Knowledge and motivation to adopt recommended health behaviours to reduce dementia risk among the elderly in Norway: a qualitative study.

OBJECTIVES: Dementia is a major healthcare challenge; however, there is evidence that modifiable risk factors may contribute to reduce dementia risk. The aim of the study was to explore the knowledge and motivation for adopting recommended health behaviours among older adults in Norway. STUDY DESIGN: The study has a qualitative, descriptive design. METHODS: Individual interviews were used for data collection. The study population comprised 15 participants, five men and 10 women, aged ≥73 years, recruited from a region in the centre of Norway. Interviews were analysed according to qualitative content analysis. RESULTS: Three categories were identified and presented as the main findings, as follows: (1) sufficient knowledge about risk reduction for dementia, including the media as the main source of information; (2) current prevention activities and motivation for risk reduction, including physical, social and cognitive activities and a healthy diet; and (3) motivation for prevention of dementia from a life-course perspective, including experience of health problems, desire to live independently and limited awareness of dementia risk factors in midlife. CONCLUSIONS: To tailor information about the modifiable risk factors of dementia and develop preventive interventions, knowledge about motivating factors is essential. Promotion of healthy ageing is required in addition to addressing the fear of future illness and dependency.

Cost analysis of day care centres in Norway.

BACKGROUND: Day care services aim to offer meaningful activities and a safe environment for the attendees and a respite for family caregivers while being cost effective. This study compares the use of formal and informal care in users and non-users of day care centres designed for persons with dementia. METHOD: Users of day care designed for dementia (DC group) and non-users (NDC group) were followed over a period of 24 months or until nursing home admission (NHA) respectively death. Demographic and clinical characteristics were collected at baseline and after 12 and 24 months. The use of care was recorded by Resource Utilization in Dementia (RUD). RESULTS: A total of 257 persons with dementia participated in the study, 181 in the DC group and 76 in the NDC group. Users of day care centres cause higher costs due to the expenses for day care, while neither the use of home nursing, secondary care, informal care nor the time until NHA did show any differences between users and non-users. The overall costs were higher in the DC group at baseline and after 12 months, but this difference was no longer present at the end of the two-year study period. CONCLUSION: Our results indicate no potential cost-saving effect of day care designed for people with dementia, as the use of day care did neither result in a reduced use of care nor in a delay of NHA. Future research should balance the non-monetary benefits of day care against its costs for a full cost-effectiveness analysis, most favourable in a RCT-design.

Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia.

Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1-0.3% O2 for 8 h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8 ± 3.5% in encapsulated and 42.9 ± 5.2% in nonencapsulated islets (P < 0.2). Nonencapsulated islets released 37.7% (median) more HMGB1 compared to encapsulated islets after hypoxic culture conditions (P < 0.001). Glucose-induced insulin release was marginally affected by hypoxia. Basal oxygen consumption was equally reduced in encapsulated and nonencapsulated islets, by 22.0 ± 6.1% versus 24.8 ± 5.7%. Among 27 tested cytokines/chemokines, hypoxia increased the secretion of IL-6 and IL-8/CXCL8 in both groups of islets, whereas an increase of MCP-1/CCL2 was seen only with nonencapsulated islets. Conclusion. Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation.

Evaluation of different types of alginate microcapsules as bioreactors for producing endostatin.

The use of nonautologous cell lines producing a therapeutic substance encapsulated within alginate microcapsules could be an alternative way of treating different diseases in a cost-effective way. Malignant brain tumors have been proposed to be treated locally using engineered cells secreting proteins with therapeutic potential encapsulated within alginate microcapsules. Optimization of the alginate capsule bioreactors is needed before this treatment can be a reality. Recently, we have demonstrated that alginate-poly-L-lysine microcapsules made with high-G alginate and a gelled core disintegrated as cells proliferated. In this study we examined the growth and endostatin secretion of 293-EBNA (293 endo) cells encapsulated in six different alginate microcapsules made with native high-G alginate or enzymatically tailored alginate. Stability studies using an osmotic pressure test showed that alginate-poly-L-lysine-alginate microcapsules made with enzymatically tailored alginate was mechanically stronger than alginate capsules made with native high-G alginate. Growth studies showed that the proliferation of 293 endo cells was diminished in microcapsules made with enzymatically tailored alginate and gelled in a barium solution. Secretion of endostatin was detected in lower amounts from the enzymatically tailored alginate microcapsules compared with the native alginate microcapsules. The stability of the alginate microcapsules diminished as the 293 endo cells grew inside the capsules, while empty alginate microcapsules remained stable. By using microcapsules made of fluorescenamine-labeled alginate it was clearly visualized that cells perforated the alginate microcapsules as they grew, destroying the alginate network. Soluble fluorescence-labeled alginate was taken up by the 293 endo cells, while alginate was not detected in live spheroids within fluorescence-labeled alginate microcapsules. Despite that increased stability was achieved by using enzymatically tailored alginate, the cell proliferation destroyed the alginate microcapsules with time. It is therefore necessary to use cell lines that have properties more suited for alginate encapsulation before this technology can be used for therapy.

