Thesis--Catholic University of America. / Bibliography: p. 30-31.

Part I. Seven healthy male subjects each received on a weekly basis placebo or 10, 20, 40, 80, or 160 mg oral propranolol (P) doses q.i.d. The effect of P on resting heart rate (HR) and the HR response to the Valsalva's maneuver, tilt, isoproterenol (ISO), and exercise were measured. The results indicate that the resting HR and the Tachycardiac response to Valsalva and tilt cannot be used to estimate beta blockade (BB). Although P serum levels correlated well (r² = 0.80) with the ISO dose ratio minus one, ISO challenges appear clinically inappropriate. Reduction in exercise tachycardia correlated best with P serum levels (r² = 0.89). In patients on P therapy, in which exercise would be contraindicated, there appears to be no reliable and safe method of clinically documenting BB. Part II. The parmacokinetics of intravenous P were studied in calves before and after biochemical induction of thyrotoxicosis. The beta adrenergic response to P was measured in both euthyroid and thyrotoxic (T) animals at steady-state serum levels of P by administration of ISO. No pharmacokinetic differences were detected between animal groups; however, T calves displayed a markedly different pharmacologic response to P. On the average, 2-9 times higher serum levels of P were required to facilitate BB in the T calves. These results suggest that in the calf model, thyrotoxicosis induces a decreased sensitivity to P independent of laterations in P's disposition. Part III. The aim of this study was to find a digitalis glycoside (DG) with a t(½) shorter than that of digitoxin (DT), but similar to that of digoxin, and whose disposition characteristics are not influenced by alterations in renal function, as is the case with digoxin. Consequently, the pharmacokinetics of two metabolites of DT, digitoxigenin-bisdigitoxoside (BIS) and digitoxigenin-monodigitoxoside (MONO), were compared to those of DT in a dog model. In normal dogs, appreciable differences were found between the systemic clearance (CL) of DT and the CL of either of the two other DG's. These differences in CL were primarily responsible for the 2.0 and 3.5 fold decrease seen in the t(½)'s of BIS and MONO, respectively. Renal disfunction did not influence the pharmacokinetic parameters of any of the DG's studied. These findings in the dog model suggest that BIS or MONO may provide a pharmacokinetic advantage over DT.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 120-124).

No description available.

Graduation date: 1997

The purpose of this study is to develop catalysts for conversion of synthesis gas (H₂ and CO) to higher alcohols, primarily ethanol and propanol. Crude oil is consumed at a rate of more than 20 million barrels a day in the United States, mainly for producing fuels and chemical feedstocks. However, the total amount of crude oil is limited, and alternative ways of producing alcohols as precursors for chemical feedstocks are desirable. In this study, using a known K/MoS₂/metal oxide catalyst as the starting point, two different approaches were explored to improve catalytic properties: 1) Co promotion on K/MoS₂/mixed metal oxide (MMO) catalysts, and 2) Preparation of K/MoS₂/metal oxide catalysts with molybdenum carbide as a precursor, instead of molybdenum oxide. With respect to Co promotion on K/MoS₂/MMO catalysts, the effect of varying the Co content in the K/Mo-Co/MMO catalysts prepared by a co-impregnation method did not produce significant changes in catalytic acitivities or selectivities. It was due to the premature precipitation of cobalt molybdate during synthesis. Cobalt molybdate precipitation can generally be prevented by using water as a solvent, but this approach is not appropriate for this study because of the use of hydrotalcite-derived mixed metal oxide as the support. Co loadings on K/Mo/MMO-Co catalysts did not change selectivities significantly, either. However, they changed catalytic activities, represented by gas hourly space velocity (GHSV) required to obtain 8% conversion while maintaining high selectivities for higher alcohols. As a result, C ₂₊ alcohol productivities reached 0.01g(alcohol)/g(catalyst)/hr with Co loadings higher than 8%. With respect to using Mo2C as the precursor of Mo species instead of MoO3, comparisons between catalysts with different precursors for Mo species and different pretreatments were investigated. In this study, both K/Mo catalysts supported on MgO and α-Al₂O₃ showed similar tendencies of catalytic activities and selectivities. The highest C₂₊ alcohol selectivities and productivities were obtained on presulfided MoO₃ catalysts on both supports. In comparison of K/Mo ₂C catalysts with different pretreatments, higher C₂₊ alcohol selectivities and lower MeOH selectivities were obtained on presulfided catalysts compared to non-pretreated catalysts.