The development of resistance to metachloridine inPlasmodium gallinaceumin Chicks

Parasitology ◽  
1953 ◽  
Vol 42 (3-4) ◽  
pp. 277-286 ◽  
Author(s):  
Ann Bishop ◽  
Elspeth W. McConnachie
Keyword(s):  
Growth Rate ◽  
Drug Resistance ◽  
Normal Population ◽  
Rapid Development ◽  
Cross Resistance ◽  
Development Of Resistance ◽  
The Gift ◽  
Higher Doses ◽  
Resistance Tests ◽  
Selection Of

1. An increase in resistance to metachloridine of more than 100-fold was obtained within a few weeks in a strain ofPlasmodium gallinaceumtreated with gradually increasing doses of the drug and maintained in young chicks by blood-inoculation at intervals of 2–3 days.2. There was no evidence that the rapid development of resistance arose by the selection of highly resistant individuals present in the normal population.3. Two strains ofP. gallinaceumpassaged through chicks treated with 0·025 mg. doses of the drug gradually became resistant to greater concentrations than that to which they had been exposed, though their growth rate decreased when they were inoculated into birds receiving higher doses of the drug.4. In both strains maintained in birds treated with 0·025 mg. doses of the drug, resistance reached a maximum beyond which it did not increase.5. Cross-resistance tests failed to show any relationship in mode of action between meta-chloridine and pamaquin, mepacrine, quinine or chloroquine. A strain ofP. gallinaceum, highly resistant to metachloridine, showed slight resistance to sulphadiazine, sulphapyridine and sulphathiazole, but none to sulphanilamide or proguanil.We are indebted to the Cyanamid Products Ltd., London, for the gift of the Folvite used in these experiments.

Eimeria tenella in chickens: development of resistance to quinolone anticoccidial drugs

Parasitology ◽  
1975 ◽  
Vol 71 (1) ◽  
pp. 41-49 ◽  
Author(s):  
H. D. Chapman
Keyword(s):  
Drug Resistance ◽  
Weight Gain ◽  
Liquid Nitrogen ◽  
Selection Pressure ◽  
Drug Tolerance ◽  
Eimeria Tenella ◽  
Cross Resistance ◽  
Drug Selection ◽  
Laboratory Conditions ◽  
Development Of Resistance

The development of drug resistance by the present Houghton strain of Eimeria tenella to the quinolones, methyl benzoquate and buquinolate, was found to take place after a single experimental passage. The development of resistance was independent of drug selection pressure and showed cross resistance to other quinolones, but not to amprolium and robenidine. When the Weybridge, Beltsville and Elberfeld strains of E. tenella were compared under similar laboratory conditions, the Weybridge and Elberfeld strains developed resistance to methyl benzoquate after 6 passages and the Beltsville after 5. Studies on the response of the Houghton strain to methyl benzoquate and buquinolate revealed that the drugs did not completely control the infection as measured by weight gain and that oocyst production was not suppressed. These observations indicate that the strain had already acquired some resistance to these drugs. This was confirmed by examining the resistance to methyl benzoquate of a culture of the Houghton strain of E. tenella which had been stored frozen in liquid nitrogen since 1969. This showed full sensitivity to the drug and developed resistance after 8 passages. This suggests that drug tolerance has been acquired by the Houghton strain since 1969.Oocyst lines were established from the Houghton strain by infecting single birds with approximately 10 oocysts. Eleven of these lines were found to be sensitive to methyl benzoquate, and nine to give rise to resistant parasites. It is concluded that the Houghton strain is contaminated by a small number of resistant oocysts which can be eliminated from a culture by dilution of the challenge inoculum. One of these Houghton oocyst lines, sensitive to methyl benzoquate, developed resistance after 8 serial passages.

Further studies on the use of chicken embryo infections for the study of drug resistance in Eimeria tenella

Parasitology ◽  
1976 ◽  
Vol 73 (3) ◽  
pp. 275-282 ◽  
Author(s):  
H. D. Chapman
Keyword(s):  
Drug Resistance ◽  
Drug Concentration ◽  
Chicken Embryo ◽  
The Other ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Mutagenic Agent ◽  
Development Of Resistance ◽  
Drug Concentrations ◽  
Resistant Lines

