Abstract Salinity has considerable adverse effects on agriculture through reduction in plant growth and water use. Sodium chloride salinity has both an osmotic effect on plant water relations, and a toxic effect on cellular processes. The relative contribution of these two effects to plant growth depends on a range of factors including plant specific tolerance mechanisms, such as Na and Cl exclusion, compartmentation of ions at a whole plant and cellular level, and synthesis of organic osmotic compounds for plant osmotic adjustment. Plants growing in saline soil would also experience reduced plant available water, due to the additional osmotic effect on soil water potential. The effect of salinity on plant growth is further complicated by the interactions of environmental conditions with plant water and ion uptake. This thesis examines the osmotic and toxic effects of salinity on wheat (Triticum aestivum L.) and chickpea (Cicer arietinum L.), with particular focus on plant water availability, effects of Na and Cl toxicity, and temperature and humidity effects. While considerable research has been undertaken into the physiological response of plants to NaCl, our understanding of the capacity of plants to extract water from saline soils has remained largely theoretical. Total plant available water is largely determined by the matric potential of the soil. Presence of sodium chloride would have an additional osmotic effect, and previous theory stated that the salt tolerance of the plant determined the extent to which this osmotic potential reduced plant available water. The capacity of wheat and chickpea to extract water from saline soils was examined in a soil experiment where water stress was imposed on established plants, which were then grown until permanent wilting point (PWP) was reached. Wheat extracted to lower soil water potentials (-1.5 MPa), than chickpea (-900 kPa) in 0 NaCl treatments. Where salinity was low to moderate, plants were able to extract water to a PWP determined by the combined total of matric and osmotic potentials. Wheat extracted water to PWP in salinity treatments up to soil ECse of 5.3 dS/m, and chickpea to 2.9 dS/m. As salinity increased, toxic effects of salinity dominated, and water extraction by plants was significantly lower than that determined by total soil water potential. Solution culture experiments investigated the comparative toxic effects of Na, Cl and salt mixtures. Growth of wheat was reduced by Na toxicity, but not Cl toxicity, with Na causing a small, but significant additional reduction in growth, compared to high Cl or a salt mixture. Reductions in growth of 50% from control treatments occurred at -500 kPa for the Na treatment, and -630 kPa for the Cl and mixed salt treatments. In contrast, growth of chickpea was significantly reduced by both Na and Cl toxicity, with a large difference in growth compared to the salt mixture. Growth reductions of 50% occurred at -330 kPa for the Cl treatments, and -450 kPa for the Na treatment. A 50% growth reduction was not observed in the mixed salt treatment. Tolerance of saline conditions is reduced under stressful environmental conditions, such as high temperature and low relative humidity. Hot and dry conditions were shown to reduce the tolerance of saline conditions by both wheat and chickpea, compared to cool or humid conditions. Tissue concentrations of Na in wheat were disproportionately high in treatments with high evaporative demand, while tissue Cl was not related to evaporative demand. Tissue concentrations of Na in chickpea increased with temperature, but not relative humidity, while tissue Cl concentrations were highly correlated with evaporative demand. The relationships between NaCl salinity, plant water use, and environmental conditions were examined, allowing further development of the two phase salinity model. In particular, the transition point between the osmotic and toxic salinity effects. While the concentration of NaCl in the soil remains the primary factor, soil water status, environmental stresses and presence of other salts may dictate whether salinity be tolerated by the plant or not. The ability of the plant to extract water to PWP, as determined by total matric and osmotic potential has been identified as a useful indicator of salinity tolerance. The point at which toxicity of Na and/or Cl is observed is associated with a rapid increase in Na and Cl uptake by the shoot tissue, and a decrease in the amount of water the plant is able to extract from the soil. Within the osmotic region of salinity stress, the plant is able to extract water to PWP, but as NaCl becomes toxic the plant is unable to utilize this water.

