Substituent effects in eta5-cyclopentadienyl (Cp) transition metal complexes have been intensely studied since the discovery of the first such complex, ferrocene. Modifications of the Cp ligand framework effect changes in the physical properties and chemical reactivity of the coordinated transition metal. This concept is useful when applied to catalysis mediated by Cp complexes, because the performance of the catalyst can be markedly improved using well-chosen ligand substituents. Studies of electronic substituent effects ideally employ a wide range of electron-donating and electron-withdrawing groups. Unfortunately, most of the available electron-withdrawing groups suffer from problems with Cp ligand synthesis, Cp anion stability, and electron-withdrawing group stability under catalytic conditions. This dissertation shows that the pentafluorophenyl (C6F5) substituent is highly electron-withdrawing but avoids all of these problems. Several new C6F5-substituted cyclopentadienes are prepared by the reaction of sodium cyclopentadienide and hexafluorobenzene (C6F6) under varying conditions. Corresponding C6F5-substituted cyclopentadienyl ligands (sodium salts) are obtained upon deprotonating the dienes with NaH. Complexes of Mn(I), Re(I), Fe(II), Co(II), Zr(IV) are synthesized by reacting these ligands with transition metal halides. The acidities of several C6F5- and C5F4N-substituted cyclopentadienes and indenes are measured using 19F NMR spectroscopy. The electron-withdrawing fluorinated aryl groups have a substantial acidifying effect. The identity and number of substituents (C6F5, C5F4N, CH3, and t-Bu), the position of the substituents on the cyclopentadiene, and the intramolecular (vicinal) steric effects also influence acidity. The electron-withdrawing ability of the C6F5 group is also characterized by infrared spectroscopic analysis of substituted CpM(CO)3 (M = Mn(I) and Re(I)) and electrochemical analysis of substituted ferrocenes. X-ray crystal structures of several C6F5-substituted Cp complexes reveal interesting structural motifs, including pi-stacking of the C6F5 substituents, Cp-M bond elongation, and CO-C6F5 interactions. In addition, dynamic Cp-C6F5 and Cp-M rotational barriers are measured by variable temperature NMR spectroscopy. Finally, ethylene polymerizations and ethylene/1-hexene copolymerizations are conducted using C6F5- and C6H5-substituted zirconocene dichlorides as catalysts. Contrary to findings published elsewhere, this study shows that substituent electronic effects induce substantial changes in comonomer incorporation. / Ph. D.

No

Doxorubicin is one of the most effective anti-cancer agents; however its use is associated with adverse cardiac effects, including cardiomyopathy and progressive heart failure. Mitochondrial function and integrity are crucial for cellular processes in general and play an important role during diseased development. These characteristics of the mitochondria make them the prime target for treatments for majority of diseases and in particular of the cardiovascular system. The mitochondria are also considered to play an integral role in the manifestation of the cardiotoxic effects of compounds such as doxorubicin. The current project is designed to investigate the cardiotoxic effects of doxorubicin at tissue, cellular and protein level. In addition, it is investigated whether the inhibition of the mitochondrial permeability transition pore (mPTP) with cyclosporin A (CsA) or the inhibition of mitochondrial fission with the mitochondrial division inhibitor (mdivi-1) protects against the detrimental effects of doxorubicin on cardiac function. We also investigated whether co-treatment of doxorubicin with either CsA or mdivi-1 has any negative interaction with the cytotoxicity of doxorubicin against cancer cells. Langendorff results indicated that doxorubicin caused a time dependent reduction in the haemodynamic function of the heart as well as causing an increase in the infarct size to risk ratio in both naïve conditions and in conditions of ischaemia and reperfusion. Detrimental effects of doxorubicin on cardiac function were abrogated by co-treatment of doxorubicin with CsA or mdivi-1 in naïve conditions and in conditions of ischaemia and reperfusion. Cell viability data of isolated cardiac myocytes revealed that doxorubicin caused a concentration dependant decrease in the viability of neonatal cardiac myocytes as well as causing a reduction in the time taken to depolarisation and hypercontracture under sustained oxidative stress, all of which were prevented when co-treated with either CsA or mdivi-1. Doxorubicin significantly elevated the levels of p-Akt, p-Erk, p-Drp1 and p-p53. Co-treatment with CsA prevented the increase in the levels of p-Akt and p-Erk caused by doxorubicin in both naïve and IR condition whereas mdivi-1 prevented the increase in the levels of p-Erk, p-Drp1 and p-p53 and caused further increase in the levels of p-Akt. Using sinusoidal muscle length change during contraction and relaxation, it is demonstrated that doxorubicin caused a decrease in the power output, peak force and force during shorting. Detrimental effects of doxorubicin on work-loop contraction were abrogated when doxorubicin was co-administered with CsA. To conclude, results demonstrated that doxorubicin caused cardiotoxicity at tissue, cellular and protein level in both naïve conditions and in conditions of ischaemia and reperfusion injury. In addition, it is shown that the inhibition of mitochondrial permeability transition pore with CsA or the inhibition of the mitochondrial fission with mdivi-1 protect against doxorubicin-induced toxicity without affecting its anti-cancer properties.

