Immunity in trypanosomiasis

Parasitology ◽  
1959 ◽  
Vol 49 (1-2) ◽  
pp. 143-152 ◽  
Author(s):  
M. A. Soltys
Keyword(s):  
Resistant Strain ◽  
Therapeutic Dose ◽  
Sensitive Strain ◽  
Drug Resistant ◽  
Chemotherapeutic Drugs ◽  
Natural Conditions ◽  
Resistant Strains ◽  
Drug Resistant Strains

Antibody-resistant strains are less sensitive to suramin and antrycide than antibody-sensitive strains. When living trypanosomes were exposed to suramin and antrycide in vitro, antibody-resistant strains needed 50 times more drugs than antibody-sensitive trypanosomes in order to make them non-infectious to mice. In therapeutic experiments in mice the minimal therapeutic dose of drugs for antibody-sensitive strains was 0·1 mg. but for resistant strains it was 0·3 mg./20 g. mice. Rabbits treated prophylactically with suramin resisted infection with the antibody-sensitive strain for a period of 4 months, but failed to resist infection with the antibody-resistant strain after 2 months.Rabbits treated prophylactically with antrycide pro-salt, resisted infection with antibody-sensitive strains for a period of 2 months, but failed to resist infection with the antibody-resistant strain even 1 month after injection with the drug. Although trypanosomes can become drug resistant without being antibody resistant it is suggested that, under natural conditions, drug-resistant strains in animals and man develop from antibody-resistant strains, particularly when trypanostatic drugs are used. It is suggested in conclusion from these experiments that strains of trypanosomes which are exposed for some time to antibodies and become antibody resistant after passage through animals like rabbits, as well as those strains frequently passaged through mice, should be used in all tests for the efficiency of chemotherapeutic drugs.

scholarly journals Modified Fixed-Ratio Isobologram Method for Studying In Vitro Interactions between Atovaquone and Proguanil or Dihydroartemisinin against Drug-Resistant Strains of Plasmodium falciparum

2004 ◽  
Vol 48 (11) ◽  
pp. 4097-4102 ◽  
Author(s):  
Quinton L. Fivelman ◽  
Ipemida S. Adagu ◽  
David C. Warhurst
Keyword(s):  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Resistant Strain ◽  
Fixed Ratio ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
In Vitro Interactions

ABSTRACT A modified fixed-ratio isobologram method for studying the in vitro interactions between antiplasmodial drugs is described. This method was used to examine the interactions between atovaquone, proguanil, and dihydroartemisinin. The interaction between atovaquone and proguanil was synergistic against atovaquone-sensitive strains K1 and T996; however, there was a loss of synergy against atovaquone-resistant strain NGATV01 isolated after Malarone (the combination of atovaquone and proguanil) treatment failure. While the interaction between atovaquone and dihydroartemisinin was indifferent against isolate NGATV01, the interaction displayed indifference tending toward antagonism against the atovaquone-sensitive strains tested. The relevance of in vitro interactions to in vivo treatment is discussed.

scholarly journals The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering the Immune Responses against Mycobacterium bovis BCG Strain in Individuals with Type 2 Diabetes

2021 ◽  
Vol 12 (1) ◽  
pp. 16-26
Author(s):  
Kimberly To ◽  
Ruoqiong Cao ◽  
Aram Yegiazaryan ◽  
James Owens ◽  
Kayvan Sasaninia ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Immune Cells ◽  
Mycobacterial Infection ◽  
Drug Resistant ◽  
Tnf Α ◽  
Resistant Strains ◽  
Ifn Γ ◽  
Drug Resistant Strains

Abstract Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to M. tb infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, M. tb still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of M. tb have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within in vitro granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of in vivo glutathione (GSH) supplementation in individuals with T2DM along with in vitro treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects’ blood was drawn pre- and post-L-GSH/or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct in vitro studies with everolimus. We found that in vitro treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular M. bovis BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with in vitro everolimus treatment produced a greater effect in inhibiting the growth of intracellular Mycobacterium bovis BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with in vitro everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, in vitro everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection.

