scholarly journals Canine multi-drug resistance-1 mutation prevalence: A South African perspective

Author(s):  
Lérica Le Roux-Pullen ◽  
Henriëtte Van der Zwan

The multi-drug resistance (mdr-1) gene mutation is a phenomenon well known to current veterinary practitioners. The mutation causes a predisposition for, amongst other phenomena, macrocyclic lactone-induced neurotoxicosis in affected canines, a condition that can be fatal. Various herding dog breeds can be heterozygous or homozygous for the mutation, and prevalence differs only slightly in dog populations between geographical regions. This report provides prevalence data of the canine mdr-1 mutation in 306 South African dogs.

Author(s):  
Anil Tulpule ◽  
Andy Sherrod ◽  
Maria Norilyn Sanchez ◽  
Byron M. Espina ◽  
Dharshika Dharmapala ◽  
...  

2005 ◽  
Vol 12 (4) ◽  
pp. 999-1009 ◽  
Author(s):  
Jörg B Engel ◽  
Andrew V Schally ◽  
Gabor Halmos ◽  
Benjamin Baker ◽  
Attila Nagy ◽  
...  

The cytotoxic analog of bombesin (BN)/gastrin releasing peptide (GRP) AN-215 consisting of 2-pyrrolinodoxorubicin (AN-201), a superactive derivative of doxorubicin linked to a bombesin analog carrier, displays a high affinity to BN/GRP receptors and can be targeted to tumors that express these receptors. We evaluated the antitumor effect and the toxicity of AN-215 in 5 human breast cancer cell lines xenografted into nude mice. In addition, we measured the mRNA expression of multi drug resistance protein 1 (MDR-1), multi drug resistance related protein 1 (MRP-1) and breast cancer resistance protein (BCRP) by real-time PCR analysis after treatment with AN-215. All five cell lines expressed BN/GRP receptors, and AN-215 significantly (P<0.05) inhibited tumor growth in all models, while its cytotoxic radical AN-201 had no significant effect in four models. In MX-1 tumors, AN-201 had a significantly weaker antitumor effect than AN-215. The effect of AN-215 was nullified by a blockade of BN/GRP receptors with a bombesin antagonist. Low or no induction of MDR-1, MRP-1 and BCRP occurred after treatment with AN-215. In conclusion, targeted chemotherapy with the cytotoxic BN/GRP analog AN-215 strongly inhibits breast cancers that express BN/GRP receptors and might provide a new treatment modality for mammary carcinoma.


2007 ◽  
Vol 21 (2) ◽  
pp. 252-257 ◽  
Author(s):  
Salim Fredericks ◽  
AnaMaria Jorga ◽  
Iain A.M. MacPhee ◽  
Sandrine Reboux ◽  
Elizabeth Shiferaw ◽  
...  

2009 ◽  
Vol 4 (02) ◽  
pp. 061-069 ◽  
Author(s):  
Rahma Udu Yusuf ◽  
Sabah Ahmed Omar ◽  
Raphael Muchangi Ngure

Background: One of the major problems to the treatment of malaria is the emergence and spread of parasite resistant to antimalarial drugs. Due to increased chloroquine (CQ) resistance, the antifolate combinations are becoming important in the chemotherapy of falciparum malaria. However, resistance to antifolate exists and they are still effective in the above combinations. This study aimed at determining the prevalence of antimalarial drug resistance markers in P. falciparum isolates, involving the detection of mutations at the mdr 1- 86 which associates with amodiaquine resistance, and dhfr mutations associated with SP resistances. Methods: The dot-blot/ probe hybridization, which is more sensitive and specific; it detects parasitaemia of less than 100 parasites/µl of blood, and can identify a minority parasite genotype down to 1% in a mixture, was adopted to determine multi-drug resistance (mdr1-86) to show the correlation of Amodiaquine (AQ) resistance and PCR/ RFLP adopted to determine dihydrofolate reductase (dhfr) baseline resistance to Sulphadoxine- Pyrimethamine (SP) resistance in Nubian region of southern Sudan. A randomized open label trial of Artesunate (AS) + SP and AS+ SP was carried out in children less than 5 years. Molecular analysis of filter paper preserved blood samples collected was carried out to provide a baseline estimate of allele prevalences. Results: Baseline of the allele prevalence of the mdr1 86 locus in the AS+ AQ was successful for 80 isolates: 71(8.11%) carried parasites harbouring the mdr1-86 Tyr resistance allele, while 7 (89.19%) carried mdr1-86 Asn sensitivity allele and 2 (2.7%) were of mixed infection, having both resistance and wild type allele. Overall, the prevalence of the dhfr point mutation, codon 51, 59 and 108: 82.5% (132/160) carried mutations at dhfr (N51I, C59R or S108N), but triple mutants were rare (3.1%) in the AS + SP arm. Conclusion: The research provides the evidence that mutations present in dhfr and mdr1 86 has a significant effect on the type of treatment following SP and AQ chemotherapy. SP resistance may spread rapidly, and AS + AQ is likely to be a better option, provided AQ use is restricted to the combination. The significance of the study shows that definitely combination of drugs improves SP therapy at the study site. Keywords: Antimalarial drugs, P. falciparum, dhfr, mdr-1, dot-blot hybridisation technique, PCR/RFLP


