Cellular pharmacokinetics of telavancin, a novel lipoglycopeptide antibiotic, and analysis of lysosomal changes in cultured eukaryotic cells (J774 mouse macrophages and rat embryonic fibroblasts)

Background Telavancin is a lipoglycopeptide with multiple mechanisms of action that include membrane-destabilizing effects towards bacterial cells. It shows bactericidal activity against forms of Staphylococcus aureus (phagolysosomal infection) with different resistance phenotypes [methicillin-resistant S. aureus, vancomycin-intermediate S. aureus or vancomycin-resistant S. aureus]. We examine here the uptake, efflux and intracellular distribution of telavancin in eukaryotic cells as well as its potential to induce lysosomal changes (in comparison with vancomycin and oritavancin). Methods J774 macrophages and rat embryo fibroblasts were exposed for up to 24 and 72 h to telavancin (5-90 mg/L). The following studies were performed: measurement of (14)C-labelled telavancin cellular uptake and subcellular distribution (cell fractionation), determination of pericellular membrane integrity (lactate dehydrogenase release), electron microscopy with morphometric analysis of changes in lysosome size and determination of total phospholipid and cholesterol content. Results The uptake of telavancin proceeded linearly as a function of time and concentration in both cell types (clearance rate of approximately 10 mL/g of protein/h). Efflux (macrophages) was approximately 5.7-fold slower. Telavancin subcellular distribution was superimposable on that of a lysosomal marker (N-acetyl-beta-hexosaminidase). It did not cause an increase in the release of lactate dehydrogenase and did not induce significant increases in total phospholipid or cholesterol content. It caused only mild morphological lysosomal alterations (similar to vancomycin and much less than oritavancin by morphometric analysis). Conclusions Telavancin is taken up by eukaryotic cells and localizes in lysosomes, causing mild morphological alterations without evidence of lipid metabolism alterations. These data support our observations that telavancin is active against intracellular S. aureus

Radioiodine scan revealing a primary lung adenocarcinoma in a patient with differentiated thyroid carcinoma

The radioiodine scan is a non-invasive imaging modality that allows for the visualization of functional thyroid tissue, as well as the detection of thyroid cancer remnants and metastases. However, it is important to note that radioiodine uptake is not exclusive to thyroid tissue and can lead to false-positive results if unexpected uptake occurs in non-thyroidal tissue. Herein, we present a case of a patient diagnosed with thyroid carcinoma, whose radioiodine scan demonstrated increased uptake in the thorax, corresponding to a lung carcinoma

Xanthoma of Bone: A Case Report

Bone xanthoma is a rare disease due to the presence of cholesterol deposits in the bone. We report a case of a 56-year-old patient who was hospitalized in orthopedic department for fracture on the left humerus. Histological examination of bone biopsy performed at this site has objectified cholesterol deposits. Laboratory tests showed hypercholesterolemia with hypertriglyceridemia. The diagnosis of bone xanthoma was selected. The fracture was treated surgically. An initial bone scan revealed bone lesions localized especially at the humerus and femur. The patient was put under fenofibrate and statins. The evolution was marked by gradual regression of lesions in bone scans of control