scholarly journals In vitro and in vivo resistance of Leishmania infantum to meglumine antimoniate: a study of 37 strains collected from patients with visceral leishmaniasis.

1997 ◽  
Vol 41 (4) ◽  
pp. 827-830 ◽  
Author(s):  
F Faraut-Gambarelli ◽  
R Piarroux ◽  
M Deniau ◽  
B Giusiano ◽  
P Marty ◽  
...  

Primary and secondary unresponsiveness to meglumine has long been described in human visceral leishmaniasis. However, no studies have been performed to elucidate if these therapeutic failures were due to strain variability in meglumine sensitivity or were related to host factors. We have studied the in vitro sensitivity of 37 strains of Leishmania infantum isolated from 23 patients (11 human immunodeficiency virus-infected and 12 immunocompetent patients) with visceral leishmaniasis. Sensitivity tests were performed by infecting murine macrophages with Leishmania parasites and culturing them in medium containing different concentrations of meglumine. For each test we calculated a 50% effective dose (ED50) corresponding to the meglumine concentration at which 50% of the Leishmania parasites survived. In vitro results were strongly correlated to immediate clinical outcome. All strains requiring an ED50 of >70 microg/ml were related to therapeutic failures, whereas all strains requiring an ED50 of <40 microg/ml corresponded to an initial efficiency of meglumine. Among those patients who were initially improved, relapses occurred in all immunocompromised patients and in most immunocompetent patients who had a short duration of treatment (15 days). Finally, we found that in vitro sensitivity of strains decreased progressively in relapsing patients treated with meglumine. Consequently, the physician may be encouraged to alternate meglumine with other treatments such as amphotericin B or pentamidine, especially in the case of relapsing patients.

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Thais Alves da Costa-Silva ◽  
Andrés Jimenez Galisteo ◽  
José Angelo Lauletta Lindoso ◽  
Leandro R. S. Barbosa ◽  
Andre Gustavo Tempone

ABSTRACT Visceral leishmaniasis is a fatal parasitic neglected disease affecting 1.5 million people worldwide. Based on a drug repositioning approach, the aim of this work was to investigate the in vitro immunomodulatory potential of buparvaquone (BPQ) and to establish a safe regimen to evaluate the in vivo efficacy of BPQ entrapped by negatively charged nanoliposomes (BPQ-LP) in Leishmania infantum-infected hamsters. Small-angle X-ray scattering, dynamic light scattering, and the ζ-potential were applied in order to study the influence of BPQ on the liposome structure. Our data revealed that BPQ was located in the polar-apolar interface, snorkeling the polar region, and protected against aggregation inside the lipophilic region. The presence of BPQ also decreased the Z-average hydrodynamic diameter and increased the surface charge. Compared to intravenous and intramuscular administration, a subcutaneous route was a more effective route for BPQ-LP; at 0.4 mg/kg, BPQ-LP reduced infection in the spleen and liver by 98 and 96%, respectively. Treatment for 5 days resulted in limited efficacy, but 10 days of treatment resulted in an efficacy similar to that of a 15-day regimen. The nanoliposomal drug was highly effective, with a mean 50% effective dose of 0.25 mg/kg, reducing the parasite load in bone marrow by 80%, as detected using quantitative PCR analysis. In addition, flow cytometry studies showed that BPQ upregulated cytokines as tumor necrosis factor, monocyte chemoattractant protein 1, interleukin-10 (IL-10), and IL-6 in Leishmania-infected macrophages, eliminating the parasites via a nitric oxide-independent mechanism. This new formulation proved to be a safe and effective treatment for murine leishmaniasis that could be a useful candidate against visceral leishmaniasis.


2021 ◽  
Vol 221 ◽  
pp. 108059
Author(s):  
Thiago A.R. Reis ◽  
João A. Oliveira-da-Silva ◽  
Grasiele S.V. Tavares ◽  
Débora V.C. Mendonça ◽  
Camila S. Freitas ◽  
...  

