Type 1 diabetes mellitus affects millions of people worldwide. Islet transplantation is a minimal invasive surgical procedure that restores euglycemia and halts the progression of diabetic complications. However, despite transplantation of islets from multiple donors most patients reverse to hyperglycemia within five years. New strategies to improve long-term outcome of islet transplantation are indispensable. This thesis studied differences in the microvasculature between endogenous and transplanted pancreatic islets, and investigated means to improve islet graft revascularization and function. Islet graft microvessels were similar to endogenous islets responsive to adenosine, angiotensin II and nitric oxide (NO). Recipient hyperglycemia induced a higher basal islet graft blood flow, which also was less dependent on NO than in normoglycemic recipients. Transplantation of freshly isolated instead of cultured islets improved graft revascularization, oxygenation and function. Pretreatment of islets with vascular endothelial growth factor decreased their expression of matrix metalloproteinase-9 (MMP-9) and impaired graft revascularization. Moreover, MMP-9 pretreatment per se improved graft revascularization. In vivo, 20-25% of all endogenous rat islets was low oxygenated (pO2 <10 mmHg). Changes in the islet mass, by means of whole-pancreas transplantation, doubled the fraction of low oxygenated islets in the endogenous pancreas of transplanted animals, whereas this fraction almost completely disappeared after a 60% partial pancreatectomy. Interestingly, oxygenation was related to metabolism, since well oxygenated islets in vivo had 50% higher leucine-dependent protein biosynthesis, which includes (pro)insulin biosynthesis. In intraportally transplanted islets, the low oxygenated fraction of islets was markedly increased one day post-transplantation, and the oxygenation remained low following revascularization. In summary, these data suggest that a better revascularization of transplanted islets can improve graft function. Furthermore, the oxygenation and metabolism of endogenous islets is tightly regulated. This regulation seems to be disturbed following transplantation, which may contribute to long-term islet graft failure.

Stress and monotonous work contribute substantially to the development of chronic musculoskeletal disorders. Yet, the pathophysiological mechanisms underlying the process, particularly the involvement of autonomic regulation, remain unclear. It has been suggested that altered motor control resulting from distorted sensory information from fatigued muscles may be an important component in the development of musculoskeletal disorders. Animal studies have shown that sympathetic nervous system activation exerts actions in skeletal muscles, such as vasoconstriction and modulation of afferent information from muscle spindles. However, few attempts have been made to address this issue in humans. Therefore, the first aim of the thesis was to investigate the impact of repetitive computer work with and without additional stressors on muscle oxygenation and position sense in the upper extremity. Assuming an important role of stress in the development of chronic musculoskeletal symptoms, one may expect open or latent manifestations of such symptoms in patients with non-specific stress-related illnesses. It is possible that sympathetic activation may influence pain perception, and that treatments aimed at reducing stress may also affect the pain experience. Thus, the second aim of the thesis was to evaluate the effects of a cognitive-behavioral training program and a physical activity program for patients with stress-related illnesses on autonomic reactivity, pain, and perceived health. First, a laboratory model of computer mouse use was characterized in terms of biomechanical exposure of the wrist, and wrist position sense was determined before and after 45 minutes of continuous mouse use. Then, the effects of performing the computer mouse work under time pressure and precision demands were determined. Autonomic activity and muscle oxygenation in the upper extremity were measured during the work, and wrist position sense was assessed before and after the work. When patients with stress-related illnesses were compared to healthy individuals in autonomic reactivity to functional tests, pressure-pain thresholds, and ratings of health, indications of a relation between autonomic reactivity and symptoms of pain was found. Hence, in a subsequent evaluation of a cognitive-behavioral training program and a physical activity program for patients with stress-related illnesses, post intervention effects on autonomic reactivity to functional tests, pressure-pain thresholds, ratings of health and return-to-work were studied during a period of 12 months after the intervention. The main findings were the following. 1) Wrist kinetics data obtained during the computer mouse work showed similarities to previously presented data for mouse-operated design tasks. 2) When time pressure and precision demands were added to the computer work, increased autonomic activity paralleled with decreased muscle oxygenation in the upper extremity was found. Wrist position sense accuracy, however, did not decrease after the work as it did when the work was performed without the additional demands. The result is intriguing, as it does not appear to be in concordance with previous animal studies. 3) Patients with stress-related illnesses showed higher autonomic reactivity to cognitive and physical laboratory tests than healthy control subjects. They also had substantially lower pressure-pain thresholds in the back, and rated poorer health and health-related behavior than the control subjects. 4) We found little difference in effect of cognitive-behavioral training and physical activity, compared to usual care, for patients with stress-related illnesses. Patients in the control group showed an improvement of about the same magnitude as in the treatment groups over the 12-month follow-up period. The present findings indicate a non-additive relation between autonomic activity during repetitive work and position sense inaccuracy. Furthermore, patients with stress-related illnesses often reported pain in the neck, shoulders, and lower back. This was associated with lower pressure-pain thresholds in the back and a modest increase in sympathetic reactivity to physical and mental tests, which might suggest a potential use of these methods in the clinical examination and rehabilitation of patients with stress-related illnesses.

