Intravenous lipid emulsion therapy in 2 dogs and 2 cats with vitamin D toxicosis.

Vitamin D toxicosis can lead to severe and prolonged hypercalcemia resulting in multi-organ damage and even death. Current treatment often involves prolonged hospitalization and may require medications with potential for adverse effects. The objective of this case series was to describe reductions in serum ionized calcium concentrations following intravenous lipid emulsion therapy in vitamin D toxicosis. Two dogs and 2 cats with vitamin D toxicosis were treated with intravenous lipid emulsion therapy in addition to standard treatment regimens. Ionized hypercalcemia was lower following intravenous lipid emulsion therapy despite a more than 24-hour delay in initiating treatment in 3 of the 4 patients, and no adverse reactions were observed. Additionally, 2 of the 4 animals in this case series had long-term monitoring of 25-hydroxyvitamin D concentrations that revealed persistent elevations at 6 d in a dog and 5 mo in a cat, despite earlier resolution of their ionized hypercalcemia. Key clinical message: This is the first documented serial report of reduction of serum ionized calcium concentrations after administration of intravenous lipid emulsion, in addition to other standard therapies, in 2 dogs and 2 cats with vitamin D toxicosis. Furthermore, a chronically elevated plasma 25-hydroxyvitamin D concentration was documented in 2 of the 4 patients, including the first report in a cat. In these 2 cases, ionized calcium concentrations normalized despite persistently elevated 25-hydroxyvitamin D concentrations.

Thérapie par émulsion lipidique intraveineuse chez 2 chiens et 2 chats atteints de toxicose à la vitamine D. La toxicose à la vitamine D peut entraîner une hypercalcémie grave et prolongée entraînant des lésions à plusieurs organes, voire la mort. Le traitement actuel implique souvent une hospitalisation prolongée et peut nécessiter des médicaments susceptibles d'entraîner des effets indésirables. L'objectif de cette série de cas était de décrire les réductions des concentrations sériques de calcium ionisé par suite d'un traitement par émulsion lipidique intraveineuse dans le traitement de la toxicose à la vitamine D. Deux chiens et 2 chats atteints d'une toxicose à la vitamine D ont été traités par émulsion lipidique intraveineuse en plus des protocoles thérapeutiques standards. L'hypercalcémie ionisée était plus faible après un traitement par émulsion lipidique intraveineuse malgré un retard de plus de 24 heures dans le début du traitement chez 3 des 4 patients, et aucun effet indésirable n'a été observé. De plus, 2 des 4 animaux de cette série de cas ont fait l'objet d'une surveillance à long terme des concentrations de 25-hydroxyvitamine D qui ont révélé des concentrations élevées persistantes à 6 jours chez un chien et à 5 mois chez un chat, malgré une résolution plus précoce de leur hypercalcémie ionisée.Message clinique clé :Il s'agit du premier rapport documenté d'une série de réduction des concentrations sériques de calcium ionisé après l'administration d'une émulsion lipidique intraveineuse, en plus d'autres traitements standards, chez 2 chiens et 2 chats atteints de toxicose à la vitamine D. De plus, une concentration plasmatique chroniquement élevée de 25-hydroxyvitamine D a été documentée chez 2 des 4 patients, y compris le premier rapport chez un chat. Dans ces 2 cas, les concentrations de calcium ionisé se sont normalisées malgré des concentrations constamment élevées de 25-hydroxyvitamine D.(Traduit par Dr Serge Messier).

Cell-Material Interactions in Direct Contact Culture of Endothelial Cells on Biodegradable Iron-Based Stents Fabricated by Laser Powder Bed Fusion and Impact of Ion Release.

Additive manufacturing is a promising technology for the fabrication of customized implants with complex geometry. The objective of this study was to investigate the initial cell-material interaction of degradable Fe-30Mn-1C-0.02S stent structures in comparison to conventional 316L as a reference, both processed by laser powder bed fusion. FeMn-based alloys have comparable mechanical properties with clinically applied AISI 316L for a corrosion-resistant stent material. Different corrosion stages of the as-built Fe-30Mn-1C-0.02S stent surfaces were simulated by pre-conditioning in DMEM under cell culture conditions for 2 h, 7 days, and 28 days. Human umbilical vein endothelial cells (HUVECs) were directly seeded onto the pre-conditioned samples, and cell viability, adherence, and morphology were analyzed. These studies were accompanied by measurements of iron and manganese ion release and Auger electron spectroscopy to evaluate the influence of corrosion products and degradation on the cells. In the initial phase (2 h of pre-conditioning), HUVECs were able to attach but the cell number decreased over the cultivation period of 14 days and the CD31 staining pattern of intercellular contacts was disordered. At later time points of corrosion (7 and 28 days of pre-conditioning), CD31 staining was distinctly located at the intercellular contacts, and the cell density increased after seeding and was stable for up to 14 days. Formation of a complex degradation layer, which had a composition and thickness dependent on the pre-conditioning time, led to a reduced ion release and finally showed a positive effect on cell survival. Concluding, our data suggest the suitability of Fe-30Mn-1C-0.02S for in vivo applications.

