Clinical hyperthermia refers to treatment of tumors by heating the lesions between 40 and 45° C. Several clinical trials have demonstrated that hyperthermia provides significant improvements in clinical outcomes for a variety of tumors, especially when combined with radiotherapy. However, its routine clinical application is still not optimal and major improvements are needed. The temperature distributions achieved are far from satisfactory and improved temperature control and monitoring are still in need of further development. The use of gold nanoparticles (GNPs) has emerged as a good method to achieve local heat delivery when combined with near-infrared (NIR) laser. GNPs have a plasmon resonance frequency that can be tuned to absorb strongly in the NIR region where tissue absorption of laser light is minimal, allowing for less tissue heating and better penetration. For further development of the technique and appropriate clinical translation, it is essential to have a computational method by which the temperature distribution within the tumor and surrounding tissue can be estimated. Previously, our group developed a technique to estimate the temperature increase in a GNP-filled medium, by taking into account the heat generated from individual GNPs. This method involved a two-step approach combining the temperature rise due to GNPs and the solution to the heat equation using the laser light as heat source. The goal of this project was to develop a one-step approach that calculates the temperature distribution using the solution to the heat equation with multiple heat source terms, the laser light, and each individual GNP. This new method can be of great use in developing a treatment planning technique for GNP-mediated thermal therapy including hyperthermia.

This investigation examined the influence of two levels of dietary sodium (Na+) intake on intramuscular and extracellular potassium (K+) content. Nine unacclimatized college males exercised. (90 minutes of treadmill walking, 5.6km/hr, 6X grade) in an environmental chamber maintained at 40.1( + .05)°C and 23.5( + . 4) %RH, during two 8-day dietary-acclimation regimens. The first regimen employed a high Na+ diet (399mEq/day), the second a low Na+ diet (98mEq/day); both diets contained 80mEq K+/day. Total body K+ stores increased during the high Na+ diet (+138mEq, 4.1%) and the-low Na+ diet (+114mEq, 3.4%). By day 8 (D8) of both treatments, subjects exhibited a significantly lower (p<.O5) mean heart rate and rectal temperature. Oxygen consumption and sweat rate were unaltered but sweat responsiveness (ml/hr/°c) progressively increased during the acclimation trials. Plasma volume increased +16.3% (D4) and +10.7% (D8) under the high Na+ diet and only +3.0% (D4) and +7.0% (D8) under the low Na+ diet. The low sodium diet was associated with a significantly higher (p<.05) mean heart rate (D3-D5), higher rectal temperature (D3-D6), lower sweat responsiveness (D2) and a delayed plasma volume expansion (D4)--resulting in less effective heat removal. The total content of K+, Na+, and C1- in plasma changed isoosmotically with plasma volume. The diets were associated with equivalent urine K+ excretion, and. during exercise in the heat both diets resulted in significantly decreased urine K+ losses. Muscle K+ and sweat K+ concentrations were not altered by dietary intervention or acclimation trials. Total muscle water-was significantly increased, in accord with Na+ and Cl- increases, on D8 of the low Na+ diet only. It was concluded that dietary intake of Na+, in combination with 8 days. of exercise in the heat and heavy sweating, does not significantly diminish the intramuscular K+ or total body K+ content.

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No description available.

