Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 45-50).

A dispersive liquid-liquid microextraction (DLLME) method has been developed, optimized and validated for the extraction of seven beta-agonists (Cimaterol, Cimbuterol, Clenproperol, Clenbuterol, Ractopamine, Isoxsuprine and Ritodrine) from bovine muscle. The homogenized tissue samples were hydrolyzed enzymaticaly by beta-glucuronidase and extracted with DLLME. The extraction parameters (pH, extraction solvent, extraction solvent volume, disperser solvent) were accurately optimized. Separation of the beta-agonists was by gradient elution on C18 LC column using acetonitrile and formic acid aqueous solutions as mobile phases, multiple reaction monitoring (MRM) scan mode was used. The seven beta-agonists were then simultaneous determined and identified in single analysis using 4000 Qtrap LC-MS/MS system. The DLLME method was validated using ISO 17025 and the EU criteria (Commission Decision 2002/657/EC) for validation of analytical method, good precision, repeatability and spiked recoveries were obtained. The limits of detection and quantification for the residues were between 0.0728 – 0.0922 μg/kg and 0.243 – 0.307 μg/kg respectively for beta-agonists. The overall recoveries were between 85% and 100% with the relative standard deviation of (RSDs) between 3.0% and 10%. The recoveries from the developed DLLME method were compared with those obtained from dSPE. DLLME proved to be comparable to SPE. The real samples test showed that the DLLME method developed is accurate and sensitive for the determination of beta-agonist residues in bovine muscle. / Chemistry / M. Sc. (Analytical Chemistry)

Vasoconstriction can be initiated via the interaction of a number of chemicals with specific "receptive sites" known as the receptors. This thesis examines two distinctly different modes by which drugs initiate a contractile response, namely, (i) the interaction of angiotensin analogues with a heterogeneous population of angiotensin receptors in vascular smooth muscles, and (ii) the conditions whereby B-adrenoceptor antagonists interact with a-adrenoceptor antagonists thereby causing a pressor response. Conscious, unrestrained, instrumented-rats were used for the study. It has been suggested that angiotensin receptors in vascular and non-vascular tissues may not be of a homogeneous population. The first study examined whether a heterogeneous population of angiotensin receptors was responsible for increasing vascular tone. Dose-response curves were constructed for angiotensin II (ANG II) and des Asp¹ angiotensin II (ANG III) on mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an index of total body venous tone, in the presence or absence of [Sar¹, Ile⁸]ANG II. The i.v. infusion of ANG II or ANG III caused dose-dependent increases in MAP and MCFP. In the presence of [Sar¹, Ile⁸]ANG II, the MAP and MCFP curves for ANG II were displaced to the right with pA₂ values of 9.2 and 8.4 for the arterioles and veins, respectively. However, the antagonist displaced dose-MCFP but not the dose-MAP response curve of ANG III. This suggests that ANG II and ANG III act on the same receptor in veins but not arterioles. This concept was further investigated by obtaining dose-MAP and dose-MCFP response curves for ANG II in the presence of ANG II or ANG III. Dose-MAP response curve to ANG II was displaced to the right in the presence of ANG II but not ANG III. Dose-MCFP response curve for ANG II was displaced to the right in the presence of ANG III but not ANG II. These results again suggest that ANG III acts on the same receptors as ANG II in the veins but not arterioles. In the last series of experiments two analogues of angiotensin III were compared as antagonists of the pressor response to ANG II and ANG III. In the presence of [Ile⁷]ANG III, the dose-MAP response curves for ANG II and ANG III were displaced to the right while in the presence of [Sar¹, Ile⁷]ANG III, the dose-MAP response curve for ANG III but not ANG II was displaced. This suggests that [Sar¹, Ile⁷]ANG III is a selective antagonist of ANG III in the arterioles. In summary, the results indicate that ANG III acts on a different sub-class of angiotensin receptors than ANG II in the arterioles but it may act as a partial agonist on the same type of receptors as ANG II in the venous bed. Thus, ANG II receptors in the arterioles appear to be different from those in veins. The administration of a non-selective β-antagonist propranolol into animals subjected to non-selective α-blockade has been observed to cause a paradoxical pressor response. This second study examines whether the paradoxical pressor response to β-antagonists was due to: (i) an interaction of a β-antagonist with an α-antagonist, (ii) blockade of vasodilator β₂-adrenoceptors or (iii) an increase in the release of catecholamines. Cumulative dose-response curves for propranolol, atenolol (β₁-antagonist) and ICI 118,551 (β₂-antagonist) were obtained in rats subjected to a continuous i.v. infusion of phentolamine, a non-selective α-antagonist. The administration of each of the β-antagonists caused a dose-dependent increase in MAP suggesting that the pressor response was not due to the blockade of vasodilator β₂-adrenoceptors. Another four groups of phentolamine-treated rats were given a single i.v. bolus injection of saline, propranolol, atenolol or ICI 118,551, and sampling of arterial blood for the determination of adrenaline (A) and noradrenaline (NA) concentration by HPLC/ec. Phentolamine caused a decrease in MAP and an increase in the plasma levels of A and NA. Subsequent injection of propranolol, atenolol and ICI 118,551 but not saline increased MAP. Neither saline nor any of the β-antagonists increased plasma NA or A levels suggesting that the pressor response was not associated with an acute increase in the release of catecholamines. It was also shown that prior injection of a β-antagonist partially antagonized the hypotensive effect of phentolamine suggesting that the pressor response was related to an interaction between α- and β-antagonists. It was further shown that a continuous infusion of either prazosin or rauwolseine caused a small but not significant decrease in MAP which was reversed by propranolol. Concurrent infusions of prazosin and rauwolscine caused a large decrease in MAP. Subsequent injection of propranolol caused a large pressor response. On the contrary, sodium nitroprusside or metha-choline each decreased MAP but the hypotension was not antagonized by propranolol. These results were consistent with the existence of a specific interaction between α- and β-antagonists. These experiments demonstrated that although the mechanisms involved in the initiation of a change in vascular tone did not share a common pathway, the final outcome shared a common denomination. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

