Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

18-hydroxycorticosterone, aldosterone and corticosterone were positively characterized in duck adrenal incubates. A compound resembling 11-dehydrocorticosterone was also present. The addition of 1 I.U. of ACTH/100 mg of adrenal tissue caused an increase in the production rate of all four steroids. The most dramatic effect however, was observed with respect to the synthesis of corticosterone. Aldosterone-4-¹⁴C and 18-hydroxycorticosterone-4-¹⁴C were isolated from the media of adrenal glands incubated in the presence of a tracer amount of corticosterone-4-¹⁴C. During the incubation the maximum specific activity recorded for aldosterone-4-¹⁴C was 66% of the specific activity of the precursor. This observation indicated that the primary pathway to aldosterone in the duck adrenal was probably via corticosterone. 18-hydroxycorticosterone may be an intermediate between corticosterone and aldosterone or may be a distinct end product of unknown biological activity. No difference in the biological half-life (T₁/2) of corticosterone was found between fresh-water maintained fresh-water loaded birds and birds maintained on fresh water or saline and loaded with saline. An increase in the apparent volume of distribution (A.V.D.) of corticosterone was found however in saline loaded ducks. This resulted in an increased secretory rate of corticosterone in those animals loaded with saline. In the saline maintained ducks an increased adrenal size was responsible for the enhanced corticosterone secretory rate. In those ducks maintained on fresh water and loaded with saline a weight specific increase in the corticosterone secretory rate was apparent. The implications of the increased corticosterone secretory rate are discussed in relation to the known dependence of nasal gland function in marine birds on a functional adrenal cortex. / Science, Faculty of / Zoology, Department of / Graduate

The purpose of this investigation was to determine whether or not the adrenocortical steroids influence the activity of the avian supra-orbital gland. In the intact saline loaded duck (Anas platyrhynchus), a diphasic excretory pattern was apparent, as an urinary diuresis was followed by activation of the supra-orbital glands. Variations in the circulating levels of adrenocortical steroids resulted in qualitative and quantitative changes in both phases of this response. Injection of exogenous, cortisol, cortexone and aldosterone caused an initial increase in the rate of nasal discharge and a consequent increase in the total output of Na⁺ and K⁺. Conditions of selective adrenocortical activity, i.e., subtotal adrenalectomy, severely impaired the extra-renal response while total adrenalectomy completely obliterated the response to an osmotic stimulus. The activity of the supra-orbital gland in the totally adrenalectomized duck was restored after treatment with cortisol. The renal phase in ducks treated with adrenocortical steroids was modified when compared to the control response. Administration of cortisol prior to saline loading resulted in a significantly lower total output of sodium although the volume of urine excreted did not differ from the control value. Treatment with aldosterone resulted in a significantly lower renal output of both Na⁺ and K⁺ as well as a decrease in urine volume. Cortexone and ACTH showed the control renal pattern of excretion. Unilateral adrenalectomy caused no apparent change in the renal excretory pattern whilst total adrenalectomy caused a significant increase in the total volume of urine excreted as well as on increase in the total output of Na⁺ and K⁺. Totally adrenalectomized birds maintained on cortisol reverted to a normal excretory pattern. The influence of adrenocortical steroids on the control of the avian supra-orbital gland is discussed. It can be said with certainty that adrenocortical steroids influence the activity of the supra-orbital gland of the Domestic Duck (Anas platyrhynchus). Furthermore, cortisol administered to the adrenalectomized animal reactivates the gland suggesting that a glucocorticoid is essential for its function. / Science, Faculty of / Zoology, Department of / Graduate

No description available.

No description available.

Thesis (M.Sc. (Pharmacy)) - Rhodes University, 2007.

No description available.

