Taux sanguins et sériques d'ions métalliques chez les patients porteurs de PHTs à col modulaire - une étude de cohorte prospective comparative

Les évidences s'accumulent concernant des problèmes de corrosion touchant les prothèses à col modulaires. Plusieurs études récentes révèlent des taux d'ions métalliques élevés. Le but de cette étude était de comparer les taux d'ions métalliques (Co, Cr, Mo, Ti), dans le sérum, chez des porteurs de prothèses à col modulaire, à tige monobloc, ainsi que sans implant. Méthodes Nous avons recruté 60 patients, dont 50 porteurs d'une PTH, unilatérale, sans aucun autre implant, non-cimentée, avec tête en céramique, à minimum 1 année postopératoire. Quarante avaient une tige SPS (Symbios) (Ti6Al4 V) modulaire (col en CoCr) et 10 une SPS monobloc (non-modulaire). Les cupules étaient toutes en alliage de Ti (Ti6Al4 V) avec insert céramique ou PE. Nous avons constitué un groupe témoin sans aucun implant. Dans le groupe o modulaires O, le col a été choisi en préopératoire sur la base d'une planification 3D et assemblé à sec avant implantation. Nous avons prélevé un échantillon sérique, un autre sanguin, qui ont été analysés par spectrométrie de masse, permettant une détermination atomique quantitative. Le résultat clinique a été estimé à l'aide du o Oxford Hip Score O. Résultats Nous avons trouvé un Co sérique moyen à 1,54 Ig L dans le groupe O modulaires O et à 0,32 Ig L dans le groupe o monobloc O avec un p < 0,001. Pour le Cr, on a 1,12 Ig L (modulaires) vs 0,60 Ig L (monoblocs) avec un p < 0,001, pour le Ti 31 Ig L (modulaires) vs 22 Ig L (monoblocs) avec p < 0,001 et pour le Mo, 0,96 Ig L (modulaires) vs 0,74 (monoblocs) avec p = 0,254. Deux patients avaient des valeurs de Co supérieures à 7 Ig L et 11 étaient au-dessus de 1 Ig L, valeur considérée comme limite. Les valeurs dans le sang complet étaient similaires. Nous n'avons pas trouvé de différence significative selon les types de col modulaires (longs vs courts et rétro vs normaux). Curieusement, le taux de Cr était significativement plus élevé chez les patients sans aucun implant que chez les porteurs de SPS monobloc, par contre les différences n'étaient pas significatives pour les autres éléments. Conclusion Les taux sériques et sanguins de ions Co, Cr et Ti étaient significativement plus élevés dans le groupe des patients avec col modulaire, avec 2 valeurs 40 extrêmement hautes et plus de la moitié (11 40) anormalement hautes. Bien que ces valeurs soient inférieures à celles d'autres études, nous avons arrêter d'utiliser de tiges à cols modulaires, et avons initié un suivi annuel des patients porteurs, similaire à celui instauré pour les grosses têtes métal-métal.

Use-dependent block of the voltage-gated Na+ channel by tetrodotoxin and saxitoxin: Effect of pore mutations that change ionic selectivity.

Voltage-gated Na(+) channels (NaV channels) are specifically blocked by guanidinium toxins such as tetrodotoxin (TTX) and saxitoxin (STX) with nanomolar to micromolar affinity depending on key amino acid substitutions in the outer vestibule of the channel that vary with NaV gene isoforms. All NaV channels that have been studied exhibit a use-dependent enhancement of TTX/STX affinity when the channel is stimulated with brief repetitive voltage depolarizations from a hyperpolarized starting voltage. Two models have been proposed to explain the mechanism of TTX/STX use dependence: a conformational mechanism and a trapped ion mechanism. In this study, we used selectivity filter mutations (K1237R, K1237A, and K1237H) of the rat muscle NaV1.4 channel that are known to alter ionic selectivity and Ca(2+) permeability to test the trapped ion mechanism, which attributes use-dependent enhancement of toxin affinity to electrostatic repulsion between the bound toxin and Ca(2+) or Na(+) ions trapped inside the channel vestibule in the closed state. Our results indicate that TTX/STX use dependence is not relieved by mutations that enhance Ca(2+) permeability, suggesting that ion-toxin repulsion is not the primary factor that determines use dependence. Evidence now favors the idea that TTX/STX use dependence arises from conformational coupling of the voltage sensor domain or domains with residues in the toxin-binding site that are also involved in slow inactivation.

