Pharmacist consultations: simplifying daily drug regimens and providing education on fall risk for older adults.

OBJECTIVE: To evaluate whether a medication review by a pharmacist in the community can simplify an older adult's daily drug regimen and improve awareness of medication-related fall risk. DESIGN: Pre- and posttest with follow-up design. SETTING: Senior centers, senior housing facilities, and community centers in Massachusetts. PARTICIPANTS: Older adults who attended a pharmacy outreach program at a community center. INTERVENTIONS: Participants engaged in a one-time, face-to-face, medication therapy management (MTM) session. The pharmacists made recommendations to simplify daily drug regimens for best therapeutic results. The participants were educated regarding the influence that medications may have on fall risk. RESULTS: For the 75 participants, daily dose regimens were significantly reduced. From the presurvey to the follow-up surveys, there was a significant increase of participants taking medication three times or fewer per day (73% to 85%) versus those participants taking medications more than three times per day (P = 0.041). Through MTM consultations, participants' awareness that medications may be a contributing factor to fall risk was increased from 28% in the presurvey to 56% in the postsurvey (P = 0.0018). CONCLUSION: A pharmacist consultation can simplify the daily drug regimen. Furthermore, consultant pharmacists can educate patients regarding the risk that medications may have on falls.

Vimentin contributes to changes in chondrocyte stiffness in osteoarthritis.

Actin and tubulin cytoskeletal components are studied extensively in chondrocytes, but less is known about vimentin intermediate filaments. In other cell types, vimentin is a determinant of cell stiffness and disruption of vimentin networks weakens the mechanical integrity of cells. Changes in vimentin organization correlate with osteoarthritis progression, but the functional consequences of these changes remain undetermined in chondrocytes. The objective of this study was to compare the contribution of vimentin to the mechanical stiffness of primary human chondrocytes isolated from normal versus osteoarthritic cartilage. Chondrocytes were embedded in alginate and vimentin networks disrupted with acrylamide. Constructs were imaged while subjected to 20% nominal strain on a confocal microscope stage, and the aspect ratios of approximately 1,900 cells were measured. Cytosolic stiffness was estimated with a finite element model, and live-cell imaging of GFP-vimentin was used to further analyze the nature of vimentin disruption. Vimentin in normal chondrocytes formed an inner cage-like network that was substantially stiffer than the rest of the cytosol and contributed significantly to overall cellular stiffness. Disruption of vimentin reduced stiffness approximately 2.8-fold in normal chondrocytes. In contrast, osteoarthritic chondrocytes were less stiff and less affected by vimentin disruption. This 3D experimental system revealed contributions of vimentin to chondrocyte stiffness previously not apparent, and correlated changes in vimentin-based chondrocyte stiffness with osteoarthritis.

Rho kinase-dependent activation of SOX9 in chondrocytes.

OBJECTIVE: The transcription factor SOX9 directly regulates the expression of the major proteoglycans and collagens comprising the cartilage extracellular matrix. The DNA binding activity and cellular localization of SOX9 is controlled through posttranslational modifications, including phosphorylation. The activity of Rho kinase (ROCK) has profound effects on the actin cytoskeleton, and these effects are instrumental in determining the phenotype and differentiation of chondrocytes. However, the mechanisms linking ROCK to altered chondrocyte gene expression remain unknown. The purpose of the present study was to test for a direct interaction between ROCK and SOX9. METHODS: Human SW1353 chondrosarcoma cells were transfected with constructs coding for RhoA, ROCK, Lim kinase, and SOX9. The interaction between ROCK and SOX9 was tested on purified proteins, and was verified within a cellular context using induced overexpression and activation of the Rho pathway. The effects of SOX9 transcriptional activation were quantified with a luciferase reporter plasmid containing SOX9 binding sites from the COL2A1 enhancer element. RESULTS: SOX9 was found to contain a consensus phosphorylation site for ROCK. In vitro, ROCK directly phosphorylated SOX9 at Ser(181), and the overexpression of ROCK or the activation of the RhoA pathway in SW1353 chondrosarcoma cells increased SOX9(Ser181) phosphorylation. ROCK caused a dose-dependent increase in the transcription of a SOX9-luciferase reporter construct, and increased phosphorylation and nuclear accumulation of SOX9 protein in response to transforming growth factor beta treatment and mechanical compression. CONCLUSION: These results demonstrate a new interaction that directly links ROCK to increased cartilage matrix production via activation of SOX9 in response to mechanical and growth factor stimulation.