Historically studies have focused on either the terrestrial or aquatic environments independently. However, these systems are inherently linked through numerous pathways including organisms with complex life cycles. Both abiotic factors and predators of these organisms can influence connections by changing the number of prey moving across habitat boundaries and by changing the phenotype of prey. When the focal organisms are primary consumers, these effects may have important implications for ecosystem processes. My study investigated how terrestrial predators and abiotic factors affect the number and phenotype of herbivorous tadpole inputs into a tropical forest pond. I found that predators and abiotic factors altered survival and timing of hatching and these effects varied temporally. Thus, temporal changes in the relative importance of these threats from abiotic sources and terrestrial predators on prey with complex life cycles may potentially have implications for connections with and food web dynamics in adjacent ecosystems.

Zhu Jian-hui. / "July 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 174-215). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Measuring public opinion on abortion is an ongoing concern for political scientists, mainly because the public does not always exhibit fixed attitudes on such topics. Most citizens express a centrist viewpoint between the pro choice and pro life extremes. These include a small group whose answers to abortion questions are so inconsistent that they give public officials an inaccurate measure of public opinion on this important issue. Inconsistent responses may result from context effects, such as the order in which the questions are asked or the way they are asked. Usually, researchers ask a battery of questions in which respondents say whether they approve of abortion generally and under a variety of circumstances, citing the reasons for which a woman might seek an abortion. This project includes an independent national survey using questions adopted from the General Social Survey. The sample is divided into four experimental groups with different question orders. Based on these findings, the recommended question order would be the one with the general question last and the remaining specific questions in a somewhat random pattern alternating between the so-called “hard” and “easy” individual abortion situations. One of the more surprising findings is that people didn’t recognize themselves as subtracting the specific situations from the general question when it was asked first; hardly any said that was what they were doing when they gave inconsistent answers. Otherwise, about an equal number of respondents admitted answering the questions off the top of their heads as those who showed ambivalence by claiming they were deeply committed to their inconsistent responses. The study found most people who inconsistent on abortion are moderates leaning towards pro choice. Also, politically conservative regular church-goers can be just as inconsistent on abortion as the non-religious, non-political, low-educated non-church goers, especially if they are basically pro choice. Without a full understanding of who is generating inconsistent answers on abortion, some researchers may be tempted to eliminate these respondents from their sample. This research should allow them to understand these respondents better and develop better question wording and question orders to reduce their numbers.

Includes addendum and corrections (leaves 390-402) / Bibliography: leaves 333-389. / xv, 402 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Analyses the effects of N-acetylcysteine (NAC) alone and in combination with glyceryl trinitrate (GTN) on three models of myocardial ischaemia and reperfusion. A sensitive and specific assay for malondialdehyde (MDA) in plasma was developed in order to assess the extent of oxidative stress in this series of studies. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1996

