Urban forests grow in stressful environments that can have negativerepercussions on tree energy reserves. The goal of this research was to evaluate theimpact of exogenously applied carbohydrates on growth and vitality of live oaks(Quercus virginiana P. Miller). An initial study focused on carbohydrate partitioningrevealed that annual mean glucose concentration in leaf tissues (49.55 mg·g-1 DW) wasalmost double that in twigs, trunks, or roots. Starch concentrations in roots and trunks(38.98 and 38.22 mg·g-1 DW of glucose, respectively) were higher during the dormantseason and approximately three times the concentrations found in other tissues. Aninvestigation of the effects of exogenous soil applications of glucose and starch on soilmicrobial activity revealed no significant differences using recoverable viable microbes.However, soil respiration was significantly increased (P<0.05) by glucose a week afterapplication, while higher starch concentrations (120 g·L-1) significantly increased(P<0.05) soil respiration after the fourth week. Although tree soil drenched withcarbohydrates in a different study showed significantly (P<0.05) greener leaf color, higher chlorophyll fluorescence, and increased soil respiration at higher concentrationsof starch (120 g·L-1), no significant differences were observed in photosynthesis or trunk,canopy, or root growth. Analysis of 13C signatures was unable to detect uptake ofexogenous carbohydrates. For trunk-injected trees with glucose and sucrose, trunkgrowth was significantly (P<0.05) increased by carbohydrate supplementation.Differences were also found in twig glucose content, root starch content, and chlorophyllfluorescence among overall concentration means. A study to compare field diagnostictools with carbohydrate laboratory analysis established that a portable blood glucosemeter can be used to measure glucose content in trees. However, ohmmeter,refractometer, chlorophyll fluorescence spectrometer, and iodine staining results did notcorrelate well with laboratory analysis of carbohydrate concentrations. Results fromthese studies reveal that soil applied carbohydrates can greatly increase soil microbialactivity, provide evidence that trunk-injected carbohydrates may improve growth andvitality of live oaks, and provide a new field diagnostic tool to increase the efficiency ofmeasuring carbohydrates in trees.

Purpose: The aim of this study was to investigate the usefulness of formulation approaches to minimise injection site reactions for poorly soluble drugs. The specific objectives were to modify the injection site reactions by identification of irritant components in the formulation and control of their release kinetics; and to gain understanding of formulation approaches to create a favourable microenvironment in the tissues allowing better tissue tolerance and drug absorption. Methods: Physicochemical properties of the model drug, ricobendazole (RBZ) were characterised using conventional methods. Three formulation approaches to minimise irritancy of the low pH RBZ solution were assessed. An in vitro method using 96-well microplates and a microtiter plate reader was used for detection of drug precipitation on dilution for formulation characterisation. Cellular damage by the formulations was investigated in L929 fibroblasts using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and lactate dehydrogenase (LDH) assays. Tissue tolerance and pharmacokinetics were simultaneously investigated after subcutaneous injection in sheep. A low pH RBZ solution was used as a reference formulation. Results: Preformulation studies showed that RBZ was practically insoluble in water and oils, and was slightly soluble in commonly used co-solvents. Solubility was slightly improved by complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD, K₁:₁ = 311 M⁻�) or a combination of low pH (> 2) with surfactants or co-solvents. A U-shaped pH-solubility profile in aqueous solutions indicated that RBZ is an ampholyte. pKa values measured by absorbance spectroscopy and pH solubility methods were 3.45 and 3.76 (basic) and 9.82 and 9.53 (acidic) respectively. The partition coefficient was 14.3 - 15.2 at pH 6 - 9 and less at higher or lower pH. In aqueous solutions, RBZ showed a V-shaped pH-degradation rate profile and was most stable at pH 4.8. Degradation pathways were identified as hydrolysis and oxidation. Three RBZ injectables (5%) were obtained by modification of the low pH RBZ solution; addition of 20% HP-β-CD, incorporation into a w/o emulsion, and a microemulsion (ME). On dilution with SPB, the onset time of drug precipitation was prolonged and the rate was reduced in the presence of HP-β-CD. The w/o emulsion had a low viscosity (< 60 mPa.s) and exhibited Newtonian flow. Drug release versus the square root of time was linear and the release rate could be adjusted by phase ratio and droplet size. Drug release was found to be by diffusion. A coarse emulsion layer appeared at the interface between the ME and buffer. Drug release from the ME was faster than from the emulsion and was linear with the square root of time. On titration into SPB, the three formulations showed controlling effects on the release of H₃O⁺ compared to the reference formulation. RBZ (0.1 mg/ml) was more toxic to L929 cells than the co-solvent propylene glycol (50 mg/ml). The formulations showed greater cytotoxicity than their vehicles in the order: ME > RBZ solution = emulsion > HP-β-CD. HP-β-CD and emulsion excipients showed little or no cytotoxicity. The MEs exhibited more toxicity in the LDH assay than in the MTS assay. A reversed phase HPLC assay for simultaneous determination of RBZ and its metabolite in sheep plasma using an isocratic system with UV detection was developed and used in the pharmacokinetic studies. Plasma samples were prepared by solid phase extraction. A suitable internal standard was selected by quantitative structure-retention relationships analysis. The composition of a ternary mobile phase was optimised with the assistance of multiple linear regression. The assays were linear over the concentration range 10 - 1000 ng/ml for both analytes (r > 0.999) with satisfactory inter-day and intra-day precision and accuracy (CV < 10%). The recoveries for all analytes were > 96%. A pilot study in sheep suggests that injection of the vehicles (the CD, emulsion and ME) caused virtually no pain on injection or site reactions. Both the reference formulation and its vehicle induced pain on injection and resulted in swollen tissues. Histology after two weeks showed granulation for the formulation, but not the vehicle. In contrast, animals showed virtually no injection site reactions with the ME and emulsion. The HP-β-CD formulation gave transient pain on injection but a two-fold increase in bioavailability compared with the reference. The emulsion produced sustained drug release and increased drug absorption. In the main study, the HP-β-CD vehicle showed good tissue compatibility. Irritation by the HP-β-CD formulation was attributed to the low pH. Cmax, tmax and AUC0-[infinity] for the reference formulation were 1.3 � 0.3 [mu]g/ml, 9.6 � 2.9 h and 36.7 � 9.2 [mu]g�h/ml respectively, while the corresponding data for the HP-β-CD formulation were 2.9 � 0.8 [mu]g/ml, 5.0 � 0.6 h and 54.5 � 15.3 [mu]g�h/ml respectively. The half-life following the injection of the HP-β-CD formulation (5.5 � 2.8 h) was shorter than that of the reference formulation (8.5 � 3.4 h). Conclusions: Injection site reactions may be minimised by identification of irritant components in a formulation and by controlling their release. Controlling the burst release of the poorly water soluble drug RBZ in a low pH solution could improve tissue tolerance and minimise post-injection precipitation, and hence increase drug bioavailability. In addition, HP-β-CD was a useful local injectable carrier which significantly enhanced the absorption of RBZ after subcutaneous injection in sheep.

Thesis (M.D.)--University of Adelaide, 1989. / Includes bibliographical references (leaves 107-109).

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 5 uppsatser.

Thesis (M.S.)--University of Wisconsin, School of Nursing. / eContent provider-neutral record in process. Description based on print version record.

Profschrift-Veeartsenijk. hoogeschool, Utrecht. / "Stellingen": leaf laid in. "Literatuur": p. [143]-145.

Thesis (Ph. D.)--Rïjksuniversiteit te Groningen, 1983. / Summary and vita in Dutch. Includes bibliographical references.

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Thesis (M.S.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / 2031-01-01

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