Heavy metal ions are potent inhibitors of protein folding.

Environmental and occupational exposure to heavy metals such as cadmium, mercury and lead results in severe health hazards including prenatal and developmental defects. The deleterious effects of heavy metal ions have hitherto been attributed to their interactions with specific, particularly susceptible native proteins. Here, we report an as yet undescribed mode of heavy metal toxicity. Cd2+, Hg2+ and Pb2+ proved to inhibit very efficiently the spontaneous refolding of chemically denatured proteins by forming high-affinity multidentate complexes with thiol and other functional groups (IC(50) in the nanomolar range). With similar efficacy, the heavy metal ions inhibited the chaperone-assisted refolding of chemically denatured and heat-denatured proteins. Thus, the toxic effects of heavy metal ions may result as well from their interaction with the more readily accessible functional groups of proteins in nascent and other non-native form. The toxic scope of heavy metals seems to be substantially larger than assumed so far.

Epithelial Ingrowth After Lasik/altk: An Immunohistological Study Of 4 Cases. Do Epithelial Inclusions Grow From Trapped Corneal Stem-like Cells?

Purpose: To characterize the clinical, morphological and immunohistological features of epithelial ingrowth cells after laser in situ keratomileusis (LASIK) or Automated Lamellar Therapeutic Keratoplasty (ALTK) with specific reference to current markers of corneal stem cells.Methods: Four patients were included in this interventional non-comparative case series. Full ophthalmologic examination was performed. Epithelial ingrowth specimens from 4 patients were removed surgically and immunostained for cytokeratin 3 (CK3), cytokeratin 15 (CK15), cytokeratin 19 (CK19), Muc5AC, p63α, C/EBPδ, Bmi-1, BCRP/ABCG2 and Ki-67.Results: The time interval between LASIK/ALTK and ingrowth surgical removal was, 3, 11, 15 and 36 months. On slit lamp examination, early epithelial ingrowth appeared as whitish pearls and late epithelial ingrowth as confluent whitish opacities. Microscopically, the epithelial ingrowths showed features of a squamous non keratinizing epithelium. No mitotic figure was seen. Ki-67 labelling of 3 cases showed a proliferation index of 3-4%. Superficial squamous cells strongly expressed CK3. Expression of C/EBPδ, BCRP/ABCG2 and p63α was seen in more than 70% of cells and Bmi-1 was positive in up to 30% of cells in the specimens tested. There was no expression of CK19 or CK15.Conclusions: Epithelial ingrowths can persist for up to 3 years following LASIK surgery. They show a capacity for self-renewal and corneal differentiation. Besides, they express p63α, C/EBPδ, Bmi-1, BCRP/ABCG2 which have been proposed as markers of stem cell phenotype. These observations suggest that post-LASIK/ALTK epithelial inclusions could derive from stem-like cells located in the peripheral corneal epithelium.

Different concentrations of Mg++ ions affect nuclear matrix protein distribution during thermal stabilization of isolated nuclei.

The nuclear matrix, a proteinaceous network believed to be a scaffolding structure determining higher-order organization of chromatin, is usually prepared from intact nuclei by a series of extraction steps. In most cell types investigated the nuclear matrix does not spontaneously resist these treatments but must be stabilized before the application of extracting agents. Incubation of isolated nuclei at 37C or 42C in buffers containing Mg++ has been widely employed as stabilizing agent. We have previously demonstrated that heat treatment induces changes in the distribution of three nuclear scaffold proteins in nuclei prepared in the absence of Mg++ ions. We studied whether different concentrations of Mg++ (2.0-5 mM) affect the spatial distribution of nuclear matrix proteins in nuclei isolated from K562 erythroleukemia cells and stabilized by heat at either 37C or 42C. Five proteins were studied, two of which were RNA metabolism-related proteins (a 105-kD component of splicing complexes and an RNP component), one a 126-kD constituent of a class of nuclear bodies, and two were components of the inner matrix network. The localization of proteins was determined by immunofluorescent staining and confocal scanning laser microscope. Mg++ induced significant changes of antigen distribution even at the lowest concentration employed, and these modifications were enhanced in parallel with increase in the concentration of the divalent cation. The different sensitivity to heat stabilization and Mg++ of these nuclear proteins might reflect a different degree of association with the nuclear scaffold and can be closely related to their functional or structural role.