Browsing by Author "Zegre, Miguel"
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- Azole resistant mycobiota in indoor environments: what implications for public healthPublication . Caetano, Liliana Aranha; Zegre, Miguel; Viegas, CarlaFungi cause a range of diseases in humans including allergic syndromes and severe fungal infections, such as acute invasive aspergillosis in immunocompromised patients. Azole resistance is an increasing problem in the management of fungal diseases. Detection of azole-resistant colonies amongst susceptible isolates in complex bioaerosols mixtures, as found in the environment, may be feasible using agar supplemented with azole drugs. The aim was to determine the prevalence of azole resistance in occupational settings using azole-supplemented agar as a screening tool.
- Azole-resistance screening in occupational exposure assessments to mycobiotaPublication . Caetano, Liliana Aranha; Zegre, Miguel; Viegas, CarlaExposure to azole-resistant fungal species in workplaces represents a health risk for workers. This study describes the prevalence of azole-resistant mycobiota in three occupational environments, namely, bakeries, waste industry, and swine farms, and it proposes complementary sampling methods for the evaluation of occupational exposure to azole-resistant mycobiota at critical worksites.
- Azole-resistant molds in environmental samples from Portuguese dwellingsPublication . Viegas, Carla; Sá, Flávio; Mateus, Margarida; Santos, Patrícia; Faria, Tiago; Zegre, Miguel; Caetano, Liliana AranhaThe indoor environment is a source of bioburden associated with serious health effects. The emergence of fungal resistance to antifungals is a problem in the management of fungal diseases, being a major concern for Candida sp., Aspergillus sp., and Mucorales order. This study determines the prevalence of azole-resistant bioburden in Portuguese dwellings through passive sampling methods and screening in azole supplemented media.
- Characterization of a novel 3D-polymeric scaffold as a co-delivery systemPublication . Zegre, Miguel; Silveira, M.; Anjos, I.; Ribeiro, I. A.; Santos, C.; Caetano, Liliana Aranha; Gonçalves, L.; Bettercourt, A.Osteomyelitis is an inflammation of the bone caused by infection, leading to necrosis and tissue destruction. It can cause persistent morbidity and become a chronic disease, being one of the infectious diseases most difficult to manage. Staphylococcus aureus is the most usual causative pathogen in osteomyelitis, and bacterial infections are often complicated by concomitant fungal infections, Candida sp. being the most common. Co-encapsulation of drugs provides a convenient means for the administration of multiple drugs directed at commonly associated diseases. Three-dimensional scaffolds have become a crucial element of bone tissue engineering and regenerative medicine, are designed to provide an ideal environment for bone formation. Thus, this work aims to develop a new local drug-delivery system for the modulation of polymicrobial activity in bone infections, through the co-delivery of minocycline and voriconazole to the local site of infection, while fostering bone repair.
- Chitosan nanoparticles loaded with minocycline targeting osteomyelitisPublication . Zegre, Miguel; Bastron, S.; Ribeiro, I. A.; Caetano, Liliana Aranha; Gonçalves, L.; Bettencourt, A.Effective control of osteomyelitis (bone infection) with reduced toxicity is a current challenge. Targeted and controlled drug delivery systems allow: decreased toxicity, upgraded drug targeting, and improved therapeutic effect. Strategy: a) Innovative chitosan nanoparticulate system: nanoparticles loaded with minocycline (antibacterial), and alternative as a local delivery system; b) Nanoparticles and biofilms: advantages: enhanced bioavailability, targeted delivery of antibiotics magnification, local release of antibiotics, controlled and sustained release, and protection against deactivating enzymes.
- Chitosan-based nanoparticles as a dual drug delivery system directed to bone infection therapyPublication . Falcão, J.; Zegre, Miguel; Bastron, S.; Ribeiro, I. A.; Gonçalves, L.; Bettencourt, A.Osteomyelitis treatment is usually described as a challenging issue, mainly because of the necessity of high levels of antimicrobials employed for extended periods, since the infection is characterized by poor blood circulation. Innovative options of targeted and controlled drug delivery systems, presenting sustained antimicrobial release, high concentrations of drugs in the infected areas, low concentrations in the bloodstream, and promotion of osteogenesis, need to be considered.
- Co-delivery of antimicrobials based on poly(D,L-lactic acid) 3D-scaffoldsPublication . Zegre, Miguel; Falcão, M.; Ribeiro, I. A.; Santos, C.; Barros, J.; Monteiro, F. J.; Ferraz, M. P.; Caetano, Liliana Aranha; Gonçalves, L.; Bettencourt, A.Bone infection treatment is a clinical challenge, often complicated by simultaneous polymicrobial infections. A growing number of studies address the co-isolation of fungal and bacterial species, such as Candida albicans and Staphylococcus aureus, from polymicrobial biofilm associated with osteomyelitis. Recent publications demonstrate that scaffolds with local drug delivery ability, display high antimicrobial efficiency rates and reduced toxicity, suppressing the progression of bone disease and decreasing the number of pathogens in mono- or polymicrobial-biofilms.