Electrodeposition of Sr-substituted hydroxyapatite on low modulus beta-type Ti-45Nb and effect on in vitro Sr release and cell response.

Beta-type Ti-based alloys are promising new materials for bone implants owing to their excellent mechanical biofunctionality and biocompatibility. For treatment of fractures in case of systemic diseases like osteoporosis the generation of implant surfaces which actively support the problematic bone healing is a most important aspect. This work aimed at developing suitable approaches for electrodeposition of Sr-substituted hydroxyapatite (Srx-HAp) coatings onto Ti-45Nb. Potentiodynamic polarization measurements in electrolytes with 1.67 mmol/L Ca(NO3)2, which was substituted by 0, 10, 50 and 100% Sr(NO3)2, and 1 mmol/L NH4H2PO4 at 333 K revealed the basic reaction steps for OH- and PO43- formation needed for the chemical precipitation of Srx-HAp. Studies under potentiostatic control confirmed that partial or complete substitution of Ca2+- by Sr2+-ions in solution has a significant effect on the complex reaction process. High Sr2+-ion contents yield intermediate phases and a subsequent growth of more refined Srx-HAp coatings. Upon galvanostatic pulse-deposition higher reaction rates are controlled and in all electrolytes very fine needle-like crystalline coatings are obtained. With XRD the incorporation of Sr-species in the hexagonal HAp lattice is evidenced. Coatings formed in electrolytes with 10 and 50% Sr-nitrate were chemically analyzed with EDX mapping and GD-OES depth profiling. Only a fraction of the Sr-ions in solution is incorporated into the Srx-HAp coatings. Therein, the Sr-distribution is laterally homogeneous but non-homogeneous along the cross-section. Increasing Sr-content retards the coating thickness growth. Most promising coatings formed in the electrolyte with 10% Sr-nitrate were employed for Ca, P and Sr release analysis in Tris-Buffered Saline (150 mM NaCl, pH 7.6) at 310 K. At a sample surface: solution volume ratio of 1:200, after 24 h the amount of released Sr-ions was about 30-35% of that determined in the deposited Srx-HAp coating. In vitro studies with human bone marrow stromal cells (hBMSC) revealed that the released Sr-ions led to a significantly enhanced cell proliferation and osteogenic differentiation and that the Sr-HAp surface supported cell adhesion indicating its excellent cytocompatibility.

Strontium-modification of porous scaffolds from mineralized collagen for potential use in bone defect therapy.

The present study describes the development and characterization of strontium(II)-modified biomimetic scaffolds based on mineralized collagen type I as potential biomaterial for the local treatment of defects in systemically impaired (e.g. osteoporotic) bone. In contrast to already described collagen/hydroxyapatite nanocomposites calcium was substituted with strontium to the extent of 25, 50, 75 and 100mol% by substituting the CaCl2-stock solution (0.1M) with SrCl2 (0.1M) during the scaffold synthesis. Simultaneous fibrillation and mineralization of collagen led to the formation of collagen-mineral nanocomposites with mineral phases shifting from nanocrystalline hydroxyapatite (Sr0) over poorly crystalline Sr-rich phases towards a mixed mineral phase (Sr100), consisting of an amorphous strontium phosphate (identified as Collin's salt, Sr6H3(PO4)5∗2 H2O, CS) and highly crystalline strontium hydroxyapatite (Sr5(PO4)3OH, SrHA). The formed mineral phases were characterized by transmission electron microscopy (TEM) and RAMAN spectroscopy. All collagen/mineral nanocomposites with graded strontium content were processed to scaffolds exhibiting an interconnected porosity suitable for homogenous cell seeding in vitro. Strontium ions (Sr2+) were released in a sustained manner from the modified scaffolds, with a clear correlation between the released Sr2+ concentration and the degree of Sr-substitution. The accumulated specific Sr2+ release over the course of 28days reached 141.2µg (~27µgmg-1) from Sr50 and 266.1µg (~35µgmg-1) from Sr100, respectively. Under cell culture conditions this led to maximum Sr2+ concentrations of 0.41mM (Sr50) and 0.73mM (Sr100) measured on day 1, which declined to 0.08mM and 0.16mM, respectively, at day 28. Since Sr2+ concentrations in this range are known to have an osteo-anabolic effect, these scaffolds are promising biomaterials for the clinical treatment of defects in systemically impaired bone.

