathy (DCM), a specific cardiovascular complication of diabetes mellitus, has recently increased. Its pathogenesis is not fully understood, and no consensus regarding therapeutic options has been reached. Experimental studies on rodents are expected to yield further data at the preclinical stage.

Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents.

Background: While the prevalence of heart failure with preserved ejection fraction (HFpEF) has increased over the last two decades, there still remains a lack of effective treatment. A key therapeutic challenge is posed by the absence of animal models that accurately replicate the complexities of HFpEF. The present review summarizes the effects of a wide spectrum of therapeutic agents on HF.

Multidimensional Interventions on Supporting Disease Management for Hospitalized Patients with Heart Failure: The Role of Clinical and Community Pharmacists.

Background: existing trials on the role of clinical pharmacists in managing chronic disease patients have focused on variety of interventions, including preparing patients for the transition from hospital to home. However, little quantitative evidence is available regarding the effect of multidimensional interventions on supporting disease management for hospitalized patients with heart failure (HF). The present paper reviews the effects of inpatient, discharge and/or after-discharge interventions performed on hospitalized HF patients by multidisciplinary teams, including pharmacists.

Training programs in preclinical studies. The example of pulmonary hypertension. Systematic review and meta-analysis.

Background: Exercise and cardiopulmonary exercise testing are essential in the evaluation of physiological, biochemical, and molecular responses in the experimental studies on chronic diseases such as diabetes, heart failure and hypertension. The exercise tolerance and seem to be a valuable contribution to the experiments that are performed in animal models of pulmonary hypertension (PH), as well. The current survey uses detailed quantitative analyses to assess the advantages of exercise training programs performed in preclinical studies based on outcomes such as exercise capacity, cardiopulmonary hemodynamics, and mortality.

The Effectiveness of Pharmacist Interventions in the Management of Patient with Renal Failure: A Systematic Review and Meta-Analysis.

The existing trials have focused on a variety of interventions to improve outcomes in renal failure; however, quantitative evidence comparing the effect of performing multidimensional interventions is scarce. The present paper reviews data from previous randomized controlled trials (RCTs), examining interventions performed for patients with chronic kidney disease (CKD) and transplants by multidisciplinary teams, including pharmacists. Methods: A systematic search with quality assessment was performed using the revised Cochrane Collaboration's 'Risk of Bias' tool.

Searching for an experimental rodent model of heart failure with preserved ejection fraction: Re-visited.

Heart failure with preserved ejection fraction (HFpEF) currently accounts for over 50% of all heart failure cases. It displays a large number of comorbidities, and the pathophysiological mechanisms underlying the disease remain uncertain and treatment options are limited. The heterogeneity and complexity of the disease, and its specific comorbidities, can limit the number of animal models that could ideally mimic it.

A review of genetically-driven rodent models of pulmonary hypertension.

An increasing number of models used to examine the role of particular signaling pathways in vasculature and the development of pulmonary hypertension (PH) are based on animals with different genetic modifications. The present study explores the severity of PH-related lesions that can be provided by a genetic particular model in accordance to the most common non-genetic PH inducers such as chronic exposure to hypoxia or single injection of monocrotaline. A review of 516 interventions on a variety of animal models was performed.

A review of rodent models for metabolic syndromes and pulmonary hypertension.

Purpose: Emerging evidence suggests that metabolic disorders, such as diabetes and obesity, may affect the pathogenesis and development of pulmonary hypertension (PH), and therefore some treatments could be beneficial for both disorders. The present study investigates whether such metabolic diseases increase susceptibility to PH in rodent models, and identifies which models are suitable for research on PH and its potential therapeutic candidates. It also explores whether particular PH model can worsen the metabolic parameters.

Reporting experimental studies on animals - The problems with translating of outcomes to clinical benefits. Methodological and statistical considerations: The example of pulmonary hypertension.

The variability inherent in animal models and the methods used to define drug response can lead to highly divergent results when evaluating new drug candidates. Several guidelines exist for high-quality and comprehensive reporting of experiments with animals. The present survey makes a quantitative demonstration of whether compliance with good preclinical practice guidelines can affect the results and reduce risk of over- or underestimation of treatment benefit.

Toward Better Reproducibility in Experimental Research on New Agents for Pulmonary Hypertension. An Analysis of Data from Four Hundred Animal Studies.

Purpose: Pre-clinical data can provide a rationale for subsequent clinical trials and they are the first step in drug development; however, the therapeutic effect observed during animal studies does not necessarily translate to similar results in humans.

Methods: Taking the example of pulmonary hypertension, the present study explores whether the methodological aspects of preclinical experiments can determine the final result.

