Cartilage stress-relaxation proceeds slower at higher compressive strains

Articular cartilage is the connective tissue which covers bone surfaces and deforms during in vivo activity. Previous research has investigated flow-dependent cartilage viscoelasticity, but relatively few studies have investigated flow-independent mechanisms. This study investigated polymer dynamics as an explanation for the molecular basis of flow-independent cartilage viscoelasticity. Polymer dynamics predicts that stress-relaxation will proceed more slowly at higher volumetric concentrations of polymer. Stress-relaxation tests were performed on cartilage samples after precompression to different strain levels. Precompression increases the volumetric concentration of cartilage biopolymers, and polymer dynamics predicts an increase in relaxation time constant. Stress-relaxation was slower for greater precompression. There was a significant correlation between the stress-relaxation time constant and cartilage volumetric concentration. Estimates of the flow-dependent timescale suggest that flow-dependent relaxation occurs on a longer timescale than presently observed. These results are consistent with polymer dynamics as a mechanism of cartilage viscoelasticity.     

Effects of the calcium antagonist, diltiazem on in vitro and in vivo/in vitro bone resorption

The effect of the calcium antagonist diltiazem on bone resorption in organ culture has been investigated. It was found that diltiazem was ineffective alone but that in concentrations above 5 mumol/l it reduced mineral and organic resorption induced in vitro by 1.25 dihydroxycholecalciferol (1.25 (OH)2D3). No additivity with calcitonin effects was observed. Diltiazem did not significantly affect bone resorbing activity stimulated by 24,25(OH)2D3. Bone resorption was measured by an in vivo/in vitro technique using 45Ca prelabelled mice. Compared with 1.25(OH)2D3 alone treated group (0.480 pmol/g), it was found that diltiazem (100 nmol/g) reduced bone resorption without effect on calcium and phosphorus plasmatic concentrations at death. These data suggest that such a calcium antagonist is able to inhibit 1.25-(OH)2D3-increased-bone resorption either in vitro or in vivo/in vitro.     

Synthesis, SAR and in vivo activity of novel thienopyridine sulfonamide pyrrolidinones as factor Xa inhibitors.

Thienopyridine sulfonamide pyrrolidinones were found to be potent and selective inhibitors of the coagulation cascade enzyme factor Xa. SAR studies led to several compounds that were selected for further in vivo investigation. These novel aryl binding pocket moieties represent a structural modification to a series of fXa inhibitors. Several compounds proved to be efficacious i.v. antithrombotic agents.     

Chemical Composition,Antimicrobial, Nitric Oxide Inhibition and Cytotoxic Activity of Essential Oils from Zanthoxylum acanthopodium DC. Leaves and Stems from Vietnam

This study was aimed to investigate the chemical composition and biological activities of leaf and stem essential oils of Zanthoxylum acanthopodium DC. from Vietnam. Their chemical composition was analyzed by GC/MS. Antimicrobial activities were evaluated by microdilution broth assay. Anti-inflammatory activity was evaluated by the ability to inhibit nitric oxide production in macrophage cells. Cytotoxic activity was evaluated using the sulforhodamine B assay on three human cancer cell lines. Forty-four compounds were identified in the leaf oil, among which dehydroaromadendrane (23.4 %), (E)-carpacin (17.6 %), 2-tridecanone (12.2 %), and 9-methyl-2-decanone (11.8 %) were the most abundant. The stem oil contained fifty-five identified constituents, mainly γ-gurjunene (51.1 %) and butyl acetate (11.8 %). Both oils exhibited inhibitory effects on three bacterial strains, namely S. aureus, E. coli, P. aeruginosa and a fungal strain C. albican, while showed insignificant effects on B. subtilis, L. fermentum, and S. enterica. Both oils showed weak NO production inhibition in LPS-induced RAW264.7 cells, but exhibited potent cytotoxic activity against all three tested cell lines SK-LU-1, MCF-7, and HepG2 with the IC₅₀ values ranging from 16.03±0.77 to 35.60±1.62 μg/mL. This is the first report on the antimicrobial, anti-inflammatory and cytotoxic activities of essential oils from the leaves and stems of Z. acanthopodium.     

Comparative effects of the ionophore A23187 and vitamin D metabolites on 45Ca desaturation curves derived from bone cells: interaction of a calcium channel channel inhibitor diltiazem

The effects of diltiazem, a calcium channel inhibitor, on the cellular transport of calcium were studied in isolated heterogenous rat bone cells. Efflux was measured after equilibrating the cells with 45Ca and adding the vitamin D metabolite (1,25dihydroxycholecalciferol-1,25(OH)2D3 or 24,25dihydrocholecalciferol-24,25(OH)2D3), the ionophore A23187 and/or diltiazem. Results were analysed by fitting the desaturation curve to a model of two exponential terms. Kinetic analyses of curve indicated the presence of 2 exchangeable pools with different rate constants of exchange between the medium and cells (expressed by K.). After incubation of bone cells with diltiazem (20 nmol/10(6) cells) the following changes were recorded: a marked decrease in the rate constant of efflux from the fast turnover calcium pool (K12) and a reduction of the calcium pool sizes. Incubation of 10(6) cells with 0.5 ng 1,25(OH)2D3 plus diltiazem significantly reduced K12 compared to incubation with 1,25(OH)2D3 alone. In presence of 24,25(OH)2D3, diltiazem did not significantly alter K12 which was raised by incubation with the metabolite alone. Ionophore A23187 (0.5 micrograms/10(6) cells) increased the value of slow turnover constants of efflux whose values were affected by diltiazem. The possible involvement of Ca movements in bone resorption does not seem confirmed in the present experiment since in vitro effects of diltiazem in organ culture (observed in an initial previous experiment) were not reflected in the calcium 45 desaturation kinetics in heterogenous bone cells.