scholarly journals Mechanism of Amphotericin B Resistance inLeishmania donovani Promastigotes

1998 ◽  
Vol 42 (2) ◽  
pp. 352-357 ◽  
Author(s):  
Nicolas Mbongo ◽  
Philippe M. Loiseau ◽  
Marie A. Billion ◽  
Malka Robert-Gero
Keyword(s):  
Amphotericin B ◽  
Leishmania Donovani ◽  
Saturated Fatty Acids ◽  
Major Fatty Acid ◽  
Fluorescence Measurement ◽  
Wild Type ◽  
Drug Pressure ◽  
Resistant Cells

ABSTRACT Amphotericin B (AmB)-resistant Leishmania donovanipromastigotes were selected by increasing drug pressure, and their biological features were compared with those of the wild-type parent strain. The 50% inhibitory concentration for resistant cells was 20 times higher than that for the wild-type. Resistance was stable after more than 40 passages in drug-free medium, and resistant promastigotes were infective to macrophages in vitro but lost their virulence in vivo. They had 2.5 times longer generation time, decreased AmB uptake, and increased AmB efflux in comparison to the wild type. Fluorescence measurement with a specific plasma membrane probe, 1-[4-(trimethylammonio)-1,6-diphenylhexa]-1,3,5-triene, showed increased membrane fluidity in drug-resistant promastigotes. Analysis of lipid composition showed that in resistant cells saturated fatty acids were prevalent, with stearic acid as the major fatty acid, and the major sterol was an ergosterol precursor, the cholesta-5, 7, 24-trien-3β-ol and not ergosterol as in the AmB-sensitive strain.

5-Methyltryptophan Resistant Cells of Catharanthus roseus

1979 ◽  
Vol 34 (7-8) ◽  
pp. 541-545 ◽  
Author(s):  
Jürgen Schallenberg ◽  
Jochen Berlin
Keyword(s):  
Catharanthus Roseus ◽  
Indole Alkaloids ◽  
Indole Alkaloid ◽  
Synthetase Activity ◽  
Wild Type ◽  
Free Tryptophan ◽  
Alkaloid Synthesis ◽  
Resistant Cells

Several cell lines resistant to 5-methyltryptophan were selected from wild type cells of different Catharanthus roseus suspension cultures. The resistant cells had up to 30 times tne normal levels of free tryptophan. Despite the increased pool size of tryptophan anthranilate synthetase activity of resistant cells was as sensitive to inhibition by ʟ-tryptophan as wild type cells. The overproduction of tryptophan did not lead to intensified accumulation of tryptamine nor of indole alkaloids. This was supported by a low conversion of tryptophan to tryptamine in vivo and in vitro. The overpro­duction of one of the primary precursors was evidently not sufficient to stimulate the rate of indole alkaloid synthesis in Catharanthus cells.

scholarly journals Immunoadjuvant Chemotherapy of Visceral Leishmaniasis in Hamsters Using Amphotericin B-Encapsulated Nanoemulsion Template-Based Chitosan Nanocapsules

2013 ◽  
Vol 57 (4) ◽  
pp. 1714-1722 ◽  
Author(s):  
Shalini Asthana ◽  
Anil K. Jaiswal ◽  
Pramod K. Gupta ◽  
Vivek K. Pawar ◽  
Anuradha Dube ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Amphotericin B ◽  
Leishmania Donovani ◽  
Transforming Growth Factor ◽  
Treatment Options ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Content Type

ABSTRACTThe accessible treatment options for life-threatening neglected visceral leishmaniasis (VL) disease have problems with efficacy, stability, adverse effects, and cost, making treatment a complex issue. Here we formulated nanometric amphotericin B (AmB)-encapsulated chitosan nanocapsules (CNC-AmB) using a polymer deposition technique mediated by nanoemulsion template fabrication. CNC-AmB exhibited good steric stabilityin vitro, where the chitosan content was found to be efficient at preventing destabilization in the presence of protein and Ca2+. A toxicity study on the model cell line J774A and erythrocytes revealed that CNC-AmB was less toxic than commercialized AmB formulations such as Fungizone and AmBisome. The results ofin vitro(macrophage-amastigote system; 50% inhibitory concentration [IC50], 0.19 ± 0.04 μg AmB/ml) andin vivo(Leishmania donovani-infected hamsters; 86.1% ± 2.08% parasite inhibition) experiments in conjunction with effective internalization by macrophages illustrated the efficacy of CNC-AmB at augmenting antileishmanial properties. Quantitative mRNA analysis by real-time PCR (RT-PCR) showed that the improved effect was synergized with the upregulation of tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and inducible nitric oxide synthase and with the downregulation of transforming growth factor β (TGF-β), IL-10, and IL-4. These research findings suggest that a cost-effective CNC-AmB immunoadjuvant chemotherapeutic delivery system could be a viable alternative to the current high-cost commercial lipid-based formulations.

