No description available.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1992. / Vita. Abstract. Includes bibliographical references (leaves 76-78). Also available via the Internet.

Renal papillary necrosis (RPN) and upper urothelial carcinoma (UUC) can both be caused by the long-term abusive consumption of analgesics and non-steroidal anti-inflammatory drugs (NSAID). A "cause-and-effect" relationship between RPN and UUC has been proposed. However, despite a considerable amount of clinical data and experimental evidence this relationship has not been proven nor is it widely accepted. Experimental models of RPN and UUC have been difficult to establish using analgesics and NSAID because of the chronic periods of dosing required with these compounds which frequently have extra-renal toxicities and there is a large biological variation in response. These problems have lead to the use of alternative models using chemicals with known papillotoxic potential such as 2-bromoethanamine (BEA) hydrobromide. This compound will induce a dose related RPN in the rat in 24-48 hr. Studies to determine which was the earliest cellular change occurring as a consequence of BEA-induced RPN were performed in a number of different species (rat, mouse, marmoset and pig), and to determine whether this acute RPN lesion was relevant to the chronic clinical situation in man. High resolution light microscopy using semithin glycolmethacrylate sections in conjunction with routine and enzyme histochemical staining was used throughout these studies to assess the histopathological changes. Comparison with renal tissue obtained from human analgesic abusers was also performed. The results from these investigations show for the first time that the earliest cell type affected, in BEA-induced RPN in the rat and mouse is the medullary interstitial cell in the renal papilla. These cells were also affected in the marmoset and pig where only terminal studies were undertaken. A degenerative cascade results affecting the medulla, cortex (in rats and nude mice) and a pronouced hyperplasia of the urothelium of the pelvis and ureter occurs in the rat and pig. Longterm changes in the rat closely resembled the changes observed in tissues from human analgesic abusers. A series of investigations was performed to try and establish the link between RPN and UUC using the classical 2-stage "initiation-promotion" model for experimental carcinogenesis. A specific urothelial carcinogen N-butyl-N-(4-hydroxybutyl)-nitros-amine (BBN) was used to initiate the urothelium of Wistar rats, followed by an acute BEA-induced RPN. The development of preneoplastic papillary and nodular hyperplasias (within 13 weeks of this regimen) and macroscopic transitional cell tumours in the renal pelvis and upper ureter (at 30-40 weeks) suggests that the localised injury associated with an acute RPN can "promote" an already initiated urothelium to induce pre-neoplastic and neoplastic changes. Studies where single analgesics were superimposed on to this BBN/BEA regimen produced results that suggest that analgesics may exacerbate these RPN related changes to induce more severe pre-neoplastic and neoplastic changes earlier than with BBN/BEA alone. A number of possible mechanisms are discussed the light of the data from these investigations to link RPN and UUC. Peroxidative metabolism of potential carcinogenic compounds seems to be the most likely mechanism although the actual mechanistic process is probably a complex one with a multifactorial basis.

Thesis (Ph. D.)--University of Hawaii at Manoa, 1995. / Includes bibliographical references (leaves 121-123). / Microfiche. / xvii, 123 leaves, bound ill. 29 cm

In wintertime hazy episodes, the air pollution in northern China has always reached to an alarming level. In the winter of 2012-13, the trans-boundary air pollution from China has attracted national and global attention. An elevated public awareness to the unprecedented pollution levels has prompted much investigation on the health effects of fine particulate matter (PM), in particular PM2.5. Since PM-elicited harmful effects primarily depends on the composition of chemical contaminants adsorbed, in this study we characterized the chemical compositions of PM2.5 and determined its associated toxicity. Samples of PM2.5 were collected using high-volume samplers installed in five northern and southern cities in China. One typical (polycyclic aromatic hydrocarbons, PAHs) and one emerging (perfluorinated compounds, PFCs) family of organic pollutants were analyzed using gas chromatographymass spectrometry (GC-MS) or liquid chromatography-MS-MS (LC-MS-MS), followed by in-vitro or/and in vivo studies. In Chapters 2 and 3, sixteen PAH congeners in PM2.5 samples collected from five different cities (Hong Kong (HK), Guangzhou (GZ), Xiamen (XM), Xi’an (XA) and Beijing (BJ)) in the winter and summer time 2012-13 was analyzed. The biological effects of the sample extracts were determined using the human bronchial epithelial cells BEAS-2B. The total PAH concentrations ranged from 3.35 to 80.45 ng/m3 air, leading by BJ, followed by XA, XM, GZ and HK. In a comparison of the physical and chemical data of the samples obtained during the winter and summer sampling periods, the amount of PM collected per unit time and the concentrations of PAHs adsorbed were found to be remarkably greater in the winter time. In the cell culture study, the expression levels of the pro-inflammatory cytokine (interleukin-6, IL-6) and detoxifying enzymes (i.e. cytochrome p450 enzymes, CYP1A1 and CYP1B1) were found to be stimulated in the treatment. The cells exposed to sample extracts prepared from XA and BJ demonstrated significant migratory activities, indicating a sign of increase of tumorigenicity. These data highlighted the risk of getting lung cancer in local population. In chapters 4 and 5, we focused on the emerging pollutants PFCs, in particular PFOS. Chemical characterization was implemented using the winter samples. Biological effects of PFOS were conducted using omics approach in a maternal-fetal model. Therefore, in the first part of chapter 4, we measured the concentrations of nine PFC congeners in PM2.5 samples using LC-MS-MS. Generally, the eight PFCs, namely PFOS, PFDoA, PFUdA, PFDA, PFNA, PFOA, PFHxA and PFBA were detected in all the sampling cities, with the exception PFHxS which was below the limit of detection. The total PFC concentrations ranged from 121.2 to 192.2pg/m3, leading by GZ, followed by XA, BJ, XM and HK. The data denoted the risk of inhalation exposure to PFCs through PM2.5, which enter into blood circulations via lung alveoli, presumably penetrates through placenta in affecting fetal health. Therefore, in the latter part of chapter 4, the potential adverse effect of prenatal exposure to the prototypical PFC congener PFOS was used in the maternal-fetal mouse model to determine its effects on fetal liver and pancreas. Transcriptomic analysis demonstrated that the in-utero exposure to PFOS affect the expression of genes associated with fatty acid metabolism, lipid transport, and steroid synthesis in fetal livers. KEGG pathway analysis showed these changes were primarily associated with modulations of arachidonic, linoleic acid, retinol metabolism and PPAR signaling pathways in fetal liver. To identify additional target fetal tissue of PFOS, in chapter 5, we investigated the effects of PFOS on the protein expression in fetal pancreas using the technique of “Isobaric tags for relative and absolute quantitation (iTRAQ). We identified changes in the protein expressions involved in pancreatic secretion, protein digestion and absorption, protein processing in endoplasmic reticulum, fat digestion and absorption, glycerolipid metabolism and steroid biosynthesis. The perturbations to these targets may increase the risk of pancreatitis in mouse offspring. Collectively, this study provided a comprehensive chemical and biological analysis of PM2.5 collected in China and demonstrated the toxicities, in vitro and in vivo of the adsorbed chemical contaminants.