scholarly journals In Vitro and In Vivo Antimalarial Activities of a Carbohydrate Antibiotic, Prumycin, against Drug-resistant Strains of Plasmodia

2004 ◽  
Vol 57 (6) ◽  
pp. 400-402 ◽  
Author(s):  
KAZUHIKO OTOGURO ◽  
AKI ISHIYAMA ◽  
MIYUKI KOBAYASHI ◽  
HITOMI SEKIGUCHI ◽  
TAKASHI IZUHARA ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals In Vitro Activity and MIC of Sitafloxacin against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis Isolated in Thailand

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Manoon Leechawengwongs ◽  
Therdsak Prammananan ◽  
Sarinya Jaitrong ◽  
Pamaree Billamas ◽  
Nampueng Makhao ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Critical Concentration ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACT New fluoroquinolones (FQs) have been shown to be more active against drug-resistant Mycobacterium tuberculosis strains than early FQs, such as ofloxacin. Sitafloxacin (STFX) is a new fluoroquinolone with in vitro activity against a broad range of bacteria, including M. tuberculosis. This study aimed to determine the in vitro activity of STFX against all groups of drug-resistant strains, including multidrug-resistant M. tuberculosis (MDR M. tuberculosis), MDR M. tuberculosis with quinolone resistance (pre-XDR), and extensively drug-resistant (XDR) strains. A total of 374 drug-resistant M. tuberculosis strains were tested for drug susceptibility by the conventional proportion method, and 95 strains were randomly submitted for MIC determination using the microplate alamarBlue assay (MABA). The results revealed that all the drug-resistant strains were susceptible to STFX at a critical concentration of 2 μg/ml. Determination of the MIC90s of the strains showed different MIC levels; MDR M. tuberculosis strains had a MIC90 of 0.0625 μg/ml, whereas pre-XDR and XDR M. tuberculosis strains had identical MIC90s of 0.5 μg/ml. Common mutations within the quinolone resistance-determining region (QRDR) of gyrA and/or gyrB did not confer resistance to STFX, except that double mutations of GyrA at Ala90Val and Asp94Ala were found in strains with a MIC of 1.0 μg/ml. The results indicated that STFX had potent in vitro activity against all the groups of drug-resistant M. tuberculosis strains and should be considered a new repurposed drug for treatment of multidrug-resistant and extensively drug-resistant TB.

In vitro efficacy of a synthetic all-d antimicrobial peptide against clinically isolated drug-resistant strains

2010 ◽  
Vol 35 (2) ◽  
pp. 208-209 ◽  
Author(s):  
Yoonkyung Park ◽  
Seong-Cheol Park ◽  
Jin-Young Kim ◽  
Jeong Ok Park ◽  
Chang Ho Seo ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals Sontochin as a Guide to the Development of Drugs against Chloroquine-Resistant Malaria

2012 ◽  
Vol 56 (7) ◽  
pp. 3475-3480 ◽  
Author(s):  
Sovitj Pou ◽  
Rolf W. Winter ◽  
Aaron Nilsen ◽  
Jane Xu Kelly ◽  
Yuexin Li ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Plasmodium Yoelii ◽  
Significant Activity ◽  
Drug Resistant ◽  
Content Type ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Derivatives Of

ABSTRACTSontochin was the original chloroquine replacement drug, arising from research by Hans Andersag 2 years after chloroquine (known as “resochin” at the time) had been shelved due to the mistaken perception that it was too toxic for human use. We were surprised to find that sontochin, i.e., 3-methyl-chloroquine, retains significant activity against chloroquine-resistant strains ofPlasmodium falciparum in vitro. We prepared derivatives of sontochin, “pharmachins,” with alkyl or aryl substituents at the 3 position and with alterations to the 4-position side chain to enhance activity against drug-resistant strains. Modified with an aryl substituent in the 3 position of the 7-chloro-quinoline ring, Pharmachin 203 (PH-203) exhibits low-nanomolar 50% inhibitory concentrations (IC50s) against drug-sensitive and multidrug-resistant strains andin vivoefficacy against patent infections ofPlasmodium yoeliiin mice that is superior to chloroquine. Our findings suggest that novel 3-position aryl pharmachin derivatives have the potential for use in treating drug resistant malaria.