scholarly journals Antileishmanial Activity, Uptake, and Biodistribution of an Amphotericin B and Poly(α-Glutamic Acid) Complex

2013 ◽  
Vol 57 (10) ◽  
pp. 4608-4614 ◽  
Author(s):  
Abeer H. A. Mohamed-Ahmed ◽  
Karin Seifert ◽  
Vanessa Yardley ◽  
Hollie Burrell-Saward ◽  
Stephen Brocchini ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Amphotericin B ◽  
Leishmania Donovani ◽  
Water Soluble ◽  
Molecular Weight Range ◽  
Acid Complex ◽  
Content Type ◽  
New Treatment

ABSTRACTA noncovalent, water-soluble complex of amphotericin B (AMB) and poly(α-glutamic acid) (PGA), with AMB loadings ranging from 25 to 55% (wt/wt) using PGA with a molecular weight range of 50,000 to 70,000, was prepared as a potential new treatment for visceral leishmaniasis (VL). The AMB-PGA complex was shown to be as active as Fungizone (AMB deoxycholate) against intracellularLeishmania donovaniamastigotes in differentiated THP-1 cells. Thein vitrouptake of the AMB-PGA complex by differentiated THP-1 cells was similar to that of Fungizone and higher than that of AmBisome (liposomal AMB). The AMB-PGA complex also displayed a dose-response profile similar to that of AmBisomein vivoin BALB/c mice againstL. donovani, with 50% effective doses (ED50s) of 0.24 ± 0.03 mg/kg of body weight for the AMB-PGA complex and 0.24 ± 0.06 mg/kg for AmBisome. A biodistribution study with mice indicated that the AMB-PGA complex cleared more rapidly from plasma than AmBisome, with a comparable low level of distribution to the kidneys.

scholarly journals Distinct Roles of Candida albicans Drug Resistance Transcription FactorsTAC1,MRR1, andUPC2in Virulence

2013 ◽  
Vol 13 (1) ◽  
pp. 127-142 ◽  
Author(s):  
Andrea Lohberger ◽  
Alix T. Coste ◽  
Dominique Sanglard
Keyword(s):  
Candida Albicans ◽  
Target Genes ◽  
Negative Impact ◽  
Antifungal Drugs ◽  
Wild Type ◽  
Drug Pressure ◽  
Content Type ◽  
Negative Effect

ABSTRACTAzoles are widely used in antifungal therapy in medicine. Resistance to azoles can occur inCandida albicansprincipally by overexpression of multidrug transporter geneCDR1,CDR2, orMDR1or by overexpression ofERG11, which encodes the azole target. The expression of these genes is controlled by the transcription factors (TFs)TAC1(involved in the control ofCDR1andCDR2),MRR1(involved in the control ofMDR1), andUPC2(involved in the control ofERG11). Several gain-of-function (GOF) mutations are present in hyperactive alleles of these TFs, resulting in the overexpression of target genes. While these mutations are beneficial toC. albicanssurvival in the presence of the antifungal drugs, their effects could potentially alter the fitness and virulence ofC. albicansin the absence of the selective drug pressure. In this work, the effect of GOF mutations onC. albicansvirulence was addressed in a systemic model of intravenous infection by mouse survival and kidney fungal burden assays. We engineered a set of strains with identical genetic backgrounds in which hyperactive alleles were reintroduced in one or two copies at their genomic loci. The results obtained showed that neitherTAC1norMRR1GOF mutations had a significant effect onC. albicansvirulence. In contrast, the presence of two hyperactiveUPC2alleles inC. albicansresulted in a significant decrease in virulence, correlating with diminished kidney colonization compared to that by the wild type. In agreement with the effect on virulence, the decreased fitness of an isolate withUPC2hyperactive alleles was observed in competition experiments with the wild typein vivobut notin vitro. Interestingly,UPC2hyperactivity delayed filamentation ofC. albicansafter phagocytosis by murine macrophages, which may at least partially explain the virulence defects. Combining theUPC2GOF mutation with another hyperactive TF did not compensate for the negative effect ofUPC2on virulence. In conclusion, among the major TFs involved in azole resistance, onlyUPC2had a negative impact on virulence and fitness, which may therefore have consequences for the epidemiology of antifungal resistance.

