Although considered to be a rare infection, mucormycosis (zygomycosis) has emerged as the second most common invasive mould infection. Despite the advent of newer antifungal agents, mortality rate of mucormycosis remains exceedingly high. Successful management of mucormycosis requires early diagnosis, reversal of underlying predisposing risk factors, surgical debridement and prompt administration of active antifungal agents. However, mucormycosis is not always amenable to cure. There are challenging obstacles that lead to difficulties in management of amphotericin B. These include unique host-based risk factors for mucormycosis, the fungus' resistance to innate host defences and distinctive features of its immunopathogenesis, such as extensive angioinvasion, increased virulence and use of chelators by the fungus as siderophores. In addition to these obstacles, the difficulties in early diagnosis, including nonspecific clinical manifestations, lack of serological methods, as well limitations of culture and molecular methods, lead to delay in initiation of antifungal therapy. Finally, the variability of susceptibility to amphotericin B and resistance to most other conventional antifungal agents leads to major limitations in successful treatment of this devastating infection.
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http://dx.doi.org/10.1111/1469-0691.12466 | DOI Listing |
J Med Microbiol
January 2025
Programa de Ps-Graduao em Cincias Farmacuticas, Faculdade de Farmcia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Ocular fungal infections are pathologies of slow progression, occurring mainly in the cornea, but can also affect the entire structure of the eyeball. The main aetiological agents are species of the genera and . Both diagnosis and treatment require speed and effectiveness.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Microbiology, Immunology and Parasitology, Laboratory of Protozoology, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
In Brazil, Visceral Leishmaniases is caused by Leishmania infantum, and domestic dogs are the main reservoirs in its urban transmission cycle. As an alternative to euthanizing dogs, miltefosine has been used to treat canine visceral leishmaniasis since 2016. In this study, we have assessed the efficacy of miltefosine for treating canine visceral leishmaniasis in a new endemic area through follow-up of naturally infected dogs was evaluated.
View Article and Find Full Text PDFBackground: Apolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) with females having higher risk than males. Compared with non-carriers, cognitively normal, middle-aged APOE4 carriers have lower cerebral blood flow (CBF) decades before clinical symptoms appear. Early intervention to protect CBF would be critical for APOE4 carriers to mitigate AD progression.
View Article and Find Full Text PDFBackground: Apolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). Compared with non-carriers, cognitively normal APOE4 individuals have shown brain atrophy and lower cerebral blood flow (CBF) decades before AD pathological and clinical symptoms appear. The goal of the study is to determine if using Sirolimus, an FDA-approved mTOR inhibitor, could restore the brain volumes in structures related to cognitive functions and global CBF (gCBF) for asymptomatic APOE4 carriers compared with non-carriers.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Miami Miller School of Medicine, Center for Therapeutic Innovation, Miami, FL, USA.
Background: Rapamycin is currently in clinical trials for AD, yet numerous studies have suggested that rapamycin inhibits mTORC2 as well as mTORC1, which could be detrimental for AD pathology. Brain insulin resistance is a known aspect of AD pathology and mTORC2 inhibition reduces AKT phosphorylation, which is a main mediator of cellular insulin signaling, perpetuating insulin resistance and further worsening brain glucose metabolism. Here, we show that rapamycin prevents insulin-induced AKT phosphorylation in human neurons and explore the differential effects of mTORC1 and mTORC2 on neuronal insulin sensitivity.
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