No description available.

This work helps to determine the extent of immune system involvement in the adaptive response to subacute ruminal acidosis (SARA) in three parts. The first (Chapter 2) uses non-lactating cows to study specific changes in inflammatory protein expression in which SARA is created. The second (Chapter 3), uses the same model as Chapter 2. However, in this case, lactating cows are used to help establish the time course for adaptation to acidosis. The third part (Chapter 4) delineates the genomic changes that occur in the rumen epithelium when a therapeutic intervention is introduced using exogenous supplemental butyrate. In the first experiment, the expression of the extracellular matrix (ECM) proteins type IV collagen and laminin β1 decreased, and the monocarboxylate transporter MCT1, increased during the acidotic challenge. Nuclear factor of activated T-cells, NFATc2, and tumour necrosis factor alpha (TNF-α) decreased while interleukin-1 beta (IL-1β) increased during the experimental treatment period. Chapter 3 measured lipopolysaccharide (LPS) and its carrier, LPS binding protein, LBP, which were found to be elevated due to SARA. Moreover, NFATc2 was reduced during this period. Exogenous butyrate resulted in increased plasma LBP, plasma beta hydroxyl butyrate (BHBA), and ruminal butyrate. Milk parameters (total protein and fat) were unaffected by treatment, as were rumen LPS, acetate, valerate, isovalerate, and isobutyrate. Moreover, exogenous butyrate increased gene transcription of genes involved in non-specific host defences (NHSD) such as mucin, and remodelling (RM), such as matrix metallopeptidase 16 (MMP16), and decreased the transcription of genes of the immune response (IR), such as nuclear factor kappa B2 (NFκB2). Together, these three experiments have demonstrated that although wound healing is mediated by the immune system in more severe models of epithelial damage, our model of SARA did not involve full-thickness, penetrating lesions and hence did not involve the systemic immune system to such a degree than was previously thought. In addition, we were able to demonstrate that the addition of butyrate to this model of grain-induced acidosis was beneficial, as it decreased the local inflammatory response and helped the epithelium adapt to its harsher environment. / Agriculture and Agri-Food Canada, the National Sciences and Engineering Council of Canada (NSERC), the Ontario Ministry of Agriculture, Food and Rural Affairs (OMAFRA), the Canadian Dairy Commission (CDC), and the Dairy Farmers of Ontario (DFO).

Introduction Keloids are formed by the excessive production of scar tissue, which extends beyond the margins of the original injury, often resulting in lesions of grotesque dimensions. Keloids present a major dilemma to surgeons because of the high recurrence rate with recurrent growth often larger than the original keloid. The high recurrence rate and the poor response of keloids to therapy present a great challenge to surgeons. The numerous therapeutic regimens demonstrate that to date there is no single therapy that is absolutely successful. Therefore, it is necessary to comprehensively establish the pathology of keloids and to determine the aetiopathogenesis of the lesion in order to eventually provide unfailing specific effective treatment and to better understand the mechanisms regulating fibrosis in various fibroproliferative diseases. Aim To evaluate the pathology and aetiopathogenesis of keloid formation. Methods The research protocol for the study was approved by the Nelson R Mandela Faculty of Medicine Ethics Committee. Informed consent was obtained before the biopsies were taken. Keloid and non-lesional skin biopsies were obtained from thirty two patients who had multiple lesions in various locations, bringing the total number of keloids and apparently normal skin biopsies processed and examined to fifty eight. The biopsied specimens were processed for paraffin wax embedment and routine haematoxylin and eosin, differential and immunocytochemical staining. Sections were scrupulously examined using the Olympus BH-2 microscope; features pertinent to the study were photographed with the Olympus DP 10 microscope digital camera system. The stored images were studied, using the Camedia graphics processing programme. Results The results of the study showed that keloids comprise many distinct regions categorized as: the zone of hyalinising collagen bundles, fine fibrous areas, areas of inflammation, zone of dense regular connective tissue, nodular fibrous area and area of angiogenesis. Fibroblastic phenotypes present ranged from spindle, fibrohistiocytic, epitheloid, elongated flattened condensed fibroblastic cells to few wavy, fuzzy, polygonal and atrophic cell types. Immunocytochemically these cells were vimentin-positive and actin- and desmin-negative. Few myofibroblastic phenotypes were also identified and these were vimentin- and alpha smooth muscle actin-positive and desmin-negative. The fibroblastic and myofibroblastic phenotypes were in proliferative or degenerative stages and pathological features exhibited were the presence of vesicular, degenerate or calcified nuclei; nuclear and plasma membrane damage; cytoplasmic and nucleoplasmic clearing; atrophy, pyknosis and swelling. Severe, moderate to mild paravascular inflammation was observed around the microvessels of the sub-papillary plexus and within the keloid. There was compression and occlusion of small blood vessels, coagulation necrosis and dissolution of mural cells of small blood vessels and small peripheral nerves. Also present in keloids were oedematous areas, disorganised and hyalinised connective tissue fibres and increased numbers of degranulated and degranulating mast cells. Elastic fibres in keloids were minimal or absent whereas at the border of keloids there was an increase.Discussion Degenerate, occluded and compressed microvessels were a widespread pathological feature in keloids. This resulted in impaired vascular supply to each of the keloid regions which impacted directly on the pathology of keloids where degeneration and necrosis, manifesting the lack of nutrients and oxygen to tissue, were found throughout the keloid. The vascular supply was impaired because of the chronic inflammatory destruction of the microvessels and the elevated stress within keloids. Factors contributing to increased intrinsic stress were: 1) the lack of elastic fibres in keloids which decreased the elastic limit, leading to effects of excessive deformational force which were compression and stiffening of tissue; 2) the high tension skin covering keloid prone areas had low stretch and a low elastic modulus; 3). protruding hard connective tissue such as bony prominences or cartilage into the dermis of keloid prone skin; 4) contractile forces exerted by wound healing fibroblastic cells; and 5) external forces. Compression and occlusion of blood vessels induced ischaemic and reperfusion tissue injury. During the reperfusion phase blood rich in growth factors returned to tissue stimulating tissue growth. Tissue growth was also promoted by elevated internal stress which stimulated increasing levels of gene expression, collagen synthesis and mitotic activity. All these growth promoting effects resulted in keloid formation. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2013.

