Bioreactions at the tissue/hydroxyapatite interface

The events at the hydroxyapatite implant material/tissue interface in the rat middle ear were studied by light microscopy, autoradiography, morphometry, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray microanalysis. Deposition of calcium, partially in the form of calcium phosphate, was found at the interface. Resorption of the implant material occurred as the result of mono- and multinuclear phagocyte activity. Resorption decreased 6 mnth after the operation, possibly due to the decreasing number of phagocytes at the interface and the increasing amount of bone in the macropores.     

Biocompatibility of six elastomers in vitro

The biocompatibility of two silicone rubbers, Silastic and Dow Corning Elastomer, and of a polyether and a polyester urethane, a polyether polyester copolymer, and polypropylene oxide was assessed in vitro. These elastomers were selected for assessment as a possible alloplastic tympanic membrane. For these studies use was made of rat middle ear mucosa explants and serially cultured epithelium. The quantitative results were based on epithelial growth curves, the morphological picture was based on the findings in epithelium, and the aging of a biomaterial was simulated. Epithelium morphology was investigated by scanning and transmission electron microscopy and x-ray microanalysis. Quantitative results showed that on Dow Corning Elastomer and polypropylene oxide, cell proliferation was significantly lower compared to normal growth curves. The morphological findings were negative for polypropylene oxide, and did not discriminate between the other biomaterials under study. The simulation results indicated better biocompatibility for the polyurethanes and the polyether polyester copolymer compared with that of polypropylene oxide and both silicone rubbers. Under the simulation conditions, cells exposed to Silastic showed silicon-containing inclusions. These in vitro results suggest that the biocompatibility of the polyurethanes and the polyether polyester copolymer is better than that of both silicone rubbers and polypropylene oxide.     

Timeliness of infant vaccination and factors related with delay in Flanders,Belgium

Achieving high vaccination coverage is a necessary, but not a sufficient indicator of the quality of a vaccination programme, in terms of control and prevention of childhood infectious diseases. For optimal protection of infants, timeliness of vaccination is increasingly recognized as another important target.     

Epithelial reactions to hydroxyapatite. An in vivo and in vitro study

The intention of this study was to investigate the epithelial reactions to hydroxyapatite ceramic in vivo and in vitro. Shortly after implantation in the rat middle ear, hydroxyapatite was found covered by a mucosal layer. In the early postoperative period the implant was almost completely covered by epithelial cells, which were found to proliferate and also showed migratory activity. After longer intervals the implant was completely covered by epithelium, which was composed predominantly of flat polygonal cells and a relatively small number of ciliated epithelium and goblet cells. All cells showed normal morphology. In vitro experiments showed preservation of the morphology of rat middle-ear mucosa explants with good outgrowth of epithelial cells. In these outgrows, the majority of the cells were flat polygonal, but ciliated epithelium was also seen. No difference was found between the absence and presence of hydroxyapatite. Serially cultured cells displayed normal polygonal morphology, but no ciliated cells were found. Ciliated cells were also absent in control experiments without hydroxyapatite. Growth curves obtained in the absence and presence of hydroxyapatite did not differ significantly from each other.     

Anticipating crisis: towards a pandemic flu vaccination strategy through alignment of public health and industrial policy

Flu pandemics (worldwide epidemics) have occurred at irregular and unpredictable intervals, and have been associated with substantial morbidity, mortality and economic cost. In response to the emerging potential for a new pandemic to occur, national and international preparedness plans are being drawn up specifying the use of antivirals and vaccines. A number of challenges to pandemic vaccine development, large-scale production and the timing of distribution have also been highlighted. This article reviews the rationale and consequential policy for aligned public- and private sector planning in the present inter-pandemic period despite the prevalent risks and uncertainties. We propose a model for product development of pandemic flu vaccine based on public–private partnership, including push and pull incentive mechanisms for stimulating work in this therapeutic area. In addition, we argue that innovative vaccination strategies, together with special vaccine formulations which may offer cross-protection against multiple flu pandemic strains might avert the worse effects of an influenza infection.     

The effect of highly active antiretroviral treatment on viral load and antiretroviral drug levels in breast milk

Viral load and drug levels were measured in the plasma and breast milk of nine mothers treated with highly active antiretroviral therapy (HAART) and one woman treated only with zidovudine during delivery. In all HAART-treated women after delivery the viral load was less than 400 copies/ml in plasma and breast milk. Compared with the plasma concentration, the breast milk concentration was between 68 and 90% for nevirapine, 6 and 24% for nelfinavir and 90 and 540% for indinavir.     

Inhibition of histone deacetylases by chlamydocin induces apoptosis and proteasome-mediated degradation of survivin

The naturally occurring cyclic tetrapeptide chlamydocin is a very potent inhibitor of cell proliferation. Here we show that chlamydocin is a highly potent histone deacetylase (HDAC) inhibitor, inhibiting HDAC activity in vitro with an IC(50) of 1.3 nM. Like other HDAC inhibitors, chlamydocin induces the accumulation of hyperacetylated histones H3 and H4 in A2780 ovarian cancer cells, increases the expression of p21(cip1/waf1), and causes an accumulation of cells in G(2)/M phase of the cell cycle. In addition, chlamydocin induces apoptosis by activating caspase-3, which in turn leads to the cleavage of p21(cip1/waf1) into a 15-kDa breakdown product and drives cells from growth arrest into apoptosis. Concomitant with the activation of caspase-3 and cleavage of p21(cip1/waf1), chlamydocin decreases the protein level of survivin, a member of the inhibitor of apoptosis protein family that is selectively expressed in tumors. Although our data indicate a potential link between degradation of survivin and activation of the apoptotic pathway induced by HDAC inhibitors, stable overexpression of survivin does not suppress the activation of caspase-3 or cleavage of p21(cip1/waf1) induced by chlamydocin treatment. The decrease of survivin protein level is mediated by degradation via proteasomes since it can be inhibited by specific proteasome inhibitors. Taken together, our results show that induction of apoptosis by chlamydocin involves caspase-dependent cleavage of p21(cip1/waf1), which is strikingly associated with proteasome-mediated degradation of survivin.