Mariana Henriques

Promising alternative therapeutics for oral candidiasis

BACKGROUNDnBackground: Candida is the main human fungal pathogen causing infections (candidiasis), mostly in the elderly and immunocompromised hosts. Even though Candida is a member of the oral microbiota in symbiosis, in some circumstances, it can cause microbial imbalance leading to dysbiosis, resulting in oral diseases. Alternative therapies are urgently needed to treat oral candidiasis (usually associated to biofilms), as several antifungal drugs activity has been compromised. This has occurred especially due to an increasing occurrence of drug-resistant in Candida spp. strains. The overuse of antifungal medications, systemic toxicity, cross-reactivity with other drugs and a presently low number of drug molecules with antifungal activity, have contributed to important clinical limitations.nnnMETHODSnWe undertook a structured search of bibliographic databases (PubMed Central, Elseviers ScienceDirect, SCOPUS and Springers SpringerLink) for peer-reviewed research literature using a focused review in the areas of alternatives to manage oral candidiasis. The keywords used were candidiasis, oral candidiasis, biofilm + candida, alternative treatment, combination therapy + candida and the reports from the last 10 to 15 years were considered for this review.nnnRESULTSnThis review identified several promising new approaches in the treatment of oral candidiasis: combination anti-Candida therapies, denture cleansers, mouth rinses as alternatives for disrupting candidal biofilms, natural compounds (e.g. honey, probiotics, plant extracts and essential oils) and photodynamic therapy.nnnCONCLUSIONnThe findings of this review confirm the importance and the urgency of the development of efficacious therapies for oral candidal infections.

Folk medicinal plant extracts as a source of biomolecules with antifungal properties against Candida species

C patients treated with chemotherapy may show impaired cognition (Chemofog) long-term after the treatment completion. Recently, targeted therapies have been developed and have been also associated with the appearance of leukoencephalopathy and major asthenia in cancer patients. Our previous work has identified a direct link between chemotherapy and impaired long-term behavioral flexibility associated with a decreased proliferation within the hippocampus and no cognitive dysfunctions after the cancer treatment everolimus in mice. In this study, we evaluated the impact of the systemic administration of an anti-VEGF antibody on cognitive function, hippocampal vascularization, cerebral metabolic activity and hippocampal synaptic activity in mice as well as on proliferation of neural stem and endothelial cells in vitro. Antibodies against the mouse VEGF (B20-4.1.1, MTA Genentech) and human VEGF (bevacizumab, Genentech, MTA, Roche) were administered to adult C57/Bl6 mice (1.5 mg/kg) every 4 days for 24 days. Note that B20-4.1.1 treatment caused a slowing of weight gain. During/or after treatment, emotional reactivity, spontaneous activity, learning and spatial memory, behavioral flexibility and object recognition memory were assessed. The selective cognitive impairments observed in B20-treated mice (spatial learning in the Morris water maze and memory consolidation in the object recognition test), were predictive of hippocampal dysfunctions. In addition, we detected modifications of the cytochrome oxidase activity in CA1-CA3 hippocampal area and markers involved in long term potentiation. However, proliferation of neural hippocampal precursors (BrdU labeling) and vascular density (Collagen IV) in vivo as well as neurosphere growth and Bend.3 endothelial cell proliferation in vitro were unaltered. Together, these data indicate that the inhibition of endogenous systemic VEGF levels does not drastically change the plasticity of the hippocampal vascular niche, but selectively alters the spatial learning dependent on the long-term potentiation in the hippocampus.