Infections in the chicken embryo have been used to study the development of drug resistance in an embryo adapted strain of E. tenella. Resistance was developed to decoquinate, clopidol and robenidine by serially passaging this strain, but evidence for the development of resistance to amprolium was inconclusive. Resistance to decoquinate developed more readily than to the other drugs. Attempts to increase resistance to clopidol, robenidine and amprolium by increasing the sporozoite inoculum and by the use of a mutagenic agent were unsuccesful. No cross-resistance was found between the 4 drugs.Drug resistant lines of the Houghton strain (H) of E. tenella, made resistant to the 4 anticoccidial drugs by passage in chickens, were found to be resistant when evaluated using chicken embryo infections. Lines made resistant to decoquinate were not controlled by any concentration of this drug, suggesting that resistance, once developed, was absolute and not dependent on drug concentration. Lines made resistant to robenidine, clopidol and amprolium, however, were controlled by higher drug concentrations suggesting that in this case resistance was dependent on drug concentration.

scholarly journals Evolution of Resistance to Sulfadoxine-Pyrimethamine in Plasmodium falciparum

2004 ◽  
Vol 48 (6) ◽  
pp. 2116-2123 ◽  
Author(s):  
Michelle L. Gatton ◽  
Laura B Martin ◽  
Qin Cheng
Keyword(s):  
Drug Resistance ◽  
Half Life ◽  
Drug Dosage ◽  
Parasite Resistance ◽  
Resistance Mutations ◽  
Correct Treatment ◽  
Development Of Resistance ◽  
Elimination Half ◽  
Treatment Dosage ◽  
Selection Of

ABSTRACT The development of resistance to sulfadoxine-pyrimethamine by Plasmodium parasites is a major problem for the effective treatment of malaria, especially P. falciparum malaria. Although the molecular basis for parasite resistance is known, the factors promoting the development and transmission of these resistant parasites are less clear. This paper reports the results of a quantitative comparison of factors previously hypothesized as important for the development of drug resistance, drug dosage, time of treatment, and drug elimination half-life, with an in-host dynamics model of P. falciparum malaria in a malaria-naïve host. The results indicate that the development of drug resistance can be categorized into three stages. The first is the selection of existing parasites with genetic mutations in the dihydrofolate reductase or dihydropteroate synthetase gene. This selection is driven by the long half-life of the sulfadoxine-pyrimethamine combination. The second stage involves the selection of parasites with allelic types of higher resistance within the host during an infection. The timing of treatment relative to initiation of a specific anti-P. falciparum EMP1 immune response is an important factor during this stage, as is the treatment dosage. During the third stage, clinical treatment failure becomes prevalent as the parasites develop sufficient resistance mutations to survive therapeutic doses of the drug combination. Therefore, the model output reaffirms the importance of correct treatment of confirmed malaria cases in slowing the development of parasite resistance to sulfadoxine-pyrimethamine.

Continuation of sunitinib following RECIST progression on first-line sunitinib.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4585-4585
Author(s):  
Mauricio Emmanuel Burotto Pichun ◽  
Julia Wilkerson ◽  
Wilfred Donald Stein ◽  
Robert John Motzer ◽  
Susan Elaine Bates ◽  
...  
Keyword(s):  
Growth Rate ◽  
Acquired Resistance ◽  
Cross Resistance ◽  
Regression Rate ◽  
Development Of Resistance ◽  
Valid Data ◽  
Vegf Pathway ◽  
The Stability ◽  
Measures Of Effectiveness ◽  
Beneficial Outcome

4585 Background: In the last seven years the FDA and the EMA have approved seven agents for treatment of RCC. Five of these target the VEGF pathway. Methods: We conducted a detailed analysis of data from the sunitinib registration trial examining the growth and regression rate constants and the stability of the growth rate as measures of effectiveness and to understand development of resistance. Results: Sufficient data was available for the analysis of 350/374 patients enrolled. Statistically valid data was obtained in 321(91.7%). The median regression rate constant was 0.0048 days-1, and in 59 patients no evidence of growth was recorded while on study, only regression. The median growth rate was 0.00082 days-1 and this rate was stable a median of 267 days, remaining stable beyond 300 days in 172 patients, beyond 600 days in 95 patients, and beyond 900 days in 49 pts. A suggestion of a possible increase of the growth rate while sunitinib was administered could be discerned in only 15/321 pts. With a median growth rate 0.00082 days-1 the estimated time to progression were sunitinib discontinued and then re-started would have been a minimum of 7.3 months. Thus a meaningful outcome could be achieved provided continued sunitinib is tolerable. Finally with an estimated 47%, 27% and 13% of tumor still sensitive to sunitinib 100, 200 and 300 days after starting therapy, shrinkage with a new TKI in patients who discontinue sunitinib before day 300 for toxicity may not be a sign of non-cross resistance, but of residual sensitive tumor. Conclusions: Prolonged stability of the growth rate of RCC on sunitinib is consistent with intrinsic and not acquired resistance. Baring toxicity, continued sunitinib beyond RECIST criteria for progression may provide a beneficial outcome and can be considered a treatment alternative in selected patients. Randomized trials to assess the value of VEGF TKI’s in patients whose disease has “progressed” on sunitinib should consider including an arm that continues sunitinib to test this hypothesis.