Background: Breathing exercises are widely used after cardiac surgery. The duration of exercises in the immediate postoperative period is not fully evaluated and only limited data regarding the effects of home-based breathing exercises after discharge from hospital have been published. Aim: The overall aim of this thesis was to evaluate the effects of deep breathing exercises with positive expiratory pressure (PEP) and describe lung function and respiratory muscle strength in patients undergoing cardiac surgery. Participants and settings: Adult participants (n=131) were randomised to perform either 30 or 10 deep breaths with PEP per hour during the first postoperative days (Study I): the main outcome was oxygenation, assessed by arterial blood gases, on the second postoperative day. In Study III, 313 adult participants were randomly assigned to perform home-based deep breathing exercises with PEP for two months after surgery or not to perform breathing exercises with PEP after the fourth to fifth postoperative day. The main outcome was lung function, assessed by spirometry, two months after surgery. Studies II and IV were descriptive and correlative and investigated pre and postoperative lung function, assessed by spirometry, and respiratory muscle strength, assessed by maximal inspiratory pressure, and maximal expiratory pressure. Results: On the second postoperative day, arterial oxygen tension (PaO2) and arterial oxygen saturation (SaO2) was higher in the group randomised to 30 deep breaths with PEP hourly. There was no improved recovery of lung function in participants performing home-based deep breathing exercises two months after cardiac surgery, compared to a control group. Subjective experience of breathing or improvement in patient perceived quality of recovery or health-related quality of life did not differ between the groups at two months. Lung function and respiratory muscle strength were in accordance with predicted values before surgery. A 50% reduction in lung function was shown on the second postoperative day. High body mass index, male gender and sternal pain were associated with decreased lung function on the second postoperative day. Two months postoperatively, there was decreased lung function, but respiratory muscle strength had almost recovered to preoperative values. / <p></p><p></p>

La transplantation d’îlots de Langerhans microencapsulés est un traitement prometteur du diabète de type 1. La microcapsule protège l’îlot du système immunitaire, tout en permettant la diffusion de petites molécules. Comme la microcapsule empêche la revascularisation des îlots, leur oxygénation se fait par diffusion d’oxygène et ils sont exposés à l’hypoxie. Le manque d’oxygène est un facteur limitant dans la survie des îlots microencapsulés. Il est connu que les plus petits îlots sont plus résistant à l’hypoxie à cause d’une meilleure diffusion de l’oxygène. À cette fin, les agrégats de cellules dispersées d’îlots seront étudiés. Lorsque les cellules des îlots sont dispersées, elles ont la propriété de se ré-assembler dans une structure semblable à celle des îlots. La présente étude a permis de mettre au point une technique de formation des agrégats, de les caractériser et de comparer la résistance à l’hypoxie des îlots et des agrégats. Ceux-ci ont une structure semblable aux îlots et ils sont de plus petite taille. Pour cette raison, ils sont plus viables après un choc hypoxique tout en renversant efficacement l’hyperglycémie de souris diabétiques. Les agrégats sont une alternative intéressante pour la transplantation d’îlots microencapsulés puisque leur oxygénation est plus efficace. / Transplantation of microencapsulated islets of Langerhans is a promising treatment for type 1 diabetes mellitus. The microcapsule allows the diffusion of small molecules, while protecting the islet from the antibodies and immune cells. However, microcapsule prevents islet revascularization, thus oxygenation depends on diffusion and islets are exposed to hypoxia. Poor oxygenation is a major limitation in microencapsulated islet survival. It was shown that smaller islets are more resistant to hypoxia because of a better oxygen diffusion. In this study, dispersed islet cell aggregates will be used to improve the oxygenation. When islet cells are dispersed into single cells, they have the ability to re-associate into an islet-like structure. This study allowed to set up a technique to form aggregates, to characterized them and to compare the resistance to hypoxia of islets and aggregates. Aggregates have a similar structure than islets and they are smaller. For this reason, they survive better to a hypoxic treatment, while restoring efficiently normoglycemia in diabetic mices. Aggregates are an interesting solution for microencapsulated islet transplantation because they have a better oxygenation.

