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Effect of Cyclooxygenase Inhibition on P-Glycoprotein Expression and Phenytoin Level in Brain Tissue of Pilocarpine Induced Epilepsy in Rats

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Journal of Biosciences and Medicines 2023年第8期11卷 169-191页

作者： Reham M. Elsayed Amira S. Mohamed mona k. tawfik Magda M. Hagras Faculty of Medicine Suez Canal University Ismailia Egypt

Back.round: Increased brain P-glycoprotein (P-gp) expression may play important role in resistance to antiseizure drugs. The present work.aimed to overcome the drug resistance that develop due to overexpression of P-gp with subsequent increase in brain phenytoin level in epileptic rats, using either non-selective (indomethacin) or selective (celecoxib) cyclooxygenase inhibitors. Methods: Fifty-six adult male albino rats were randomly divided into seven groups. Epilepsy was induced using the lithium pilocarpine model. Rats received indomethacin (2.5 mg/k.) or celecoxib (20 mg/k.), either alone or combined with phenytoin (50 mg/k.). Seizures were evaluated using Racine score. Motor coordination was assessed using open field and rotarod tests. Phenytoin brain level was measured using High Performance Liquid Chromatography (HPLC), glutamate expression was measured using Enzyme Link.d Immunosorbent Assay (ELISA), ATP Binding Cassette Subfamily B Member 1 (ABCB1) gene expression was assessed using Real Time-Polymerase Chain Reaction (RT-PCR), and immunohistochemical analysis was done for P-gp expression. Results: Phenytoin combination with either indomethacin or celecoxib had improved the Racine score, motor coordination on rotarod apparatus, and open field test results. Also, phenytoin combination with either indomethacin or celecoxib decreased brain glutamate level, ABCB1 gene and P-gp expression, and increased brain phenytoin level compared to treatment with phenytoin alone. This indicated that both P-gp inhibitors indomethacin and celecoxib, increased the level of phenytoin that reached the brain of rats. However, brain uptak. of phenytoin was significantly enhanced using celecoxib rather than indomethacin (CI 95%, 17.092: 32.808, P-value Conclusion: Cyclooxygenase inhibition using either celecoxib or indomethacin resulted in downregulation of P-gp expression, with subsequent increase in brain phenytoin level in epileptic rats.

关键词： P-Glycoprotein Glutamate Phenytoin Indomethacin Celecoxib Epilepsy

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In Frail Elderly Patients, Low-Dose Gemcitabine over 6-Hour Infusion Is Equally Effective and Less Toxic Than the Standard Gemcitabine Protocol for Advanced Pancreatic Adenocarcinoma: A Randomized Phase II Trial

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Journal of Cancer Therapy 2020年第3期11卷 124-141页

作者： Salah Mabrouk.k.allaf Elsayed Mostafa Ali Ahmed MMak.ad Mohamed Medhat Samir Anwar tawfik Amin Muhammad Abbas El-masry mona MSayed Dalia Osama Medical Oncology Department South Egypt Cancer InstituteAssiut UniversityAssiutEgypt Clinical Oncology and Nuclear Medicine Department Sohag UniversitySohagEgypt Surgical Oncology Department South Egypt Cancer InstituteAssiut UniversityAssiutEgypt Division of gastroenterology-Department of internal medicine Assiut UniversityAssiutEgypt Radiation Oncology Department South Egypt Cancer InstituteAssiut UniversityAssiutEgypt

Back.round:?Treatment of frail elderly patients with pancreatic cancer is still a major problem due to intolerance to standard chemotherapy doses. Aim:?This study aims to compare the low-dose gemcitabine over 6 hours (LD6H) to the standard gemcitabine protocol in terms of clinical benefit, survival, and safety in the frail elderly patients with advanced pancreatic adenocarcinoma. Methods:?Patients enrolled in this trial were randomly assigned by in a 1:1 fashion via closed envelope method to either receive gemcitabine of 1000 mg/m2?over 30-minute infusion on days 1, 8, and 15 of every 4-week.cycle (standard protocol arm) or gemcitabine as a week.y low-dose (250 mg/m2) over 6-hour infusion (LD6H arm). Results:?We enrolled eighty-two eligible frail elderly patients with advanced pancreatic cancer. The patients were randomly assigned to receive either standard gemcitabine protocol (40 patients) or low-dose (250 mg/m2) gemcitabine over 6-hour infusion, given week.y (42 patients). There was no significant difference between the standard group and low-dose group as regard of the overall response rate (p = 0.654), the disease control rate (DCR) (p = 0.845), the median progression-free survival (PFS) (p = 0.908) and the overall survival (OS) (p = 0.331). The low-dose regimen had a significantly lower incidence of adverse effects grades 3 or 4 when compared to the standard regimen: (p = 0.024 for fatigue, p = 0.027 for hypotension, p = 0.012 for each anemia as well as thrombocytopenia, and p = 0.006 for neutropenia). Conclusion:?Low-dose gemcitabine over 6-hour infusion is equally effective and less toxic when compared to standard gemcitabine protocol in frail elderly patients with advanced pancreatic adenocarcinoma. So, we recommend the low-dose gemcitabine for frail elderly patients with advanced pancreatic cancer.

关键词： Continuous Infusion Elderly Frail Low Dose Gemcitabine Pancreatic Cancer

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