scholarly journals In VitroActivity andIn VivoEfficacy of Anidulafungin in Murine Infections byAspergillus flavus

2010 ◽  
Vol 55 (3) ◽  
pp. 1290-1292 ◽  
Author(s):  
Enrique Calvo ◽  
F. Javier Pastor ◽  
Emilio Mayayo ◽  
Valentina Salas ◽  
Josep Guarro
Keyword(s):  
High Activity ◽  
Aspergillus Flavus ◽  
Murine Model ◽  
Serum Levels ◽  
Serum Concentrations ◽  
Broth Microdilution ◽  
Disseminated Infection ◽  
Tissue Burden ◽  
Murine Infections

ABSTRACTAnidulafungin (AFG) showed high activity against 27 strains ofAspergillus flavusby use of broth microdilution and disk diffusion methods. This drug was effectivein vivoin a murine model of disseminated infection with five isolates tested. AFG was able to prolong survival and reduce tissue burden of infected mice but not able to reduce galactomannan serum concentrations. The AFG serum levels were above the corresponding minimum effective concentrations (MEC) for all of the strains tested.

scholarly journals Efficacy of Amphotericin B at Suboptimal Dose Combined with Voriconazole in a Murine Model of Aspergillus fumigatus Infection with PoorIn VivoResponse to the Azole

2013 ◽  
Vol 57 (9) ◽  
pp. 4540-4542 ◽  
Author(s):  
Marcelo Sandoval-Denis ◽  
F. Javier Pastor ◽  
Javier Capilla ◽  
Josep Guarro
Keyword(s):  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Murine Model ◽  
Combined Treatment ◽  
Content Type ◽  
Disseminated Infection ◽  
Suboptimal Dose ◽  
Tissue Burden

ABSTRACTThe combination of amphotericin B at a suboptimal dose (0.3 mg/kg) with voriconazole has shown efficacy in prolonging survival and reducing tissue burden in a murine model of disseminated infection by an isolate ofAspergillus fumigatusthat had showed a poorin vivoresponse to the azole. The efficacy of the combined treatment was higher than that obtained with amphotericin B at 0.8 mg/kg.

scholarly journals In VitroActivity andIn VivoEfficacy of Posaconazole in Treatment of Murine Infections by Different Isolates of theAspergillus terreusComplex

2010 ◽  
Vol 55 (2) ◽  
pp. 676-679 ◽  
Author(s):  
Valentina Salas ◽  
F. Javier Pastor ◽  
M. M. Rodríguez ◽  
Enrique Calvo ◽  
Emilio Mayayo ◽  
...  
Keyword(s):  
Body Weight ◽  
Murine Model ◽  
Aspergillus Terreus ◽  
Broth Microdilution ◽  
Level Of Activity ◽  
Tissue Burden ◽  
Different Strains ◽  
High Level ◽  
Murine Infections

ABSTRACTPosaconazole (PSC) is an antifungal drug recommended as an alternative for the treatment of invasive aspergillosis in patients who are refractory or intolerant to primary antifungal therapy. We have evaluated thein vitroactivity of PSC against 21 strains of theAspergillus terreuscomplex using both broth microdilution and disk diffusion (Neo Sensitabs) methods. PSC showed the same high level of activity against all the strains with the twoin vitromethods used. We developed a murine model of disseminated infection to evaluate the efficacy of PSC at 5, 10, or 20 mg/kg of body weight twice a day by using 6 different strains chosen randomly. PSC showed good efficacy, especially at 20 mg/kg, as measured by prolonged survival, tissue burden reduction, histopathology, and lowered galactomannan levels. The PSC levels in serum on the fourth day of treatment were higher than the MICs for the strains tested.

scholarly journals Activities of Flucytosine, Fluconazole, Amphotericin B, and Micafungin in a Murine Model of Disseminated Infection by Candida glabrata

2005 ◽  
Vol 49 (11) ◽  
pp. 4757-4759 ◽  
Author(s):  
Marçal Mariné ◽  
Carolina Serena ◽  
Belkys Fernández-Torres ◽  
F. Javier Pastor ◽  
Josep Guarro
Keyword(s):  
Amphotericin B ◽  
Murine Model ◽  
Candida Glabrata ◽  
Disseminated Infection ◽  
Tissue Burden

ABSTRACT We compared the efficacies of amphotericin B, fluconazole, flucytosine, and micafungin in a systemic murine infection by three isolates of Candida glabrata. Amphotericin B showed the best results, although none of the drugs dramatically reduced mortality or tissue burden in liver or spleen.

scholarly journals MIC Values of Voriconazole Are Predictive of Treatment Results in Murine Infections by Aspergillus terreus Species Complex

