Evidence that keratinocyte microvesicle particles carrying platelet-activating factor mediate the widespread multiorgan damage associated with intoxicated thermal burn injury.

Thermal burn injuries can result in significant morbidity and mortality. The combination of ethanol intoxication with thermal burn injury results in increased morbidity through an exaggerated inflammatory response involving many organs. Recent studies have linked involvement of the lipid mediator platelet-activating factor (PAF) in the pathology associated with intoxicated thermal burn injury (ITBI).

Topical Photodynamic Therapy Generates Bioactive Microvesicle Particles: Evidence for a Pathway Involved in Immunosuppressive Effects.

Although effective in treating actinic damage, topical photodynamic therapy (PDT) has been shown to be immunosuppressive through unknown mechanisms, which could potentially limit its effectiveness. Multiple types of environmental stressors, including PDT, can produce the immunosuppressive lipid mediator platelet-activating factor (PAF). Because PAF can produce subcellular microvesicle particles (MVPs), these studies tested whether PDT can generate PAF and MVP release and whether these are involved in PDT-induced immunosuppression.

Platelet-activating factor and microvesicle particles as potential mediators for the toxicity associated with intoxicated thermal burn injury.

Thermal burn injuries (TBIs) in patients who are alcohol-intoxicated result in greater morbidity and mortality. The systemic toxicity found in human patients, which includes both immediate systemic cytokine generation with multiple organ failure and a delayed systemic immunosuppression, has previously been replicated in mouse models combining ethanol and localized TBI. Though considerable insights have been provided with these models, the exact mechanisms for these pathologic effects are unclear.

Acute ethanol exposure stimulates microvesicle particle generation in keratinocytes.

Ethanol has been demonstrated to exert profound effects upon cells and tissues via multiple mechanisms. One recently appreciated means by which cells can communicate with other cells is via the production and release of extracellular vesicles. Though smaller exosomes have been demonstrated to be released in response to ethanol exposure, the ability of ethanol to modulate the generation and release of larger microvesicle particles (MVP) is lesser studied.

A genomic survey of sarcomas on sun-exposed skin reveals distinctive candidate drivers and potentially targetable mutations.

Sarcomas on photodamaged skin vary in prognosis and management, but can display overlapping microscopic and immunophenotypic features. Improved understanding of molecular alterations in these tumors may provide diagnostic and therapeutic insights. We characterized 111 cutaneous sarcomatoid malignancies and their counterparts, including primary cutaneous angiosarcoma (n = 7), atypical fibroxanthoma (AFX) (n = 21), pleomorphic dermal sarcoma (PDS) (n = 17), extracutaneous undifferentiated pleomorphic sarcoma (n = 8), cutaneous leiomyosarcoma (LMS) (n = 5), extracutaneous LMS (n = 9), sarcomatoid squamous cell carcinoma (spindle cell squamous cell carcinoma) (S-SCC) (n = 24), and conventional cutaneous squamous cell carcinoma (SCC) (n = 20), by next-generation sequencing (NGS) using the StrataNGS panel for copy number variations, mutations, and/or fusions in more than 60 cancer-related genes.

Vitreal pathogenic role in optic pit foveolar retinoschisis and central serous retinopathy.

Purpose: To expand on current theories concerning the vitreal-induced mechanism underlying the development of foveolar retinoschisis and macular sensory detachments associated with optic nerve head pits. To propose the notion that vitreal traction may contribute to the pathogenesis of serous detachments in central serous chorioretinopathy (CSC).

Reports: We describe two patients, one with macular retinoschisis and the other with central serous detachment.