scholarly journals Novel isoniazid derivative as promising antituberculosis agent

2020 ◽  
Vol 15 (10) ◽  
pp. 869-879
Author(s):  
Galyna P Volynets ◽  
Michail A Tukalo ◽  
Volodymyr G Bdzhola ◽  
Nataliia M Derkach ◽  
Mykola I Gumeniuk ◽  
...  
Keyword(s):  
Resistant Strain ◽  
Inhibitory Concentration ◽  
Binding Assay ◽  
Isonicotinic Acid ◽  
Drug Resistant ◽  
Major Focus ◽  
Unbound Fraction ◽  
Protein Binding Assay ◽  
Resistant Strains ◽  
Drug Resistant Strains

Background: A major focus of tuberculosis drug discovery is aimed at the development of novel antibiotics with activity against drug-resistant strains of Mycobacterium tuberculosis. Results: We have synthesized ten isoniazid derivatives and investigated for antibacterial activity toward M. tuberculosis H37Rv and isoniazid-resistant strain SRI 1369. It was revealed that only one compound, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide (1), is active toward isoniazid-resistant strain with minimum inhibitory concentration value of 0.14 μM. This compound is not cytotoxic toward human liver cells (HepG2; IC50 >100 μM), demonstrates good permeability in Caco-2 cells. Accordingly to the results of plasma protein binding assay, unbound fraction of compound 1, which potentially exhibits pharmacologic effects, is 57.9%. Conclusion: Therefore, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide is a promising compound for further preclinical studies.

Synthesis, antitrypanosomal and antimycobacterial activities of coumarinic N-acylhydrazonic derivatives

2020 ◽  
Vol 16 ◽  
Author(s):  
Camila Capelini ◽  
Vitória R. F. Câmara ◽  
José D. Figueroa Villar ◽  
Juliana M. C. Barbosa ◽  
Kelly Salomão ◽  
...  
Keyword(s):  
Resistant Strain ◽  
Sensitive Strain ◽  
Moderate Activity ◽  
Active Compounds ◽  
Meaningful Activity ◽  
The World ◽  
Resistant Strains ◽  
Vitro Effect ◽  
Tuberculosis Activity

Background: Near to 5-7 million people are infected with T. cruzi in the world, and about 10,000 people per year die of problems associated to this disease. Method: We reported herein the synthesis, antitrypanosomal and antimycobacterial activities of seventeen coumarinic N-acylhydrazonic derivatives. Results: These compounds were synthesized using methodology with reactions global yields ranging from 46%-70%. T. cruzi in vitro effect were evaluated against trypomastigote and amastigote forms and M. tuberculosis activity were towards H37Rv sensitive strain and resistant strains. Discussion: Against T. cruzi, the more active compounds revealed only moderate activity IC50/96h~20 µM for both trypomastigotes and amastigotes intracellular forms. (E)-2-oxo-N'-(3,4,5-trimethoxybenzylidene)-2H-chromene-3-carbohydrazide showed meaningful activity in INH resistant/RIP resistant strain. Conclusion: These compound acting as multitarget could be good leads for the development of new trypanocidal and bactericidal agents.

scholarly journals Role of Alanine Racemase Mutations in Mycobacterium tuberculosisd-Cycloserine Resistance

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Yoshio Nakatani ◽  
Helen K. Opel-Reading ◽  
Matthias Merker ◽  
Diana Machado ◽  
Sönke Andres ◽  
...  
Keyword(s):  
Alanine Racemase ◽  
Drug Resistant ◽  
Evolutionary Patterns ◽  
Content Type ◽  
Direct Measurements ◽  
Resistant Strains ◽  
Selection For ◽  
Drug Resistant Strains

ABSTRACT A screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to d-cycloserine.

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