Morphological Evaluation of Pneumocystis carinii after Extraction from Infected Lung

Soulez, B; Dei‐Cas, Eduardo; Palluault, F; Camus, Daniel

doi:10.2307/3283134

Cited by 22 publications

(24 citation statements)

References 10 publications

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“…Rats were euthanized at 0.5 (12 h), 2.5 days, and 8.5 days postinoculation and then parasites were extracted from lungs [29]. After staining with RAL-555, trophic forms (in grey) or cystic forms (in black) were microscopically quantified [26-28].…”

Section: Resultsmentioning

confidence: 99%

“…(3) Since TD-PCR at the mtLSUrRNA locus revealed to be negative for receiver rats, nested-PCR (nPCR) at the same locus was subsequently performed on whole lung tissue extract to increase sensitivity [5]. (4) Following 7 weeks of immunosuppression, PcP development was microscopically monitored on smears of lung tissue extracts stained with RAL-555 [26-29]; as careful microscopical screening revealed to be negative, nPCR at the mtLSUrRNA was performed on all lung tissue extracts. Whole lung tissue extracts of all sentinel rats ( n = 6) were also screened for the presence of P. carinii gDNA by nPCR at the mtLSUrRNA locus and all samples were negative.…”

Section: Resultsmentioning

confidence: 99%

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Growth and Airborne Transmission of Cell-Sorted Life Cycle Stages of Pneumocystis carinii

et al. 2013

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Pneumocystis organisms are airborne opportunistic pathogens that cannot be continuously grown in culture. Consequently, the follow-up of Pneumocystis stage-to-stage differentiation, the sequence of their multiplication processes as well as formal identification of the transmitted form have remained elusive. The successful high-speed cell sorting of trophic and cystic forms is paving the way for the elucidation of the complex Pneumocystis life cycle. The growth of each sorted Pneumocystis stage population was followed up independently both in nude rats and in vitro. In addition, by setting up a novel nude rat model, we attempted to delineate which cystic and/or trophic forms can be naturally aerially transmitted from host to host. The results showed that in axenic culture, cystic forms can differentiate into trophic forms, whereas trophic forms are unable to evolve into cystic forms. In contrast, nude rats inoculated with pure trophic forms are able to produce cystic forms and vice versa. Transmission experiments indicated that 12 h of contact between seeder and recipient nude rats was sufficient for cystic forms to be aerially transmitted. In conclusion, trophic- to cystic-form transition is a key step in the proliferation of Pneumocystis microfungi because the cystic forms (but not the trophic forms) can be transmitted by aerial route from host to host.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Growth and Airborne Transmission of Cell-Sorted Life Cycle Stages of Pneumocystis carinii

et al. 2013

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“…All animals remained on immunosuppressive therapy with dexamethasone throughout the study. Before treatment, PCP was microscopically verified as previously reported (28). Animals were divided into groups of six, and then, sordarin derivatives (GM 191519, GM 237354, and GM 219771) were dosed at 0.1, 1.0 and 5.0 mg/kg by subcutaneous route.…”

Section: Vol 44 2000 Sordarin Pharmacodynamics Against P Carinii 1285mentioning

confidence: 99%

In Vitro Pharmacodynamic Parameters of Sordarin Derivatives in Comparison with Those of Marketed Compounds against Pneumocystis carinii Isolated from Rats

Aviles¹,

Aliouat

Martı́nez³

et al. 2000

Antimicrob Agents Chemother

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Pneumocystis carinii pneumonia remains one of the most serious complications of immunosuppressed patients. In this study, the in vitro pharmacodynamic parameters of four sordarin derivatives (GM 191519, GM 237354, GM 193663, and GM 219771) have been evaluated by a new quantitative approach and compared with the commercially available drugs pentamidine, atovaquone, and trimethoprim-sulfamethoxazole (TMP-SMX). In vitro activities and in vivo therapeutic efficacies of sordarin derivatives against P. carinii were also evaluated. In vitro activity was determined by the broth microdilution technique, comparing the total number of microorganisms in treated and drug-free cultures by using Giemsa staining. The in vitro maximum effect (E max ), the drug concentrations to reach 50% of E max (EC 50 ), and the slope of the dose-response curve were then estimated by the Hill equation (