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Endotoxins or lipopolysaccharides (LPS), highly toxic component of the outer membrane of gram-negative bacteria, are normally present in the mammalian gut lumen.In this thesis, I investigated, in laboratory animals, whether these gut-derived endotoxins play a role in pathophysiology resulting from intestinal dysfunctions caused by intestinal ischaemia and heat-stress.In primates, reperfusion of the splanchnic region after a temporary ischaemia was followed by a rapid increase in LPS concentration, first in the hepatic portal plasma and, ten minutes later, in the systemic arterial plasma. Rises in plasma LPS concentrations during or following the temporary intestinal ischaemia was prevented by prophylactic administrations of corticosteroids, anti-LPS IgG antibodies and oral, non-absorpable, antibiotics agents which appear to stabilize cellular membranes, aid the reticuloendothelial system in removal of LPS from the circulation and destroy the intestinal aerobic gramnegative bacteria respectively. In addition, administration of therapeutic anti-LPS antibodies also rapidly reduced the plasma LPS concentrations to baseline during an endotoxaemia. In a control heat-stress model, elevations in plasma LPS concentration commenced at rectal temperatures greater than 41,SoC. Like the intestinal ischaemia model, this occurred first in the hepatic portal plasma, and 10-15 minutes later, in the systemic arterial plasma. Peak plasma LPS levels of about 0,3 ng/ml, measured in heat-stressed primates, have proved in previous studies, to be toxic. A rapid decline in mean arterial pressure was followed by increases in plasma LPS concentrations and heart rates. Reductions in splanchnic blood flow and consequent local ischaemia coupled with thermal injury to the intestinal wall and the liver, may have permitted rises in plasma LPS concentration. Furthermore, as in the ischaemia model, prophylactic administrations of corticosteroids, anti-LPS IgG antibodies, and oral, nonabsorbable antibiotics prevented a rise in plasma LPS concentration. Of importance, prophylaxis with intravenous corticosteroids and 'anti-LPS IgG antibodies increased the survival rates significantly in heat stroke in primates. In addition, monkeys having high titres of "natural" antiLPS IgG antibodies had lower plasma LPS concentrations and survived the induced-heat stroke. It is suggested that other pathophysiologic conditions which compromise the integrity of the gut wall would also lead to the development of an endotoxaemia, and that gutderived endotoxins contribute to the athogenesis of heat stroke and treatments with corticosteroids and anti-LPS IgG antibodies may prove beneficial in other endotoxinrelated disorders. / Thesis (Ph.D.)-University of Natal, Durban, 1988.

Cultured tobacco cells (Nicotiana tabacum L., cv Wisconsin-38) were subjected to temporary sub-lethal heat and salt shock treatments to determine the effects of these treatments on various physiological parameters after subsequent lethal heat or salt stresses. Tobacco cells developed a tolerance to a non-permissive temperature stress (54C for 14 min) when pretreated with heat shock of 38C for 2h but not when pretreated at 42C for 2h. Cells pretreated at 38 (2h) exhibited less than 30% normal growth when the 54C stress came immediately after the 38C treatment. Tolerance to the 54C stress developed with increased interval between shock and stress with cells exhibiting 95% normal regrowth when the 54C stress was administered 8h after the 38C shock. The developement of heat tolerance was inhibited if heat shock was done in the presence of a non-injuring level of EGTA (.0.5mM). Cells treated with EGTA during heat shock grew normally at 23C but not after a 54C heat stress. EDTA (0.5mM) had little effect on the acquisition of tolerance to heat stress.Wisconsin-38 cells developed a tolerance to a non-permissive salt stress (2% NaCl for 16h) when pretreated at a lower salt level (1.2% NaCl) for 3h. Cells heat shocked at 38C exhibited increased tolerance of the lethal salt stress up to 8h. Conversely, cells heat shocked at 42C exhibited immediate tolerance to lethal salt stress and this tolerance decayed over eight hours. The heat shock-induced acquisition of salt tolerance was inhibited by both EGTA and EDTA.Proteins synthesized during heat and salt stress treatments were labeled with [35S]-methionine and/or [3H]-leucine and separated using Sodium dodecylsulfate polyacrylamide gel electrophoresis. Fluorographic analysis of the gels indicate that a number of proteins are produced in response to heat shock. Similar analysis of proteins from salt shocked cells indicates that no salt shock proteins are produced in response to a brief low-level sodium chloride shock.

While a great deal of research has been directed towards the phenomena of excess post exercise oxygen consumption (EPOC), the effect of thermal stress on EPOC is not well defined. To assess the effect of heat stress on EPOC, seven healthy, active subjects (4 female, 3 male; 23.9 ± 2.0 years of age) performed 4 trials: one control (quiet rest) and one exercise (45 minutes of cycling at 65% VO2max workload) trial in moderate (23° C, 50% humidity) and hot (35° C, 50% humidity) environments. Oxygen consumption (V02), heart rate (HR) and rectal temperature (RT) were assessed pre, during and post control or exercise. Subjects were monitored until post exercise VO2 had returned to within ±2% of baseline. EPOC was determined by subtracting baseline VO2 from total V02 during the post exercise period. During the first 15 minutes (acute) post exercise, a significant EPOC (p = 0.0019) was seen in both exercise conditions over both control conditions. During the slow phase (> 15 minutes post exercise to baseline), there was no significant difference between the hot control (HC), moderate exercise (ME), or hot exercise (HE) EPOC. Total time post exercise until baseline was achieved was 35, 44, and 51 minutes for HC, ME, and HE respectively. HR was significantly elevated in both exercise conditions. During the acute post exercise period, HR in HE was elevated above MC, ME and HC (p < 0.05). RT was elevated in both exercise conditions during and post exercise. The present data indicate that heat stress does not have a significant effect on the magnitude or duration of EPOC. / School of Physical Education

