Differences in Health-Related Quality of Life After Gastric Bypass Surgery: a Cross-Sectional Study.

BACKGROUND: Gastric bypass (GBP) is a surgical method with good evidence of sustainable weight loss, reduced obesity-related comorbidities, and improved health-related quality of life (HRQoL). However, long-term data post-GBP is scarce on HRQoL related to other factors than weight loss, such as impact of socio-economic, age, and gender. AIM: To investigate long-term HRQoL in GBP patients. METHODS: The study was conducted as a cross-sectional study covering 3 to 9 years post-GBP measuring HRQoL using RAND-36. Association to weight loss, time since surgery, gender, educational level, occupation, and age was analyzed. The participants were included on the basis that they had received a GBP that was performed by Region Skåne, the southernmost administrative healthcare region in Sweden. Recruitment to the study was by mail invitation for an online survey. RESULTS: Of the total population of 5310 persons receiving the questionnaire, 1339 of the 1372 responders fulfilled the inclusion criteria. Those with low educational level, unemployed, persons on sick leave or disability support, and those with less weight loss reported the lowest HRQoL. The longer time since surgery, the lower the HRQoL. CONCLUSION: Less weight loss, longer time since GBP, lower educational level, and lower degree of employment all affect HRQoL negatively after GBP surgery.

Association of coronary calcium score with endothelial dysfunction and arterial stiffness.

BACKGROUND AND AIMS: The aim of the study was to determine potential associations between endothelial dysfunction and arterial stiffness, measured by peripheral arterial tonometry, and coronary artery calcium score (CACS) assessed by computed tomography (CT). METHODS AND RESULTS: The BIG3 study is a prospective longitudinal, non-interventional, pulmonary-cardiovascular cohort study exploring the three major smoking-induced diseases: cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer, in a 45-75 aged cohort (mean 62 years), enriched in smokers. Computed tomography of the chest with assessment of CACS was performed in a selected subset of the participants (n = 2080). Peripheral arterial tonometry (EndoPAT) was used to assess endothelial function and arterial stiffness measured as reactive hyperaemia index (RHI) and augmentation index (AI), respectively. We observed significant associations of CACS, endothelial dysfunction, and arterial stiffness with several risk factors for coronary heart disease including age, sex, BMI, diabetes mellitus, and blood pressure. There was significant association of CACS, classified into three levels of severity, with RHI and AI (p = 0.0005 and p = 0.0009, respectively). For groups of increasing CACS (0, 1-400 and > 400 Agatston score), RHI decreased from median 1.89 (1.58-2.39), and 1.93 (1.62-2.41) to 1.77 (1.51-2.10). AI increased from median 14.3 (5.7-25.2), and 16.4 (8.1-27.6) to 18.0 (9.1-29.2). RHI, but not AI, remained significantly associated with CACS after risk factors adjustment. CONCLUSIONS: In this large study of coronary artery calcium and vascular function, we found an association between CACS and both endothelial dysfunction and arterial stiffness, indicating that they may reflect similar mechanisms for development of cardiovascular disease.

Sustained survival of xenografted human neural stem/progenitor cells in experimental brain trauma despite discontinuation of immunosuppression.

Neural stem cells have emerged as a promising therapeutic tool in CNS disease and injuries. In the clinical setting, cultured human neural stem/progenitor cells (hNSC) are an attractive possibility for transplantation to the damaged brain. However, transplantation of hNSC requires toxic immunosuppressive treatment to avoid rejection. The aim of the current study was to evaluate if shortening the duration of immunosuppression by cyclosporin A would affect hNSC survival and differentiation after transplantation to the site of a focal brain injury in the rat. hNSC were xenografted to the hippocampus and the medial limit of an experimentally induced cortical contusion. The animals received immunosuppression for either 6 or 3 weeks or no immunosuppression. The status of the grafted human cells was analysed by immunohistochemistry. No statistically significant differences were observed between the two immunosuppressed groups regarding graft survival, migration or proliferation at 6 weeks post-transplantation. In contrast, the graft survival was extremely poor in the non-immunosuppressed group. Furthermore, the expression of the differentiation markers nestin, neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) in the transplanted cells did not differ significantly between the two immunosuppressed groups. Moreover, a fourth group of eight animals that were immunosuppressed for 3 weeks were allowed to survive for 6 months. Five of these rats demonstrated robust graft survival in the hippocampus and scattered cells in the cortex. This study demonstrates the importance of immunosuppression but also the possibility of shortening immunosuppression without impacting on the phenotype of the grafted hNSC.

MHC expression after human neural stem cell transplantation to brain contused rats.

Human neural stem cells survive and improve motor function after transplantation to the contused brain. However, the transplants might be rejected and that depends on the graft immunogenicity, the host immunological status and the immunosuppression strategy. We transplanted human neural stem cells to rats with brain contusion and analyzed the donor and host MHC antigen expression and the effect of a short-term immunosuppression with cyclosporine. In vitro human neural stem cells expressed only MHC-II antigens. This expression was down-regulated 6 weeks after transplantation. The host response was characterized by an increased MHC-II expression which was down-regulated by a longer term of immunosuppression. These findings are novel and necessary in order to understand the immunogenicity of human neural stem cell grafts.

