netilmicin and Lipidoses

Phospholipidosis is an adverse effect caused by numerous cationic amphiphilic drugs and can affect many cell types. It is characterized by the excess accumulation of phospholipids and is most reliably identified by electron microscopy of cells revealing the presence of lamellar inclusion bodies. The development of phospholipidosis can cause a delay in the drug development process, and the importance of computational approaches to the problem has been well documented. Previous work on predictive methods for phospholipidosis showed that state of the art machine learning methods produced the best results. Here we extend this work by looking at a larger data set mined from the literature. We find that circular fingerprints lead to better models than either E-Dragon descriptors or a combination of the two. We also observe very similar performance in general between Random Forest and Support Vector Machine models.

Topics: Animals; Artificial Intelligence; Databases, Factual; Drug Discovery; Humans; Lipidoses; Models, Biological; Phospholipids; Support Vector Machine

A single intravitreal injection of aminoglycoside antibiotics in the rabbit induces changes in the retinal pigment epithelial layer that consist of disseminated yellow-white dots that are apparent six to ten months after injection. With fluorescein angiography, these dots have the characteristics of window defects or drusen. Histologic examination disclosed subepithelial amorphous material that stained positively with both periodic acid-Schiff and oil red O. Ultrastructural examination disclosed lipidic inclusions in the retinal pigment epithelial cells, basally directed cellular evagination, and basal accumulation of granular material, findings consistent with the reported morphologic features of hard drusen. These findings suggest that aminoglycoside-induced lesions may represent a model for retinal pigment epithelial degeneration and drusen formation.

Topics: Amikacin; Aminoglycosides; Animals; Fluorescein Angiography; Gentamicins; Lipidoses; Microscopy, Electron; Netilmicin; Ophthalmoscopy; Pigment Epithelium of Eye; Rabbits; Vitreous Body

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Gentamicins; Kidney Cortex; Kidney Diseases; Lipidoses; Liver; Netilmicin; Phospholipids; Rats; Rats, Inbred Strains; Time Factors