Metal release and cell biological compatibility of beta-type Ti-40Nb containing indium.

Small indium (In) additions up to 5 wt % to the beta-type Ti-40Nb alloy effectively improve its mechanical biofunctionality. The impact on its biocompatibility is addressed in this work. Comparative electrochemical polarization studies and inductively coupled plasma optical emission spectrometry analyses were conducted in Tris-buffered saline (on the basis of 150 mM NaCl) with pH 7.6 and 2.0 at 310 ± 1 K with Ti-6Al-4V as reference. The metal ion releases from beta-type alloys were generally very low, for example, those of In3+ ions from (Ti-40Nb)-4In specimens were below 6 × 10-7 mmol/cm2 . X-ray photoelectron spectroscopy revealed the passivation mainly by Ti- and Nb-oxides with traces of In-oxides as the dominating surface process. In vitro studies demonstrate a better human bone marrow stromal cells (hBMSC) activity on the beta-type alloys in comparison to CP-Ti (grade 2), which is mainly due to their high Nb content. At 24 h after seeding on (Ti-40Nb)-4In the metabolic activity of hBMSC was 1.5-fold higher and after 11 days, the tissue non-specific alkaline phosphatase activity was 1.8-fold higher relative to values for CP-Ti. Surface treatments, like chemical etching or plasma oxidation, change the surface topography and the thickness and composition of the oxide layers, but they are not effective in further improving the cell response. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1686-1697, 2018.

Effect of timolol maleate gel-forming solution on intraocular pressure, pupil diameter, and heart rate in normal and glaucomatous cats.

OBJECTIVE: To determine the effects of once-daily topical treatment with timolol maleate gel-forming solution (GFS) on intraocular pressure (IOP), pupil diameter (PD), and heart rate (HR) in normal cats and cats with feline primary congenital glaucoma (FCG). ANIMALS STUDIED AND PROCEDURES: A single drop of timolol maleate 0.5% GFS was administered topically to one randomly assigned eye of 18 adult cats (8 normal, 10 FCG) at 8 am for 8 days; the opposite eye served as the untreated control. IOP was measured in both eyes (OU) every 2 h (PD and HR were measured every 4 h), for 14 h total, 1 day prior to and on days 1 and 8 of treatment. In a second treatment phase, a single drop of timolol was administered at 8 pm for 3 nights and IOP, PD, and HR were measured, as above, beginning at 8 am on day 4. Slit-lamp examinations were conducted prior to and after treatment phases. Comparisons of mean IOP, PD, and HR were made at each time point and between treated and untreated eyes by repeated-measures ANOVA and Tukey-Kramer post hoc test, with P < 0.05 considered significant. RESULTS: Timolol maleate 0.5% GFS had an inconsistent effect on IOP, with maximum IOP-lowering effect (mean = 5.6 mmHg, 17.4%) observed 6 h post-treatment in FCG. The drug caused significant miosis (from 4 to 8 h post-treatment), but had no effect on HR. CONCLUSION: Once-daily application of timolol maleate 0.5% GFS may be of limited clinical benefit in the management of feline congenital glaucoma.

Surface treatment, corrosion behavior, and apatite-forming ability of Ti-45Nb implant alloy.

The low modulus ß-type Ti-45Nb alloy is a promising new implant alloy due to its excellent mechanical biocompatibility and composition of non-toxic elements. The effect of surface treatments on the evolution of controlled topography and roughness was investigated by means of scanning electron microscopy and optical profilometry. Severe mechanical treatments, for example sand-blasting, or etching treatments in strongly oxidizing acidic solutions, like HF:HNO(3) (4:1) or H(2)SO(4):H(2)O(2) (1:1) piranha solution were found to be very effective. In particular, the latter generates a nanopatterned surface topography which is expected to be promising for the stimulation of bone tissue growth. Compared to Ti and Ti-6Al-4V, the ß-type Ti-45Nb alloy requires significantly longer etching durations due to the high chemical stability of Nb. Severe surface treatments alter the passive film properties, but do not deteriorate the outstanding corrosion resistance of the Ti-45Nb alloy in synthetic body fluid environments. The Ti-45Nb appears to have a lower apatite-formation ability compared to Ti. Etching with H(2)SO(4):H(2)O(2) (1:1) piranha solution inhibits apatite formation on Ti, but not on Ti-45Nb.