This study combines noninvasive hybrid diffuse optical spectroscopies [near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS)] with occlusive calibration for continuous measurement of absolute blood flow (BF), tissue blood oxygenation (StO2), and oxygen consumption rate (VO2) in exercising skeletal muscle. Subjects performed rhythmic dynamic handgrip exercise, while an optical probe connected to a hybrid NIRS/DCS flow-oximeter directly monitored oxy-, deoxy-, and total hemoglobin concentrations ([HbO2], [Hb], and [tHb]), StO2, relative BF (rBF), and relative VO2 (rVO2) in the forearm flexor muscles. Absolute baseline BF and VO2 were obtained through venous and arterial occlusions, respectively, and used to calibrate continuous relative parameters. Previously known problems with muscle fiber motion artifact in optical measurements were mitigated with a novel dynamometer-based gating algorithm. Nine healthy young subjects were measured and results validated against previous literature findings. Ten older subjects with fibromyalgia and thirteen age-matched healthy controls were then successfully measured to observe differences in hemodynamic and metabolic response to exercise. This study demonstrates a novel application of NIRS/DCS technology to simultaneously evaluate quantitative hemodynamic and metabolic parameters in exercising skeletal muscle. This method has broad application to research and clinical assessment of disease (e.g. peripheral vascular disease, fibromyalgia), treatment evaluation, and sports medicine.

The technique of micro-oxygenation involves the deliberate addition of continuous, metered amounts of oxygen into a vessel of bulk wine during the maturation period (between the end of fermentation and bottling). The aim of the process is to improve the sensory properties of red wine, particularly the mouthfeel characteristics associated with the various polyphenol constituents. The success of the process appears to depend strongly on the ability to control the rate of oxygen dosage. The effect of dosage rate on the chemical and corresponding sensory changes of a red wine is the central theme of this thesis. A method of dosing oxygen (at typical micro-oxygenation rates) into small volumes of wine (<100 litres) was developed using a dense polymer membrane diffuser. It was clearly demonstrated that wine could be reliably oxygenated at very low rates using a coiled length of FEP as the diffuser material. Oxygen dosage was regulated by adjusting the oxygen pressure inside the tube. The advantage with a dense polymer diffuser is that no bubbles are generated and the oxygenation efficiency is 100%. The diffuser was fully modeled and characterised for use in the laboratory scale trials detailed in Chapters Four and Six. The small scale oxygenation equipment was used to conduct a fully replicated experiment to investigate the evolution of a Cabernet Sauvignon wine under four oxygenation treatments at dosage rates of 0, 10, 23 and 36 mg/L/mth. The total period of the trial was 105 days. HPLC analysis indicated that the rate change of low molecular weight polyphenols is directly related to the oxygen dosage rate. The concentration of the majority of the identifiable monomers, most notably the anthocyanins decreased throughout the course of the trial. The rate of decrease was directly related to oxygen dosage rate. Thiolysis results showed an increase in mDP for all treatments over the course of the trial until day 77 when they were observed to decrease for all treatments. The decrease in mDP coincided with an addition of SO2 which was investigated in a subsequent trial. Spectrophotometric results indicated that the rate of formation of non-bleachable pigments was directly related to the rate of oxygen dosage with significant differences between the high rates (23 and 36 mg/L/mth) and the low rates (0 and 10 mg/L/mth). The trend for all treatments was for increased levels of stable pigments. The sensory results show that the measured organoleptic temporal development exhibits a similar oscillatory behaviour compared to the anecdotally derived curve presented in figure 1-2. The distinction between the respective phases described in section 1.1.1 was, however less clear. The most significant factor in the model weighting was mouthfeel and astringency which correlates with the observed changes occurring in the wine polypenols during maturation. Overall the laboratory scale trial showed that the chemical polyphenol development was directly related to the oxygen dosage rate. The sensory evolution also appeared to be accelerated with higher oxygen dosage rates, although the oscillatory nature of the sensory response given a single linear input indicates a complex underlying mechanism driving the changes. The effect of SO2 on the development of wine polyphenols with and without oxygen was also investigated. The presence of SO2 was found to have a significant effect on both mDP and the concentration of non-bleachable pigments. mDP was observed to decrease over the six week trial period irrespective of whether oxygen had been added or not. The mDP for the treatments without SO2 increased steadily over the course of the trial. Similarly the formation of non-bleachable pigments was suppressed and even retarded with SO2 present whereas for the treatments without SO2 a steady increase was observed. The implication of these results is that SO2 may have a much larger effect on tannin development than oxygen. The use of electrochemical micro-oxidation (or ELMOX) was examined ostensibly to determine proof of concept and also compare the performance of glassy carbon and titanium as electrode materials against traditional micro-oxygenation. Notable transformations occurred with titanium showing higher levels of ethanal than the other treatments both chemically and by sensory measure. A greater rate of stable pigment formation was also observed for the titanium compared to the other treatments. The respective dosage rates for the glassy carbon ELMOX and traditional micro-oxygenation treatments were too low to be able to discriminate any significant differences compared to the control wine. / AGMARDT Doctoral Scholarship

