TLR-2, IL-10 and IL-17-mediated immunity in experimental chemotherapy murine model of systemic candidiasis; cyclophosphamides' impact and roles

2018 ◽  
Vol 119 ◽  
pp. 183-192 ◽  
Author(s):  
Parvin Dehghan ◽  
Sepideh Tolouie ◽  
Behzad Baradaran ◽  
Sanam Nami ◽  
Hamid Morovati
Keyword(s):  
Murine Model ◽  
Systemic Candidiasis ◽  
Experimental Chemotherapy

scholarly journals PCR-detectable Candida DNA exists a short period in the blood of systemic candidiasis murine model

2020 ◽  
Vol 15 (1) ◽  
pp. 677-682
Author(s):  
Zheng-Xin He ◽  
Hui-Hai Zhao ◽  
Fu-Kun Wang
Keyword(s):  
Heat Shock ◽  
Murine Model ◽  
Fungal Pathogens ◽  
Clinical Medicine ◽  
Diagnostic Techniques ◽  
Systemic Candidiasis ◽  
Blood Samples ◽  
Short Period ◽  
Polymerase Chain ◽  
Medicine Today

AbstractInvasive candidiasis is a major challenge to clinical medicine today. However, traditional fungal diagnostic techniques and empirical treatments have shown great limitations. Although efforts are necessarily needed in methodology standardization and multicenter validation, polymerase chain reaction (PCR) is a very promising assay in detecting fungal pathogens. Using a “heat-shock” DNA preparation method, a rapid and simple PCR protocol for quantification of the Candida albicans (C. albicans) ribosomal DNA was established. The PCR assay could detect Candida DNA as low as 10 CFU/mL in samples prepared by the heat-shock protocol, without any cross-reaction with DNA prepared from other Candida spp. and bacterial pathogens. For simulated blood samples, the PCR test sensitivity of whole blood samples was better than that of plasma and blood cells. In the systemic candidiasis murine model, detectable DNA was only observed within 24 h after C. albicans SC5314 injection, which is much shorter than that observed in the kidney.

Impact of serial systemic infection on Candida albicans virulence factors

2020 ◽  
Vol 15 (13) ◽  
pp. 1249-1263
Author(s):  
Glaucia S Arita ◽  
Daniella R Faria ◽  
Karina M Sakita ◽  
Franciele AV Rodrigues-Vendramini ◽  
Isis RG Capoci ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Murine Model ◽  
Systemic Infection ◽  
Systemic Candidiasis ◽  
Fungal Burden ◽  
Histopathological Findings ◽  
Phenotypic Profile ◽  
Proteomic Data ◽  
Repeated Contact

Aim: To evaluate changes in virulence and pathogenicity approaches from Candida albicans after successive passages in a murine model of systemic candidiasis. Materials & methods: Phenotypic assays were performed using colonies recovered from animals infected serially, totalizing five passages. Results: A progressive infection was observed along the passages, with increased fungal burden and the presence of greater inflammatory areas in the histopathological findings. Recovered strains exhibited increased filamentation and biofilm abilities, along with modulation of phospholipase and proteinase activities. Conclusion: Repeated contact between yeast and host increased the expression of virulence factors. Furthermore, a correspondence between phenotypic profile and proteomic data obtained previously was observed.

scholarly journals Pharmacodynamics of Caspofungin in a Murine Model of Systemic Candidiasis: Importance of Persistence of Caspofungin in Tissues to Understanding Drug Activity

2005 ◽  
Vol 49 (12) ◽  
pp. 5058-5068 ◽  
Author(s):  
Arnold Louie ◽  
Mark Deziel ◽  
Weiguo Liu ◽  
Michael F. Drusano ◽  
Tawanda Gumbo ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Murine Model ◽  
Dose Fractionation ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Systemic Candidiasis ◽  
Serum Concentrations ◽  
Pharmacodynamic Parameter ◽  
Concentration Time ◽  
Drug Concentrations

