Diabetes impairs mobilization of mouse bone marrow-derived Lin(-)/VEGF-R2(+) progenitor cells.

Endothelial progenitor cells circulating in the peripheral blood (PB) contribute to vascular repair. This study aimed to evaluate the potential of a 'cocktail' consisting of erythropoietin, granulocyte colony-stimulating factor and tetrahydrobiopterin to mobilize hematopoietic lineage negative/vascular endothelial growth factor receptor 2 positive (Lin(-)/VEGF-R2(+)) cells from the bone marrow (BM) to PB in non-diabetic and diabetic mice. Diabetes was induced in mice by intraperitoneal injection of streptozotocin. Diabetic mice were studied after 16weeks of hyperglycemia. Half the mice in each group (non-diabetic and diabetic) received daily intraperitoneal injections of the cocktail for 6 consecutive days while the other half received vehicle buffer. Mobilization of Lin(-)/VEGF-R2(+) cells, which were expanded in MCP301 medium, was evaluated after isolating them from BM and PB and their phenotypic and morphological properties were studied. We found that 16weeks of diabetes affected neither the total number of BM mononucleated cells nor the number of Lin(-)/VEGF-R2(+) cells in BM compared with non-diabetic controls. In non-diabetic mice, cocktail treatment resulted in a significant decrease in BM Lin(-)/VEGF-R2(+) cells, paralleled by a significant increase of these cells in PB. Such changes in the number of Lin(-)/VEGF-R2(+) cells in BM and PB after the cocktail treatment were less marked in diabetic mice. In vitro studies of BM Lin(-)/VEGF-R2(+) cells from diabetic and non-diabetic mice did not reveal any differences in either phenotypes or colony forming potential. These findings indicate that diabetes impairs the mobilization of Lin(-)/VEGF-R2(+) cells from BM to PB. Impaired mobilization of BM Lin(-)/VEGF-R2(+) cells soon after the onset of diabetes may contribute to complications such as diabetic retinopathy.

Successful Single-Lung Transplant for Severe Lung Graft-Versus-Host Disease Two Years After Sibling Allograft for Acute Lymphoblastic Leukemia: A Case Report.

Bone marrow transplantation (BMT) has been performed as a successful life-saving treatment for hematological and neoplastic diseases. Despite the predictable long-term survival rates in BMT, pulmonary complications reduce the survival rates significantly mainly because of chronic graft-versus-host disease (GVHD). This report briefly discusses a successful lung transplantation case for severe lung GVHD after allograft for acute lymphoblastic leukemia. This case report supports the scarce evidence in the literature for the importance of lung transplantation as a therapeutic option for patients who develop respiratory failure secondary to BMT.

A quantitative method to detect fucoidan in human plasma using a novel antibody.

We have developed an antibody-based method to assess plasma uptake of a proprietary Undaria-derived fucoidan galactofucan sulfate (GFS(TM)) after oral ingestion by human volunteers. Fucoidans have high-molecular-weights but exert biological effects in experimental animals after oral intake. By using a novel antibody raised against sulfated polysaccharides, we carried out a competitive ELISA to quantitate GFS in plasma samples from healthy volunteers who ingested 3 g/day of whole Undaria containing 10% GFS fucoidan, purified 75% GFS fucoidan, or 3 g of a nonsulfated placebo polysaccharide over 12 days. Increased reactivity to the novel antibody, as measured against preingestion levels, was detected at all time points. Assuming the measured material to be intact GFS, the concentration detected (median) was 4.002 and 12.989 mg/l when 3 g of 10% or 75% pure fucoidan was ingested orally over a period of 12 days, respectively. High-molecular-weight fucoidan can be detected in plasma using an ELISA competitive assay based on a novel antibody to sulfated polysaccharides.

Exposure of human erythrocytes to oxygen radicals causes loss of deformability, increased osmotic fragility, lipid peroxidation and protein degradation.

The effects of two oxygen radical generating systems (H2O2 and ascorbate/Fe+2) on erythrocyte deformability, osmotic fragility, lipid peroxidation and protein degradation were studied. Incubation of erythrocytes with different concentrations of H202 (5-20 mM) or ascorbate/Fe+2 (10/0.1-40/0.4 mM) caused a loss of deformability and increased osmotic fragility. The loss of deformability has occurred in a dose-dependent fashion and was proportional to the extent of malonyldialdehyde (an indicator of lipid peroxidation) and alanine production (an indicator of protein degradation). Prior exposure of the erythrocytes to carbon monoxide (known to inhibit heme-protein degradation) prevented almost completely the loss in deformability caused by H2O2, indicating that the loss in deformability was due mainly to protein degradation rather than to lipid peroxidation. Erythrocytes incubated with either of the two systems have also shown morphologic changes characterized by a dose-dependent increase in echinocyte formation. The results indicate the importance of oxidatively damaged proteins in compromising the rheologic behaviour of the erythrocytes, particularly when the free radicals are involved.

Dietary algae and HIV/AIDS: proof of concept clinical data.

Dietary algae have been reported to decrease HIV viral fusion/entry and replication and increase immune response, suggesting that regular consumption of algae by people in Japan, Korea, and Chad could be an important factor in their relatively low HIV/AIDS rates. Five antiretroviral-naïve people with HIV (three females, two males; five African Americans) living in Columbia SC participated in the phase I study of acute toxicity. Subjects were randomly assigned to 5 g day(-1) brown seaweed (Undaria pinnatifida), Spirulina (Arthrospira platensis), or a combination of both. Endpoints included HIV viral load, complete blood count (CBC), metabolic and lipid panel, and quality of life questionnaire data. When no short-term toxicities were observed, six additional subjects (four females, two males; five African Americans, one Latina) were recruited to further evaluate short- and long-term toxicities (phase II). No adverse effects were observed for the 11 subjects in the phase I trial, and quality of life indicators improved at 3 weeks. No significant changes were observed in CBC, metabolic or lipid panel analyses. CD4 cells (milliliters) and HIV-1 viral load remained stable over the first 3-month phase II study period. One subject continued in the study for 13 months and had clinically significant improvement in CD4 (>100 cells mL(-1)) and decreased HIV viral load of 0.5 log(10). Our pilot data suggest that Undaria, Spirulina, and a combination of both were nontoxic and over time may improve clinical endpoints of HIV/AIDS.