Results: The present paper describes a systematic analysis of 409 studies conducted on a variety of animal models to identify potential drug candidates for PH treatment; it explores the influence of various aspects of study design on the final outcome, e.

Comparative tolerability of targeted therapies in pulmonary hypertension.

Introduction: The objective of this study was to estimate the safety profile of pulmonary hypertension-specific therapies using placebo-controlled and active comparator trials.

Material And Methods: The search corpus comprised Medline, Scopus, Embase and Clinical Trials databases. A systematic review and meta-analysis was performed to assess the relative risk of severe events and discontinuations as well as of adverse drug reactions (ADRs) classified into 26 categories and 21 subcategories defined by the Medical Dictionary for Regulatory Activities (MedRA).

Systematic review and meta-analysis of interventions tested in animal models of pulmonary hypertension.

A systematic review and meta-analysis was performed to test candidate therapeutic approaches in pulmonary hypertension (PH). The efficacy of 522 interventions with >200 unregistered drugs was tested on 7254 animals. We propose a modified formula to assess meta-data that concerns the contribution of PH animal model to the denoted efficacy of tested agents.

Involvement of vascular endothelial growth factor (VEGF) and mitogen-activated protein kinases (MAPK) in the mechanism of neuroleptic drugs.

Background: Recent evidence suggests that the mitogen activated protein kinase (MAPK)-associated signaling pathway in the frontal cortical areas demonstrates abnormal activity in cases of schizophrenia. Moreover, schizophrenia patients often display alterations in the regional cellular energy metabolism and blood flow of the brain; these are shown to parallel changes in angiogenesis primarily mediated by vascular endothelial growth factor (VEGF).

Methods: The present study examines the differential effects of time-dependent treatment with haloperidol, olanzapine and amisulpride (20μM) on VEGF and MAPK mRNA expression and VEGF level, using the T98 cell line as an example of nerve cells.

WHAT MOTIVATES POLISH COMMUNITY PHARMACISTS TO PURSUIT OF POSTGRADUATE EDUCATION?

Due to increasing importance of the advisory role for physicians and patients played by the pharmacist over the last decade, it seems appropriate to evaluate if and why pharmacists are interested in postgraduate medical education. The purpose of the study was to develop and validate an instrument to assess such motives, with special interest to Polish community pharmacists. A self-administered questionnaire was completed by a sample of participants of community pharmacist specialization programs and it was analyzed in relation to participants of other postgraduate courses.

MOTIVATIONS SURROUNDING THE PURSUIT OF A PHARMACY CAREER - THE CASE OF POLISH STUDENTS.

The objective was to examine the motivation for studying pharmacy. A self-administered questionnaire, developed and validated by the authors, was completed by a sample of 414 Polish pharmaceutical students (Year I - Year 5). The students ranked their motives on a Likert-like scale and their underlying dimensions were identified using exploratory and confirmatory techniques.

The differential effects of neuroleptic drugs and PACAP on the expression of BDNF mRNA and protein in a human glioblastoma cell line.

Despite numerous studies, the molecular mechanisms underpinning the action of antipsychotic drugs remain not fully understood. It has been suggested that, in addition to the modulation of monoaminergic neurotransmission, antipsychotic drugs can also affect the expression of neurotrophic factors in the brain. The present study examines the effects of a first-generation neuroleptic drug (FGA; haloperidol) and two second-generation neuroleptic drugs (SGAs; olanzapine and amisulpride) on the expression and levels of brain-derived neurotrophic factor (BDNF) in an astrocyte-like T98G glioblastoma cell line.

[Current issues in etiology, diagnostics and management in pulmonary hypertension].

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions characterizing with by an abnormal increase in mean pulmonary arterial pressure. It is a rare, debilitating disease with a poor prognosis. Despite significant progress in diagnosis and management, including disease-targeted therapies as well as development of specialized centres, PH remains a chronic disease without a cure.

Animal models of pulmonary arterial hypertension: A systematic review and meta-analysis of data from 6126 animals.

Numerous animal models of pulmonary hypertension are currently available. A systematic review and meta-analysis was performed of a number of experimental studies of disease induction based on several animal models. A meta-analysis was performed of 291 publications discussing the efficacy of 611 interventions to introduce disease pulmonary hypertension in 6126 animals.

Novel strategies for treatment of pulmonary arterial hypertension.

Pulmonary hypertension (PH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. Special population include patents with pulmonary arterial hypertension (PAH). A greater understanding of the epidemiology, pathogenesis, and pathophysiology of PAH has led to significant advances over the past few years.