Intravital microscopy reveals novel antivascular and antitumor effects of endostatin delivered locally by alginate-encapsulated cells.

The current study describes new, antivascular, and antitumor effects of human endostatin. A novel system for continuous, localized delivery of antiangiogenic compounds to brain tumors was used. The delivery system was composed of endostatin-producing 293 cells encapsulated into immuno-isolating sodium alginate. Intravital multifluorescence microscopy was used to assess vascular and antitumor effects of endostatin in C6 glioma spheroids implanted into an ectopic as well as an orthotopic setting. Analysis of total and functional vascular density, microvascular diameters, vessel perfusion, tumor growth, and tumor cell migration were performed repetitively. Tumor growth was reduced by 35% in treated animals. It was of interest that tumor cell invasion into the surrounding tissue was also inhibited. The total vascular density was reduced by 67.6%, perfusion by 67%, and vessel diameters by 37%. This resulted in a significant reduction in tumor perfusion, although the vessel permeability was not influenced. We have demonstrated that human endostatin not only reduces total vascular density, as shown previously, but also greatly reduces the functionality and the diameters of the vessels. Furthermore, we show that this therapeutic approach also inhibits tumor cell invasion, thus supporting the hypothesis that tumor angiogenesis and invasion represent two interrelated processes. Finally, this work further confirms the new therapeutic concept using alginate cell-encapsulation technology for the localized delivery of therapeutic compounds to central nervous system malignancies.

Poly-L-Lysine induces fibrosis on alginate microcapsules via the induction of cytokines.

Alginate-poly-L-lysine (PLL) microcapsules can be used for transplantation of insulin-producing cells for treatment of type I diabetes. In this work we wanted to study the inflammatory reactions against implanted microcapsules due to PLL. We have seen that by reducing the PLL layer, less overgrowth of the capsule is obtained. By incubating different cell types with PLL and afterwards measuring cell viability with MTT, we found massive cell death at concentrations of PLL higher than 10 microg/ml. Staining with annexin V and propidium iodide showed that PLL induced necrosis but not apoptosis. The proinflammatory cytokine, tumor necrosis factor (TNF), was detected in supernatants from monocytes stimulated with PLL. The TNF response was partly inhibited with antibodies against CD14, which is a well-known receptor for lipopolysaccharide (LPS). Bactericidal permeability increasing protein (BPI) and a lipid A analogue (B-975), which both inhibit LPS, did not inhibit PLL from stimulating monocytes to TNF production. This indicates that PLL and LPS bind to different sites on monocytes, but because they both are inhibited by a p38 MAP kinase inhibitor, they seem to have a common element in the signal transducing pathway. These results suggest that PLL may provoke inflammatory responses either directly or indirectly through its necrosis-inducing abilities. By combining soluble PLL and alginate both the toxic and TNF-inducing effects of PLL were reduced. The implications of these data are to use alginate microcapsules with low amounts of PLL for transplantation purposes.

Transplantation of alginate microcapsules with proliferating cells in mice: capsular overgrowth and survival of encapsulated cells of mice and human origin.

Alginate microcapsules may be used to encapsulate therapeutic cells and, thereby, to protect them from the host immune system. Both the biomaterial, as well as the therapeutic cells, may give rise to immunological reactions. We have developed methods that are useful in the study of capsule biocompatibility, as well as reactions against the grafts. These imply investigation of the survival of the encapsulated cells as well as fibrotic reactions against the microcapsules. Studies were performed in Balb/c mice with empty alginate-PLL-alginate microcapsules as well as microcapsules containing cells of human or mouse origin. Confocal laser scanning microscopy (CLSM) was used to visualize live and dead cells within the microcapsules and to define some of the cells involved in the fibrotic reaction against the microcapsules. In both grafts, live cells were detected seven days after transplantation. Minor fibrotic reactions were found against empty alginate-PLL-alginate microcapsules and to microcapsules containing mouse cells. An extensive fibrotic reaction was found one week after transplantation against microcapsules containing human cells, and the secretion of therapeutic protein endostatin had ceased. Fibroblasts and macrophages were involved in the fibrotic reaction against the xenograft.