Proliferation, migration, and differentiation of human neural stem/progenitor cells after transplantation into a rat model of traumatic brain injury.

OBJECT: Cultures containing human neural stem and progenitor cells (neurospheres) have the capacity to proliferate and differentiate into the major phenotypes of the adult brain. These properties make them candidates for therapeutic transplantation in cases of neurological diseases that involve cell loss. In this study, long-term cultured and cryopreserved cells were transplanted into the traumatically injured rat brain to evaluate the potential for human neural stem/progenitor cells to survive and differentiate following traumatic injury. METHODS: Neural stem/progenitor cell cultures were established from 10-week-old human forebrain. Immunosuppressed adult rats received a unilateral parietal cortical contusion injury, which was delivered using the weight-drop method. Immediately following the injury, these animals received transplants of neural stem/progenitor cells, which were placed close to the site of injury. Two or 6 weeks after the procedure, these animals were killed and their brains were examined by immunohistochemical analysis. At both 2 and 6 weeks postoperatively, the transplanted human cells were found in the perilesional zone, hippocampus, corpus callosum, and ipsilateral subependymal zone of the rats. Compared with the 2-week time point, an increased number of HuN-positive cells was observed at 6 weeks. In addition, at 6 weeks post-injury/transplantation, the cells were noted to cross the midline to the contralateral corpus callosum and into the contralateral cortex. Double labeling demonstrated neuronal and astrocytic, but not oligodendrocytic differentiation. Moreover, the cortex appeared to provide an environment that was less hospitable to neuronal differentiation than the hippocampus. CONCLUSIONS: This study shows that expandable human neural stem/progenitor cells survive transplantation, and migrate, differentiate, and proliferate in the injured brain. These cells could potentially be developed for transplantation therapy in cases of traumatic brain injury.

Neuroprotection by human neural progenitor cells after experimental contusion in rats.

Neural progenitor/stem cells (HNPC) have been suggested to contribute essential trophic factors and promote survival of degenerating neurons after traumatic brain injury. For these reasons we hypothesize that the addition of HNPC to a post-injury region could possibly protect injured neurons. Experimental brain contusions were carried out in 18 rats. Immediately post-injury, rats were injected with 0.1 ml of medium (n=8), dead cells (n=4), or live cells (n=6) in the medial border of the lesion. The rats were sacrificed 6 days post-surgery and evaluated by immunohistochemistry using a human nuclear marker (huN), hematoxylin and Fluoro-Jade (FJ). Human neural stem cells showed engraftment detectable by positive huN staining in 5/6 animals. The non-grafted animal was excluded from further analyses. Those given dead HNPC or medium showed no detectable huN immunoreactivity. A statistical comparison between the numbers of FJ positive degenerating endogenous neurons was made between rats receiving vehicle and dead cells to evaluate whether the presence of human cells would increase neuronal degeneration in comparison to vehicle alone. The rats receiving vehicle had a median of 117.5 FJ positive cells and dead progenitor cell recipients 175.0 per counted section (P<0.05, Mann-Whitney). Consequently, the animals receiving dead human cells were chosen as controls to the animals receiving live progenitor cells. The rats that received live HNPC demonstrated significantly fewer FJ positive cells per counted section than controls (58.0 vs. 175.0, P<0.01, Mann-Whitney). The post-traumatic perilesional environment allowed for the engraftment of live HNPC. The stepwise analysis indicated that host neuronal degeneration was higher in animals transplanted with non-viable human neuronal progenitor cells than in those receiving vehicle, indicating a bystander effect from introducing foreign antigen. In contrast, transplantation of viable progenitor cells attenuated neuronal degeneration, indicating that a potentially beneficial effect in progenitor cell transplantation is not limited to restoration by transplanted cells, but also improving survival of host cells.

Characterization of Bax and Bcl-2 in apoptosis after experimental traumatic brain injury in the rat.

This study was undertaken to fulfill the need for additional data on the dynamics of Bax and Bcl-2 expression in conjunction to the cell death that ensues following experimental brain contusion. Adult Sprague-Dawley rats were subjected to a unilateral experimental controlled cortical contusion and killed at 1, 2, 4, 6 and 10 days post injury (dpi). Cell death was examined by the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method together with immunohistochemistry for cellular markers. Expression of Bax and Bcl-2 were analyzed by immunohistochemistry and in situ hybridization. The number of TUNEL-positive cells was highest at 1 dpi and decreased with time. At all time points, 10-16% of the TUNEL-positive cells showed an apoptotic nuclear morphology. The apoptotic features were restricted to neurons and some inflammatory cells. Immunohistochemistry for Bax revealed a translocation of Bax from a diffuse to a granular distribution in neurons. An up-regulation of Bax mRNA at 6 dpi was discernible. This increase was associated with a statistically significant increase in number of cells with up-regulated and translocated Bax protein. Moreover, a statistically significant increase of Bcl-2 mRNA was detected at 10 dpi. The potential window for anti-apoptotic treatment to salvage neurons is wide. The susceptibility of neurons to necrosis and apoptosis through different pathways during a prolonged post-traumatic period indicate that different pharmacological strategies may be required at different time points after trauma.