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“…All animals remained on immunosuppressive therapy with dexamethasone throughout the study. Before the start of treatment, two animals were sacrificed to microscopically confirm the presence of acute PCP, as previously described (20). The sordarin derivatives GM193663 and GM237354 were administered at doses of 0.2, 2, and 10 mg/kg/day by the subcutaneous route.…”

Section: Microorganisms C Albicans 4711e Andmentioning

confidence: 99%

Activities of Sordarins in Experimental Models of Candidiasis, Aspergillosis, and Pneumocystosis

Martı́nez

Aviles

Jiménez

et al. 2000

Antimicrob Agents Chemother

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Sordarin derivatives represent a new class of antifungal agents that act as potent inhibitors of fungal protein synthesis and possess a broad spectrum of activity. The in vivo activity of GM193663 and GM237354 was studied in mouse models of disseminated candidiasis and aspergillosis and in a rat model of pneumocystosis. The pharmacokinetic behavior of both sordarin derivatives was studied in mice and rats. In all studies, compounds were administered by the subcutaneous route. After a subcutaneous dose of 50 mg/kg of body weight to mice, the maximum level in serum, area under the concentration-time curve, half-life, and clearance for GM193663 and GM237354 were 51.8 and 23 g/ml, 79.5 and 46 g ⅐ h/ml, 0.8 and 0.85 h, and 21 and 25 ml/h, respectively. Systemic candidiasis and aspergillosis were established in CD-1 male mice infected with Candida albicans or Aspergillus fumigatus. For systemic candidiasis, compounds were given three times per day for seven consecutive days at 15, 30, 60, or 120 mg/kg/day. GM193663 and GM237354 showed dose-related efficacy against C. albicans, with 50% effective doses, 1 month after infection, of 25.2 and 10.7 mg/kg/dose, respectively. In experimental infections with A. fumigatus, GM237354 was given three times per day at 30, 60, or 120 mg/kg/day for five consecutive days. Animals treated with GM237354 demonstrated irregular responses. The survival of animals treated with GM237354 was 0, 30, and 0% at 30, 60, and 120 mg/kg/day, respectively. The therapeutic efficacy of GM193663 and GM237354 against Pneumocystis carinii was studied in an experimental P. carinii pneumonia (PCP) rat model. After a subcutaneous dose of 10 mg/kg given to rats, the maximum level in serum, area under the concentration-time curve, half-life, and clearance for GM193663 and GM237354 were 6.6 and 7.2 g/ml, 8.5 and 11.8 g ⅐ h/ml, 0.7 and 0.8 h, and 230 and 133 ml/h, respectively. To induce spontaneous PCP, rats were chronically immunosuppressed with dexamethasone. Infected animals were treated twice daily for 10 days at 0.2, 2, or 10 mg/kg/day. The therapeutic effect was estimated by the reduction in the number of cysts in the lungs of treated versus untreated animals. GM193663 and GM237354 significantly reduced the mean (؎ standard deviation) log number of cysts from 7.6 ؎ 0.2 in the untreated group to 4.7 ؎ 0.2 and 4.6 ؎ 0.1, respectively, when the drugs were administered at a dose of 2 mg/kg/day. The log number of cysts was also reduced in infected animals given lower doses of the compounds (0.2 mg/kg/day). In summary, GM193663 and GM237354 are new sordarin derivatives that may potentially play a major role in the treatment of candidiasis and PCP. Further testing with Aspergillus in other animal models is warranted.

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Morphological Evaluation of Pneumocystis carinii after Extraction from Infected Lung

Cited by 22 publications

References 10 publications

Growth and Airborne Transmission of Cell-Sorted Life Cycle Stages of Pneumocystis carinii

Growth and Airborne Transmission of Cell-Sorted Life Cycle Stages of Pneumocystis carinii

In Vitro Pharmacodynamic Parameters of Sordarin Derivatives in Comparison with Those of Marketed Compounds against Pneumocystis carinii Isolated from Rats

Activities of Sordarins in Experimental Models of Candidiasis, Aspergillosis, and Pneumocystosis

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