scholarly journals Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosis.

1996 ◽  
Vol 40 (10) ◽  
pp. 2243-2247 ◽  
Author(s):  
K Hata ◽  
J Kimura ◽  
H Miki ◽  
T Toyosawa ◽  
M Moriyama ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Broad Spectrum ◽  
Antifungal Agent ◽  
Oral Candidiasis ◽  
Experimental Models ◽  
Therapeutic Effects ◽  
Murine Models ◽  
Pulmonary Aspergillosis ◽  
Wide Range ◽  
Fluconazole Resistant

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. In the present study, we investigated the therapeutic effects of oral ER-30346 on experimental local infections caused by Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans and compared them with those of itraconazole and fluconazole. In experimental murine models of pulmonary aspergillosis, candidiasis, and cryptococcosis, ER-30346 reduced the numbers of CFU in the lungs significantly compared with the numbers of CFU in the lungs of the controls (P < 0.05). ER-30346 was as effective as or more effective than itraconazole against pulmonary aspergillosis. Against pulmonary candidiasis and cryptococcosis, ER-30346 was more effective than itraconazole and was as effective as fluconazole. ER-30346 was also effective against pulmonary candidiasis caused by fluconazole-resistant C. albicans. In mice with intracranial cryptococcosis, ER-30346 reduced the numbers of CFU in the brains significantly compared with the numbers of CFU in the brains of the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. In an experimental model of oral candidiasis in rats, ER-30346 reduced the numbers of CFU in oral swabs significantly compared with the numbers of CFU in oral swabs from the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. Thus, ER-30346 shows efficacy in murine aspergillosis, candidiasis, and cryptococcosis models. Further studies are needed to determine the potential of ER-30346 for use in the treatment of these infections.

scholarly journals In Vitro Antifungal Activities of a Series of Dication-Substituted Carbazoles, Furans, and Benzimidazoles

1998 ◽  
Vol 42 (10) ◽  
pp. 2503-2510 ◽  
Author(s):  
Maurizio Del Poeta ◽  
Wiley A. Schell ◽  
Christine C. Dykstra ◽  
Susan K. Jones ◽  
Richard R. Tidwell ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Fusarium Solani ◽  
Antifungal Agents ◽  
Antifungal Drugs ◽  
Inhibitory Compounds ◽  
Wide Range ◽  
Fluconazole Resistant ◽  
Resistant Strains

ABSTRACT Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities againstCandida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C. albicans was 0.39 μg/ml, and it was the most potent compound against C. neoformans (MIC, ≤0.09 μg/ml). Selected compounds were also found to be active againstAspergillus fumigatus, Fusarium solani,Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents.

scholarly journals Candida albicans—The Virulence Factors and Clinical Manifestations of Infection

2021 ◽  
Vol 7 (2) ◽  
pp. 79
Author(s):  
Jasminka Talapko ◽  
Martina Juzbašić ◽  
Tatjana Matijević ◽  
Emina Pustijanac ◽  
Sanja Bekić ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Oral Candidiasis ◽  
Clinical Manifestations ◽  
The Body ◽  
Host Immune System ◽  
Normal Flora ◽  
Virulence Traits ◽  
Organ Systems ◽  
Wide Range

Candida albicans is a common commensal fungus that colonizes the oropharyngeal cavity, gastrointestinal and vaginal tract, and healthy individuals’ skin. In 50% of the population, C. albicans is part of the normal flora of the microbiota. The various clinical manifestations of Candida species range from localized, superficial mucocutaneous disorders to invasive diseases that involve multiple organ systems and are life-threatening. From systemic and local to hereditary and environmental, diverse factors lead to disturbances in Candida’s normal homeostasis, resulting in a transition from normal flora to pathogenic and opportunistic infections. The transition in the pathophysiology of the onset and progression of infection is also influenced by Candida’s virulence traits that lead to the development of candidiasis. Oral candidiasis has a wide range of clinical manifestations, divided into primary and secondary candidiasis. The main supply of C. albicans in the body is located in the gastrointestinal tract, and the development of infections occurs due to dysbiosis of the residential microbiota, immune dysfunction, and damage to the muco-intestinal barrier. The presence of C. albicans in the blood is associated with candidemia–invasive Candida infections. The commensal relationship exists as long as there is a balance between the host immune system and the virulence factors of C. albicans. This paper presents the virulence traits of Candida albicans and clinical manifestations of specific candidiasis.

scholarly journals Erythropoietin Treatment Leads to Reduced Blood Glucose Levels and Body Mass: Insights From Murine Models.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4557-4557
Author(s):  
Odelia Katz ◽  
Matthew Stuible ◽  
Nataliya Golishevski ◽  
Lilach Lifshitz ◽  
Michel Tremblay ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Murine Models ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Wide Range ◽  
Anti Cancer ◽  
Diabetes And Obesity

