京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18900号 / 医博第4011号 / 新制||医||1009(附属図書館) / 31851 / 京都大学大学院医学研究科医学専攻 / (主査)教授 影山 龍一郎, 教授 野田 亮, 教授 楠見 明弘 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctorate of Philosophy. / Senecio serratuloides is widely used for wound healing in South Africa but minimal information regarding its efficacy is available. Furthermore toxic pyrrolizidine alkaloids may be present. The following investigation sought firstly to evaluate the efficacy and safety of Senecio serratuloides in a porcine wound model; secondly to assess for a potential mechanism and finally isolate and identify fractions in in-vitro assays. Assessment of Efficacy and Safety Materials and Methods: Deep partial thickness and full thickness wounds were created on 9 pigs. Treatment included an occlusive dressing (negative control), activated carbon, or the Senecio preparation. Wounds were monitored using photographic documentation, pH measurement and histological analysis (skin thickness and collagen content). Toxicity was monitored on blood and liver samples. Results and Discussion: Efficacy of Senecio serratuloides was established with a significantly thicker epidermis, maximal at day 7 post-operative, 2 days before the controls. Effects on collagen content was negligible with no toxicity detected. Mechanistic investigation Materials and Methods: Wound fluid was analysed for IL-10, IL-12, IL-1β, IL-6, IL-8, TNF-α using flow cytometry based assays. Tyrosine phosphorylation and cellular proliferation was assessed using dual immunofluorescence staining. Results and Discussion: IL-1β levels were significantly greater in the Senecio treatment. Tyrosine phosphorylation increased to day 9 post-operative where it stabilised in all groups. In the same period, cellular proliferation was sustained in the Senecio treated wounds but not in the controls. Keratinocyte proliferation was identified as the target for in-vitro assays. Extraction, Isolation and Partial Identification using In-vitro Proliferation Assays. Materials and Methods: The plant was fractionated using solid phase extraction cartridges. Keratinocytes were grown under standard conditions in 96-well plates. Cellular proliferation was assessed spectrophotometrically using a resazurin dye technique. Active fractions were analysed using gas chromatography and mass spectrometry. Results and Discussion: Identified fractions increased the rate of proliferation by 300- 400%. Potential lead compounds were identified. Importantly, pyrrolizidine alkaloids could not be detected. Conclusion Senecio serratuloides is efficacious in treating deep partial thickness wounds without inducing liver toxicity. Sustained keratinocyte proliferation linked to tyrosine phosphorylation may be an underlying mechanism. Although successful, in-vitro detection of active fractions requires further characterisation.

Skin is the largest organ of the body. Its integrity plays a crucial role in maintaining physiological homeostasis, protects against mechanical forces and infections, fluid imbalance, and thermal dysregulation. Numerous pathological states, such as diabetes mellitus, peripheral vascular disease, thermal injuries, or degloving lead to inadequate wound healing, necessitating medical intervention. Established wound healing techniques such as autologous and allogeneic skin grafts are inefficient due to the limited availability of donor tissues or probable immunogenic reactions. Current research in the field of tissue engineering aims to facilitate wound healing and restore skin functionality, focusing on key aspects of wound healing, such as extracellular matrix (ECM) reorganization, cell growth, and collagen synthesis/deposition. The research aims at developing and characterizing an in-vitro fibrin gel culture model system that stimulates the process of wound healing. The specific goal of this research is to investigate how the varied chemical composition of fibrin hydrogels can enhance fibroblast proliferation and promote accelerated collagen matrix formation, which is a significant step in tissue repair and regeneration.The fibrin gels are optimized by modulating the primary gel constituents (i.e. the concentrations of fibrin and thrombin). The ensuing hydrogels are characterized using Scanning Electron Microscope and compression testing to test for fiber size, porosity, elasticity, and mechanical properties. Cultured fibroblasts are used to investigate the effects of varying fibrin concentrations on cell-biomaterial interactions, including cell proliferation, cellular infiltration, and network formation. Furthermore, matrix formation and maturation as a function of fibrinogen concentration as defined by collagen matrix deposition, are also studied. Increasing the fibrinogen concentration, lead to an increase in elasticity and Young’s modulus, while a decrease in thrombin concentration generated a stronger fiber structure. Additionally, a decrease in fibrinogen concentration resulted in an increased proliferation rate of fibroblast cells, suggesting better cell adhesion and network formation within the gel substrate. These results were consistent and confirmed by quantifying a mature collagen matrix deposited by fibroblasts when subjected to ascorbic acid. In summary, this research investigates how the varied chemical composition of fibrin hydrogels can enhance fibroblast proliferation and promote accelerated collagen matrix formation, which is a significant step in tissue repair and regeneration. / Bioengineering

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24137号 / 医博第4877号 / 新制||医||1060(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 上野 英樹, 教授 森本 尚樹, 教授 寺田 智祐 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Angiogenesis is a central process to both physiological and pathological aspects of living organisms. Understanding the angiogenic system via the key mediator, vascular endothelial growth factor (VEGF), has led to the development of biophotonic models capable of monitoring how this process is programmed. The whole animal model tested here is based on the involvement of angiogenesis in a wound healing environment. This model proved to be functional as a system monitor but lacked the precision to yield significant results between the biological compounds tested (estrogen, methoxychlor, and relaxin). The in vitro model is based on angiogenesis in a cancer environment. This model proved to be both a valid and functional way of monitoring the biological compounds tested (CoCl2, epinephrine, and norepinephrine).

No description available.

No description available.

No description available.

Introduktion/Bakgrund: Negative Pressure Wound Therapy är en sårbehandling som är vanlig vid sekundär sårläkning och kan användas på många olika typer av sår. Undertryck skapas med ett specifikt skumförband som placeras i sårhålan och kopplas till en vakuumpump. Syfte: Syftet med litteraturstudien var att beskriva patienters erfarenhet av Negative Pressure Wound Therapy (NPWT). Metod: Litteraturstudien utformades utifrån Polit och Becks (2021) nio steg. I databaserna Cinahl och PubMed genomfördes litteratursökning, samt en kompletterande manuell sökning. Totalt elva artiklar var relevanta för studiens syfte och granskades utifrån granskningsmallarna ”Guide to a Focused Critical Appraisal of Evidence Quality in an Qualitative Research Report” samt “Guide to a Focused Critical Appraisal of Evidence Quality in a Quantitative Research Report. Resultat: Artiklar som belyste patienters erfarenhet av Negative Pressure Wound Therapy resulterade i tre teman: ”Sjuksköterskans kompetens vid NPWT”, ”Påverkan på livssituationen vid NPWT”, samt ”Oro och smärta”. Slutsats: Sjuksköterskans kompetens inom sårbehandling samt Negative Pressure Wound Therapy visade sig ha en stor betydelse för patienters negativa och positiva erfarenheter av Negative Pressure Wound Therapy. Därav finns ett behov av adekvat kompetens hos sjuksköterskor för att patienters behov ska tillgodoses samt för att styrka patientsäkerheten.