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6 results on '"Győző Kulcsár"'

1. Multifactor Quality and Safety Analysis of Semaglutide Products Sold by Online Sellers Without a Prescription: Market Surveillance, Content Analysis, and Product Purchase Evaluation Study

Author

Amir Reza Ashraf, Tim Ken Mackey, Róbert György Vida, Győző Kulcsár, János Schmidt, Orsolya Balázs, Bálint Márk Domián, Jiawei Li, Ibolya Csákó, and András Fittler

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundOver the past 4 decades, obesity has escalated into a global epidemic, with its worldwide prevalence nearly tripling. Pharmacological treatments have evolved with the recent development of glucagon-like peptide 1 agonists, such as semaglutide. However, off-label use of drugs such as Ozempic for cosmetic weight loss has surged in popularity, raising concerns about potential misuse and the emergence of substandard and falsified products in the unregulated supply chain. ObjectiveThis study aims to conduct a multifactor investigation of product quality and patient safety risks associated with the unregulated online sale of semaglutide by examining product availability and vendor characteristics and assessing product quality through test purchases. MethodsWe used a complex risk and quality assessment methodology combining online market surveillance, search engine results page analysis, website content assessment, domain traffic analytics, conducting targeted product test purchases, visual quality inspection of product packaging, microbiological sterility and endotoxin contamination evaluation, and quantitative sample analysis using liquid chromatography coupled with mass spectrometry. ResultsWe collected and evaluated 1080 links from search engine results pages and identified 317 (29.35%) links belonging to online pharmacies, of which 183 (57.7%) led to legal pharmacies and 134 (42.3%) directed users to 59 unique illegal online pharmacy websites. Web traffic data for the period between July and September 2023 revealed that the top 30 domains directly or indirectly affiliated with illegal online pharmacies accumulated over 4.7 million visits. Test purchases were completed from 6 illegal online pharmacies with the highest number of links offering semaglutide products for sale without prescription at the lowest price range. Three injection vial purchases were delivered; none of the 3 Ozempic prefilled injection pens were received due to nondelivery e-commerce scams. All purchased vials were considered probable substandard and falsified products, as visual inspection indicated noncompliance in more than half (59%-63%) of the evaluated criteria. The semaglutide content of samples substantially exceeded labeled amounts by 28.56%-38.69%, although no peptide-like impurities were identified. The lyophilized peptide samples were devoid of viable microorganisms at the time of testing; however, endotoxin was detected in all samples with levels ranging between 2.1645 EU/mg and 8.9511 EU/mg. Furthermore, the measured semaglutide purity was significantly low, ranging between 7.7% and 14.37% and deviating from the 99% claimed on product labels by manufacturers. ConclusionsGlucagon-like peptide 1 agonist drugs promoted for weight loss, similar to erectile dysfunction medications more than 2 decades ago, are becoming the new blockbuster lifestyle medications for the illegal online pharmacy market. Protecting the pharmaceutical supply chain from substandard and falsified weight loss products and raising awareness regarding online medication safety must be a public health priority for regulators and technology platforms alike.

Published
2024
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2. Investigation of Intestinal Absorption and Excretion of Paracetamol in Streptozotocin-Induced Hyperglycemia

Author

Petra Mészáros, Sára Kovács, Győző Kulcsár, Melinda Páskuj, and Attila Almási

Subjects
Sulfates, paracetamol, acetaminophen, intestinal elimination, HPLC, streptozotocin, hyperglycemia, glutathione, cysteine, Organic Chemistry, Cytochrome P-450 CYP2E1, General Medicine, Glutathione, Catalysis, Streptozocin, Computer Science Applications, Acetylcysteine, Rats, Inorganic Chemistry, Glucuronides, Intestinal Absorption, Prostaglandin-Endoperoxide Synthases, Hyperglycemia, Animals, Cytochrome P-450 CYP3A, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Acetaminophen
Abstract

The phenolic drug molecules can be metabolized, among others, by the small intestine’s enterocytes. The conjugation reactions (glucuronidation and sulfation) show great importance in these transformations, although the oxidation reactions can be significant. These processes are dependent on the substituents of the phenolic compounds or the reacting functional groups (hydroxyl or carboxyl). Pathologic conditions, e.g., permanent hyperglycemia and diabetes, can alter the activities of the conjugative and possibly the oxidative enzymes, thus forming a change in the metabolic pattern and eventually provoking oxidative stress. A rat intestinal perfusion model was used to investigate the way in which experimental hyperglycemia affects the paracetamol’s intestinal elimination and metabolism. Hyperglycemia was induced by the administration of streptozotocin. Two hundred and fifty µM paracetamol was used in the intestinal perfusion solution. For the quantitation of the paracetamol and its major metabolites in the intestinal perfusate, an isocratic high-performance liquid chromatography method with UV-Vis detection was developed. The results revealed that quantities of all of the measured metabolites (glucuronide, sulfate, cysteine, and mercapturic acid conjugates) increased as the effect of the streptozotocin-induced hyperglycemia also did. In the small intestine’s homogenate, the glutathione levels showed that there was a decrease in the hyperglycemia levels after the paracetamol administration. In contrast, the tissue levels of the cysteine were lower in the streptozotocin-induced hyperglycemia and increased after the administration of the paracetamol. The changes in the activity of the intestinal CYP 3A4, CYP 2E1, and cyclooxygenase (COX) enzymes were determined in the control and the hyperglycemic cases. Still, there was a significant observable enzyme activity elevation in the intestinal COX enzymes, but there was a decrease in the amount of activity of the intestinal CYP3A4 enzymes, and the CYP2E1 enzyme activity was practically changeless. The results on the cysteine levels in the intestinal homogenate, at least partly, can be explained by the regulation function of the cysteine during the occurrence of oxidative stress.

Published
2022

3. Novel cyclic C

Author

Imre, Huber, Edina, Pandur, Katalin, Sipos, Lilla, Barna, András, Harazin, Mária A, Deli, Levente, Tyukodi, Gergely, Gulyás-Fekete, Győző, Kulcsár, and Zsuzsanna, Rozmer

Subjects
Neuroblastoma, Structure-Activity Relationship, Blood-Brain Barrier, Diarylheptanoids, Albumins, Animals, Endothelial Cells, Antineoplastic Agents, Astrocytoma, Rats
Abstract

Novel series of cyclic C

Published
2022

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