Abstract Abstract 4557 Erythropoietin (EPO) regulates proliferation and differentiation of erythroid precursor cells into erythrocytes. The last decade has revealed non-renal sites of EPO production and extrahematopoietic expression of the EPO-receptor (EPO-R), suggesting that EPO has pleiotropic functions. We have previously shown anti-cancer and immunomodulating effects of the hormone in humans and mice. Here we addressed the interplay among EPO, glucose metabolism, and body weight by employing a panel of relevant experimental murine models. The models focused on situations of increased EPO levels, including EPO-injected C57BL/6 and BALB/c mice, as well as transgenic mice (tg6) constitutively overexpressing human EPO and thus exposed to constantly high EPO serum levels. As experimental models for diabetes and obesity we employed protein Tyr phosphatase 1B (PTP1B) knockout mice associated with resistance to diabetes (PTP1B-/-), and ob/ob mice susceptible to diabetes and obesity. Our data demonstrated an EPO-associated decrease in blood glucose levels in all mice models tested. The tg6 mice, continuously exposed to EPO, were hypoglycemic even under non-fasting conditions. Blood glucose reduction in the experimental models tested was evident already one week following EPO administration in all models, including the PTP1B-/- and ob/ob mice. This conclusion gained further support by the glucose tolerence test (GTT). EPO overexpression or administration led to improved glucose clearance in all the tested murine models. Notably, in the ob/ob mice we observed EPO-associated attenuation of body weight gain and reduction of hemoglobin A1C. Preliminary clinical observations with several diabetic patients support these data and will be discussed further. Taken together our data bear significant clinical implications for EPO treatment in the management of a wide range of metabolic diseases and add an important novel therapeutic potential to this pleiotropic hormone. Disclosures: Mittelman: BioGAL- Start up (inactive): Equity Ownership, Patents & Royalties. Off Label Use: Non erythroid effects: immune, anti-cancer (all under investigation).

scholarly journals Antifungal Efficacy of GM237354, a Sordarin Derivative, in Experimental Oral Candidiasis in Immunosuppressed Rats

2001 ◽  
Vol 45 (4) ◽  
pp. 1008-1013 ◽  
Author(s):  
Antonio Martinez ◽  
Javier Regadera ◽  
Elena Jimenez ◽  
Inmaculada Santos ◽  
Domingo Gargallo-Viola
Keyword(s):  
Oral Candidiasis ◽  
Drug Efficacy ◽  
Morphometric Study ◽  
Control Group ◽  
Infection Model ◽  
Therapeutic Effects ◽  
Small Areas ◽  
Epithelial Regeneration ◽  
Wide Range ◽  
Fungal Protein Synthesis

ABSTRACT GM237354 is a novel sordarin derivative with a broad spectrum of potent activity against a wide range of fungi. The members of this new class of antifungal agents act as potent inhibitors of fungal protein synthesis. In this study, the therapeutic effects of GM237354 were investigated in a novel experimental oral Candida albicansinfection model in immunosuppressed rats. The animals were immunosuppressed with dexamethasone in their drinking water and infected on three alternate days. GM237354 was given three times per day for seven consecutive days at 1.25, 2.5, 5, or 10 mg/kg of body weight per dose. In addition, to provide a preliminary idea of the correlation between regimen administration and therapeutic efficacy, GM237354 was administered to two additional groups of rats at 5 mg/kg once or twice a day for 7 days. The drug efficacy was assessed microbiologically, histologically, and by a morphometric study of lesions. Evident agreement was observed among results obtained by the different methods in all of the animals studied. Microbiologically, the efficacy of GM237354 was determined by measuring the number of C. albicans organisms in the oral cavities of rats in the middle (day 4) and at the end (day 7) of the treatment. GM237354 administered at 5, 7.5, 10, 15, or 30 mg/kg/day for 7 days significantly reduced the number of CFU in the oral cavities of treated rats compared with the number of CFU in the oral cavities of the untreated controls. A significant reduction was also observed when GM237354 was administered at 7.5, 10, 15, or 30 mg/kg/day for 4 days. Furthermore, C. albicans was not detected in oral swabs from any infected rats after 1 week of treatment when GM237354 was administered at 15 or 30 mg/kg/day or after 4 days of treatment at 30 mg/kg/day. Histologically, untreated control animals showed extensive colonization of the epithelium of the dorsal tongue by numerous hyphae. Animals treated with GM237354 at 7.5 mg/kg/day showed small areas with superficial hyphal penetration into the epithelium that produced intraepithelial microabscesses. However, animals treated with GM237354 at 15 mg/kg/day showed multiple regenerative areas of the covering epithelium, and only focalized zones of the tongue surface were occupied by hyphae. No hyphal colonization of the epithelium was seen in rats treated with GM237354 at 30 mg/kg/day and which showed extensive areas of epithelial regeneration of the tongue. The histopathology findings were confirmed by morphometry studies, and the percentage of epithelium occupied byC. albicans hyphae decreased from 17.5% in the control group to 4.8 and 0.1% in animals treated with GM237354 at 7.5 and 15 mg/kg/day, respectively. These results demonstrated that the sordarin derivative GM237354 was effective against experimental oral candidiasis in immunosuppressed rats, and further studies are needed to determine the potential of GM237354 for use in the treatment of this infection in humans.

