192 results match your criteria: "Centre for Preclinical Research and Technology CEPT[Affiliation]"

Rebound effect, discontinuation, and withdrawal syndromes associated with drugs used in psychiatric and neurological disorders.

Pharmacol Rep

December 2024

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, Banacha 1B, Warszawa, 02-097, Poland.

Sudden cessation of the drug can cause withdrawal syndrome, discontinuation syndrome, or rebound effect. The common feature of these phenomena is a quick onset, usually limited duration depending on the drug's half-life and remission after restarting the therapy. They are characterized by varying clusters of somatic, autonomic, and psychiatric symptoms.

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It is common knowledge that the cerebellum is a structure of the central nervous system that influences the processes of balance and motor coordination. Recently its influence on social interactions has also been emphasized. The sigma receptor agonist: 3-di-o-tolylguanidine (DTG) is characterized by high affinity for sigma 1 and sigma 2 receptors, widely distributed in the cerebellum.

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Correction: AOTMiT reimbursement recommendations compared to other HTA agencies.

Eur J Health Econ

October 2024

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Banacha 1B, Warsaw, 02-097, Poland.

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Time from approval to reimbursement recommendations in healthcare systems with centralized HTA processes. Focus on the Polish HTA agency.

Expert Rev Pharmacoecon Outcomes Res

October 2024

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Warsaw, Poland.

Article Synopsis
  • - The study analyzed the time it takes for drugs registered by the EMA from 2014 to 2019 to receive reimbursement recommendations in Poland and 11 other countries.
  • - Results showed that Poland had a significantly longer time from drug registration to recommendation compared to other countries, although many countries are trending towards faster recommendations between 2014 and 2019.
  • - The findings indicate potential improvements in the processes of health authorities and data providers, with Poland experiencing a yearly decrease in the time for reimbursement recommendations despite starting from a longer baseline.
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Cnicus benedictus: Folk Medicinal Uses, Biological Activities, and In Silico Screening of Main Phytochemical Constituents.

Planta Med

October 2024

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Warszawa, Poland.

Traditional medicine has long recognized the therapeutic potential of , and recent scientific research has shed light on the pharmacological properties of this plant. The bioactive compounds that can be extracted from it, such as the sesquiterpene lactones arctigenin, arctiin, and cnicin, are very interesting to researchers.In this article, based on available data from pre-clinical and studies, we delve into the pharmacology of the active constituents of this plant to explore its potential therapeutic applications and underlying mechanisms of action.

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Article Synopsis
  • Leaflet thrombosis (LT) is a complex and poorly understood complication that can occur after transcatheter aortic valve implantation (TAVI), prompting the need for better prediction models to identify at-risk patients.
  • A study involving 101 TAVI patients utilized imaging and lab tests to determine various clinical and biological factors associated with LT, discovering that certain elevated and decreased lab values could predict its occurrence.
  • The researchers created an EFFORT score to quantify the risk, finding that patients scoring 2 or higher had an 85.7% likelihood of developing LT, indicating the score's potential as a powerful tool for risk assessment post-TAVI.
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Parkinson's disease is one of the most common neurodegenerative disorders characterized by a multitude of motor and non-motor clinical symptoms resulting from the progressive and long-lasting abnormal loss of nigrostriatal dopaminergic neurons. Currently, the available treatments for patients with Parkinson's disease are limited and exert only symptomatic effects, without adequate signs of delaying or stopping the progression of the disease. Atsttrin constitutes the bioengineered protein which ultrastructure is based on the polypeptide chain frame of the progranulin (PGRN), which exerts anti-inflammatory effects through the inhibition of TNFα.

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The primary problem in the treatment of epilepsy is poor seizure control. Several studies have shown that non-adherence to doctors' recommendations regarding drug dosage, time of drug administration as well as lifestyle modifications are the most frequent causes of the persistence or reoccurrence of seizures, other than cases of misdiagnosis and poor drug selection. The aim of this study was to assess the prevalence of non-compliance with medical recommendations, both in relation to medicine dosage, regularity of administration and lifestyle, and also to determine the factors affecting patients with diagnosed epilepsy.

