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Future Medicinal Chemistry Sep 2023The development of safe and effective therapies for treating paracoccidioidomycosis using computational strategies were employed to discover anti- compounds. We 1)...
The development of safe and effective therapies for treating paracoccidioidomycosis using computational strategies were employed to discover anti- compounds. We 1) collected, curated and integrated the largest library of compounds tested against spp.; 2) employed a similarity search to virtually screen the ChemBridge database and select nine compounds for experimental evaluation; 3) performed an experimental evaluation to determine the minimum inhibitory concentration and minimum fungicidal concentration as well as cytotoxicity; and 4) employed computational tools to identify potential targets for the most active compounds. Seven compounds presented activity against spp. These compounds are new hits with a predicted mechanisms of action, making them potentially attractive to develop new compounds.
Topics: Antifungal Agents; Paracoccidioides; Cheminformatics; Paracoccidioidomycosis; Microbial Sensitivity Tests
PubMed: 37727967
DOI: 10.4155/fmc-2022-0288 -
Anais Brasileiros de Dermatologia 2020Paracoccidoiomycosis is a systemic mycosis with a higher incidence in males with history of exposure to the rural environment; its classic clinical manifestation is an...
Paracoccidoiomycosis is a systemic mycosis with a higher incidence in males with history of exposure to the rural environment; its classic clinical manifestation is an oro-pulmonary lesion. The authors report a case of a female, urban, 76-year-old patient with atypical clinical-dermatological presentation and diagnostic conclusion after histopathological examination. The clinical response was quick and complete after treatment with itraconazole 400mg/day in the first month, decreased to 200mg/day until the sixth month of treatment.
Topics: Aged; Antifungal Agents; Female; Humans; Itraconazole; Lung; Male; Paracoccidioidomycosis
PubMed: 32912801
DOI: 10.1016/j.abd.2020.06.001 -
Parasite Immunology Nov 2023We present a patient referred for investigation of adrenal insufficiency, confirmed due to disseminated paracoccidioidomycosis (PCM), with abdominal and central nervous...
We present a patient referred for investigation of adrenal insufficiency, confirmed due to disseminated paracoccidioidomycosis (PCM), with abdominal and central nervous system (CNS) involvement. Establishing the pathogenesis and immunological processes involved in chronic or latent infections by PCM has been challenging. Medical doctors caring for patients with immunodeficiencies should learn about these fungal infections to properly guide travel planning and have this possibility in the diagnostic arsenal when the patient returns from endemic areas. After 13 months of treatment, the patient showed good clinical evolution, and we repeated imaging exams, showing partial improvement of the preview lesions. Diagnosis and treatment can prevent catastrophic events.
PubMed: 37614116
DOI: 10.1111/pim.13008 -
Revista Da Sociedade Brasileira de... 2023
Topics: Humans; Paracoccidioidomycosis; Constriction, Pathologic
PubMed: 37792840
DOI: 10.1590/0037-8682-0343-2023 -
Microbes and Infection 2021During pathogen interaction with the host, several mechanisms are used to favor or inhibit the infectious process; one is called nutritional immunity, characterized by...
During pathogen interaction with the host, several mechanisms are used to favor or inhibit the infectious process; one is called nutritional immunity, characterized by restriction of micronutrients to pathogens. Several studies on fungi of the Paracoccidioides complex, have demonstrated that these pathogens remodel their metabolic pathways to overcome the hostile condition imposed by the host. However, molecular mechanisms that control the regulation of those metabolic changes are not fully understood. Therefore, this work characterizes the expression profile of miRNAs during iron deprivation and describes metabolic pathways putatively regulated by those molecules. Through analysis of RNAseq, 45 miRNAs were identified and eight presented alterations in the expression profile during iron deprivation. Among the differentially regulated miRNAs, five were more abundant in yeast cells during iron deprivation and interestingly, the analyses of genes potentially regulated by those five miRNAs, pointed to metabolic pathways as oxidative phosphorylation, altered in response to iron deprivation. In addition, miRNAs with more abundance in iron presence, have as target genes encoding transcriptional factors related to iron homeostasis and uptake. Therefore, we suggest that miRNAs produced by Paracoccidioides brasiliensis may contribute to the adaptive responses of this fungus in iron starvation environment.