2013 ◽  
Vol 57 (3) ◽  
pp. 1532-1534 ◽  
Author(s):  
Valentina Salas ◽  
F. Javier Pastor ◽  
Deanna A. Sutton ◽  
Enrique Calvo ◽  
Emilio Mayayo ◽  
...  
Keyword(s):  
Species Complex ◽  
Aspergillus Terreus ◽  
Serum Levels ◽  
Treatment Results ◽  
Cutoff Value ◽  
Content Type ◽  
Fungal Load ◽  
Tissue Burden ◽  
Murine Infections

ABSTRACTWe evaluated the efficacy of voriconazole against nine strains ofAspergillus terreuswith different MICs (0.12 to 4 μg/ml) by using a murine model. Markers of efficacy included survival, tissue burden, galactomannan antigenemia, and drug serum levels. Voriconazole was especially effective in prolonging survival and reducing the fungal load in infections by strains that showed MICs that were less than or equal to the epidemiological cutoff value (1 μg/ml).In vitrodata might be useful for predicting the outcome ofA. terreusinfections.

scholarly journals Posaconazole Combined with Amphotericin B, an Effective Therapy for a Murine Disseminated Infection Caused by Rhizopus oryzae

2008 ◽  
Vol 52 (10) ◽  
pp. 3786-3788 ◽  
Author(s):  
M. Mar Rodríguez ◽  
Carolina Serena ◽  
Marçal Mariné ◽  
F. Javier Pastor ◽  
Josep Guarro
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Murine Model ◽  
Rhizopus Oryzae ◽  
Effective Therapy ◽  
Prolonged Survival ◽  
Low Doses ◽  
Disseminated Infection ◽  
Tissue Burden

ABSTRACT In a murine model of disseminated zygomycosis, low doses of amphotericin B (0.3 mg/kg body weight/day) combined with posaconazole (40 mg/kg/day) prolonged survival and reduced tissue burden with respect to that of controls and that of both drugs administered alone. Results were similar to those obtained with amphotericin B given alone at 0.8 mg/kg/day.

scholarly journals In vivo Efficacy of Posaconazole (POS) against Voriconazole Resistant (VCZ-R) Aspergillus flavus in an Inhalational Neutropenic Murine Model of Invasive Pulmonary Aspergillosis

2019 ◽  
pp. 1-7
Author(s):  
Suganthini Krishnan Natesan ◽  
Jessica L. Cutright
Keyword(s):  
Aspergillus Flavus ◽  
Murine Model ◽  
Invasive Pulmonary Aspergillosis ◽  
Environmental Isolates ◽  
Viable Option ◽  
Pulmonary Aspergillosis ◽  
Patients With Cancer ◽  
The Usa ◽  
Life Threatening

Invasive aspergillosis (IA) is a life-threatening infection in patients with cancer. Recent studies have reported that non-fumigatus Aspergillus spp., including Aspergillus flavus, are emerging as predominant pathogens in various transplant and cancer centers in the USA and around the world. Clinical and environmental isolates of Aspergillus species showing reduced susceptibility to VCZ have been reported. Mortality, despite therapy, remains high, and drug resistance might partly account for treatment failures. In this in vivo study, the virulence of a VCZ-R cyp51A mutant of A. flavus and the efficacy of POS against this mutant were evaluated using a neutropenic inhalational murine model of invasive pulmonary aspergillosis. VCZ-R A. flavus mutant was virulent in vivo, and had similar infectivity as the VCZ-S parent. Posaconazole had superior activity to that of VCZ in reducing fungal burden (p <0.05) and mortality (p <0.05) in this experimental model of VCZ-R A. flavus murine infection. This study demonstrated that POS may be a viable option for certain strains of VCZ-R A. flavus.

IL10 -Transduced Mesenchymal Stem Cells Improve the Acute Graft-Versus-Host Disease Protection in a Murine Model.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3242-3242
Author(s):  
Feng Chen ◽  
De Pei Wu ◽  
Ai Ning Sun ◽  
Wei Rong Chang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Murine Model ◽  
Acute Gvhd ◽  
Clinical Signs ◽  
Serum Levels ◽  
Quantitative Score ◽  
Wbc Count

