MRI findings, metal ion levels and clinical outcome of a complete series of large metal on metal THA: what's really going on?

INTRODUCTION:: Metal-on-metal (MoM) large head total hip arthroplasties (THAs) were discontinued early after their introduction because of the high number of failures due to adverse reaction to metal debris (ARMD). Aim of this study is to report the clinical outcome at a mid-term follow-up (FU) of a series of large-head MoM THA. METHODS:: In this prospective study, 25 hips (24 patients, 3 males, 21 females, mean age 62.44 years) who have undergone primary THA with large head (diameter ⩾36 mm) MoM prosthesis were evaluated. Each patient underwent a standard follow-up after surgery, that included blood tests with metal ion levels (Co and Cr), x-ray of the pelvis, metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) and clinical evaluation. RESULTS:: At an average follow-up of 7.3 years, 4 hips have been surgically reviewed: 2 for causes not related to ARMD (1 heterotopic ossification and 1 periprosthetic fracture); the other 2 on the same patient (bilateral) with ARMD, who was eventually found to be allergic to nickel. Increased metal ions, osteolysis and severe MRI alterations were found in patients with ARMD. Asymptomatic alterations at MRI were found in 8 patients. Harris Hip Score improved after surgery from a mean of 51 points to a mean of 90 points ( p < 0.01). CONCLUSIONS:: The findings of this study show that not all the patients with MoM THA will develop clear symptoms of ARMD at mid-term follow-up. Patients should be closely monitored following protocols such as that proposed in the European Consensus Statement.

Polypyrrole-polysaccharide thin films characteristics: electrosynthesis and biological properties.

Polypyrrole-polysaccharide thin films were electropolymerized from starting solutions containing pyrrole and a polysaccharide, namely, heparin, chondroitin-4-sulphate or hyaluronic acid. The synthesized samples showed good chemical and physicochemical properties determined by the synthesis parameters such as the current density and time. For instance, the sample morphology was strictly correlated to the current density as follows: a smooth surface morphology was observed when the current density was in the range of 100-700 microA/cm(2), whereas high current (I > 1.0 mA/cm(2)) or longer time (synthesis charge > 100 mC/cm(2)) led to rough surfaces. The presence of polysaccharide within the polymeric matrix assured proper hydrophilicity to the samples. The optimized surface chemistry due to the presence of a polysaccharide and the controllable morphology allowed positive cell/substrate interactions and these are proved by cellular tests using MC3T3-E1 osteoblast cultures.

Prostaglandin F2alpha involves heparan sulphate sugar chains and FGFRs to modulate osteoblast growth and differentiation.

The present investigation extends our previous studies on PGF2alpha-mediated signalling in osteoblast metabolism. In particular, the role of PGF2alpha as modulator of heparan sulphate proteoglycans (HSPGs), fibroblast growth factor 2 (FGF-2) and fibroblast growth factor receptors (FGFRs) was evaluated. We hereby reported the novel observation that PGF2alpha was able to promote the formation of HSPGs/FGF-2/FGFRs complexes. Moreover, our data suggested that PGF2alpha could induce new synthesis of heparan sulphate (HS) chains on osteoblasts by a mechanism involving a modulation of MAPK signalling and that HS is required for the regulation of FGF-2 induced by PGF2alpha. Indeed, a proteolytic cleavage of HSPGs with heparinase III (Hep III) prior to PGF2alpha administration down-regulated the basal expression of phospho-p44/42, likely inhibiting FGFRs tyrosine kinase activity. Interestingly, MAPK signalling influenced syntheses and subcellular localization of FGF-2, its specific receptor and HS. In addition, the proteolytic cleavage by Hep III and the MAPK kinase inhibition by PD-98059 also revealed that PGF2alpha induced cell proliferation is dependent on HSPGs and FGF-2 specific receptor, respectively. Of further relevance of this study, we demonstrated, by using a specific siRNA for FGFR1, that PGF2alpha modulates Runx2 expression by FGFR1 and HS.

Anti-apoptotic Bcl-2 enhancing requires FGF-2/FGF receptor 1 binding in mouse osteoblasts.

In this study, we investigated the role of prostaglandin F2alpha (PGF2alpha) in mouse osteoblast survival and the function of fibroblast growth factor 2 (FGF-2) and fibroblast growth factor receptor 1 (FGFR1) in this process. In particular, for the first time, we demonstrated that PGF2alpha increased osteoblast survival in a dose-dependent manner and we showed that the effect is correlated with an increase in Bcl-2/Bax ratio. Furthermore, we demonstrated that PGF2alpha caused a decrement of the active caspases 9 and 3. By blocking FGF-2 with the specific neutralizing antibody and by depletion of FGFR1 gene with a specific siRNA, we showed that FGFR1 and FGF-2 are critical for the increment of Bcl-2/Bax ratio and the decrement of the active caspases 9 and 3, induced by PGF2alpha. Moreover, transmission electron microscopy studies showed that PGF2alpha increased binding of FGF-2 and FGFR1 and co-localization of reactive sites at plasma membrane level. In conclusion, we report a novel mechanism in which PGF2alpha induces FGF-2 binding to its specific cell surface receptor 1 leading to a cascade pathway that culminates with increased mouse osteoblast survival.