ABSTRACT Pharmacokinetic and pharmacodynamic studies were conducted in a murine model of systemic candidiasis to determine the pharmacodynamic parameter linked with caspofungin efficacy. Additional studies defined the importance of persistent tissue drug concentrations to treatment outcome. The pharmacokinetics of caspofungin were determined in the serum and kidneys of infected mice over 96 h. Population pharmacokinetic analysis demonstrated a serum terminal half-life (t 1/2) for caspofungin of 20.2 h when only serum concentrations were considered, but the terminal t 1/2 increased to 59.2 h when serum and kidney concentration-time data were comodeled. In dose-range studies, the dose-response effect was well described by an inhibitory sigmoid curve for the exposure-effect killing caused by the drug (r 2 > 0.96; P ≪ 0.001). In dose-fractionation studies, fungal counts in kidneys were not statistically different for total doses given as one, two, or four equally divided doses over 96 h, indicating that the area under the concentration-time curve/MIC is the pharmacodynamic parameter that predicts caspofungin efficacy in our infection model. In a separate study, mice infected with Candida albicans 24 h after serum concentrations of caspofungin fell below the MIC for the fungal isolate had significant reductions in fungal densities in their kidneys compared with the growth of fungi in the kidneys of untreated controls (P = 0.005). This in vivo biological assay demonstrates that therapeutic concentrations of caspofungin persist at the site of infection in kidney tissue well after serum concentrations fall below the MIC, underscoring the primacy of caspofungin levels in tissues on determining treatment outcome.

scholarly journals Pharmacokinetics-Pharmacodynamics of a Sordarin Derivative (GM 237354) in a Murine Model of Lethal Candidiasis

2000 ◽  
Vol 44 (9) ◽  
pp. 2333-2340 ◽  
Author(s):  
P. Aviles ◽  
C. Falcoz ◽  
R. San Roman ◽  
D. Gargallo-Viola
Keyword(s):  
Murine Model ◽  
Therapeutic Efficacy ◽  
Elongation Factor ◽  
Systemic Candidiasis ◽  
Dose Selection ◽  
Time Curve ◽  
Animal Therapy ◽  
Kaplan Meier ◽  
Drug Concentrations

ABSTRACT Sordarins are a new class of antifungal agents which selectively inhibit fungal protein synthesis (FPS) by impairing the function of elongation factor 2. The present study investigates possible correlations between sordarin pharmacokinetic (PK) properties and therapeutic efficacy, based on a murine model of invasive systemic candidiasis, and provides a rationale for dose selection in the first study of efficacy in humans. A significant correlation between PK parameters and the in vivo activity of GM 237354, taken as a representative FPS inhibitor, was demonstrated in a murine model of lethal systemic candidiasis. Area under the concentration-time curve (AUC) and maximum concentration of drug in serum (C max) over 24 h were determined after a single GM 237354 subcutaneous (s.c.) dose (50 mg/kg of body weight) in healthy animals (no significant PK changes with infection were observed for other sordarin derivatives). These results have been used to simulate PK profiles obtained after several doses and/or schedules in animal therapy. A PK-pharmacodynamic (PD) parameter such as the time that serum drug concentrations remain above the MIC (t> MIC) was also determined. Treatment efficacies were evaluated in terms of the area under the survival time curve (AUSTC), using Kaplan-Meier survival analysis and in terms of kidney fungal burden (log CFU/gram) after s.c. doses of 2.5, 5, 10, 20, and 40 mg/kg every 4, 8, or 12 h (corresponding to total daily doses of 5 to 240 mg/kg). The results show all treatments to significantly prolong survival versus that of infected and nontreated controls (P < 0.05). Relationships between simulated PK and PK-PD parameters and efficacy were explored. A good correlation independent of the dosing interval was observed with AUC (but notC max or t > MIC) and both AUSTC and kidney burden. Following repeated dosing every 8 h, AUC50 (AUC at which 50% of the maximum therapeutic efficacy is obtained) was estimated as 21.7 and 37.1 μg · h/ml (total concentrations) for AUSTC and kidney burden using a sigmoidE max and an inhibitory sigmoidE max PK-PD model, respectively. For an efficacy target of 90% survival, AUC was predicted as 67 μg · h/ml. We conclude that the PK-PD approach is useful for evaluating relationships between PK parameters and efficacy in antifungal research. Moreover, the results obtained with this approach could be successfully applied to clinical studies.