The technique of micro-oxygenation involves the deliberate addition of continuous, metered amounts of oxygen into a vessel of bulk wine during the maturation period (between the end of fermentation and bottling). The aim of the process is to improve the sensory properties of red wine, particularly the mouthfeel characteristics associated with the various polyphenol constituents. The success of the process appears to depend strongly on the ability to control the rate of oxygen dosage. The effect of dosage rate on the chemical and corresponding sensory changes of a red wine is the central theme of this thesis. A method of dosing oxygen (at typical micro-oxygenation rates) into small volumes of wine (<100 litres) was developed using a dense polymer membrane diffuser. It was clearly demonstrated that wine could be reliably oxygenated at very low rates using a coiled length of FEP as the diffuser material. Oxygen dosage was regulated by adjusting the oxygen pressure inside the tube. The advantage with a dense polymer diffuser is that no bubbles are generated and the oxygenation efficiency is 100%. The diffuser was fully modeled and characterised for use in the laboratory scale trials detailed in Chapters Four and Six. The small scale oxygenation equipment was used to conduct a fully replicated experiment to investigate the evolution of a Cabernet Sauvignon wine under four oxygenation treatments at dosage rates of 0, 10, 23 and 36 mg/L/mth. The total period of the trial was 105 days. HPLC analysis indicated that the rate change of low molecular weight polyphenols is directly related to the oxygen dosage rate. The concentration of the majority of the identifiable monomers, most notably the anthocyanins decreased throughout the course of the trial. The rate of decrease was directly related to oxygen dosage rate. Thiolysis results showed an increase in mDP for all treatments over the course of the trial until day 77 when they were observed to decrease for all treatments. The decrease in mDP coincided with an addition of SO2 which was investigated in a subsequent trial. Spectrophotometric results indicated that the rate of formation of non-bleachable pigments was directly related to the rate of oxygen dosage with significant differences between the high rates (23 and 36 mg/L/mth) and the low rates (0 and 10 mg/L/mth). The trend for all treatments was for increased levels of stable pigments. The sensory results show that the measured organoleptic temporal development exhibits a similar oscillatory behaviour compared to the anecdotally derived curve presented in figure 1-2. The distinction between the respective phases described in section 1.1.1 was, however less clear. The most significant factor in the model weighting was mouthfeel and astringency which correlates with the observed changes occurring in the wine polypenols during maturation. Overall the laboratory scale trial showed that the chemical polyphenol development was directly related to the oxygen dosage rate. The sensory evolution also appeared to be accelerated with higher oxygen dosage rates, although the oscillatory nature of the sensory response given a single linear input indicates a complex underlying mechanism driving the changes. The effect of SO2 on the development of wine polyphenols with and without oxygen was also investigated. The presence of SO2 was found to have a significant effect on both mDP and the concentration of non-bleachable pigments. mDP was observed to decrease over the six week trial period irrespective of whether oxygen had been added or not. The mDP for the treatments without SO2 increased steadily over the course of the trial. Similarly the formation of non-bleachable pigments was suppressed and even retarded with SO2 present whereas for the treatments without SO2 a steady increase was observed. The implication of these results is that SO2 may have a much larger effect on tannin development than oxygen. The use of electrochemical micro-oxidation (or ELMOX) was examined ostensibly to determine proof of concept and also compare the performance of glassy carbon and titanium as electrode materials against traditional micro-oxygenation. Notable transformations occurred with titanium showing higher levels of ethanal than the other treatments both chemically and by sensory measure. A greater rate of stable pigment formation was also observed for the titanium compared to the other treatments. The respective dosage rates for the glassy carbon ELMOX and traditional micro-oxygenation treatments were too low to be able to discriminate any significant differences compared to the control wine. / AGMARDT Doctoral Scholarship