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Background: The study aimed to assess the influence of a single valproate (VPA) administration on inhibitory and excitatory neurotransmitter concentrations in the brain structures involved in epileptogenesis in pentylenetetrazol (PTZ)-kindled rats.

Methods: Adult, male Wistar rats were kindled by repeated intraperitoneal (ip) injections of PTZ at a subconvulsive dose (30 mg/kg, three times a week). Due to the different times required to kindle the rats (18-22 injections of PTZ), a booster dose of PTZ was administrated 7 days after the last rats were kindled.

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AOTMiT reimbursement recommendations compared to other HTA agencies.

Eur J Health Econ

November 2024

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Banacha 1B, 02-097, Warsaw, Poland.

Our objective was to compare AOTMiT (Polish: Agencja Oceny Technologii Medycznych i Taryfikacji) recommendations to other HTA (Health Technology Assessment) agencies for newly registered drugs and new registration indications issued by the European Medicines Agency between 2014 and 2019. The study aims to assess the consistency and justifications of AOTMiT recommendations compared to that of other HTA agencies in 11 countries. A total of 2496 reimbursement recommendations published by 12 HTA agencies for 464 medicinal products and 525 indications were analyzed.

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The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Cells

January 2024

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies.

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Intranasal administration of antiseizure medications in chronic and emergency treatment: Hopes and challenges.

Seizure

February 2024

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Banacha 1B Street, Warsaw 02- 097, Poland.

Despite the availability of many antiseizure medications (ASMs), 30 % of patients experience pharmacoresistant seizures. High-throughput screening methods undoubtedly remain one of the most important approaches for discovering new molecules to treat seizures. However, the costly and time-consuming nature of drug development prompts us to explore alternative strategies to counteract drug-resistant seizures.

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Recent findings suggest an important role for the dysregulation of stromal interaction molecule (STIM) proteins, activators of store-operated Ca channels, and the prolonged activation of N-methyl-D-aspartate receptors (NMDARs) in the development of neurodegenerative diseases. We previously demonstrated that STIM silencing increases Ca influx through NMDAR and STIM-NMDAR2 complexes are present in neurons. However, the interplay between NMDAR subunits (GluN1, GluN2A, and GluN2B) and STIM1/STIM2 with regard to intracellular trafficking remains unknown.

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Reimbursement decision-making system in Poland systematically compared to other countries.

Front Pharmacol

October 2023

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Warsaw, Poland.

Our objective was to analyze and compare systematically and structurally reimbursement systems in Poland and other countries. The systems were selected based on recommendations issued by the Polish Agency for Health Technology Assessment and Tariffication (AHTAPol), which explicitly referred to other countries and agencies). Consequently, apart from Poland, the countries included in the analysis were England, Scotland, Wales, Ireland, France, Netherlands, Germany, Norway, Sweden, Canada, Australia and New Zealand.

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Finding the ideal antimicrobial drug with improved efficacy and a safety profile that eliminates antibiotic resistance caused by pathogens remains a difficult task. Indeed, there is an urgent need for innovation in the design and development of a microbial inhibitor. Given that many promising antimicrobial peptides with excellent broad-spectrum antibacterial properties are secreted by some frog species (e.

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Obesity is considered a risk factor for type 2 diabetes mellitus, which has become one of the most important health problems, and is also linked with memory and executive function decline. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that regulates cell death/survival and the inflammatory response via its specific receptors (S1PRs). Since the role of S1P and S1PRs in obesity is rather obscure, we examined the effect of fingolimod (an S1PR modulator) on the expression profile of genes encoding S1PRs, sphingosine kinase 1 (Sphk1), proteins engaged in amyloid-beta (Aβ) generation (ADAM10, BACE1, PSEN2), GSK3β, proapoptotic Bax, and proinflammatory cytokines in the cortex and hippocampus of obese/prediabetic mouse brains.

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Estrogen-regulated miRs in bone enhance osteoblast differentiation and matrix mineralization.

Mol Ther Nucleic Acids

September 2023

Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.