- Dual-loaded chitosan-based nanoparticles: a novel approach for treating polymicrobial osteomyelitisPublication . Zegre, Miguel; Barros, J.; David, A. B.; Fialho, L.; Ferraz, M. P.; Monteiro, F. J.; Caetano, Liliana Aranha; Gonçalves, L.; Bettencourt, A.Developing innovative approaches to target osteomyelitis caused by polymicrobial infections remains a significant therapeutic challenge. In this study, monodispersed chitosan nanoparticles co-loaded with antibacterial (minocycline) and antifungal (voriconazole) agents were successfully prepared. Minocycline presented higher encapsulation efficiency as compared to voriconazole. Thermostability analysis suggested interactions between the co-loaded drugs within the dual-delivery system, potentially limiting voriconazole release. The dual-loaded chitosan nanoparticles exhibited significant in vitro anti-biofilm activity, achieving up to a 90% reduction in polymicrobial biofilms of S. aureus and C. albicans. Additionally, the nanoparticles showed cytocompatibility with a human osteoblast cell line. These findings highlight the potential of this dual-delivery chitosan-based nanoparticle system to address a critical gap in osteomyelitis treatment by targeting both bacterial and fungal pathogens.
- Evaluation of a dual function minocycline polymeric bone scaffoldPublication . Anjos, I.; Zegre, Miguel; Santos, C.; Alves, M. M.; Ribeiro, I.; Gonçalves, L.; Bettencourt, A. F.It is estimated that orthopedic procedures will rise due to population growth along with aging and increasing chronic diseases. Consequently, orthopedic infections associated with these procedures can be a serious complication, leading to a state of morbidity. Current strategies for treating bone infections and defects present several limitations, namely low local concentrations and systemic toxicity. To overcome these limitations, synthetic and biocompatible bone grafts substitutes (scaffolds) are being developed as platforms for local drug delivery, a strategy that allows high antibiotics concentration in bone for orthopedic infections treatment. Thus, this work aims to develop a drug delivery system with osteoconductive and osteoinductive properties for bone regeneration and capable of treating the infection. For this purpose, porous PDLLA scaffolds were produced by the solvent casting technique, functionalized with bioglass (BG) and collagen (Col), and loaded with 0.5, 0.25, 0.1, or 0.05 mg/mL of minocycline hydrochloride (MH), a dual function drug that beyond its antibiotic role, also induce osteoblastic cells differentiation. Scaffolds’ surface morphology was characterized by scanning electron microscopy (SEM) and elemental chemical composition was performed by X-ray energy dispersive spectrometer (EDS). These drug delivery systems were also characterized in terms of drug release profiles and cytocompatibility through in vitro studies. SEM analysis demonstrated a porous surface and confirmed the functionalization. Regarding drug release profiles, the obtained results suggest a two-phase stage release, with an initial burst release of approximately 60%, 30%, and 10% of MH in the first 15 min, for the two most MH concentrated groups, 0.1 mg/mL of MH group and 0.05 mg/mL of MH group, respectively, followed by a sustained release. In vitro cell studies were promising for scaffolds adsorbed with 0.1 and 0.05 mg/mL of MH, not revealing cytotoxicity, contrary to what was seen for scaffolds with higher concentrations of MH (0.5 and 0.25 mg/mL).In conclusion, due to release profiles of the drug and in vitro cell assays, scaffolds adsorbed with the two lowest MH concentrations seem a promising strategy for acute infection treatment, however, antimicrobial assays must be conducted.
- Exposure assessment to azole resistant mycobiota: a demand in high load occupational environmentsPublication . Viegas, Carla; Zegre, Miguel; Caetano, Liliana Aranha; Viegas, SusanaThe emergence of microbial drug resistance is a well-known threat to public health. However, although bacterial resistance to antibiotics is widely described, scientific knowledge is scarce about fungal drug resistance. Driven by this necessity several occupational environments were assessed and mycobiota and azole-resistant fungal species distribution was characterized aiming to suggest a refined protocol to tackle this public and occupational health menace. Swine, bakeries, and waste industry were assessed, and shortly data from aquaculture and dairies will be also available. Passive methods for sampling, besides active ones, were chosen in order to collect contamination from a longer period and specific environmental samples were obtained. The prevalence of azole resistance was determined through azole-supplemented media by seeding 150 µL of the wash suspension on Saboraud agar supplemented with 4 mg/L itraconazole, 1 mg/L voriconazole, or 0.5 mg/L posaconazole. Azole-resistant species were isolated in 40 out of 91 (44%); Aspergillus sp. and Mucorales order were identified in azole-supplemented media being non-susceptible to 1 mg/L voriconazole and non-susceptible to 4 mg/L itraconazole; Aspergillus section Nigri was isolated in three different azole-supplemented media. Considering the obtained results and the sampling strategy followed a protocol to ensure, besides mycobiota, the azole-resistant mycobiota exposure assessment, in high load occupational environments, will be suggested aiming to overcome the information scarcity related with this occupational risk factor.