scholarly journals Design and Antileishmanial Activity of Amphotericin B-Loaded Stable Ionic Amphiphile Biovector Formulations

2002 ◽  
Vol 46 (5) ◽  
pp. 1597-1601 ◽  
Author(s):  
P. M. Loiseau ◽  
L. Imbertie ◽  
C. Bories ◽  
D. Betbeder ◽  
I. De Miguel
Keyword(s):  
Amphotericin B ◽  
Delivery System ◽  
Leishmania Donovani ◽  
Phosphatidyl Glycerol ◽  
In Vivo Efficacy ◽  
Anionic Lipids ◽  
Further Development ◽  
Polysaccharide Matrix

ABSTRACT A new delivery system, Ionic Amphiphilic Biovector (ABV), comprised of anionic lipids (dipalmitoyl phosphatidyl glycerol) included in a cationic cross-linked polysaccharide matrix was used as a reservoir for amphotericin B (AmB). Two ABV formulations exhibited an in vitro and in vivo efficacy similar to commercial AmBisome against Leishmania donovani-infected mice. The higher stability of these ABV formulations indicates their potential for further development and applications.

In-vitro evaluation of nano-liposomal formulation of Fluconazole and Amphotericin B against visceral leishmaniasis

2021 ◽  
pp. 4929-4933
Author(s):  
Atul Tripathi ◽  
Amber Vyas
Keyword(s):  
Visceral Leishmaniasis ◽  
Amphotericin B ◽  
Cellular Uptake ◽  
Leishmania Donovani ◽  
In Vitro Release ◽  
Physicochemical Characterization ◽  
Production Costs ◽  
Liposomal Formulation

Objectives: The aim of the present study was to compare the efficacy of a dual and single drug loaded nano-liposomal formulation of Amphotericin B and Fluconazole for the treatment of visceral leishmaniasis with plain drugs. Methods: We have formulated nano-liposomes (200-250 nm) from Amphotericin B and Fluconazole using dry film hydration method and have tested their efficacy on promastigotes and amastigotes of Leishmania donovani strain. Physicochemical characterization, entrapment study, stability study, in-vitro release study, in-vitro macrophagic uptake studies (Confocal microscopy) and in-vitro antileishmanial activity were evaluated for various formulations containing Amphotericin B and Fluconazole. Results: The in-vitro cellular uptake confocal studies revealed that NR-loaded AmpB + Flu nanoliposomes have enhanced cellular uptake of formulation. The in-vitro inhibition of promastigotes and amastigotes with liposome containing both Amphotericin B and Fluconazole was significantly more than with liposomes containing individual drugs. The IC50 and CC50 of AmpB + Flu nanoliposomes against promastigotes was found to be 3.308μg/mL and 73.48μg/mL respectively, while the IC50 against axenic and intramacrophagic amastigotes was found to be 3.412 and 3.7028μg/mL respectively. Conclusion: In conclusion, Liposomal formulation containing both Amphotericin B and Fluconazole had significantly greater efficacy than conventional combination and other formulation with individual drugs. Current dual drug loaded formulation may have a favourable safety profile, and if production costs are low, it may prove to be a feasible alternative to currently available therapy after in-vivo testing.

COVID-19: Opinion in Prevention and dietary based management hypothesis

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Ashraf Talaat Youssef
Keyword(s):  
Fatty Acids ◽  
Saturated Fatty Acids ◽  
Lung Damage ◽  
Gastric Aspirate ◽  
Enveloped Viruses ◽  
Multiple Organs ◽  
Fold Reduction ◽  
Antiviral Activities

The pandemic of COVID-19 had started in Wuhan city china in late 2019 with a subsequent worldwide spread. The viral infection can seriousely affect multiple organs mainly lungs, kidneys, heart, liver and brain and may lead to respiratory, renal, cardiac or hepatic failure.Vascular thrombosis of unexplained mechanism that may lead to widespread blood clots in multiple organs and cytokine storms that result of overstimulation of the immune system subsequent of lung damage may lead to sudden decompensation due to hypotension and more damage to liver, kidney, brain or lungs.Until now no drug had proved efficient in getting rid of the problem and controlling the pandemic mainly depends on preventive measures.Many preventive measures can be considered to prevent the worldwide spread of viral transmission. Polyunsaturated long chain fatty acids (PUFAs) and the medium chain saturated fatty acids (MCSFAs) and their corresponding monoglycerides had high antiviral activities against the enveloped viruses which reach to more than 10,000 -fold reduction in the viral titres in vitro and in vivo after testing of its gastric aspirate, and can contribute to the systemic immunity against the enveloped viruses.

Sign in / Sign up

Export Citation Format

Share Document