Storage of canine packed red blood cells (pRBCs) can increase erythrocyte phosphatidylserine (PS) expression and eicosanoid concentrations. The objective of this study was to determine the effects of leukoreduction on erythrocyte PS expression and eicosanoid concentrations in stored units of canine pRBCs. Units of whole blood were leukoreduced (LR) or non-leukoreduced (non-LR), and stored (10 and 21 days) as pRBCs. Samples were collected at donation, and before and after a simulated transfusion. PS expression was measured by flow cytometry, and concentrations of arachidonic acid (AA), prostaglandin F2α (PGF2α), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α) and leukotriene B4 (LTB4) were quantified by liquid chromatography-mass spectrometry. Our study demonstrated that PS expression on the surface of erythrocytes was not affected by leukoreduction or storage duration. Additionally, the passage of blood through a leukoreduction filter causes an immediate and dramatic increase in TXB2 and PGF2α concentrations, but these concentrations then decrease during subsequent storage. Despite leukoreduction, the concentration of 6-keto-PGF1α continued to increase during storage and simulated transfusion. Overall, when compared to non-LR units, the addition of a leukoreduction step prior to storage had a minimal impact on the accumulation of eicosanoids in canine units of pRBCs. While leukoreduction may be beneficial in other aspects of transfusion medicine, based on the results in this study, using leukoreduction to decrease PS expression and eicosanoid concentrations does not appear to be effective.

Lesions of the ventromedial hypothalamus (VMH) result in an obesity syndrome characterized by metabolic and behavioral disturbances. It has recently been indicated that damage to the paraventricular nucleus of the hypothalamus (PVH) also leads to changes characteristic of obesity. Although deficits following VMH lesions have been characterized extensively, less is known about the consequences of PVH damage. This thesis presents a series of experiments providing a detailed comparison of the two hypothalamic lesion syndromes. Initially, to assess the basic features of the syndromes, rats underwent VMH, PVH, or sham lesions and were maintained ad libitum for 15 weeks on a series of test diets. Overall, lesion groups gained similar amounts of weight (significantly more than controls) and were equally hyperphagic. However, carcass analyses revealed that although both lesion groups had larger body fat compartments than controls, VMH rats were fatter than PVH animals. Similarly, although insulin levels in both lesion groups were elevated, only VMH rats had a significant hyperinsulinemia. A defining feature of the VMH obesity is the development of certain disturbances of visceral secretion and excessive adipose stores even in the absence of hyperphagia. To assess whether the PVH obesity shares these characteristics, food intake of PVH and VMH rats were restricted postlesion to control body weights. First, gastric acid secretion was measured to index lesion-induced changes in visceral secretion. VMH rats developed a persisting hypersecretion immediately postlesion; acid secretion levels of PVH rats were normal. In a second experiment, PVH and VMH rats were maintained at control weights for 28 days postlesion by restricted feeding of either a standard pellet or high fat diet. In both diet conditions, VMH rats became obese but PVH rats did not. Finally, the effects of PVH and VMH lesions on behavioral reactivity to orosensory properties of food were assessed by comparing the sham feeding responses of PVH, VMH and control rats to liquid diets varying in palatability. Control animals increased sham feeding with ascending sucrose concentrations. VMH animals showed disproportionately large increases in consumption with increased sucrose. PVH animals showed sham feeding changes similar to VMH rats. These data indicate similar effects of PVH and VMH lesions on behavioral measures; specifically, in normal, and sham, feeding. However, these two lesions produce different effects on metabolic and secretion measures. It is concluded that the etiologies of the two obesity are fundamentally different. / Thesis / Doctor of Philosophy (PhD)

