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 Paracoccidioides, 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.
Paracoccidioidomycosis (PCM) is the most prevalent endemic mycosis in Latin America. The disease is caused by fungi of the genus Paracoccidioides and mainly affects low-income rural workers after inhalation of fungal conidia suspended in the air. The current arsenal of chemotherapeutic agents requires long-term administration protocols. In addition, chemotherapy is related to a significantly increased frequency of disease relapse, high toxicity, and incomplete elimination of the fungus. Due to the limitations of current anti-PCM drugs, we developed a computational drug repurposing-chemogenomics approach to identify approved drugs or drug candidates in clinical trials with anti-PCM activity. In contrast to the one-drug-one-target paradigm, our chemogenomics approach attempts to predict interactions between drugs, and Paracoccidioides protein targets. To achieve this goal, we designed a workflow with the following steps: (a) compilation and preparation of Paracoccidioides spp. genome data; (b) identification of orthologous proteins among the isolates; (c) identification of homologous proteins in publicly available drug-target databases; (d) selection of Paracoccidioides essential targets using validated genes from Saccharomyces cerevisiae ; (e) homology modeling and molecular docking studies; and (f) experimental validation of selected candidates. We prioritized 14 compounds. Two antineoplastic drug candidates (vistusertib and BGT-226) predicted to be inhibitors of phosphatidylinositol 3-kinase TOR2 showed antifungal activity at low micromolar concentrations (<10 μM). Four antifungal azole drugs (bifonazole, luliconazole, butoconazole, and sertaconazole) showed antifungal activity at low nanomolar concentrations, validating our methodology. The results suggest our strategy for predicting new anti-PCM drugs is useful. Finally, we could recommend hit-to-lead optimization studies to improve potency and selectivity, as well as pharmaceutical formulations to improve oral bioavailability of the antifungal azoles identified.
Vulvovaginal candidiasis is a serious health problem affecting numerous women around the world. Its treatment is based on antifungals which may not provide an effective cure because of the resistance presented by its etiological pathogens Candida spp. Candida albicans is the most prevalent species related to vulvovaginal candidiasis. Here, we evaluated the in vivo antifungal potential of thiosemicarbazide and thiosemicarbazide encapsulated within chitosan nanoparticles in a murine model of vulvovaginal candidiasis. The results demonstrated the antifungal capacity of free or nanoencapsulated thiosemicarbazide within chitosan to reduce the fungal load in the vaginal tissue of infected mice. In addition, histological analyses indicated the absence or a mild to moderate infection in thiosemicarbazide-treated groups. Statistical tests confirmed the existence of significant differences between the treated and the control groups. Therefore, our results suggest a potential application of thiosemicarbazide and encapsulated thiosemicarbazide as an alternative vulvovaginal candidiasis therapy.
Background Radical pulp therapy is an important and a relatively frequent procedure in pediatric dental offices. Aim This study presents two clinical cases of pulpectomies in deciduous teeth using electronic apex locator and rotary instrumentation. Case descriptions In Case 1, pulpectomy was performed in a deciduous incisor with diagnosis of pulp necrosis in a 3-year-old patient using an electronic apical locator and manual instrumentation. In Case 2, it was performed in a primary molar with diagnosis of irreversible acute pulpitis in a 9-year-old patient with the use of electronic apical locator and rotational instrumentation. The used technologies contributed to favorable final result of the endodontic treatments in deciduous teeth in both cases. Conclusion The incorporation of technology to the endodontic treatment of primary teeth favored the gain of time and conicity of the root canal preparation. However, studies still need to be performed to consolidate the technique. Clinical significance Endodontic treatment of primary teeth still generates much discussion about the materials and techniques employed. The use of electronic apical locator and rotational instrumentation is successful treatment alternatives for teeth with pulp necrosis, with the advantage of limiting clinical time and presenting a favorable outcome. How to cite this article Gomes LAS, Oliveira AA, de Campos Neves ATS, et al. Technology Incorporation in Primary Teeth Endodontics: Case Reports. Int J Clin Pediatr Dent 2020;13(2):180–185.