Comparison of protective effect of protein and DNA vaccines hsp90 in murine model of systemic candidiasis

2005 ◽  
Vol 50 (1) ◽  
pp. 77-82 ◽  
Author(s):  
M. Raska ◽  
J. Běláková ◽  
N. K. Wudattu ◽  
L. Kafková ◽  
K. Růžičková ◽  
...  
Keyword(s):  
Protective Effect ◽  
Murine Model ◽  
Dna Vaccines ◽  
Systemic Candidiasis

scholarly journals Paucibacillary Tuberculosis in Mice after Prior Aerosol Immunization with Mycobacterium bovis BCG

2004 ◽  
Vol 72 (2) ◽  
pp. 1065-1071 ◽  
Author(s):  
E. L. Nuermberger ◽  
T. Yoshimatsu ◽  
S. Tyagi ◽  
W. R. Bishai ◽  
J. H. Grosset
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Bovis ◽  
Murine Model ◽  
Low Dose ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Intravenous Route ◽  
Experimental Chemotherapy ◽  
New Treatments

ABSTRACT To develop a murine model of paucibacillary tuberculosis for experimental chemotherapy of latent tuberculosis infection, mice were immunized with viable Mycobacterium bovis BCG by the aerosol or intravenous route and then challenged six weeks later with virulent Mycobacterium tuberculosis. The day after immunization, the counts were 3.71 ± 0.10 log10 CFU in the lungs of aerosol-immunized mice and 3.65 ± 0.11 and 4.93 ± 0.07 log10 CFU in the lungs and spleens of intravenously immunized mice, respectively. Six weeks later, the lungs of all BCG-immunized mice had many gross lung lesions and splenomegaly; the counts were 5.97 ± 0.14 and 3.54 ± 0.07 log10 CFU in the lungs and spleens of aerosol-immunized mice, respectively, and 4.36 ± 0.28 and 5.12 ± 0.23 log10 CFU in the lungs and spleens of intravenously immunized mice, respectively. Mice were then aerosol challenged with M. tuberculosis by implanting 2.37 ± 0.13 log10 CFU in the lungs. Six weeks after challenge, M. tuberculosis had multiplied so that the counts were 6.41 ± 0.27 and 4.44 ± 0.14 log10 CFU in the lungs and spleens of control mice, respectively. Multiplication of M. tuberculosis was greatly limited in BCG-immunized mice. Six weeks after challenge, the counts were 4.76 ± 0.24 and 3.73 ± 0.34 log10 CFU in the lungs of intravenously immunized and aerosol-immunized mice, respectively. In contrast to intravenously immunized mice, there was no detectable dissemination to the spleen in aerosol-immunized mice. Therefore, immunization of mice with BCG by the aerosol route prior to challenge with a low dose of M. tuberculosis resulted in improved containment of infection and a stable paucibacillary infection. This model may prove to be useful for evaluation of new treatments for latent tuberculosis infection in humans.

scholarly journals Pharmacodynamics of Fluconazole in a Murine Model of Systemic Candidiasis

1998 ◽  
Vol 42 (5) ◽  
pp. 1105-1109 ◽  
Author(s):  
Arnold Louie ◽  
George L. Drusano ◽  
Partha Banerjee ◽  
Qing-Feng Liu ◽  
Weiguo Liu ◽  
...  
Keyword(s):  
Total Dose ◽  
Murine Model ◽  
Dose Fractionation ◽  
Maximal Effect ◽  
Systemic Candidiasis ◽  
Pharmacodynamic Parameter ◽  
Dose Response Relationship ◽  
Time Curve ◽  
Dose Ranging ◽  
Fractionation Schedules

ABSTRACT In this study we defined the pharmacodynamic parameter that optimizes outcome in deep-seated Candida albicansinfections treated with fluconazole. Using a murine model of systemic candidiasis, we conducted single-dose dose-ranging studies with fluconazole to determine the dosage of this drug that resulted in a 50% reduction in fungal densities (50% effective dose [ED50]) in kidneys versus the fungal densities in the kidneys of untreated controls. We found that the ED50 of fluconazole given intraperitoneally was 4.56 mg/kg of body weight/day (95% confidence interval, 3.60 to 5.53 mg/kg/day), and the dose-response relationship was best described by an inhibitory sigmoid maximal effect (E max) curve. To define the pharmacodynamics of fluconazole, we gave dosages lower than, approximating, and higher than the ED50 of fluconazole (range, 3.5 to 5.5 mg/kg/day, equivalent to the ED16 to the ED75) to various groups of infected animals using three dose-fractionation schedules. For each total dose of fluconazole examined, the dose-fractionation schedules optimized the ratio of the area under the concentration-time curve (AUC) to the MIC (the AUC/MIC ratio), the ratio of the maximum concentration of drug in serum (C max) to the MIC, and the time that the drug remained above the MIC for the infecting C. albicansisolate. Similar reductions in fungal densities in kidneys were seen between groups that received the same total dose of fluconazole in one, two, or four equally divided doses. Thus, dose-fractionation studies demonstrated that the pharmacodynamic parameter of fluconazole that best predicted outcome was the AUC/MIC ratio.

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