Parallel Networks to Predict TIMP and Protease Cell Activity of Nucleus Pulposus Cells Exposed and Not Exposed to Pro-Inflammatory Cytokines.

Background: Intervertebral disc (IVD) degeneration is characterized by a disruption of the balance between anabolic and catabolic cellular processes. Within the nucleus pulposus (NP), this involves increased levels of the pro-inflammatory cytokines interleukin 1beta (IL1B) and tumor necrosis factor (TNF) and an upregulation of the protease families matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS). Primary inhibitors of these proteases are the tissue inhibitors of matrix metalloproteinases (TIMP).

Vinblastine pharmacokinetics in mouse, dog, and human in the context of a physiologically based model incorporating tissue-specific drug binding, transport, and metabolism.

Vinblastine (VBL) is a vinca alkaloid-class cytotoxic chemotherapeutic that causes microtubule disruption and is typically used to treat hematologic malignancies. VBL is characterized by a narrow therapeutic index, with key dose-limiting toxicities being myelosuppression and neurotoxicity. Pharmacokinetics (PK) of VBL is primarily driven by ABCB1-mediated efflux and CYP3A4 metabolism, creating potential for drug-drug interaction.

Lysosomal Biogenesis and Implications for Hydroxychloroquine Disposition.

Lysosomes act as a cellular drug sink for weakly basic, lipophilic (lysosomotropic) xenobiotics, with many instances of lysosomal trapping associated with multiple drug resistance. Lysosomotropic agents have also been shown to activate master lysosomal biogenesis transcription factor EB (TFEB) and ultimately lysosomal biogenesis. We investigated the role of lysosomal biogenesis in the disposition of hydroxychloroquine (HCQ), a hallmark lysosomotropic agent, and observed that modulating the lysosomal volume of human breast cancer cell lines can account for differences in disposition of HCQ.

Dermoscopy findings of a one mm lentigo maligna.

A 66-year-old man presented with a grayish 1mm macule on the left cheek. Dermatoscopic examination revealed annular-granular structures partially surrounding a single follicular ostium. Histopathologic examination demonstrated atypical, confluent single melanocytes at the basal layer with nesting, crowding, and upward migration descending along the hair follicle, consistent with the diagnosis of lentigo maligna (LM).

Norepinephrine potentiates proinflammatory responses of human vaginal epithelial cells.

The vaginal epithelium provides a barrier to pathogens and recruits immune defenses through the secretion of cytokines and chemokines. Several studies have shown that mucosal sites are innervated by norepinephrine-containing nerve fibers. Here we report that norepinephrine potentiates the proinflammatory response of human vaginal epithelial cells to products produced by Staphylococcus aureus, a pathogen that causes menstrual toxic shock syndrome.