AI Article Synopsis
- - About 30% of epilepsy patients experience refractory seizures due to a lack of response to anti-epileptic drugs, potentially linked to increased activity of drug-efflux transporters like P-glycoprotein and multidrug-resistance associated protein-1.
- - A study examined the expression of these transporters in hippocampal tissues from 15 epilepsy surgery patients and compared them to tissues from 15 non-epileptic individuals, revealing a significant overexpression in the epilepsy cases.
- - The findings suggest that these transporters may contribute to multi-drug resistance in epilepsy, indicating that targeting them could improve the effectiveness of anti-epileptic drugs by enhancing their availability in the brain.
Article Abstract
Introduction: About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein () and multidrug-resistance associated protein-1 (). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue.
Methods: We have studied and drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15).
Results: Statistically significant over expression of both (P<0.0001) and (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of was more pronounced than . Immunohistochemistry of the patient group showed increased immunoreactivity of at blood-brain barrier and increased reactivity of in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy.
Conclusion: Our results suggested that in association with might be responsible for the multi-drug resistance in epilepsy. and could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016880 | PMC |
| http://dx.doi.org/10.32598/bcn.2021.2554.3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy.
Cancer Cell Int
December 2024
Department of Veterinary Clinical Medicine, College of Veterinary Medicine and Animal Science, University of Gondar, Gondar, Ethiopia.
Cancer remains a significant global challenge, and despite the numerous strategies developed to advance cancer therapy, an effective cure for metastatic cancer remains elusive. A major hurdle in treatment success is the ability of cancer cells, particularly cancer stem cells (CSCs), to resist therapy. These CSCs possess unique abilities, including self-renewal, differentiation, and repair, which drive tumor progression and chemotherapy resistance.
View Article and Find Full Text PDFFrom ancestor to pathogen: Expansion and evolutionary adaptations of multidrug resistance causing MFS efflux pumps in mycobacteria.
Gene
December 2024
Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow 226025, UP, India. Electronic address:
Multidrug resistance (MDR) in Mycobacterium tuberculosis (Mtb) is a growing threat. Efflux pumps, particularly those belonging to the Major Facilitator Superfamily (MFS), play a key role in MDR. This study investigated MFS transporters across Mycobacterium spp.
View Article and Find Full Text PDFPlasmodium falciparum African PfCRT Mutant Isoforms Conducive to Piperaquine Resistance are Infrequent and Impart a Major Fitness Cost.
J Infect Dis
December 2024
Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Background: Piperaquine, used in combination with dihydroartemisinin, has been identified as a promising partner drug for uncomplicated treatment and chemoprevention of Plasmodium falciparum malaria in Africa. In light of the earlier spread of piperaquine resistance in Southeast Asia, mediated primarily by mutations in the drug efflux transporter PfCRT, we have explored whether PfCRT mutations would represent a probable path to piperaquine resistance becoming established in Africa.
Methods: We edited PfCRT mutations known to mediate piperaquine resistance in Southeast Asia into P.
Resistance characterization and transcriptomic analysis of imipenem-induced drug resistance in .
PeerJ
December 2024
College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, China.
Background: Bacteria can develop resistance to various antibiotics under selective pressure, leading to multifaceted changes in resistance mechanisms. Transcriptomic sequencing allows for the observation of transcriptional level alterations in cells under antibiotic stress. Understanding the bacterial response to such stress is essential for deciphering their strategy against drug-resistant antibiotics and identifying potential targets for antibiotic development.
View Article and Find Full Text PDFDesign, synthesis and biological evaluation of biaryl amide derivatives as modulators of multi-drug resistance.
Eur J Med Chem
January 2025
School of Pharmacy, Fudan University, Shanghai, 201203, China. Electronic address:
Article Synopsis
- - The study highlights the challenge of multi-drug resistance (MDR) in cancer treatment, mainly due to the overexpression of ABC transporters like P-glycoprotein (P-gp), which affects the effectiveness of chemotherapy drugs.
- - Researchers explored the biaryl amide skeleton for potential agents to reverse MDR and identified a compound, D2, that significantly reversed resistance to drugs like paclitaxel and cisplatin in various cancer cell lines.
- - Compound D2 works by binding to P-gp, lowering its expression, and enhancing drug accumulation in cells, showing promise as a solution to combat MDR in cancer treatments.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!