Background: Alzheimer's disease is a disease that primarily affects the elderly but also younger people. Alzheimer's disease is a type of dementia which means that you get changes in the cerebral cortex and cells gradually die. The disease causes memory loss and things that were obvious before will be difficult for the sufferer. Alzheimer's disease also affects next of kin to a large degree; they will have to take a great responsibility. The next of kin are entitled to support from healthcare. Aim: The aim was to highlight next of kin' experiences of healthcare to their family members with Alzheimer's disease. Method : The study was based on narratives, which in this case means analysis of autobiographies. Five biographies were analyzed in accordance with Dahlborg-Lyckhage Results : Four categories and eleven subcategories emerged which were based on what the next of kin had experienced. The experiences were reflected in four categories: powerlessness, joy in caring, grief and lack of trust. This result shows gaps in knowledge and treatment of relatives. To make it easier for the next of kin caregivers should for example provide information on the course of the disease, get individual support and caregivers should take next of kin seriously. Conclusion : Alzheimer's disease affects the entire family. It is important that nurses take their responsibility by providing information and support to the next of kin so that they can better deal with the situation. The next of kin are an important part of the sufferer's life and have influence for the development of the disease.

Bakgrund: Demens tillhör en av Sveriges största folksjukdomar och idag finns det cirka 150 000 personer som lider utav någon form av demenssjukdom, varav Alzheimers sjukdom är den vanligaste formen. Sjukdomen medför kognitiv nedsättning som successivt försämras under sjukdomsförloppet och ställer då allt högre krav på den sjukes familj. Syfte: Att beskriva upplevelsen av att vara anhörig till en person med Alzheimers sjukdom. Metod: Studien utfördes som en litteraturöversikt där 15 kvalitativa artiklar granskades och analyserades. Resultat: I resultatet framkom det att anhöriga upplevde en mängd olika känslor under sjukdomsprocessen, vilka kunde skilja sig beroende på vilken relation de hade till den sjuke. Känslorna var såväl positiva som negativa, med dominans av den negativa upplevelsen. Anhöriga upplevde bland annat ovisshet, sorg, förändrade roller, skuld och längtan efter det tidigare livet. Slutsats: När en person drabbas av Alzheimers sjukdom påverkas hela familjen och en stor livsförändring sker. Eftersom sjuksköterskan ofta är en naturlig samtalspartner är det viktigt att hon uppmärksammar den anhöriges upplevelser och genom förståelsen kan hon hjälpa anhöriga att uppleva situationen som meningsfull. Denna studie är menad att belysa anhörigas upplevelser och medvetandegöra att såväl den sjuke som dess anhörige är i behov av omtanke och stöd. / Background: Dementia is one of Sweden's most common diseases, and there are today currently about 150 000 people suffering of some form of dementia, of which Alzheimer's disease is the most common form. The disease results in cognitive impairment that gradually deteriorate during the course of the disease and be more demanding for their family. Aim: To describe the experience of being a relative of a person with Alzheimer's disease. Method: The study was performed as a literature study in which 15 qualitative articles were reviewed and analyzed. Result: The results revealed that relatives experienced a variety of emotions during the disease process, which could vary depending on the relationship they had for the ill familymember. The feelings were both positive and negative, with the dominance of the negative experience. Relatives perceived among other things uncertainty, grief, changing roles, guilt and longing for the past life. Conclusion: Since nurses often are a natural interlocutor, it´s important that they recognizes relative's experiences and through this understanding, they can support relatives to experience the situation as meaningful. This study is meant to highlight the family's experiences and awareness that both the ill family member and his or her relative is in need of kindness and support.

