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1.
J Fungi (Basel) ; 9(7)2023 Jul 18.
Article in English | MEDLINE | ID: mdl-37504746

ABSTRACT

Azoles are the main antifungal agents employed in clinical practice to treat invasive candidiasis. Nonetheless, their efficacy is limited by fungal resistance mechanisms, mainly the overexpression of efflux pumps. Consequently, candidiasis has a worrisome death rate of 75%. One potential strategy to overcome efflux-mediated resistance is to inhibit this process. Ailanthus altissima is a Chinese tree that produces several active substances, including altissimacoumarin D. Due to the low yield of its extraction and the need to search for new drugs to treat candidiasis, this study aimed to synthesize altissimacoumarin D and its analogues, as well as evaluating their ability to reverse the resistance phenotype of Candida albicans. Coumarin isofraxidin was prepared via total synthesis through a solvent-free Knoevenagel condensation as the key step. Isofraxidin and other commercially available coumarins were alkylated with prenyl or geranyl groups to yield the natural product altissimacoumarin D and seven analogues. The antifungal activity of the coumarins and their ability to reverse the fungal resistance phenotype were assessed using microbroth methodologies. Toxicity was evaluated using erythrocytes and an in silico prediction. All compounds improved the antifungal activity of fluconazole by inhibiting efflux pumps, and ACS47 and ACS50 were the most active. None of the coumarins were toxic to erythrocytes. In silico predictions indicate that ACS47 and ACS50 may be safe for human use. ACS47 and ACS50 are promising candidates when used as adjuvants in the antifungal therapy against C. albicans-resistant strains.

2.
J Nanosci Nanotechnol ; 12(9): 7155-66, 2012 Sep.
Article in English | MEDLINE | ID: mdl-23035447

ABSTRACT

Ultraviolet radiation can bring both harm and benefits to human health. Among those harms are erythemas, photosensitivity, photoaging, and the most worrying, skin cancer. Nanoencapsulation of sunscreen agents (SA) by using a biocompatible and biodegradable polymer such as poly(epsilon-caprolactone) (PCL) is advantageous as it increases the retention of UV absorbers in the skin, avoids systemic absorption, and consequently, improves water resistance and stability of the preparation. The aim of this work is to develop, characterize, and study the encapsulation of 3 different SA: 2-ethylhexyl-p-methoxycinnamate, benzophenone-3, and octocrylene in PCL nanoparticles (Nps). Nps were prepared by the solvent emulsification and evaporation method. The process yield was calculated, and the Nps were characterized in terms of size, polydispersity index (PI), morphology, zeta potential (ZP), encapsulation efficiency (EE) (%), and sunscreen agent content (SAC). The final formulations were submitted to the hen's egg test-chorioallantoic membrane (HET-CAM), chorioallantoic membrane-trypan blue staining (CAM-TBS), red blood cell (RBC), Draize tests, in vitro release, in vitro sun protection factor (SPF), UVA protection factor (PF-UVA), and photostability. All the Nps were in the nanometric scale. PI showed monodisperse systems. ZP became more negative as the Np were lyophilized and were added to the formulations. EE varied from 84 to 90%. The SAC went from 44 to 65 microg of sunscreen agents by milligram of Np. The process yield went from 60 to 76%. Nps were predominantly spherical and elliptical forms. The addition of Np diminished the release of the SA. The SPF increased with Np presence and helped to maintain the PF-UVA after irradiation. The HET-CAM assay evaluated the formulation as slightly irritant, CAM-TBS and RBC tests as non irritant, and the Draize test as moderately irritant.


Subject(s)
Acrylates/analysis , Benzophenones/analysis , Cinnamates/analysis , Nanoparticles , Polyesters/pharmacology , Sunscreening Agents/pharmacology , Animals , Chick Embryo , Cosmetics , Eye/drug effects , Irritants/chemistry , Irritants/pharmacology , Microscopy, Electron, Transmission , Polyesters/chemistry , Rabbits , Sunscreening Agents/chemistry , Ultraviolet Rays
3.
J. bras. ginecol ; 101(9): 377-9, set. 1991. tab, graf
Article in Portuguese | LILACS | ID: lil-198326

ABSTRACT

Os autores apresentam a avaliaçäo de ansiedade trato e ansiedade estado feita em pacientes ambulatoriais que apresentavam manifestaçöes de síndromes androgênicas ovarianas (síndrome dos ovários policísticos, hipertecose e hirsutismo idiopático). Säo mostradas as diferentas encontradas entre as pacientes e as possíveis relaçöes existentes entre essas sfndromes e o stress. Encontrou-se relaçäo entre os níveis de androstenediona e ansiedade nas pacientes com síndrome dos ovários policísticos e síndromes androgênicas. A presenta de hirsutismo também se relaciona com níveis maiores de ansiedade.


Subject(s)
Humans , Female , Adult , Androgens , Anxiety/physiopathology , Hirsutism/physiopathology , Polycystic Ovary Syndrome/physiopathology , Androstenedione , Prospective Studies , Stress, Physiological , Syndrome
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