The technique of micro-oxygenation involves the deliberate addition of continuous, metered amounts of oxygen into a vessel of bulk wine during the maturation period (between the end of fermentation and bottling). The aim of the process is to improve the sensory properties of red wine, particularly the mouthfeel characteristics associated with the various polyphenol constituents. The success of the process appears to depend strongly on the ability to control the rate of oxygen dosage. The effect of dosage rate on the chemical and corresponding sensory changes of a red wine is the central theme of this thesis. A method of dosing oxygen (at typical micro-oxygenation rates) into small volumes of wine (<100 litres) was developed using a dense polymer membrane diffuser. It was clearly demonstrated that wine could be reliably oxygenated at very low rates using a coiled length of FEP as the diffuser material. Oxygen dosage was regulated by adjusting the oxygen pressure inside the tube. The advantage with a dense polymer diffuser is that no bubbles are generated and the oxygenation efficiency is 100%. The diffuser was fully modeled and characterised for use in the laboratory scale trials detailed in Chapters Four and Six. The small scale oxygenation equipment was used to conduct a fully replicated experiment to investigate the evolution of a Cabernet Sauvignon wine under four oxygenation treatments at dosage rates of 0, 10, 23 and 36 mg/L/mth. The total period of the trial was 105 days. HPLC analysis indicated that the rate change of low molecular weight polyphenols is directly related to the oxygen dosage rate. The concentration of the majority of the identifiable monomers, most notably the anthocyanins decreased throughout the course of the trial. The rate of decrease was directly related to oxygen dosage rate. Thiolysis results showed an increase in mDP for all treatments over the course of the trial until day 77 when they were observed to decrease for all treatments. The decrease in mDP coincided with an addition of SO2 which was investigated in a subsequent trial. Spectrophotometric results indicated that the rate of formation of non-bleachable pigments was directly related to the rate of oxygen dosage with significant differences between the high rates (23 and 36 mg/L/mth) and the low rates (0 and 10 mg/L/mth). The trend for all treatments was for increased levels of stable pigments. The sensory results show that the measured organoleptic temporal development exhibits a similar oscillatory behaviour compared to the anecdotally derived curve presented in figure 1-2. The distinction between the respective phases described in section 1.1.1 was, however less clear. The most significant factor in the model weighting was mouthfeel and astringency which correlates with the observed changes occurring in the wine polypenols during maturation. Overall the laboratory scale trial showed that the chemical polyphenol development was directly related to the oxygen dosage rate. The sensory evolution also appeared to be accelerated with higher oxygen dosage rates, although the oscillatory nature of the sensory response given a single linear input indicates a complex underlying mechanism driving the changes. The effect of SO2 on the development of wine polyphenols with and without oxygen was also investigated. The presence of SO2 was found to have a significant effect on both mDP and the concentration of non-bleachable pigments. mDP was observed to decrease over the six week trial period irrespective of whether oxygen had been added or not. The mDP for the treatments without SO2 increased steadily over the course of the trial. Similarly the formation of non-bleachable pigments was suppressed and even retarded with SO2 present whereas for the treatments without SO2 a steady increase was observed. The implication of these results is that SO2 may have a much larger effect on tannin development than oxygen. The use of electrochemical micro-oxidation (or ELMOX) was examined ostensibly to determine proof of concept and also compare the performance of glassy carbon and titanium as electrode materials against traditional micro-oxygenation. Notable transformations occurred with titanium showing higher levels of ethanal than the other treatments both chemically and by sensory measure. A greater rate of stable pigment formation was also observed for the titanium compared to the other treatments. The respective dosage rates for the glassy carbon ELMOX and traditional micro-oxygenation treatments were too low to be able to discriminate any significant differences compared to the control wine. / AGMARDT Doctoral Scholarship

The technique of micro-oxygenation involves the deliberate addition of continuous, metered amounts of oxygen into a vessel of bulk wine during the maturation period (between the end of fermentation and bottling). The aim of the process is to improve the sensory properties of red wine, particularly the mouthfeel characteristics associated with the various polyphenol constituents. The success of the process appears to depend strongly on the ability to control the rate of oxygen dosage. The effect of dosage rate on the chemical and corresponding sensory changes of a red wine is the central theme of this thesis. A method of dosing oxygen (at typical micro-oxygenation rates) into small volumes of wine (<100 litres) was developed using a dense polymer membrane diffuser. It was clearly demonstrated that wine could be reliably oxygenated at very low rates using a coiled length of FEP as the diffuser material. Oxygen dosage was regulated by