Benzyl butyl phthalate influences actin distribution and cell proliferation in rat Py1a osteoblasts.

We previously reported that transient administration of phthalates induced actin cytoskeleton disruption in Py1a osteoblasts. However, the mechanism of this transient effect was not elucidated. In this study we provided evidence that the actin cytoskeletal re-established conditions are dependent on new actin expression and synthesis. To assess the role of phthalates in modulating the distribution of actin, confocal and electron microscopy studies were carried out. Results indicated a modification of actin distribution after phthalate administration. In addition, a relation with the nucleoskeletal component lamin A supports the hypothesis that phthalates may participate in regulatory cell processes involving actin in Py1a osteoblasts. The present study also supports the mitogenic effects of phthalates, which involve microfilament disruption, nuclear actin and lamin A. In particular, the increased levels of cyclin D3, which in mammalian cells plays a critical role in G1 to S transition and is a putative proto-oncogene in benzyl butyl phthalate treated cells, suggested a possible effect of the endocrine disruptor in cancer processes.

PGF2alpha increases FGF-2 and FGFR2 trafficking in Py1a rat osteoblasts via clathrin independent and importin beta dependent pathway.

Previous studies showed that prostaglandin F2alpha (PGF2alpha) stimulated fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor 2 (FGFR2) cytosolic and nuclear accumulation, however, the endocytic pathway has not been elucidated. This study demonstrates that although PGF2alpha increased the formation of clathrin-coated structures in Py1a rat osteoblasts, they were not involved in FGF-2 and FGFR2 trafficking. PGF2alpha increased binding of FGF-2 and FGFR2 and co-localization of reactive sites in addition to nuclear translocation at the nuclear pore complex level. FGF-2 and FGFR2 were in close spatial correlation with importin beta, further supporting nuclear import of the FGF-2/FGFR2 complex. Immunogold and immunofluorescence techniques as well as Western blotting demonstrated increased importin beta protein labeling in response to PGF2alpha. Similar to PGF2alpha, phorbol 12-myristate 13-acetate (PMA) also increased importin beta protein. These data strongly suggest that prostaglandins may regulate osteoblast metabolism via FGF-2/FGFR2/importin beta nuclear trafficking.

Cell type-specific and developmentally regulated expression of the AE1 anion exchanger in the chicken chorioallantoic membrane.

Antibodies specific for the chicken AE1 anion exchanger have been used to determine the cell-type specific pattern of expression of this electroneutral transporter in the chick chorioallantoic membrane (CAM) during embryonic development. Immunolocalisation analyses demonstrated that the AE1 anion exchanger accumulated in the basolateral membrane of a subset of cells in both the chorionic and allantoic epithelial layers. Double immunostaining indicated that the AE1-positive cells in the chorionic and allantoic epithelia were also positive for the carbonic anhydrase isoform, CAII, which serves as a marker for the villus cavity (VC) cells of the chorionic epithelium and the mitochondria-rich cells of the allantoic epithelium. Immunoelectron microscopy revealed that AE1 accumulated in extensive projections that extended from the lateral membrane of VC cells towards the adjacent capillary covering cells. These results represent the first demonstration of anion exchanger expression in the chick CAM, and they suggest a role for basolateral AE1 in bicarbonate reabsorption that is required in the embryo for maintaining acid-base balance during development.

Developmental expression of glycocomponents in the chick chorioallantoic membrane.

Widespread interest has focused on the research of the chorioallantoic membrane (CAM) and its functional contribution to gaseous exchange, calcium reabsorption, water and electrolyte transport during chick embryogenesis. Nevertheless, very little information is available on the glycoconjugate components of this extra-embryonic structure. In the present study, we investigated by lectin histochemistry, the glycosylation pattern expressed in the CAM epithelia during embryonic development. Occurrence of sialic acid-associated glycoproteins was detailed by either specific lectins, which discriminate alpha2,3 and alpha2,6 sialoderivatives, or sialidase digestion combined with appropriate lectins to identify the sialic acid acceptor sugars. Lectin affinities proved to depend greatly on differentiation of the CAM epithelia which showed highest expression of binding sites during the second half of incubation up to hatching. Differences emerged between the chorionic and the allantoic epithelium, regarding qualitative, quantitative and temporal expression of sugar moieties. A cell type-specific distribution of glycocomponents was found in the chorionic epithelium where lectin binding sites were specifically located in the villus cavity cells. In the allantoic epithelium, high and heterogeneous occurrence of sialoglycoconjugates as well as specific presence of fucose residues were evidenced mostly in the granule cells. We conclude from these findings that various glycoconjugates in the CAM could participate in different physiological functions characteristic of the chorionic and the allantoic epithelium.