Drug-induced gingival overgrowth is a disfiguring condition that is a side effect encountered in susceptible responder patients common to three groups of drugs - immunosupressants, calcium channel blockers and anticonvulsant agents. The altered overgrown gingiva can be aesthetically displeasing but in severe cases it can cause functional problems and such patients may eventually require excision of excess tissue. The underlying mechanisms that mediate drug-induced gingival overgrowth is uncertain and the various investigations into the pathogenesis of this disease suggest that it is multifactorial. This study investigated the effects of exogenous addition of cycJosporin and amlodipine on the growth and proliferation of human gingival fibroblasts and the production of collagen by these cells. Results showed that these drugs have a direct stimulatory effect on the gingival fibroblasts of responder patients in vitro and there seems to be a synergistic effect between the two drugs. Findings of this study have important relevance as it suggests that fibroblast proliferation and collagen production must play a significant role in the pathogenesis of drug-induced gingival overgrowth. / Dissertation (MSc (Odontology))--University of Pretoria, 2006. / Dental Management Sciences / unrestricted

lsoflurane interacts with cytochrome P-450 in rat and human hepatic microsomes and the Δ6- and Δ5-desaturases in rat hepatic microsomes. The interaction of isoflurane with cytochrome P-450 results in its metabolism to fluoride ion and organofluorine metabolites. The cytochrome P-450 isozymes catalysing the defluorination of isoflurane were assessed in hepatic microsomes from phenobarbital-, β-naphthoflavone- and pregnenolone-16α-carbonitrilepretreated and untreated rats. One or more of the cytochrome P-450 isozymes induced by phenobarbital and pregnenolone-16α-carbonitrile appear to defluorinate isoflurane, but those induced by β-naphthoflavone do not. From a comparison of the extent of defluorination of isoflurane in hepatic microsomes from phenobarbital- and pregnenolone-16α-carbonitrile-pretreated rats, and their Kₘ and Vₘₐₓ values, it appears that isoflurane is defluorinated by one or more isozymes induced by both phenobarbital and pregnenolone-16α-carbonitrile. The major isozyme is probably cytochrome P-450PCN1. The metabolites of isoflurane were identified in human and phenobarbital-induced rat hepatic microsomes. In microsomes from phenobarbital-pretreated rats, isoflurane is metabolised to fluoride ion and trifluoroacetaldehyde; trifluoroacetic acid is not produced in measureable amounts. The trifluoroacetaldehyde produced binds to microsomal constituents. In human hepatic microsomes, the organofluorine metabolite is identified as trifluoroacetic acid. It is proposed that isoflurane is metabolised by different pathways in human and phenobarbital-induced rat hepatic microsomes. The interaction of isoflurane with the cyanide-sensitive factors was assessed by several criteria. Firstly, using the reoxidation of cytochrome b₅ as an index of fatty acid desaturase activity, isoflurane appears to interact with the Δ6- and/or Δ5-desaturases, but not the Δ9-desaturase. Secondly, these results were confirmed and clarified by the use of direct assays to measure the fatty acid desaturase activity. Using the direct assay, we confirmed that isoflurane did not inhibit the Δ9-desaturase and inhibited Δ6-desaturation of linoleic acid, but not the Δ6-desaturation of α-linolenic acid. The inhibition of the Δ6-desaturation of linoleic acid occurred at low millimolar concentrations of isoflurane. lsoflurane inhibits the Δ5-desaturation of eicosa-8, 11, 14-trienoic acid to a small extent which is only apparent at much higher concentrations of isoflurane than that which inhibits the Δ6-desaturase. Further studies focussed on measurement of the activity of Δ6-desaturase in order to attempt to study the kinetics of the inhibition of the Δ6-desaturase by isoflurane: Δ6-desaturase activity was assessed using hepatic microsomes as the source of the enzyme and linoleic acid as substrate precursor. In the course of these studies, we identified a number of factors that affected the apparent activity of the Δ6-desaturase in hepatic microsomes. These included significant levels of endogenous substrate and competing reactions in the hepatic microsomes. Endogenous substrate levels were quantified and corrected for. We then resorted to computer modelling to extract the kinetics of the Δ6-desaturase free of contributions from acyl-CoA synthetase and lysophospholipid acyltransferase, as well as enzyme decay. The kinetics of isoflurane inhibition of the Δ6-desaturase were then superimposed and studied by computer modelling.

No description available.