It is well documented that the incidence of renal disease, and therefore renal dysfunction, increases with age in many species of mammals. Such alterations in renal structure and function may significantly affect long-term toxicology studies. The purpose of this study was to assess the temporal evolution of glomerulosclerosis, an important renal lesion, in laboratory housed dogs, an important model system in chronic toxicological studies. We histopathologically examined representative sections of dog kidneys, quantified glomerular lesions (using the 0-5 scale of the World Health Organization classification system) and performed of statistical analysis of the extent and distribution of such changes. The kidney samples were obtained by necropsy, and occasionally biopsy, procedures from a collection of 159 purebred Beagle dogs maintained for their entire lifespan in well-controlled conditions. The lesions were correlated with sex, age, and intra-renal location of affected glomeruli to determine the relationship of each in the development of glomerulosclerosis. All dogs examined had some degree of glomerulosclerosis. In the youngest (up to 2 years of age), this was minimal, but was more advanced by middle age (3-7 years). The condition progressed with further aging and was associated with progressive fibrosis and tubular loss. Location and advancing age were significantly related to the development of glomerulosclerosis such that as age increases, the incidence of glomerulosclerosis increases, with the inner medullary ray and inner cortex demonstrating the highest occurrence. Using immunohistochemical analysis, the percentage of type IV collagen within glomeruli was determined. No significant increase in type IV collagen in glomeruli due to age or location was seen. An increase in type III or type V collagen within glomeruli was not apparent either, upon visual examination. This study indicates that renal lesions, including glomerulosclerosis, occur commonly and progress over the lifetime in a genetically similar population of laboratory Beagle dogs maintained under optimal standard environmental conditions. Such typical, age-related change needs to be taken into consideration when conducting chronic toxicological experiments using such animals. / Master of Science

No description available.

In addition all patients examined by means of using testicular angiography before the first of November 1978» have been included. 123 patients were intended for angiography, 13 of them bilaterally. The intention with the investigation was to determine whether selective angiography of the testicular artery might be a useful examination in cases of a non-palpable testis and in patients with different intrascrotal lesions. There is a description of a useful method of investigation. The normal angiographic anatomy of the testicular artery is also de­scribed, both retroperitoneally and in the scrotum. In cases with a non-palpable testis it is shown that it is easy to distinguish between agenesis and cryptorchism. The normal magnification angiography of the testis is shown and how various intrascrotal lesions alter the picture. Finally some cases with retroperitoneal lesions are presented in which the testicular artery is committed. / <p>Diss. Umeå : Umeå universitet, 1979, härtill 4 uppsatser</p> / digitalisering@umu

No description available.

No description available.

No description available.

No description available.