The effect of heat acclimatization on aerobic exercise tolerance in the heat, and on subsequent anaerobic exercise performance was investigated. Ten male subjects were acclimatized by exercising 90 minutes per day for eight days in the heat (39.7 C db, 31.0% RH) on a bicycle ergometer at a workload corresponding to 54% of V02 max. Prior to, and following heat acclimatization, the subjects performed six hours of intermittent, submaximal (50% V02 max) exercise in the heat (HET). A 45 sec maximal bicycle ride was performed before (sprint 1) and after (sprint 2) each HET. Mean ( ± SE) resting plasma volume was higher (+9.2 + 1.7%) in acclimatized subjects (ACC) compared with unacclimatized (UN) subjects (P<0.001). Acclimatization resulted in reductions in the mean exercise heart rate (160 + 3 vs. 144 ± 3, P<0.001) and mean rectal temperature (38.13 + 0.08 vs 37.91 + 0.05, P<0.01). Muscle glycogen utilization during the HET was greater in the UN trial (57.4 + 5.1 mmol/kg) than the ACC trial (28.6 + 6.4 mmol/kg, P<0.05). No differences were noted between the UN and ACC trials with respect to blood glucose, lactate (LA), or respiratory exchange ratio during the HET. Total work output during sprint 2 was reduced compared with sprint 1 in the UN trial (24.01 ± 0.80 vs. 21.56 + 1.18 kJ, P<0.05). Post exercise muscle pH was significantly (P<0.05) higher following sprint 2 (6.86) than sprint 1 (6.67) in the UN trial. Associated with this reduction in anaerobic exercise performance, an attenuated accumulation of LA and fall in pH was noted in the blood. No differences between sprints 1 and 2 were observed for the ACC trial in total work, musce pH, or blood LA. As a result of sprint exercise in both UN and ACC trials, a decrease in muscle potassium (K+) was noted (P<0.05), which was accompanied by a 0.8 to 2.2 mmol/l increase in antecubital venous blood K+. Following sprint exercise, serum K+ was below pre sprint values for up to 15 minutes, suggesting a rapid and accelerated uptake of K+.These data indicate that eight days of heat acclimatization produced a shift in fuel selection during submaximal exercise in the heat through an enhanced delivery of blood borne substrate. The observed muscle glycogen sparing during submaximal exercise may be associated with the enhanced ability to maintain high levels of anaerobic energy release and performance of highly intense exercise following prolonged exertion in the heat.

Exposure of broiler cockerels to between 35.0 to 37.8 C for 24 hr at 5 days of age increases their survival when exposed to a heat challenge at 6 weeks of age (35.0-37.8 C; RH 50% ). This' phenomenon does not resemble acclimation since the physiological changes known to occur in acclimated birds exposed to heat have not been observed in the neonatally stressed birds. A series of experiments were conducted to elucidate the mechanisms of neonatally induced thermotolerance. In Experiment 1, the erythrocyte protein profile of control and 5 days heated birds prior to and during exposure to acute heat were determined. Prior to juvenile heat exposure no differences in the erythrocytic protein profile of neonatally stressed and control birds were observed at any age (10, 17, 24, 31 and 38 days of age) when maintained under control conditions. However, upon exposure to an acute heat challenge (40.5 C; 52 days of age) temporal and differential expressions of proteins similar in molecular weight to heat shock proteins (HSPs) were observed between the neonatally stressed and control birds. In Experiment 2, the effects of neonatal heat stress at various ages (5, 8, 12, 16 days of age) on the protein synthesis profile of heart, brain (telencephalon, diencephalon, brain stem, cerebellum) and liver tissues during exposure to an acute heat challenge were studied. In addition, body temperature during neonatal heat exposure was monitored. A significant increase in body temperature was observed during neonatal heat stress. A steady increase in the magnitude of the temperature change was noticed up to 12 days of age. Body temperature of birds exposed to neonatal heat at 16 days of age was similar to that of birds heated at 5 days of age. / Ph. D.