2012 ◽  
Vol 19 (4) ◽  
pp. 490-498 ◽  
Author(s):  
Kevin W. Bruhn ◽  
Ron Birnbaum ◽  
Jacquelyn Haskell ◽  
Veena Vanchinathan ◽  
Stephanie Greger ◽  
...  

ABSTRACTThere are currently no effective vaccines for visceral leishmaniasis, the second most deadly parasitic infection in the world. Here, we describe a novel whole-cell vaccine approach usingLeishmania infantum chagasipromastigotes treated with the psoralen compound amotosalen (S-59) and low doses of UV A radiation. This treatment generates permanent, covalent DNA cross-links within parasites and results inLeishmaniaorganisms termed killed but metabolically active (KBMA). In this report, we characterize thein vitrogrowth characteristics of both KBMAL. majorand KBMAL. infantum chagasi. Concentrations of S-59 that generate optimally attenuated parasites were identified. Like liveL. infantum chagasi, KBMAL. infantum chagasiparasites were able to initially enter liver cellsin vivoafter intravenous infection. However, whereas liveL. infantum chagasiinfection leads to hepatosplenomegaly in mice after 6 months, KBMAL. infantum chagasiparasites were undetectable in the organs of mice at this time point.In vitro, KBMAL. infantum chagasiretained the ability to enter macrophages and induce nitric oxide production. These characteristics of KBMAL. infantum chagasicorrelated with the ability to prophylactically protect mice via subcutaneous vaccination at levels similar to vaccination with live, virulent organisms. Splenocytes from mice vaccinated with either liveL. infantum chagasior KBMAL. infantum chagasidisplayed similar cytokine patternsin vitro. These results suggest that KBMA technology is a potentially safe and effective novel vaccine strategy against the intracellular protozoanL. infantum chagasi. This approach may represent a new method for whole-cell vaccination against other complex intracellular pathogens.


Author(s):  
Rafaella R. Costa ◽  
João A. Oliveira-da-Silva ◽  
Thiago A. R. Reis ◽  
Grasiele S. V. Tavares ◽  
Débora V. C. Mendonça ◽  
...  

2011 ◽  
Vol 128 (3) ◽  
pp. 279-284 ◽  
Author(s):  
Vasiliki Christodoulou ◽  
Ippokratis Messaritakis ◽  
Eleni Svirinaki ◽  
Christos Tsatsanis ◽  
Maria Antoniou

1979 ◽  
Vol 236 (3) ◽  
pp. H508-H512 ◽  
Author(s):  
C. A. Astley ◽  
A. R. Hohimer ◽  
R. B. Stephenson ◽  
O. A. Smith ◽  
F. A. Spelman

Twenty-three electromagnetic flow transducers with lumen diameters of 3.5-6.0 mm were implanted in rhesus monkeys and baboonss for 12 h to 120 days. Each flow transducer was calibrated 1) in vitro on dialysis tubing with saline before implantation, 2) in vivo the last day of the implant period, and 3) again in vitro after the flow transducer was recovered. Three other flow transducers were implanted on femoral arteries of baboon just central to an arteriovenous Silastic shunt, and were calibrated in vivo daily for 23-47 days. In vitro sensitivity was not affected by implant durations of up to 120 days. In vivo sensitivity fluctuated unpredictably for the first 3-4 wk of implant, after which it followed a systematic course that depended on the lumen size. In vivo sensitivity at any time during implant (after the initial period) could be accurately predicted by knowing either the in vitro sensitivity or the terminal in vivo sensitivity.


2009 ◽  
Vol 63 (9) ◽  
pp. 643-649 ◽  
Author(s):  
Denise C. Arruda ◽  
Danilo C. Miguel ◽  
Jenicer K.U. Yokoyama-Yasunaka ◽  
Alejandro M. Katzin ◽  
Silvia R.B. Uliana

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