The presence of complex mixtures of compounds in ambient air, many of which are either unknown or uncharacterised makes an assessment of risk associated with these exposures problematic. Bioanalytical methods can provide an integrative assessment of complex mixture potency for specific mechanisms of toxicity within these contexts. The aim of this study was to evaluate the suitability of monitoring ambient air exposures as sampled by (polyurethane foam) PUF passive air samplers (PAS) using effect based techniques (bioanalytical methods). Passive samplers have the advantage of offering a low-tech inexpensive monitoring strategy which can thereby increase sampling capacity across a broader range of scenarios simultaneously. One challenge posed by the application of passive samplers in particular for these assessments has been the expression of potency estimates in relatively non-comparable terms specific to a given dose of the sampler or for a specific deployment period. The project was therefore designed in order to address these aims and previously identified challenges by investigating the applicability of these techniques for: monitoring in both indoor and outdoor air, the determination of seasonal exposure gradients; the determination of exposure gradients in different locations (urban capitals, regional centres, background); and the application of in-situ calibration to provide comparable effect measurements in terms of equivalent reference compound air concentrations. Air sampled using PUF PAS was monitored for its capacity to induce biological responses which are mechanistically relevant to critical health endpoints in these scenarios. The mechanisms assessed included genotoxicity (DNA damage – umuC assay), Aryl hydrocarbon receptor (AhR) activity (CAFLUX assay), and estrogenicity (ESCREEN assay). The findings from this effect based monitoring revealed that the level of biological response measured changes with the exposure scenario (indoor vs. outdoor; summer vs. winter; urban capital cities vs. background locations). Estrogenicity for example assessed as estradiol equivalent air concentrations (E Eq BIO) averaged 54 pg.m-3 (1.5 - 185 pg.m-3) in indoor air, while samples from ambient air were found to be not estrogenic. Total aryl hydrocarbon receptor (AhR) activity assessed as 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent air concentrations (TCDD Eq BIO) averaged 4.1 pg.m-3 (1.3 – 7.2 pg.m-3) in indoor air while samples from ambient air averaged 15 pg.m-3 (1.5 – 46 pg.m-3)in summer and 53 pg.m-3 (2.2 – 251 pg.m-3) in winter. The relationship for both direct (-S9) and indirect (+S9) acting genotoxicity and AhR activity were found to be relatively consistent with respect to both season (elevated in winter) and location (elevated in urban capital cities). Overall suitable techniques were developed for combining passive sampling with multiple end-point toxicity testing and it was demonstrated that these techniques may be applied across different exposure scenarios. During the course of this method development and interpretation process a range of limitations were identified relating to: the use and application of effect based techniques to monitor environmental samples; the use of passive samplers within this context specifically; and also with the application of in-situ calibration techniques to passive samplers to improve the comparability of these assessments.

No description available.

Mucositis manifesting as diarrhoea is a common side effect of chemotherapy which remains poorly understood. It is one of a number of manifestations of alimentary mucositis, which affects the entire gastrointestinal tract. The exact number of patients that are affected by diarrhoea as a result of treatment is uncertain, although it is believed that approximately 10% of patients with advanced cancer will be afflicted. Despite advances in the understanding of oral and small intestinal mucositis over recent years, large intestinal mucositis, including diarrhoea, has not been well defined and the underlying mechanisms of the condition are yet to be established. The majority of the literature available concerning diarrhoea is based on clinical observations, with very little basic research existing. However, from the research conducted, it is likely that the intestinal microflora and mucins play a role in the development of chemotherapy-induced diarrhoea. This thesis will examine in detail what is known about the mechanisms of chemotherapy-induced diarrhoea (CID). Furthermore it will explore the potentially important relationship between intestinal microflora, the luminal environment and the subsequent development of chemotherapy-induced mucositis and diarrhoea. 