A doença periodontal abrange uma gama variada de condições inflamatórias da gengiva, osso e ligamento periodontal dependentes da microbiota do biofilme, de respostas imunes inatas, inflamatórias e adaptativas do hospedeiro e, ainda, fatores individuais genéticos e ambientais. Já as fissuras labiopalatinas são deformidades anatômicas decorrentes da fusão parcial dos processos maxilares nas primeiras semanas de vida intrauterina, especialmente, envolvendo o rebordo alveolar, resultando em alterações no arco dentário e vestíbulo, podendo provocar anomalias dentárias, mal posicionamento dentário e alterações na oclusão, como atresia maxilar e mordida cruzada. Este trabalho tem como objetivo revisar a literatura a respeito da prevalência de alterações periodontais em indivíduos com fissura labiopalatina em diferentes grupos etários e tipos de fissura, bem como comparar os achados com indivíduos sem fissura labiopalatina. Indivíduos com fissura labiopalatina têm sido considerados mais suscetíveis ao desenvolvimento de doença periodontal em função de sua condição anatômica particular e das consequências da fissura para o indivíduo, como muitas vezes o tratamento ortodôntico prolongado, que leva a maior acúmulo de biofilme. Entretanto, conhecimentos mais recentes têm demonstrado que a doença periodontal é uma alteração multifatorial mediada por complexos mecanismos, além do acúmulo de biofilme, como por exemplo, a condição imunológica individual, preponderante para a evolução da doença. Assim, novos estudos são necessários para compreender melhor o comportamento das doenças periodontais nos indivíduos com fissura labiopalatina. Palavras-chaves: Fenda Labial. Fissura Palatina. Doenças Periodontais. Abstract Periodontal disease covers a wide range of inflammatory conditions of the gingiva, bone and periodontal ligament dependent on the biofilm microbiota, host’s innate, inflammatory and adaptive immune responses, as well as individual genetic and environmental factors. Cleft lip and palate are anatomical deformities resulting from the maxillary processes partial fusion in the first weeks of intrauterine life, especially involving the alveolar ridge, resulting in changes in the dental arch and vestibule, which can also cause dental anomalies, dental malposition and changes in occlusion such as maxillary atresia and crossbite. This work aims to review the literature regarding the prevalence of periodontal changes in individuals with cleft lip and palate in different age groups and types of cleft, as well as to compare the findings with individuals without cleft lip and palate. Individuals with cleft lip and palate have been considered more susceptible to the development of periodontal disease due to their particular anatomical condition and the consequences of the cleft for the individual, such as often the prolonged orthodontic treatment that leads to greater biofilm accumulation. However, more recent knowledge has shown that periodontal disease is a multifactorial alteration mediated by complex mechanisms in addition to the biofilm accumulation, such as, for example, the individual immune condition, which is preponderant for the disease evolution. Thus, further studies are needed to better understand the periodontal diseases behavior in individuals with cleft lip and palate. Keywords: Cleft Lip. Cleft Palate. Periodontal Diseases.
Fungal infections increased substantially in the last years, becoming a relevant public health problem. Many of these infections account for high rates of morbidity and mortality. The emergence of resistant fungal clinical isolates have also motivate studies to find new antifungal therapies. Candida albicans is an oportunistic pathogen and affects a great number of immunocompromised patients worldwide. The marine ecosystem has been considered a rich source of bioactive metabolites due to the complexity and originality of its structures. Proteins and peptides from marine organisms have been shown to have antiviral, anti-inflammatory, antimalarial, anticancer, antimicrobial and antifungal properties. Arenicins are antimicrobial peptides isolated from the marine lugworm Arenicola marina with 21 amino acid residues in a β-hairpin structure. Dihydrofolate reductase, exo-b-(1,3)-glucanase and sterol 14α-demethylase are essential C. albincas enzymes that take part in DNA, cell wall and membrane metabolism, respectively. The present study evaluates the interaction of arenicin with important enzymes of C. albicans related to cell wall, ergosterol and DNA metabolism in order to elucidate possible molecular targets. We showed through an in silico approach, that a single compound from a marine worm (A. marina), can bind to three C. albicans essential proteins. The interaction occurs in regions inside the active site or at least near, with amino acid residues evaluated as hot spots. Arenicin is a new promising antifugal drug. The next step is to investigate protein-protein interactions performed by DHFR, EBG and CYP51 and assess whether arenicin is able to disrupt essential interaction or not.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.