adjusting the oxygen pressure inside the tube. The advantage with a dense polymer diffuser is that no bubbles are generated and the oxygenation efficiency is 100%. The diffuser was fully modeled and characterised for use in the laboratory scale trials detailed in Chapters Four and Six. The small scale oxygenation equipment was used to conduct a fully replicated experiment to investigate the evolution of a Cabernet Sauvignon wine under four oxygenation treatments at dosage rates of 0, 10, 23 and 36 mg/L/mth. The total period of the trial was 105 days. HPLC analysis indicated that the rate change of low molecular weight polyphenols is directly related to the oxygen dosage rate. The concentration of the majority of the identifiable monomers, most notably the anthocyanins decreased throughout the course of the trial. The rate of decrease was directly related to oxygen dosage rate. Thiolysis results showed an increase in mDP for all treatments over the course of the trial until day 77 when they were observed to decrease for all treatments. The decrease in mDP coincided with an addition of SO2 which was investigated in a subsequent trial. Spectrophotometric results indicated that the rate of formation of non-bleachable pigments was directly related to the rate of oxygen dosage with significant differences between the high rates (23 and 36 mg/L/mth) and the low rates (0 and 10 mg/L/mth). The trend for all treatments was for increased levels of stable pigments. The sensory results show that the measured organoleptic temporal development exhibits a similar oscillatory behaviour compared to the anecdotally derived curve presented in figure 1-2. The distinction between the respective phases described in section 1.1.1 was, however less clear. The most significant factor in the model weighting was mouthfeel and astringency which correlates with the observed changes occurring in the wine polypenols during maturation. Overall the laboratory scale trial showed that the chemical polyphenol development was directly related to the oxygen dosage rate. The sensory evolution also appeared to be accelerated with higher oxygen dosage rates, although the oscillatory nature of the sensory response given a single linear input indicates a complex underlying mechanism driving the changes. The effect of SO2 on the development of wine polyphenols with and without oxygen was also investigated. The presence of SO2 was found to have a significant effect on both mDP and the concentration of non-bleachable pigments. mDP was observed to decrease over the six week trial period irrespective of whether oxygen had been added or not. The mDP for the treatments without SO2 increased steadily over the course of the trial. Similarly the formation of non-bleachable pigments was suppressed and even retarded with SO2 present whereas for the treatments without SO2 a steady increase was observed. The implication of these results is that SO2 may have a much larger effect on tannin development than oxygen. The use of electrochemical micro-oxidation (or ELMOX) was examined ostensibly to determine proof of concept and also compare the performance of glassy carbon and titanium as electrode materials against traditional micro-oxygenation. Notable transformations occurred with titanium showing higher levels of ethanal than the other treatments both chemically and by sensory measure. A greater rate of stable pigment formation was also observed for the titanium compared to the other treatments. The respective dosage rates for the glassy carbon ELMOX and traditional micro-oxygenation treatments were too low to be able to discriminate any significant differences compared to the control wine. / AGMARDT Doctoral Scholarship

[Truncated abstract] Therapeutic Radiation has been used for the treatment of cancer and other diseases for nearly a century. Over the past 20 years, Hyperbaric Oxygen Treatment (HBOT) has been used to assist wound healing in the prevention and treatment of the more severe complications associated with the side effects of Therapeutic Radiation Treatment (TRT). The use of HBOT is based on the premise that increased oxygen tissue tension aids wound healing by increasing the hypoxic gradient and stimulating angiogenesis and fibroblast differentiation. As it takes up to 6 months for a hypoxic state to develop in treated tissue, following radiation treatment, current recommendations for HBOT state that it is not effective until after this time. During this 6 month period, immediately following TRT, many specialized tissues in or adjacent to the field of irradiation, such as salivary glands and bone, are damaged due to a progressive thickening of arteries and fibrosis, and these tissues are never replaced. Currently, HBOT is used to treat the complications of TRT, but it would be far better if they could be prevented . . . In summary, this experimental model has fulfilled its prime objective of demonstrating that HBOT is effective in reducing the long-term side effects of therapeutic radiation treatment in normal tissue, when given one week after the completion of the radiation treatment and statistically disproves the Null Hypothesis that there is no difference in the incidence of postoperative complications or morbidity of TRT when 20 intermittent daily HBOT are started one week after completion of TRT. This project provides an extensive description of the histological process and also proposes a hypothesis for the molecular events that may be taking place.