Stem cells have the ability to reproduce themselves for a long period and differentiate into specific morphological and functional cells. The stem cells are an important material in the developmental biology, genomics, and transgenic methods, as well as in potential clinical applications, gene therapy and tissue engineering. The pluripotent stem cells will be a valuable source in numerous functional degenerated pathologies. Therefore, the objective of this research program was to establish transgenic porcine embryonic stem (pES) cell lines which can express green fluorescent protein (GFP) report gene stably for tracking after transplantation. We also developed a directed differentiation of pES into neural lineages and applied in rat Parkinson¡¦s disease model. Although the establishment of pluripotent ES cell lines from domestic species is much more difficult than that in murine species, our results had successfully isolated and established pES cell lines from pre-implantation blastocysts. Furthermore, we established the novel GFP-expressing pES cell lines (pES/GFP+), which were obtained by electroporation- mediated transfection with exogenous GFP gene. These pES/GFP+ cells exhibited pluripotent markers including Oct-4, AP, SSEA-4, TRA-1-60, and TRA-1-81 as that of human ES cells. The strategy of directed neural differentiation was to culture pES with neurogenic stimulators such as retinoic acid (RA), sonic hedgehog (SHH), and fibroblast growth factor (FGF). Upon directed differentiation toward neural differentiation, these pES-derived cells exhibited typical neuronal morphology and expressed neural lineage-specific markers such as nestin, NFL, MAP2, GFAP, A2B5, TH, ChAT, and GABA. These results showed the pES cells had the potential to differentiate into neural lineages. When pES/GFP+ cells were transplanted into the SD rat¡¦s brain, and their survival and development was determined by the non-invasive In Vivo Imaging System (IVIS 50), and the invasive fibered confocal Cellvizio® Imaging System (Cellvizio®). The results showed that fluorescent signals from pES/GFP+ cells on the injection site of SD rats¡¦ brain could be detected through the experimental period of 3 months. The level of fluorescent signals detected in treatment groups was two folds above that of the control group. Besides, the functional behavior recovery analysis by amphetamine-induced rotation test indicated the PD rat grafted with pES/GFP+ cells and their derived neural progenitors showed no significant recovery of rotation rate in these two treatments because a progressively increased relative rotation through 3 months duration. However, the relative rotation of PD rats grafted with the pES/GFP+-derived mature neurons, showed a stably decrease relative rotation and resulted in a functional recovery from Parkinsonian behavioral defects. Following 3 months completion of behavioral analyses, PD rats were sacrificed for immunohistochemical analysis. In the section of injected site without tumorgenesis and showed the survival and dopaminergic differentiation of grafted pES/GFP+ derived cells when stained with anti-TH and anti-DA. To our knowledge, there have been no reports of establishing GFP-expressing pES cell lines. These novel pES/GFP+ cell lines established in this study might serve as a non-rodent model and could benefit to the studies involving ES cell transplantation, cell replacement therapy, tissue regeneration, and actual approach for pre-clinical research due to their traceable capacity.

Discovery of the ability of mesenchymal stem cells (MSCs) to differentiate into cells of non-mesodermal tissues, particularly neuronal cells, have raised the possibility of utilising MSCs in regenerative/reparative therapies for neurological disorders. However, a number of hurdles remain to be resolved. This thesis aims to address some of these issues by investigating the characteristics of bone marrow-derived human MSCs (hMSCs) during long-term culture, the potential of hMSCs to differentiate in vitro toward the neuronal lineage under the influence of cytokines, and the effects of intracerebral transplantation in the hemiparkinsonian rat model. During expansion culture hMSCs were found to display the expected characteristics of MSC populations, and also constitutively expressed neural and pluripotency markers simultaneously with mesodermal markers. Analysis of hMSC long-term subcultivation revealed an optimal period for commencing neuronal differentiation (first 6-8 passages), and also showed the absence of spontaneous neural differentiation. Application of neural-inducing cytokines and culture conditions resulted in the generation of an immature neuronal-like phenotype by hMSCs. Through live cell microscopy it was demonstrated for the first time that cytokine-based hMSC neuronal differentiation occurs through active and dynamic cellular processes involving outgrowth and motility of cellular extensions. In addition, single- and multiple-stage cytokine-based strategies for inducing dopaminergic neuronal-like cells from hMSCs were investigated. These studies revealed that FGF-2 and EGF exerted the greatest benefits for hMSC neuronal differentiation. Undifferentiated and neuronal-primed hMSCs were transplanted intracerebrally into the striatum and substantia nigra of cyclosporine-treated hemiparkinsonian rats. Grafted hMSCs could be clearly identified at 1-day and 7-days post-transplantation; however, grafts were gradually lost over time, with complete absence by 21-days. Co-transplantation with olfactory ensheathing cells, neuronal-priming prior to grafting, and nigral as well as striatal grafting could not provide engraftment and differentiation advantages. Immunohistological analysis demonstrated the presence of innate inflammatory responses (microglia and astrocyte activation) at graft sites, fibronectin deposition by hMSCs, and lack of endogenous host neurogenesis. The results of my PhD work indicate that cytokine-based culture methods are capable of differentiating hMSCs to an immature neuronal-like phenotype, and host-mediated innate inflammatory responses may be a key contributing factor for the failure of in vivo hMSC engraftment.