Estrogen signaling is critical for the development and maintenance of healthy bone, and age-related decline in estrogen levels contributes to the development of post-menopausal osteoporosis. Most bones consist of a dense cortical shell and an internal mesh-like network of trabecular bone that respond differently to internal and external cues such as hormonal signaling. To date, no study has assessed the transcriptomic differences that occur specifically in cortical and trabecular bone compartments in response to hormonal changes.

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: MicroRNAs (miRNA, miR) are small, non-coding RNAs which have become increasingly relevant as diagnostic and prognostic biomarkers. The objective of this study was the investigation of blood-derived miRNAs and their link to long-term all-cause mortality in patients who suffered from non-ST-segment elevation acute coronary syndrome (NSTE-ACS). : This study was an observational prospective study, which included 109 patients with NSTE-ACS.

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Article Synopsis
  • This study investigates whether thrombectomy alone is as effective as combining it with intravenous thrombolysis for patients with acute ischemic stroke caused by large-vessel blockage.
  • A meta-analysis of six trials involving 2,334 patients showed that functional independence at 90 days was similar between the two treatments, with slight variations in success and risk of hemorrhage.
  • While thrombectomy alone proved to be non-inferior at a wider margin, there might still be important differences in outcomes that need further exploration.
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  • The text discusses a new approach to treating advanced renal cancer by combining immunotherapy and targeted therapy, particularly focusing on cabozantinib + nivolumab.
  • The review compares this combination with other therapies recommended in current guidelines, looking at their effectiveness in clinical trials for metastatic clear-cell renal cell carcinoma (RCC).
  • A network meta-analysis (NMA) indicated that cabozantinib + nivolumab outperformed other treatments like axitinib + pembrolizumab and nivolumab + ipilimumab in terms of overall survival and progression-free survival, with statistically significant advantages under certain conditions.
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The purpose of this research was to investigate the effects of protocatechuic acid (PCA) at doses of 50 and 100 mg/kg on the development of unfavourable changes in cognitive processes in a pyrithiamine-induced thiamine deficiency (PTD) model of the Wernicke-Korsakoff syndrome (WKS) in rats. The effects of PCA were assessed at the behavioural and biochemical levels. Behavioural analysis was conducted using the Foot Fault test (FF), Bar test, Open Field test, Novel Object Recognition test (NOR), Hole-Board test and Morris Water Maze test (MWM).

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miR-9a-5p expression is decreased in the hippocampus of rats resistant to lamotrigine: A behavioural, molecular and bioinformatics assessment.

Neuropharmacology

April 2023

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Banacha 1B Street, 02-097, Warsaw, Poland.

The major obstacle in developing new treatment strategies for refractory epilepsy is the complexity and poor understanding of its mechanisms. Utilizing the model of lamotrigine-resistant seizures, we evaluated whether changes in the expression of sodium channel subunits are responsible for the diminished responsiveness to lamotrigine (LTG) and if miRNAs, may also be associated. Male rats were administered LTG (5 mg/kg) before each stimulation during kindling acquisition.

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Frequent mislabelled causal relationship between drug hypersensitivity reactions and culprit drugs reinforces the need for an accurate diagnosis. The systematic reviews and meta-analyses of assays published so far focused on immediate reactions and the most severe delayed reactions, while the most frequent drug-induced delayed reactions-nonsevere exanthemas-have been underestimated. We aim to fill this gap.

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Background: Long-term cocaine exposure leads to dysregulation of the reward system and initiates processes that ultimately weaken its rewarding effects. Here, we studied the influence of an escalating-dose cocaine regimen on drug-associated appetitive behavior after a withdrawal period, along with corresponding molecular changes in plasma and the prefrontal cortex (PFC).

Methods: We applied a 5 day escalating-dose cocaine regimen in rats.

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The sigma-1 and sigma-2 (σ and σ) receptors are found in high concentrations in the brain, and their altered expression leads to a variety of neuropsychiatric disorders. 3-di-tolylguanidine (DTG) stimulates the activity of both of these receptors. We assessed the effects of administering DTG to adult male Sprague Dawley rats on learning and memory consolidation processes and on the levels of neurotransmitters in selected brain structures.

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