Photodynamic Detection (PDD) is a diagnostic technique involving administration of a photosensitizer to the targeted cells that can be stimulated by short wavelength light which then leads to emission of light at a different wavelength (lower energy). The light emitted by the cells can be detected and analysed (by a spectroscope). All cells have the innate ability (due to endogenous fluorophores) to fluoresce, termed autofluorescence. Any cellular, metabolic or structural changes can alter the fluorescence intensity peaks. In this study 5-aminolevulinic acid (5-ALA) photosensitizer prodrug was used, which is metabolised in highly active cells to protoporphyrin IX (PpIX). Excitation of a cell at 405nm wavelength (light) leads to emission of autofluorescence at 500nm and PpIX at 635nm. The purpose of this investigation was to evaluate the use of compact spectroscopy together with the photosensitizer prodrug 5-ALA, in assessing clinically suspicious oral lesions. To that end the followings were assessed: • The fluorescence intensity ratio (FIR) or Red/Green ratio at 635/500nm measurements of normal anatomical sites at ten oral anatomical sites to map and create baseline readings for normal oral mucosal site fluorescence. • The effect of participants’ characteristics on the normal oral mucosal site FIR measurements. • The use the fluorescence intensity ratio (FIR) measurements to determine any differences between the lesion and the normal oral readings and whether the FIR from clinically suspicious oral lesions is associated with the histopathology grade. In addition to the sensitivity and specificity of the technique in assessing clinically suspicious (premalignant) oral lesions for potential malignant change.Prior to the trial commencing, approval were obtained from the Research Ethics Committee (REC), local NHS Research and Development (R&D), and Medicine Healthcare product Regulatory Agency (MHRA) and the University of Dundee Research Innovation Services (RIS). A total of thirty five participants with clinically suspicious oral lesions were recruited in Dundee (Dundee Dental Hospital) and Glasgow (Southern General Hospital). A Photodynamic Detection method using compact fluorescence spectroscopy and 5-ALA mouth rinse was applied. FIR measurements from ten normal anatomical sites were obtained in every patient to study the variation at different normal oral sites and the effect of the participant’s characteristics on these readings. In addition, two FIR measurements were obtained from each lesion and a further one taken from normal looking mucosa well beyond the lesion boundary (i.e. more than 5mm away) prior to biopsy. The readings were compared to study the reliability, reproducibility and efficacy of the photodynamic method in detecting mucosal abnormality. A total of 292 spectral readings obtained from normal mucosa were used to study the FIR measurements at normal oral anatomical sites. The results showed that the oral regions could be grouped into two broad categories with similar readings, the palatal and tongue readings in one group and buccal, ventral tongue, floor of the mouth, gingiva and lip mucosa on the other (essentially keratinized and non keratinized groups). The same set of readings were further analysed to study the effect of individual characteristics (age, gender, presence of oral prosthesis, metabolic diseases, smoking and alcohol consumptions) on the FIR measurements. There was no significant difference between FIR measurements within each of the groups studied, although at times sample sizes were very small.A total of 134 spectral readings obtained from 47 lesions that were biopsied from 35 patients recruited to the trial were used for the next part of the study. There were 91 spectra obtained from the lesions and 43 spectra obtained from the normal sites (more than 5mm away from the borders of the lesion) for comparison. There was a significant difference between the lesion and normal site readings. The FIR readings for the dysplastic lesions were significantly different when compared with the normal and benign hyperkeratoses. However there was no significant difference between dysplastic and inflammatory lesions (lichen planus, lichenoid lesions and candidal leukoplakia) on the one hand and inflammatory lesions and hyperkeratotic lesion on the other. Further analysis showed the sensitivity in detecting all the clinically suspicious oral lesions from the normal sites was 59.5% and specificity was 73.8%. The sensitivity in detecting dysplasia from normal sites was 100% and specificity 100%.Photodynamic Detection was able to detect a difference between the oral lesions from normal mucosa (but so is the naked eye!). However there was variation in the sensitivity and specificity in detecting a range of different pathological conditions. The technique was highly sensitive in detecting dysplasia from normal mucosa but unfortunately the technique is not able to discriminate reliably between dysplasia and inflammatory lesions whose clinical appearance can be very similar. In conclusion, the photodynamic detection method used in this study would not appear to offer a reliable screening tool for the early detection of oral dysplasia/cancer. The need to consider adjunctive tests that discriminate inflammation from dysplasia is required. Photodynamic Detection (PDD) is a diagnostic technique involving administration of a photosensitizer to the targeted cells that can be stimulated by short wavelength light which then leads to emission of light at a different wavelength (lower energy). The light emitted by the cells can be detected and analysed (by a spectroscope). All cells have the innate ability (due to endogenous fluorophores) to fluoresce, termed autofluorescence. Any cellular, metabolic or structural changes can alter the fluorescence intensity peaks. In this study 5-aminolevulinic acid (5-ALA) photosensitizer prodrug was used, which is metabolised in highly active cells to protoporphyrin IX (PpIX). Excitation of a cell at 405nm wavelength (light) leads to emission of autofluorescence at 500nm and PpIX at 635nm. The purpose of this investigation was to evaluate the use of compact fluorescence spectroscopy together with the photosensitizer prodrug 5-ALA, in assessing clinically suspicious oral lesions. To that end the followings were assessed: • The fluorescence intensity ratio (FIR) or Red/Green ratio at 635/500nm measurements of normal anatomical sites at ten oral anatomical sites to map and create baseline readings for normal oral mucosal site fluorescence. • The effect of participants’ characteristics on the normal oral mucosal site FIR measurements. • The use the fluorescence intensity ratio (FIR) measurements to determine any differences between the lesion and the normal oral readings and whether the FIR from clinically suspicious oral lesions is associated with the histopathology grade. In addition to the sensitivity and specificity of the technique in assessing clinically suspicious (premalignant) oral lesions for potential malignant change. Prior to the trial commencing, approval were obtained from the Research Ethics Committee (REC), local NHS Research and Development (R&D), and Medicine Healthcare product Regulatory Agency (MHRA) and the University of Dundee Research Innovation Services (RIS). A total of thirty five participants with clinically suspicious oral lesions were recruited in Dundee (Dundee Dental Hospital) and Glasgow (Southern General Hospital). A Photodynamic Detection method using compact fluorescence spectroscopy and 5-ALA mouth rinse was applied. FIR measurements from ten normal anatomical sites were obtained in every patient to study the variation at different normal oral sites and the effect of the participant’s characteristics on these readings.