No description available.

Thesis (Ph. D.)--University of Rhode Island, 2005. / Typescript. Includes bibliographical references (leaves 120-131).

A análise de fluidos biológicos para detecção de usuários de Cannabis não é rotina em nossos serviços de toxicologia forense pela falta de um método aplicável às condições de trabalho desses laboratórios. Neste trabalho foi estudado um método que utiliza a cromatografia de camada delgada de alta eficiência (CCDAE) como técnica de identificação. Cinco mililitros de urina são submetidos à hidrólise alcalina e à extração Iíquido/líquido, com posterior aplicação do resíduo obtido na cromatoplaca. O limite de detecção em estudo realizado com adicionados foi de 5ng/ml. Urina de usuários de Cannabis quando submetidas a esta metodologia apresentaram resultado semelhante ao do padrão de THCCOOH, principal produto de biotransformação do THC. As amostras utilizadas como branco de referência não apresentaram mancha semelhante. Na análise das amostras de usuários por imunoensaio de fluorescência polarizada (\"cutoff\' 50ng/ml) obteve-se resultado negativo para usuários moderados e ocasionais. Com auxilio de curva-padrão observou-se que a concentração provável de canabinóides nessas amostras estaria entre 20-50ng/ml. No estudo comparativo dos resultados obtidos nas duas técnicas, foi verificada uma correspondência de 100% para as amostras de usuários com padrão de uso intenso. Nos usuários moderados e ocasionais não foi observada boa correspondência entre os resultados. / Abstract not available.

The effects of controlled atmosphere on the metabolism of Golden Delicious and Rome Beauty apples, Anjou pears, and Lambert and Bing cherries were studied with respect to changes caused in the normal metabolic functions carried on during storage of these fruits. Atmospheres consisting of 1.5 per cent CO2 and 2.5 per cent O2 for the apples and pears and 10.5 per cent CO2 and 2.5 per cent O2 for the cherries were employed. Fungi of the strains Botrytis alli, Rhizopus nigricans, and Penicillium expansum were subjected to controlled atmospheres at 21° C to determine the toxic effect of CA. The fungi were grown on agar plates instead of fruit to prevent bias, such as condition of the fruit. Periodically, fruit was taken directly from the storage treatments and analyzed for CO2 evolution, for total and reducing sugars, organic acids, amino acids, and cytochrome c oxidase. Fruits were also taken from the storage treatments and held for a specific time at 15° C before analysis. The CA used in this experiment had an inhibitory effect on the fungi that were used. Botrytis alli and Penicillium expansum were particularly susceptible. It was found the height of the mycelial mat was less, the mycelium growth was less, and while sporulation was not eliminated, it was severely retarded. Combinations of CA and lowered temperatures should attain a high degree of fungal control. The results showed that CA had an inhibitory effect on the metabolic system of stored fruits. The specific areas of metabolic inhibition are not known exactly. This inhibition does not appear to be of a permanent nature as shown by the post storage analysis. Any differences that occurred in the CA stored fruit as contrasted to the fruit from the conventional stored fruit appeared to be able to correct themselves once they were removed from the CA.

Bibliography: leaves 129-146. / ix, 146 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The studies described in this thesis are concerned with the release, diffusion through dentine, local pharmacology and local toxicology of active components of materials which are applied to teeth with therapeutic intent. The method of study of zinc oxide-eugenol (ZOE) release is combined with test methods for cytotoxicity in vitro to give a new model system for the prediction of pulpal toxicity of restorative materials where the potential toxins might be unknown. / Thesis (D.D.S.)--University of Adelaide, Dept. of Dentistry, 1990