Discovery of the ability of mesenchymal stem cells (MSCs) to differentiate into cells of non-mesodermal tissues, particularly neuronal cells, have raised the possibility of utilising MSCs in regenerative/reparative therapies for neurological disorders. However, a number of hurdles remain to be resolved. This thesis aims to address some of these issues by investigating the characteristics of bone marrow-derived human MSCs (hMSCs) during long-term culture, the potential of hMSCs to differentiate in vitro toward the neuronal lineage under the influence of cytokines, and the effects of intracerebral transplantation in the hemiparkinsonian rat model. During expansion culture hMSCs were found to display the expected characteristics of MSC populations, and also constitutively expressed neural and pluripotency markers simultaneously with mesodermal markers. Analysis of hMSC long-term subcultivation revealed an optimal period for commencing neuronal differentiation (first 6-8 passages), and also showed the absence of spontaneous neural differentiation. Application of neural-inducing cytokines and culture conditions resulted in the generation of an immature neuronal-like phenotype by hMSCs. Through live cell microscopy it was demonstrated for the first time that cytokine-based hMSC neuronal differentiation occurs through active and dynamic cellular processes involving outgrowth and motility of cellular extensions. In addition, single- and multiple-stage cytokine-based strategies for inducing dopaminergic neuronal-like cells from hMSCs were investigated. These studies revealed that FGF-2 and EGF exerted the greatest benefits for hMSC neuronal differentiation. Undifferentiated and neuronal-primed hMSCs were transplanted intracerebrally into the striatum and substantia nigra of cyclosporine-treated hemiparkinsonian rats. Grafted hMSCs could be clearly identified at 1-day and 7-days post-transplantation; however, grafts were gradually lost over time, with complete absence by 21-days. Co-transplantation with olfactory ensheathing cells, neuronal-priming prior to grafting, and nigral as well as striatal grafting could not provide engraftment and differentiation advantages. Immunohistological analysis demonstrated the presence of innate inflammatory responses (microglia and astrocyte activation) at graft sites, fibronectin deposition by hMSCs, and lack of endogenous host neurogenesis. The results of my PhD work indicate that cytokine-based culture methods are capable of differentiating hMSCs to an immature neuronal-like phenotype, and host-mediated innate inflammatory responses may be a key contributing factor for the failure of in vivo hMSC engraftment.

This thesis describes management of the patients with Alzheimer's disease. I elucidate the issues of Alzheimer's disease. I identify and quantify costs by Cost of Illness from the patient's perspective. I find the level of awareness of the nursing staff on Alzheimer's disease. In conclusion I evaluate results of research.

No description available.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23070号 / 医博第4697号 / 新制||医||1049(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 花川 隆, 教授 溝脇 尚志, 教授 高橋 淳 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Magister Pharmaceuticae - MPharm / Neurodegenerative diseases (ND) are chronic and progressive in nature, and characterized by the gradual loss of neurons in various regions of the central nervous system (CNS). ND include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and cerebral ischemia/reperfusion (CIR). They have various progressive neurodegenerative pathologies that can result in several severe functional impairments for patients, and ultimately lead to serious health-related issues. According to more recent data, AD accounts for the most common cause of dementia and is believed to contribute to approximately 60–70% of cases. AD is thus seen as the most common form of dementia.

Mycobacterium avium subspecies paratuberculosis (map) is an intracellular pathogen that is known to parasitize macrophages and monocytes. Map infiltrates gastrointestinal tract host tissue where it is the known etiological agent of johne's disease in ruminants and implicated in the etiology of crohn's disease in humans. Map's ability to survive within macrophages enables it to disseminate throughout the rest of the host, possibly infecting other circulating blood leukocytes. In this study, the survival and fate of map strain atcc 43015 (human isolate) following phagocytosis was determined using in vitro murine macrophage cell line j774a.1 and polymorphonuclear cells (pmnc's) from five crohn's disease patients. Pmnc's from three healthy individuals and two ulcerative colitis patients, as well as escherichia coli (atcc 11303) and mycobacterium tuberculosis strain h37ra (atcc 25177), were included as controls (moi 10:1). Maturation of the phagosome was determined by evaluating the presence of stage specific markers on the surface of the phagosomal membrane. The endosomal protein, transferrin receptor, and the lysosomal marker, lamp-1, were then immunostained with cy-5 conjugated secondary antibodies, and colocalization of bacteria with each marker was evaluated separately using confocal scanning laser microscopy (cslm). In both tissue models, colocalization of viable map and m. Tuberculosis with the early endosomal marker, transferrin receptor occurred with an estimated five fold higher frequency than did association with the late lysosomal marker, lamp-1, as compared to live e. Coli, and all dead bacterial species. Using differential live/dead staining and fluorescent microscopy, survival of m. Tuberculosis and map was estimated at 85% and 79%, respectively compared to only 14% for e. Coli. The outcome was similar for both tissue culture and pmncs from all patients tested, suggesting that map and m. Tuberculosis can survive readily in both cell types, and regardless of the disease state of the host or the killing power of the cell. Map's survival appears to mimic m. Tuberculosis', suggesting the ability to resist phagolysosome fusion, by maintaining association with the early endosomes. Overall, the data confirms map virulence in host human blood leukocytes.