scholarly journals Antimicrobial Pressure of Ciprofloxacin and Gentamicin on Biofilm Development by an Endoscope-Isolated Pseudomonas aeruginosa

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Idalina Machado ◽  
Joana Graça ◽  
Hélder Lopes ◽  
Susana Lopes ◽  
Maria O. Pereira
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Benzalkonium Chloride ◽  
Reference Strain ◽  
Bacterial Attachment ◽  
Cross Resistance ◽  
Persister Cells ◽  
Development Of Resistance ◽  
Biofilm Development ◽  
Selection Of

This work aims at characterizing endoscope biofilm-isolated (PAI) and reference strain P. aeruginosa (PA) adhesion, biofilm formation and sensitivity to antibiotics. The recovery ability of the biofilm-growing bacteria subjected to intermittent antibiotic pressure (ciprofloxacin (CIP) and gentamicin (GM)), as well as the development of resistance towards antibiotics and benzalkonium chloride (BC), were also determined. The capacity of both strains to develop biofilms was greatly impaired in the presence of CIP and GM. Sanitization was not complete allowing biofilm recovery after the intermittent cycles of antibiotic pressure. The environmental pressure exerted by CIP and GM did not develop P. aeruginosa resistance to antibiotics nor cross-resistance towards BC. However, data highlighted that none of the antimicrobials led to complete biofilm eradication, allowing the recovery of the remaining adhered population possibly due to the selection of persister cells. This feature may lead to biofilm recalcitrance, reinforcement of bacterial attachment, and recolonization of other sites.

Eimeria tenella: experimental studies on the development of resistance to robenidine

Parasitology ◽  
1976 ◽  
Vol 73 (3) ◽  
pp. 265-273 ◽  
Author(s):  
H. D. Chapman
Keyword(s):  
Drug Resistance ◽  
Selection Pressure ◽  
Experimental Studies ◽  
Eimeria Tenella ◽  
Parasite Population ◽  
Cross Resistance ◽  
Drug Selection ◽  
Development Of Resistance

The development of resistance by the Houghton strain (H) of E. tenella to robenidine has been studied, in the laboratory, by serially passaging the strain in chickens fed increasing concentrations of drug. Resistance to robenidine developed more readily in experiments using larger numbers of birds with higher numbers of oocysts in the inoculum. Both these factors increased the parasite population and increased the chance of selecting parasites resistant to the drug. E. tenella (H) was made resistant to 264 ppm robenidine and showed no cross-resistance to other anticoccidial agents. Resistance arose in a series of ‘steps’ as the concentration of drug was increased. E. tenella (H) was continuously passaged at concentrations ranging from 2 to 33 ppm of robenidine. After 16 passages, lines passaged at 2, 4 and 8 ppm were not resistant to 33 ppm robenidine, suggesting that the degree of resistance developed was dependent upon the drug selection pressure.

A Selection of Bandung City Travel Route Using The FLOYD-WARSHALL Algorithm

2020 ◽  
Vol 12 (7) ◽  
Author(s):  
Muhammad Ghifari Arfananda ◽  
◽  
Surya Michrandi Nasution ◽  
Casi Setianingsih ◽  
◽  
...  
Keyword(s):  
Traffic Congestion ◽  
Rapid Development ◽  
Route Selection ◽  
Tourist Attractions ◽  
Tourist Destinations ◽  
A Value ◽  
Distance Data ◽  
Simple Additive Weighting ◽  
The City ◽  
Selection Of

The rapid development of information and technology, the city of Bandung tourism has also increased. However, tourists who visit the city of Bandung have problems with a limited time when visiting Bandung tourist attractions. Traffic congestion, distance, and the number of tourist destinations are the problems for tourists travel. The optimal route selection is the solution for those problems. Congestion and distance data are processed using the Simple Additive Weighting (SAW) method. Route selection uses the Floyd-Warshall Algorithm. In this study, the selection of the best route gets the smallest weight with a value of 5.127 from the Algorithm process. Based on testing, from two to five tourist attractions get an average calculation time of 3 to 5 seconds. This application is expected to provide optimal solutions for tourists in the selection of tourist travel routes.

