High weekly doses of liposomal amphotericin B as secondary prophylaxis after cerebral aspergillosis in a paediatric patient

Brazzola, Pierluigi; Rossi, Mario

doi:10.1016/j.mmcr.2013.10.003

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…The dosage of Amphotericin B used in our study has been determined to be non‐toxic in an animal model [ 57 ]. Amphotericin B has low CSF penetrance but has shown promising results in managing fungal brain infections and glioma stem cells elimination by immune activation [ 66 , 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

Neurotherapeutic implications of sense and respond strategies generated by astrocytes and astrocytic tumours to combat pH mechanical stress

K.G

Krishna

Mishra

2021

Neuropathology Appl Neurobio

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Aims Astrocytes adapt to acute acid stress. Intriguingly, cancer cells with astrocytic differentiation thrive even better in an acidic microenvironment. How changes in extracellular pH (pHe) are sensed and measured by the cell surface assemblies that first intercept the acid stress, and how this information is relayed downstream for an appropriate survival response remains largely uncharacterized. Methods In vitro cell‐based studies were combined with an in vivo animal model to delineate the machinery involved in pH microenvironment sensing and generation of mechanoadaptive responses in normal and neoplastic astrocytes. The data was further validated on patient samples from acidosis driven ischaemia and astrocytic tumour tissues. Results We demonstrate that low pHe is perceived and interpreted by cells as mechanical stress. GM3 acts as a lipid‐based pH sensor, and in low pHe, its highly protonated state generates plasma membrane deformation stress which activates the IRE1‐sXBP1‐SREBP2‐ACSS2 response axis for cholesterol biosynthesis and surface trafficking. Enhanced surface cholesterol provides mechanical tenacity and prevents acid‐mediated membrane hydrolysis, which would otherwise result in cell leakage and death. Conclusions In summary, activating these lipids or the associated downstream machinery in acidosis‐related neurodegeneration may prevent disease progression, while specifically suppressing this key mechanical ‘sense‐respond’ axis should effectively target astrocytic tumour growth.

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Section: Discussionmentioning

confidence: 99%

Neurotherapeutic implications of sense and respond strategies generated by astrocytes and astrocytic tumours to combat pH mechanical stress

K.G

Krishna

Mishra

2021

Neuropathology Appl Neurobio

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“…120 Souza et al 129 tested an alternative delivery system to D-AmB, the NANO-D-AmB that has antifungal efficacy against P. brasiliensis with lower levels of cytotoxicity compared to that of D-AmB formulation both in vivo and in vitro, thus confirming a better delivery of AmB.…”

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confidence: 99%

Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

Voltan¹,

Quindós²,

Alarcón³

et al. 2016

IJN

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Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis.

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High weekly doses of liposomal amphotericin B as secondary prophylaxis after cerebral aspergillosis in a paediatric patient

Cited by 4 publications

References 19 publications

Neurotherapeutic implications of sense and respond strategies generated by astrocytes and astrocytic tumours to combat pH mechanical stress

Neurotherapeutic implications of sense and respond strategies generated by astrocytes and astrocytic tumours to combat pH mechanical stress

Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

Voriconazole

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