An experiment was conducted using forty-one Bonsmara steers (age ± 7 months) to determine the effect of zilpaterol hydrochloride (ZH) on the growth performance and carcass characteristics. The trial was structured using a completely randomized design with two treatments, control and ZH group. The steers were fed ZH for 28 consecutive days at the end of the finishing period and ZH was withdrawn from the diet 2 days prior to slaughter of the animals. The steers were placed in individual pens and weighed fortnightly throughout the 4 months trial. Zilpaterol hydrochloride (ZH) was included in the diet at a rate of 8.3 mg/kg of DM. Feeding of ZH increased (P< 0.05) body weight (BW) gain and ADG (1.102 vs. 1.444) and tended to increase (P = 0.067) feed efficiency (F:G) during the last month of the finishing period. There were no significant differences (P> 0.05) in daily dry matter intakes (DMI). For the control group, high treatment weight gains were significantly associated with high initial weight (r = 0.424, P = 0.049) and also high pre-treatment body weight (r = 0.678, P= 0.001). Treatment weight gain increased as the initial and pre-treatment weight gain increased in the control group. For the steers that were fed ZH, there was no significant correlation between the treatment body weight gain with initial weight (r = 0.097, P = 0.694) and also pre- treatment live weight (r = 0.393, P = 0.096). Supplementation of ZH significantly increased (P < 0.0001) the dressing percentage (56.4% vs. 58.4%) and had no significant (P>0.05) effect on the carcass weight. The outcome of the study suggest that supplementation of ZH in the diet during the last month of the finishing period enhances growth performance and shows the repartitioning capacity of the feed additive as a beta- agonist. / Agriculture and  Animal Health / M. Sc. (Agriculture (Animal Science)

An experiment was conducted using forty-one Bonsmara steers (age ± 7 months) to determine the effect of zilpaterol hydrochloride (ZH) on the growth performance and carcass characteristics. The trial was structured using a completely randomized design with two treatments, control and ZH group. The steers were fed ZH for 28 consecutive days at the end of the finishing period and ZH was withdrawn from the diet 2 days prior to slaughter of the animals. The steers were placed in individual pens and weighed fortnightly throughout the 4 months trial. Zilpaterol hydrochloride (ZH) was included in the diet at a rate of 8.3 mg/kg of DM. Feeding of ZH increased (P< 0.05) body weight (BW) gain and ADG (1.102 vs. 1.444) and tended to increase (P = 0.067) feed efficiency (F:G) during the last month of the finishing period. There were no significant differences (P> 0.05) in daily dry matter intakes (DMI). For the control group, high treatment weight gains were significantly associated with high initial weight (r = 0.424, P = 0.049) and also high pre-treatment body weight (r = 0.678, P= 0.001). Treatment weight gain increased as the initial and pre-treatment weight gain increased in the control group. For the steers that were fed ZH, there was no significant correlation between the treatment body weight gain with initial weight (r = 0.097, P = 0.694) and also pre- treatment live weight (r = 0.393, P = 0.096). Supplementation of ZH significantly increased (P < 0.0001) the dressing percentage (56.4% vs. 58.4%) and had no significant (P>0.05) effect on the carcass weight. The outcome of the study suggest that supplementation of ZH in the diet during the last month of the finishing period enhances growth performance and shows the repartitioning capacity of the feed additive as a beta- agonist. / Agriculture and  Animal Health / M. Sc. (Agriculture (Animal Science)

Abstract not available

Diss. (sammanfattning) Linköping : Linköpings universitet, 2004. / Härtill 5 uppsatser.

No description available.

Dissertation (Ph.D.)--University of South Florida, 2008. / Title from PDF of title page. Document formatted into pages; contains 201 pages. Includes vita. Includes bibliographical references.

OBJECTIVE: Human myometrium contains both beta1-adrenergic and beta2-adrenergic receptors. This study was designed to assess the importance of each beta-adrenergic receptor subtype in relaxation of human myometrial muscle strips. STUDY DESIGN: Radioligand binding studies were used to establish the presence of each beta-adrenergic receptor subtype, whereas highly selective beta1-antagonists and beta2-antagonists were used to assess the contribution of beta-adrenergic receptor subtypes to myometrial relaxation after exposure to (-)-isoproterenol. RESULTS: Membranes prepared from myometrium contained 82% +/- 4% beta2-adrenergic receptors. After contraction produced by exposure to potassium chloride (35 mmol/L), isoproterenol produced relaxation with half maximal effect at 0.02 micromol/L and a maximal relaxation of 52% +/- 3%. Beta1-antagonist CGP-20712A had no significant effect, whereas beta2-antagonist ICI-118551 produced a characteristic rightward shift of the isoproterenol concentration-relaxation relationship. CONCLUSIONS: Although both beta1-adrenergic receptors and beta2-adrenergic receptors are present in human myometrial tissue at term, relaxation by nonselective beta-agonist isoproterenol is mediated exclusively by beta2-adrenergic receptors.