Topics: Fungal Proteins; Gene Expression Regulation, Fungal; Homeostasis; Humans; Iron; MicroRNAs; Paracoccidioides; Paracoccidioidomycosis; RNA, Fungal
PubMed: 33157279
DOI: 10.1016/j.micinf.2020.10.008 -
Journal of Fungi (Basel, Switzerland) Nov 2020Paracoccidioidomycosis is a neglected disease that causes economic and social impacts, mainly affecting people of certain social segments, such as rural workers. The... (Review)
Review
Paracoccidioidomycosis is a neglected disease that causes economic and social impacts, mainly affecting people of certain social segments, such as rural workers. The limitations of antifungals, such as toxicity, drug interactions, restricted routes of administration, and the reduced bioavailability in target tissues, have become evident in clinical settings. These factors, added to the fact that Paracoccidioidomycosis (PCM) therapy is a long process, lasting from months to years, emphasize the need for the research and development of new molecules. Researchers have concentrated efforts on the identification of new compounds using numerous tools and targeting important proteins from , with the emphasis on enzymatic pathways absent in humans. This review aims to discuss the aspects related to the identification of compounds, methodologies, and perspectives when proposing new antifungal agents against PCM.
PubMed: 33228010
DOI: 10.3390/jof6040300 -
Biomedica : Revista Del Instituto... Aug 2023
PubMed: 37721895
DOI: 10.7705/biomedica.7219 -
Biomedica : Revista Del Instituto... Aug 2023
PubMed: 37721901
DOI: 10.7705/biomedica.6977 -
The Journal of Venomous Animals and... 2022The lungs have great importance in patients with paracoccidioidomycosis since they are the portal of entry for the infecting fungi, the site of quiescent foci, and one... (Review)
Review
The lungs have great importance in patients with paracoccidioidomycosis since they are the portal of entry for the infecting fungi, the site of quiescent foci, and one of the most frequently affected organs. Although they have been the subject of many studies with different approaches, the severity classification of the pulmonary involvement, using imaging procedures, has not been carried out yet. This study aimed to classify the active and the residual pulmonary damage using radiographic and tomographic evaluations, according to the area involved and types of lesions.
PubMed: 36465893
DOI: 10.1590/1678-9199-JVATITD-2022-0053 -
Biomedica : Revista Del Instituto... Jun 2021The tropical verrucous syndrome includes infectious, chronic, and granulomatous skin conditions appearing with plaques, nodules, or ulcers with a warty surface which... (Review)
Review
The tropical verrucous syndrome includes infectious, chronic, and granulomatous skin conditions appearing with plaques, nodules, or ulcers with a warty surface which gives name to the syndrome. It includes forms of chromoblastomycosis, sporotrichosis, paracoccidioidomycosis, lobomycosis, leishmaniasis, and tuberculosis verrucosa cutis with ample distribution in tropical and subtropical areas. The diagnoses may be difficult and confused among them, especially between sporotrichosis and leishmaniasis. Clinical, epidemiologic, intradermal reactions, direct smears, skin biopsies, cultures, immunofluorescence, and PCR are used to differentiate them, although several of these methods are not commonly used. We present an 18-year-old man with extensive verrucous plaques in one knee interpreted by clinic, epidemiology, and biopsy as verrucous cutaneous leishmaniasis. He was treated with Glucantime® for 20 days without improvement. A new biopsy was made that was also interpreted as cutaneous leishmaniasis. The revision of both biopsies showed inflammation with abscessed granulomas and asteroid sporotrichotic bodies at the center of the granulomas that led to the diagnosis of sporotrichosis later confirmed by the fungus culture. The patient responded to the treatment with itraconazole. As clinical and epidemiological findings of leishmaniasis and sporotrichosis can be similar, skin biopsy and other paraclinical studies are necessary to establish a proper diagnosis. The asteroid sporotrichotic body is pathognomonic of this mycosis. We review here the essential concepts of leishmaniasis and sporotrichosis and the criteria to differentiate them.
Topics: Adolescent; Antifungal Agents; Granuloma; Humans; Itraconazole; Leishmaniasis, Cutaneous; Male; Skin; Sporotrichosis
PubMed: 34214265
DOI: 10.7705/biomedica.5757