2019 ◽  
pp. 65-72
Author(s):  
Rasmaya Niruri ◽  
Rini Noviyani ◽  
Indah Mei Rahajeng

Multi Drug Resistance-1 (MDR-1) gene polymorphisms encoding for P-glycoprotein can affect clopidogrel intestinal absorption. This systematic review aim to identify the impact of MDR-1 gene 3435 variants on clopidogrel pharmacokinetics. Literature review were retrieved from MEDLINE, Science Direct, Scopus, Clinical Key, ProQuest and Google Scholar databases. The articles are critically reviewed and analyzed to answer this systematic review’s aim. The result showed that, in patients with cardiovascular disease, the peak plasma concentration (Cmax) and the total area under the plasma concentration–time curve (AUC) of clopidogrel and its active metabolites were lower in 3435TT compared to 3435CC. Nevertheless, the variants of MDR-1 gene were not significantly correlated to the plasma concentration in healthy subjects. Clopidogrel pharmacokinetic profile varied widely between MDR-1 3435 variants and subjects.


2021 ◽  
Author(s):  
Kathirvel Kandasamy ◽  
Bharanidharan Devarajan

Pseudomonas aeruginosa, is a gram-negative bacterium causes opportunistic or nosocomial infections in immunocompromised individuals. In recent years, a steady increase in human corneal infections of P. aeruginosa has been reported with increased multi-drug resistance (MDR) or extensively drug resistance (XDR). Several non-coding sRNAs, has been identified to regulate various physiological processes in P. aeruginosa, including biofilm formation, quorum sensing. However, the regulatory mechanism of sRNAs in MDR/XDR pathways of P. aeruginosa keratitis strains is not yet studied. In this study, we identified bacterial sRNAs in publicly available P. aeruginosa keratitis genomes and investigated their regulatory role in MDR/XDR pathways using bioinformatic analysis. Totally, 46 P. aeruginosa keratitis strains from different geographical regions were included. Of 46, Eight (30%) out of Twenty-seven and Nine (52%) out of Nineteen P. aeruginosa strains from India and Australia were identified as not-MDR. Whereas, 10 (38%) Indian and 9 (47%) Australian strains were identified as MDR. Eight Indian strains were identified as XDR. Out of 46 strains, 23 (50%) carried ExoU, 21(45%) carried ExoS and two (5%) strains carried both ExoU and ExoS, exotoxins for their virulence. The sRNA, SPA0021 was identified in 18 MDR/XDR and 6 not-MDR strains along with UCBPP-PA14. Interestingly, majority of the imipenem resistant P. aeruginosa keratitis strains from the present study was found to be carried SPA0023 sRNA (18 out of 30 strains). The outer membrane porin protein OprD, identified as binding target of SPA0023. Negative regulation or inactivation of OprD, reported in increased imipenem resistance in P. aeruginosa. Mutation analysis revealed that SPA0023 carrying P. aeruginosa keratitis strains contains a lesser number of amino acid changes in OprD protein than other strains. These findings indicate, imipenem resistance in SPA0023 carried strains might arose from the negative regulation or inhibition of OprD by SPA0023. However, functional studies are warranted with large number of P. aeruginosa keratitis strains to confirm the negative regulation of OprD by SPA0023 and imipenem resistance.


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