The mechanisms responsible for the healing of corneal surface wounds are the subject of biological controversy. In particular, the role and source of the regulatory chemical epidermal growth factor (EGF) is an area of intense debate. In the first part of this thesis, we propose a reaction-diffusion model which focuses on the stimulus for increased mitotic and migratory activity due to secretion of EGF. A detailed numerical study of various possible models, with parameter values based on biological data, reveals that, for realistic healing times, EGF must be released by the underlying layers of the cornea, in addition to the tear film source. The model exhibits travelling wave solutions and further analysis elucidates the interaction and role of the parameters in determining the speed of healing. Furthermore, we consider the effect of topical application of EGF and investigate the effect of curvature of the eye. We show that our model is consistent with many of the key features of corneal wound healing. Adult dermal wounds, in contrast to foetal wounds, heal with the formation of scar tissue. A crucial factor in determining the nature of the healed tissue is the ratio of collagen 1 to collagen 3, which indicates the fibril diameter. We develop a reaction-diffusion model which focuses on the stimulus for collagen synthesis due to the secretion of the different isoforms of the regulatory chemical transforming growth factor β (TGFβ). Numerical simulations of the model without diffusion lead to a value of this ratio consistent with that of healthy tissue for the foetus but corresponding to scarring in the adult. The model equations evolve to waves moving into the wound, but addition of TGFβ only has a transient effect on the final collagen levels. We investigate this effect by developing a caricature model. The model indicates that the main source of the fibroblasts is the underlying subcutaneous tissue and we determine key parameters which explain the difference between adult and foetal wound healing. Furthermore we make clinically testable predictions on the effects that topical application of various chemicals will have on scar formation.