Mycobacterial DNA Replication as a Target for Antituberculosis Drug Discovery

2017 ◽  
Vol 17 (19) ◽  
pp. 2129-2142 ◽  
Author(s):  
Renata Płocinska ◽  
Malgorzata Korycka-Machala ◽  
Przemyslaw Plocinski ◽  
Jaroslaw Dziadek
Keyword(s):  
Drug Resistance ◽  
Dna Replication ◽  
Drug Targets ◽  
Rapid Development ◽  
New Drugs ◽  
Drug Resistant ◽  
Antituberculosis Drug ◽  
Nucleotide Synthesis ◽  
Antituberculosis Therapy ◽  
Optimal Drug

Background: Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is a leading infectious disease organism, causing millions of deaths each year. This serious pathogen has been greatly spread worldwide and recent years have observed an increase in the number of multi-drug resistant and totally drug resistant M. tuberculosis strains (WHO report, 2014). The danger of tuberculosis becoming an incurable disease has emphasized the need for the discovery of a new generation of antimicrobial agents. The development of novel alternative medical strategies, new drugs and the search for optimal drug targets are top priority areas of tuberculosis research. Factors: Key characteristics of mycobacteria include: slow growth, the ability to transform into a metabolically silent - latent state, intrinsic drug resistance and the relatively rapid development of acquired drug resistance. These factors make finding an ideal antituberculosis drug enormously challenging, even if it is designed to treat drug sensitive tuberculosis strains. A vast majority of canonical antibiotics including antituberculosis agents target bacterial cell wall biosynthesis or DNA/RNA processing. Novel therapeutic approaches are being tested to target mycobacterial cell division, twocomponent regulatory factors, lipid synthesis and the transition between the latent and actively growing states. Discussion and Conclusion: This review discusses the choice of cellular targets for an antituberculosis therapy, describes putative drug targets evaluated in the recent literature and summarizes potential candidates under clinical and pre-clinical development. We focus on the key cellular process of DNA replication, as a prominent target for future antituberculosis therapy. We describe two main pathways: the biosynthesis of nucleic acids precursors – the nucleotides, and the synthesis of DNA molecules. We summarize data regarding replication associated proteins that are critical for nucleotide synthesis, initiation, unwinding and elongation of the DNA during the replication process. They are pivotal processes required for successful multiplication of the bacterial cells and hence they are extensively investigated for the development of antituberculosis drugs. Finally, we summarize the most potent inhibitors of DNA synthesis and provide an up to date report on their status in the clinical trials.

scholarly journals A microfluidic device enabling drug resistance analysis of leukemia cells via coupled dielectrophoretic detection and impedimetric counting

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yağmur Demircan Yalçın ◽  
Taylan Berkin Töral ◽  
Sertan Sukas ◽  
Ender Yıldırım ◽  
Özge Zorlu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
K562 Cells ◽  
Leukemia Cells ◽  
Drug Resistant ◽  
Wild Type ◽  
Gene Expressions ◽  
Before And After ◽  
The Difference ◽  
Selection Of ◽  
Resistant Cells

AbstractWe report the development of a lab-on-a-chip system, that facilitates coupled dielectrophoretic detection (DEP-D) and impedimetric counting (IM-C), for investigating drug resistance in K562 and CCRF-CEM leukemia cells without (immuno) labeling. Two IM-C units were placed upstream and downstream of the DEP-D unit for enumeration, respectively, before and after the cells were treated in DEP-D unit, where the difference in cell count gave the total number of trapped cells based on their DEP characteristics. Conductivity of the running buffer was matched the conductivity of cytoplasm of wild type K562 and CCRF-CEM cells. Results showed that DEP responses of drug resistant and wild type K562 cells were statistically discriminative (at p = 0.05 level) at 200 mS/m buffer conductivity and at 8.6 MHz working frequency of DEP-D unit. For CCRF-CEM cells, conductivity and frequency values were 160 mS/m and 6.2 MHz, respectively. Our approach enabled discrimination of resistant cells in a group by setting up a threshold provided by the conductivity of running buffer. Subsequent selection of drug resistant cells can be applied to investigate variations in gene expressions and occurrence of mutations related to drug resistance.

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