Abstract Recent research has suggested that mesenchymal stem cells(MSCs) have some immunosuppressive properties which may be of interest to lessen GVHD after transplant. Although encouraging, very limited systematic study has been performed to assess the ability of MSCs to suppress GVHD in vivo. In the early study, we failed to demonstrate murine MSCs attenuate the acute GVHD in an established murine model of acute GVHD (C57BL/6 mice → CB6F1 mice). Because of its anti-inflammatory properties and its association with dendritic cells and regulatory T cells, IL10 may has substantial benefit on the induction of immune tolerance and graft survival. In this study, we investigated whether the co-transplantation of genetically transduced MSCs expressing IL10 could improve the GVHD protection. Methods: 8–9 week old male CB6F1 mice (C57BL/6×Balb/c) were given 12Gy (100cGy/min) total body irradiation (6mv,X-ray). 4 hours after the lethal irradiation, the mice received one of four groups of donor mice cells (8–10 week old female C57BL/6 mice) via tail vein injection: 1×107 bone marrow MNC+3×107 splenic MNC (n=10) (aGVHD inoculum, control); 1×107 bone marrow MNC+3×107 splenic MNC+1×105 murine marrow-derived MSCs (n=15); 1×107 bone marrow MNC+3×107 splenic MNC+1×105 IL10-transduced MSCs (transfected with IL10- recombinant adenoviral vector)(n=15); 1×107 bone marrow MNC+3×107 splenic MNC+5×105 IL10-transduced MSCs (n=15). The weight, survival time, WBC count and chimerism of recipient mice were observed, the severity of aGVHD was assessed with both an aGVHD scoring system for physical signs and a semi-quantitative score for histologic examination. The serum of recipient mice was collected on the day 14, 28, 35,or the brink of death after transplant, then be used to detect the levels of cytokines (IL10,IL4,INF-γ and TNF-α) by ELISA. Results: The injection of 1×107 bone marrow MNCs plus 3×107 splenic MNCs from C57BL/6 donor into CB6F1 recipient following 12Gy irradiation resulted in a reliable model of aGVHD: the clinical signs and histologic degree was relatively coincident, the incidence of aGVHD were 100% and all mice died within +27d∼+33d. The co-transplant of 1×105 MSCs failed to decrease the incidence and severity of aGVHD significantly(81.8% vs 100%, score 6.0±2.83 vs 9.0±0.38, P>0.05).Compared with the group of 1×105 MSCs or control, 1×105 IL10-transduced MSCs demonstrated significantly reduced the incidence and severity of aGVHD(0%,score 0.5±0.05,P<0.01), while increased cell dose(5×105) failed to enhance the effect significantly. Serum levels of cytokines showed the significant increase of IL-10 (46.7±3.4 pg/ml vs 17.5 ±2.6 pg/ml, P<0.05), the corresponding increase of IL-4 (20.7±2.5 pg/ml vs 17.7±3.8 pg/ml, P=0.13),and more dramatic decrease of INF-γ (90.4±16.1 pg/ml vs 234.0 ±83.2 pg/ml, P<0.01) in the group of IL10-transduced MSCs. Conclusion: Benefical effects on aGVHD protection could be observed when MSCs were engineered to expressed IL10. The significant increase of Th2 type cytokines and decrease of INF-γ may be one of the mechanisms for the aGVHD protection in this murine model.

scholarly journals Herpes Murine Model as a Biological Assay to Test Dialyzable Leukocyte Extracts Activity

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Nohemí Salinas-Jazmín ◽  
Sergio Estrada-Parra ◽  
Miguel Angel Becerril-García ◽  
Alberto Yairh Limón-Flores ◽  
Said Vázquez-Leyva ◽  
...  
Keyword(s):  
Murine Model ◽  
Serum Levels ◽  
Blood Leukocytes ◽  
Health Authorities ◽  
Healthy Donors ◽  
Average Survival ◽  
Batch Release ◽  
Clinical Responses ◽  
Hsv 1

Human dialyzable leukocyte extracts (DLEs) are heterogeneous mixtures of low-molecular-weight peptides that are released on disruption of peripheral blood leukocytes from healthy donors. DLEs improve clinical responses in infections, allergies, cancer, and immunodeficiencies. Transferon is a human DLE that has been registered as a hemoderivate by Mexican health authorities and commercialized nationally. To develop an animal model that could be used routinely as a quality control assay for Transferon, we standardized and validated a murine model of cutaneous HSV-1 infection. Using this model, we evaluated the activity of 27 Transferon batches. All batches improved the survival of HSV-1-infected mice, wherein average survival rose from 20.9% in control mice to 59.6% in Transferon-treated mice. The activity of Transferon correlated with increased serum levels of IFN-γand reduced IL-6 and TNF-αconcentrations. Our results demonstrate that (i) this mouse model of cutaneous herpes can be used to examine the activity of DLEs, such as Transferon; (ii) the assay can be used as a routine test for batch release; (iii) Transferon is produced with high homogeneity between batches; (iv) Transferon does not have direct virucidal, cytoprotective, or antireplicative effects; and (v) the protective effect of Transferonin vivocorrelates with changes in serum cytokines.

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