Purpose: The aim of this thesis was to investigate a suitable formulation for the topical delivery of growth factors to chronic wounds, and then to determine the concentrations reached within an animal wound model. A secondary aim was to determine if the chosen growth factor was present at levels able to stimulate the production of other cytokines, specifically IL-1β and MCP-1. Methods: An in vitro testing apparatus was designed and made and the release of model actives [bromophenol blue (BPB) and horseradish peroxidase (HRP)] from gels and films of hydroxylpropylmethylcellulose (HPMC) (E4M CR, K4M CR and E10M CR) was determined. In this study, Fibroblast Growth Factor -2 (FGF-2) (0.3 [mu]g) was incorporated into three formulations (solution, gel and dried gel film on Melolin[TM] backing) and together with a control formulation were administered to punch biopsy wounds in rats. The in vivo release was followed over three time periods (two, five and eight hours) and the amount of FGF-2 at various wound depths was quantified by ELISA. Two biological markers IL-1β and MCP-1 were quantified using ELISA. The FGF-2 was additionally tagged with a fluorescent dye so that visualisation of the penetration could be obtained via confocal microsopy. Results: For the HPMC gels, the more viscous gel (E10M) provided a greater diffusional barrier and slowed the release of BPB (12 � 3.5 [mu]g/min compared with 16 � 1.7 [mu]g/min and 18 � 1.4 [mu]g/min for K4M and E4M respectively). However, when HPMC was formulated as a dried film a burst release was seen and release of BPB was slowest from the more rapidly hydrating K4M. With the larger model active HRP, there was a slower diffusion through the gel barrier formed upon film hydration, such that time of 100% release was up to 300 minutes compared to approximately 60 minutes for BPB. When the film was dried onto a supportive backing, the initial burst release was minimised as the film did not break apart on contact with the wound, and hence film integrity was maintained and release prolonged. The in vivo studies showed that, two hours after application, the highest concentration of FGF-2 was seen in the surface granulation tissue of rats that received the solution formulation (2280 � 790 pg/g). The concentration decreased with increasing tissue depth but was significantly greater than the saline control in the surface granulation and subcutaneous fat layers (p<0.05). Tissue concentrations following application of the gel and film formulations were only marginally greater than control in the surface granulation layer. After eight hours, rats that received the solution retained elevated surface tissue concentrations (surface granulation and subcutaneous fat) of FGF-2. Repeated measures ANOVA using a general linear model showed statistically significant differences in the mean FGF-2 level with respect to formulation and length of time of application of the formulation (p<0.05). In terms of other cytokines, there was a release of both IL-1β and MCP-1 in all groups, immediately post-wounding, probably in response to cellular damage. After eight hours, the film formulation appeared to elevate IL-1β levels which may be useful to drive wound healing. Confocal microscopy images showed diffuse distribution of FGF-2 eight hours after application of the solution formulation after eight hours and that with the gel formulation FGF-2 initially aggregated at the wound surface. Conclusion: In vitro experiments investigating the effect of hydration rate and viscosity of HPLC polymers allowed a formulation to be chosen for further in vivo study. Elevated FGF-2 could be measured in superficial wound tissues up to eight hours after application of a solution. However, application of a comparable amount of FGF-2 in HPMC gels or films did not produce appreciable elevations in FGF-2 in wound tissues, although confocal microscopy indicated the penetration of FGF-2 into the wound for up to eight hours.

This research project investigated the impact of an action research intervention implemented to reducing surgical wound infection in one of the acute care hospitals in India. The study aimed to develop and implement a clinical practice improvement program in reducing surgical wound infection by improving the hand washing and wound dressing practices of nurses. The study also aimed to identify the important contributing factors to a model that predicts surgical wound infection. Pre-post evaluation measures were taken to compare the results of surgical wound infection rate before and after the implementation of the intervention. Surgical wounds of two thousand patients (one thousand before the intervention and another one thousand after) were assessed to determine the wound infection rate and severity of wound infection. The hand washing and wound dressing practices of forty nurses were observed. These same nurses were involved in the intervention using a participatory action research process. The results of the study suggest that there was a marked, significant reduction in the rate and severity of wound infection following the implementation of the intervention. By increasing the hand washing facilities in the ward, educating nurses on the importance of better hygiene, pre-operative shaving and post-operative wound care, the hand washing and wound dressing practices of nurses improved considerably. These improvements resulted in a reduction in the number and severity of patients' surgical wound infections. The study also examined the contribution of different factors to surgical wound infection in a Indian hospital. Significant predictive factors were the patients' age, longer pre-operative hospital stay, extended pre-operative shaving time before surgery, wound class, and co-morbidity of the patient. The identification of risk factors that contributed to increased surgical wound infection for example pre-operative skin preparation, pre-operative hospital stay of the patient would help in taking appropriate measures at the ward level and organisation as a whole. Nosocomial infections extends to an unnecessary lengthy hospital stay, additional treatment increased mortality and morbidity, and increased cost to the patients and the nation as a whole. This project proved that educational mentoring, data surveillance processes and involving the nurses in an action research process were effective in enabling participants to improve their clinical practice and thereby reduce the incidence of patients' surgical wound infections. Establishing infection control teams, ongoing surveillance and feedback to staff of nosocomial infection rates is an urgent need in all Indian hospitals. Organisational management, as a priority, need to provide funding and staff dedicated to undertaking this essential work. Health care professionals can no longer plead ignorance of a situation for which all have a moral and professional responsibility.

Thesis (M.A.)--Northern Kentucky University, 2007. / Made available through ProQuest. Publication number: AAT 1445115. ProQuest document ID: 1342744201. Includes bibliographical references (p. 35-36)

Thesis (M.S.)--University of Alabama at Birmingham, 2007. / Additional advisors: Dale S. Feldman, Mary J. MacDougall, Laura Timares. Description based on contents viewed Feb. 4, 2008; title from title screen. Includes bibliographical references (p. 39-40).

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 76-85).

Diss. (sammanfattning) Uppsala : Univ., 2005. / Härtill 4 uppsatser.