5-Fluorouracil (5-FU) is a commonly used chemotherapy agent in clinical oncology practice. Two of its major side effects are mucositis and diarrhoea. The structure of mucins offers mucosal protection, and allows maintenance of intestinal flora by providing attachment sites and preventing bacterial overgrowth and/or penetration. Following treatment with 5-FU, we showed decreases in Clostridium spp., Lactobacillus spp. and Streptococcus spp., and an increase in Escherichia spp. in the jejunum. In the colon, 5-FU caused decreases in Enterococcus spp., Lactobacillus spp. and Streptococcus spp. Real time PCR of faecal samples showed decreasing trends in Lactobacillus spp. and Bacteroides spp., and an increasing trend in E. coli. Significant increases (p<0.05) were seen in Clostridium spp. and Staphylococcus spp. at 24 h. Goblet cell numbers decreased significantly in the jejunum from 24-72 h, with a significant increase in the percentage of cavitated goblet cells, suggesting 5-FU treatment causes significant changes in intestinal flora and mucin secretion in rats. These changes could result in systemic effects, and in particular may contribute to the development of chemotherapy-induced mucositis. Irinotecan causes cholinergic and delayed onset diarrhoea in patients, in which β-glucuronidase produced by gut bacteria is thought to be involved. Diarrhoea was observed in treated rats, as expected, following irinotecan treatment. β-glucuronidase expression increased in the jejunum and colon. Faecal flora changed quantitatively after treatment also, with increases in E. coli, Staphylococcus spp., and Clostridium spp. (all β-glucuronidase producing), and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (β-glucuronidase producing, major component of intestinal flora), suggesting that irinotecan-induced diarrhoea may be caused by an increase in β-glucuronidase producing bacteria. However, the increase in bacteria may also be caused by irinotecan, further exaggerating the toxicity of the drug, and emphasising the need for these specific bacteria to be therapeutically targeted for successful treatment regimens to be accomplished. Mucus production appears to be increased after irinotecan treatment, which may contribute to the development of diarrhoea. Goblet cells were demonstrated to decrease significantly after irinotecan treatment. However, mucin secretion increased. Mucin expression changed significantly after treatment. Muc2 and Muc4 decreased significantly in the villi of the jejunum after treatment, Muc2 and Muc4 decreased significantly in the crypts. Muc2 decreased significantly in the colon. This indicates that irinotecan causes an increase in mucin secretion and a net decrease in mucin-producing goblet cells, and the expression of Muc2 and Muc4 in the gastrointestinal tract is altered following treatment. Increased mucin secretion is likely to be related to altered mucin expression, and may contribute to chemotherapy-induced diarrhoea. To determine if the changes to the intestinal microflora caused by chemotherapy could be translated to the clinic, a pilot clinical study was carried out. Sixteen patients experiencing CID were recruited to the study with two control subjects. A large proportion of patients (75%) demonstrated a reduced anaerobic component of their faecal microflora. A reduced diversity of species was also observed in patients. The majority of patients exhibited decreases in Clostridium spp., Lactobacillus spp. and Bifidobacterium spp., whilst all patients exhibited decreases in Bacteroides spp. and Enterococcus spp. Patients receiving antibiotics did not exhibit any marked differences to patients not receiving antibiotics. This indicates that the results observed in the animal studies are clinically relevant, and further research into this area should be undertaken. CID is associated with marked changes in the intestinal microflora. These changes may result in diminished bacterial functions within the gut, altering gut function and initiating intestinal damage, resulting in the onset of diarrhoea. In conclusion, there is clear evidence demonstrating chemotherapy treatment results in changes to the intestinal microflora and mucin secretion, which may be responsible in part for the development of severe mucositis and diarrhoea. Irinotecan toxicity may be compounded by the increase in β-glucuronidase producing bacteria. The intestinal flora of cancer patients experiencing CID is also noticeably different to that of healthy subjects. Irinotecan causes changes to mucin secretion, and the specific expression of Muc2, Muc4 and Klf4, suggesting that secretory control by the enteric nervous system may also be affected by chemotherapy. This research has extended the understanding of chemotherapy-induced mucositis and diarrhoea, complex side effects of chemotherapy. However, new areas for future research have also been identified. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352119 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2009

Diss. (sammanfattning) Sundsvall : Mittuniversitetet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2007. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2006. / Härtill 4 uppsatser.