Acquired by inhalation of the thermal dimorphic fungi Paracoccidioides spp. conidia, paracoccidioidomycosis ranges from symptomatic to severe and potentially fatal disseminated disease. The main focus of this review is to highlight clinical aspects of paracoccidioidomycosis and, its pathogens' diversity ecology and particularities. In addition, we present strategies for therapy, including DNA vaccines and nanostructured drugs. Molecular and morphological data supported the split of the Paracoccidioides genus into two species, Paracoccidioides brasiliensis and Paracoccidioides lutzii. An acute form of the disease affects approximately 5% of cases and involves the phagocytic mononuclear system, resulting in progressive lymphadenopathy. The chronic form affects adult men and frequently involves lungs, skin and mucous membranes, lymph nodes, and adrenal glands. The clinical manifestations depend on the ability of the host to control the fungal multiplication and dissemination. The long survival time of the fungus in the host tissues allows it to evade immune responses; therefore, successful treatment often requires long-time therapy. The consensus for treatment must consider the severity of the disease and includes sulfone derivatives, amphotericin B and azoles. Novel strategies for therapy, based on DNA vaccines and nanostructured drugs are also presented and discussed in this review.
Immobilization is one of the most effective and powerful tools used in industry, which has been studied and improved since the last century. Various immobilization techniques and support materials have been used on both laboratory and industrial scale. Each immobilization technique is applicable for a specific production mostly depending on the cost and sensibility of process. Compared to free biocatalyst systems, immobilization techniques often offer better stability, increased activity and selectivity, higher resistance, improved separation and purification, reuse of enzymes, and consequently more efficient process. Recently, many reviews have been published about immobilization systems; however, most of them have focused on a specific application or not emphasized in details. This review focuses on most commonly used techniques in industry with many recent applications including using bioreactor systems for industrial production. It is also aimed to emphasize the advantages and disadvantages of the immobilization techniques and how these systems improve process productivity compared to non-immobilized systems.
The D-AMB-coated PLGA-DMSA nanoparticle showed antifungal efficacy, fewer undesirable effects and a favourable extended dosing interval. Nano-D-AMB comprises an AMB formulation able to lessen the number of drug administrations. Further studies would elucidate whether Nano-D-AMB would be useful to treat systemic fungal infections such as paracoccidioidomycosis, candidiasis, aspergillosis and cryptococcosis.
Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs.
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