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- Ström, Lena, et al.
(författare)
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Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility
- 2021
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Ingår i: BMC Veterinary Research. - : BioMed Central (BMC). - 1746-6148. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Topical ophthalmic atropine sulfate is an important part of the treatment protocol in equine uveitis. Frequent administration of topical atropine may cause decreased intestinal motility and colic in horses due to systemic exposure. Atropine pharmacokinetics are unknown in horses and this knowledge gap could impede the use of atropine because of the presumed risk of unwanted effects. Additional information could therefore increase safety in atropine treatment.Results Atropine sulfate (1mg) was administered in two experiments: In part I, atropine sulfate was administered intravenously and topically (manually as eye drops and through a subpalpebral lavage system) to six horses to document atropine disposition. Blood-samples were collected regularly and plasma was analyzed for atropine using UHPLC-MS/MS. Atropine plasma concentration was below lower limit of quantification (0.05 mu g/L) within five hours, after both topical and IV administration. Atropine data were analyzed by means of population compartmental modeling and pharmacokinetic parameters estimated. The typical value was 1.7L/kg for the steady-state volume of distribution. Total plasma clearance was 1.9L/h?kg. The bioavailability after administration of an ophthalmic preparation as an eye drop or topical infusion were 69 and 68%, respectively. The terminal half-life was short (0.8h). In part II, topical ophthalmic atropine sulfate and control treatment was administered to four horses in two dosing regimens to assess the effect on gastro-intestinal motility. Borborygmi-frequency monitored by auscultation was used for estimation of gut motility. A statistically significant decrease in intestinal motility was observed after administration of 1mg topical ophthalmic atropine sulfate every three hours compared to control, but not after administration every six hours. Clinical signs of colic were not observed under any of the treatment protocols.Conclusions Taking the plasma exposure after topical administration into consideration, data and simulations indicate that eye drops administrated at a one and three hour interval will lead to atropine accumulation in plasma over 24h but that a six hour interval allows total washout of atropine between two topical administrations. If constant corneal and conjunctival atropine exposure is required, a topical constant rate infusion at 5 mu g/kg/24h offers a safe alternative.
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| 5. |
- Stenlund, Patrik, et al.
(författare)
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Bone response to a novel Ti-Ta-Nb-Zr alloy
- 2015
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 20, s. 165-175
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Tidskriftsartikel (refereegranskat)abstract
- Commercially pure titanium (cp-Ti) is regarded as the state-of-the-art material for bone-anchored dental devices, whereas the mechanically stronger alloy (Ti-6Al-4V), made of titanium, aluminum (Al) and vanadium (V), is regarded as the material of choice for high-load applications. There is a call for the development of new alloys, not only to eliminate the potential toxic effect of Al and V but also to meet the challenges imposed on dental and maxillofacial reconstructive devices, for example. The present work evaluates a novel, dual-stage, acid-etched, Ti-Ta-Nb-Zr alloy implant, consisting of elements that create low toxicity, with the potential to promote osseointegration in vivo. The alloy implants (denoted Ti-Ta-Nb-Zr) were evaluated after 7 days and 28 days in a rat tibia model, with reference to commercially pure titanium grade 4 (denoted Ti). Analyses were performed with respect to removal torque, histomorphometry and gene expression. The Ti-Ta-Nb-Zr showed a significant increase in implant stability over time in contrast to the Ti. Further, the histological and gene expression analyses suggested faster healing around the Ti-Ta-Nb-Zr, as judged by the enhanced remodeling, and mineralization, of the early-formed woven bone and the multiple positive correlations between genes denoting inflammation, bone formation and remodeling. Based on the present experiments, it is concluded that the Ti-Ta-Nb-Zr alloy becomes osseointegrated to at least a similar degree to that of pure titanium implants. This alloy is therefore emerging as a novel implant material for clinical evaluation.
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