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Alkaloid toxicities negatively impact livestock health and production and are of serious economic concern to animal industries. To date, few strategies have been developed to evaluate alkaloid levels in feed or to counteract alkaloid toxicities. The present research evaluated the applicability of imprinting technology to synthesize polymers that have potential to interact with ergot alkaloids and therefore reduce their bioavailability in the GIT. The studies also evaluated applicability of synthesized polymers for use in the ruminal environment using an in vitro ruminal fermentation model, and for the ability to ameliorate vasoconstriction using ex vivo myographic evaluations. In the first experiment, styrene-based molecularly imprinted polymer (MIP) was synthesized using ergotamine as the imprinting template and evaluated for specificity of adsorption to various ergot alkaloids. Cross reactivity with related alkaloids exists due to similarities in structure and functional groups. Both polymers (MIP and NIP) showed strong adsorption intensity and no difference was observed for estimated maximum adsorption capacity between MIP and NIP. Morphologically, MIP was highly porous with greater surface area than NIP. Solid phase extraction indicated stronger adsorption of MIP than NIP to ergot alkaloids suggesting the potential for MIP as a sorbent material for solid phase extraction (SPE) columns used for sample clean-up prior to HPLC or LC-MS/MS analysis of complex samples. In Experiment 2, methacrylic acid-based polymers were synthesized with ergotamine as a template. Among the 4 alkaloids evaluated for selectivity, adsorption difference between MIP and NIP interacted with alkaloid concentration, although differences were generally consistent across concentrations. Imprinting did not affect lysergol and bromocriptine adsorption, but resulted in higher adsorption to methylergonovine. However, there was no difference between MIP and NIP for adsorption of ergotamine. Hydrophobic interactions and H-bonding were the primary interactive forces between polymers and alkaloid adsorbents. Morphologically, MIP had greater surface area and porosity implying a larger surface for adsorption. In addition to its application as SPE sorbent, this MIP was a suitable candidate for application as a feed adsorbent to reduce the bioavailability of certain alkaloid in the gut. In experiment 3, methacrylic acid-based polymers were evaluated for their effect on in vitro ruminal fermentation. There were no interactions between polymer type and inclusion level, and no differences between polymer types for cumulative gas production or rate of gas production. Total gas production and rate of gas production were unaffected by inclusion level. Polymers did not affect total or individual VFA concentrations, ammonia-N or methane concentration at any inclusion level. However, a logarithmic increase in polymer dose level decreased the pH linearly with maximum depression of 0.24 units. This study indicated that, within the range of expected use levels, polymers were essentially inert and would not be expected to affect ruminal fermentation. In experiment 4, ex vivo myographic bioassays were used to determine the impact of polymers on ergotamine bioavailability. Responses measured in the ex vivo myographic studies had similar trend as the responses generated from in vitro isothermal adsorption studies. Results of that study also showed that ex vivo myographic responses could be predicted from in vitro isothermal adsorption studies with more than 80% accuracy. These studies indicate that synthetic polymers are potentially effective adsorbents to mitigate ergot toxicity with little evidence of substantial differences between MIP and NIP.

The knowledge of blood vessel biomechanics is used for understanding and developing treatments for cardiovascular disease. The objective of this project was to develop an experimental protocol, for education and research, that separates active diameter response from the passive, as a function of the intraluminal pressure in a pressure myograph. The design process was performed in three steps. First the protocol was designed for an artificial vessel and then expanded to include passive properties of blood vessels, finally further developments needed to analyze active blood vessels were suggested. The system was built as a pressure myograph containing a vessel chamber where the vessel was mounted on two cannulas, two pressure sensors for calculating the intraluminal pressure, and one microscope equipped with a camera for diameter observations. Reference data for the artificial vessel material was acquired from a uniaxial tensile test. The results was in the form of stress-stretch relations. Both the results from the artificial vessel and the passive blood vessel was in a acceptable reference range. The results indicate that the experimental protocol can be used for testing passive properties of both artificial vessels and small blood vessels. No results were obtained for active blood vessels, thus the experimental protocol can not be used for separating the active response to diameter change of blood vessels. However, further developments of the experimental protocol are discussed. / Kunskap om blodkärlens biomekanik används för att förstå och utveckla behandlingsmetoder mot hjärt- och kärlsjukdomar. Syftet med det här projektet var att utveckla ett experiment som mäter små blodkärls diameter och vätsketryck in vitro. Experimentet skulle sedan separera det aktiva muskelbidraget till diameterförändring från det passiva bidraget. Genom att göra detta kan kunskapen om biomekaniken hos blodkärl utvecklas inom såväl forskning som utbildning. Experimentet utvecklades i tre steg. Först utvecklades det för artificiella blodkärl och anpassades sedan för passiva blodkärl. Slutligen diskuteras vidareutvecklingar av experimentet gällande de aktiva egenskaperna för blodkärl. Experimentet utformades genom att ett kärl placerades i en kammare. Blodkärlet fästes i vardera ände på varsin kanyl som var kopplade till trycksensorer. För att registrera diametern placerades kammaren under ett kameramikroskop. Resultatet består av spänning-sträcknings diagram. Både resultatet för det artificiella blodkärlet och det passiva blodkärlet var inom ett godkänt referensintervall. Dessa resultat stödjer antagandet att experimentet kan användas för att studera passiva egenskaper av artificiella och verkliga blodkärl med storlek mellan 1.9-4.4 mm i ytterdiameter. Ingen mätdata från aktiva blodkärl kunde samlas in, utan utvecklingskrav på systemet för hantering av aktiva blodkärl har föreslagits.