Current Pharmaceutical Design - Volume 19, Issue 20, 2013

Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised children. Disease control depends on prevention, early diagnosis, predictive microbiological information, prompt and appropriate treatment and restoration of host defenses. Relative to adults, invasive aspergillosis in children and adolescents is unique in its clinical presentation, epidemiology, and in particular, the utility of newer Read More

Aspergillus infections are a threat to in patients with hematological malignancies. Known risk factors are profound and long lasting neutropenia, uncontrolled graft versus host disease, continuous administration of steroids and environmental factors such as hospital construction. Numerous efforts have been undertaken for prophylaxis of invasive aspergillosis in high-risk populations. Most of them failed to demonstrate surviv Read More

Invasive fungal infections are a major cause of morbidity and mortality in immunosuppressed patients with fatality rates ranging from 30 % to 80 % in neutropenic patients. This results at least partly in difficulties obtaining a reliable and early diagnosis, followed by the fact that clinical symptoms are unspecific and of very limited use. Conventional methods may be difficult and are often delayed. Serological tests like the galactoma Read More

Aspergillus is one of the most important fungal genera for the man, for its industrial use, its ability to spoil food and not least its medical impact as cause of a variety of diseases. Currently hundreds of species of Aspergillus are known; nearly fifty of them are able to cause infections in humans and animals. Recently, the genus Aspergillus is subdivided into 8 subgenera and 22 sections. The spectrum of diseases caused by Asper Read More

Amphotericin B has been the only therapeutic option for invasive aspergillosis over decades. It acts by binding to membrane ergosterol, lipid peroxidation and proton-ATPase inhibition. Amphotericin B is eliminated unchanged via urine and feces. It displays a considerable toxicity, particularly infusion-related adverse events and renal damage. Continuous infusion and administration of lipidformulations of amphoteri Read More

Cerebral Aspergillosis is the most lethal manifestation of infection due to Aspergillus species arising most commonly as hematogenous dissemination from a pulmonary focus, direct extension from paranasal sinus infection or direct inoculation through trauma and surgery of the central nervous system (CNS). Voriconazole is currently considered the standard of treatment of CNS aspergillosis with liposomal ampho Read More

Patients with cystic fibrosis (CF) suffer from chronic infective lung disease, which determines morbidity and mortality. While bacteria, such as Pseudomonas aeruginosa, are well-known to contribute to pulmonary pathology, the relevance of fungi in CF airways remains poorly understood. The best studied fungus in CF is Aspergillus fumigatus, which frequently colonizes CF airways and causes a disease condition termed alle Read More

Disease manifestations with Aspergillus spp. are very diverse and dependent on interaction between the fungus and the host. Invasive aspergillosis (IA) is the most severe form of Aspergillus - associated disease found in immunocompromised hosts. Infections are mainly due to Aspergillus (A.) fumigatus, an air-borne opportunistic pathogen that causes 90% of IA. Mortality rate of this disease is still very high (50-95%), partly bec Read More

Despite the availability of new antifungal compounds, morbidity and mortality of invasive aspergillosis are still unacceptably high, in particular in immunocompromised patients such as patients with hematological malignancies or allogeneic hematopoietic stem cell or solid organ transplant recipients. Over the last decades, our knowledge of the immunopathogenesis of invasive aspergillosis has greatly advanced. This, in turn Read More

NADPH-oxidase mediated production of Reactive Oxygen Species (ROS) by alveolar macrophages and neutrophils is a critical mechanism for immune defence against Aspergillus fumigatus. Fungal oxidative stress response includes enzymatic response by superoxide dismutases (SOD), catalases, and enzymes from the thioredoxin and glutathione systems, which are regulated by the transcription factor Yap1. Secondary Read More

Being external, the fungal cell wall plays a crucial role in the fungal life. By covering the underneath cell, it offers mechanical strength and acts as a barrier, thus protecting the fungus from the hostile environment. Chemically, this cell wall is composed of different polysaccharides. Because of their specific composition, the fungal cell wall and its underlying plasma membrane are unique targets for the development of drugs ag Read More