Genetic dissimilarity of two fluconazole-resistant Candida albicans strains causing meningitis and oral candidiasis in the same AIDS patient.

1996 ◽  
Vol 34 (6) ◽  
pp. 1542-1545 ◽  
Author(s):  
J Berenguer ◽  
T M Diaz-Guerra ◽  
B Ruiz-Diez ◽  
J C Bernaldo de Quiros ◽  
J L Rodriguez-Tudela ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Oral Candidiasis ◽  
Fluconazole Resistant ◽  
Genetic Dissimilarity

Effect of RI-331, a new antifungal antibiotic, on the ultrastructure of Candida albicans

1990 ◽  
Vol 48 (3) ◽  
pp. 632-633
Author(s):  
Yayoi Nishiyama ◽  
Yukiyo Asagi ◽  
Tamio Hiratani ◽  
Maki Yamaguchi ◽  
Hideyo Yamaguchi ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Candida Albicans ◽  
Amino Acid ◽  
Antifungal Agent ◽  
Intact Cells ◽  
Antifungal Antibiotic ◽  
Transmission Electron ◽  
Wide Range ◽  
Medical Importance

An amino acid antibiotic RI-331, (S)-2-amino-5-hydroxy-4-oxopentanoic acid, produced by a Streptomyces sp., is a novel antifungal agent active against a wide range of yeasts of medical importance including Candida albicans. This antibiotic was found out as one of those natural compounds which preferentially inhibited regeneration of C.albicans protoplasts to intact cells during our screening works. In the present study, the effect of RI-331 on C.albicans growing cells and protoplasts prepared therefrom were investigated morphologically by transmission electron microscopy.

scholarly journals Efficacy of Oral E1210, a New Broad-Spectrum Antifungal with a Novel Mechanism of Action, in Murine Models of Candidiasis, Aspergillosis, and Fusariosis

2011 ◽  
Vol 55 (10) ◽  
pp. 4543-4551 ◽  
Author(s):  
Katsura Hata ◽  
Takaaki Horii ◽  
Mamiko Miyazaki ◽  
Nao-aki Watanabe ◽  
Miyuki Okubo ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Broad Spectrum ◽  
Fungal Infections ◽  
Survival Rates ◽  
Control Treatment ◽  
Murine Models ◽  
Pulmonary Aspergillosis ◽  
Content Type ◽  
Disseminated Candidiasis ◽  
Treatment Onset

ABSTRACTE1210 is a first-in-class, broad-spectrum antifungal with a novel mechanism of action—inhibition of fungal glycosylphosphatidylinositol biosynthesis. In this study, the efficacies of E1210 and reference antifungals were evaluated in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. Oral E1210 demonstrated dose-dependent efficacy in infections caused byCandidaspecies,Aspergillusspp., andFusarium solani. In the treatment of oropharyngeal candidiasis, E1210 and fluconazole each caused a significantly greater reduction in the number of oral CFU than the control treatment (P< 0.05). In the disseminated candidiasis model, mice treated with E1210, fluconazole, caspofungin, or liposomal amphotericin B showed significantly higher survival rates than the control mice (P< 0.05). E1210 was also highly effective in treating disseminated candidiasis caused by azole-resistantCandida albicansorCandida tropicalis. A 24-h delay in treatment onset minimally affected the efficacy outcome of E1210 in the treatment of disseminated candidiasis. In theAspergillus flavuspulmonary aspergillosis model, mice treated with E1210, voriconazole, or caspofungin showed significantly higher survival rates than the control mice (P< 0.05). E1210 was also effective in the treatment ofAspergillus fumigatuspulmonary aspergillosis. In contrast to many antifungals, E1210 was also effective against disseminated fusariosis caused byF. solani. In conclusion, E1210 demonstrated consistent efficacy in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. These data suggest that further studies to determine E1210's potential for the treatment of disseminated fungal infections are indicated.

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