Thesis (Ph. D.)--University of Sydney, 2008. / Title from title screen (viewed May 8, 2009) Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Discipline of Pharmacology, Faculty of Medicine. Degree awarded 2008; thesis submitted 2007. Includes bibliography. Also available in print form.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1956. / Typescript. Vita. Includes (as Chapter II): Effect of pregnancy and lactation on granuloma tissue formation and joint permeability in rats / Roland K. Meyer, Jacob C. Stucki, and K.A. Aulsebrook, reprinted from Proceedings of the society for experimental biology and medicine, v. 84 (1953), p. 624-628. Includes bibliographical references.

Currently, clinical trials in patients are required by most regulatory authorities for the assessment of bioequivalence of topical products where the drug is not intended for systemic absorption. Hence there is a dire need for suitable methods for the assessment of bioavailability and bioequivalence of such products since clinical safety and efficacy studies are expensive, time-consuming and require very large numbers of patients. Except for topical corticosteroid products where the human skin blanching assay/vasoconstrictor assay has been approved by the US FDA for bioequivalence assessment of those products, no other method has been “officially” approved for use in those investigations. However, a few alternative methods such as tape stripping and microdialysis have been pursued and considered to have the potential for use in ioequivalence/bioavailability studies. The human skin blanching assay was used to assess the bioequivalence of commercially available topical products containing 0.05% clobetasol propionate. Both visual and chromameter data were obtained and a commercially available topical corticosteroid product, Dermovate® cream was used as both the “Test” and the “Reference” product. The results indicated that both visual and chromametric assessments were comparable to each other and that either could be used for the assessment of the bioequivalence of topical products containing clobetasol propionate. The screening procedure was optimized to identify potential “detectors” for inclusion in the bioequivalence studies. This resulted in fewer subjects being required in a bioequivalence pivotal study, still having the necessary power to confirm bioequivalence using the human skin blanching assay. Another objective of this research was to re-visit tape stripping and other possible alternative methods such as dermal microdialysis and to optimize these procedures for bioequivalence assessment of topical formulations where the drug is not intended for systemic absorption. In the past few decades, tape stripping has been used to investigate bioavailability/bioequivalence of various topical formulations. This technique involves the removal of the stratum corneum to assess drug penetration through the skin. A draft FDA guidance for tape stripping was initially published but was subsequently withdrawn due to high variability and poor reproducibility. This research project used an optimized tape stripping procedure to determine bioavailability and establish bioequivalence between three commercially available formulations containing 0.05 % m/m clobetasol propionate. Furthermore, tape stripping was validated by undertaking a study to assess the bioequivalence of a 0.05% topical cream formulation (Dermovate® cream) using the same cream as both the “Test” and “Reference” product, in which bioequivalence was confirmed. The findings highlight the potential of tape stripping as an alternative method for the assessment of bioequivalence of clobetasol propionate formulations and may possibly be extended for use in other topical products. Microdialysis is another useful technique that can assess the penetration of topically applied substances which diffuses through the stratum corneum and into the dermis. Microdialysis has previously been successfully used for in vivo bioavailability and bioequivalence assessments of topical formulations. However, the drugs which were under investigation were all hydrophilic in nature. A major problem with the use of microdialysis for the assessment of lipophilic substances is the binding/adherence of the substance to the membrane and other components of the microdialysis system. As a result, this necessitates the development of a microdialysis system which can be used to assess lipophilic drugs. Intralipid® 20% was investigated and successfully utilized as a perfusate to recover a lipophilic topical corticosteroid, clobetasol propionate, in microdialysis studies. Hence, the bioavailability of clobetasol propionate from an extemporaneous preparation was determined in healthy human volunteers using microdialysis. These findings indicate that in vivo microdialysis can be used to assess lipophilic drug penetration through the skin. A novel approach to investigate drug release from topical formulations containing 0.05% clobetasol propionate using in vitro microdialysis was also undertaken. The in vitro findings were found to be in agreement with the results obtained using tape stripping to assess bioequivalence of the same commercially available products, namely Dermovate® cream, Dovate® Cream and Dermovate® ointment. These results indicate the potential to correlate in vitro with in vivo data for bioequivalence assessment of such topical dosage forms.