29 research outputs found

    Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor

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    Induction of lipolysis in murine white adipocytes, and stimulation of adenylate cyclase in adipocyte plasma membranes, by a tumour-produced lipid mobilizing factor, was attenuated by low concentrations (10−7–10−5 M) of the specific β3-adrenoceptor antagonist SR59230A. Lipid mobilizing factor (250 nM) produced comparable increases in intracellular cyclic AMP in CHOK1 cells transfected with the human β3-adrenoceptor to that obtained with isoprenaline (1 nM). In both cases cyclic AMP production was attenuated by SR59230A confirming that the effect is mediated through a β3-adrenoceptor. A non-linear regression analysis of binding of lipid mobilizing factor to the β3-adrenoceptor showed a high affinity binding site with a Kd value 78±45 nM and a Bmax value (282±1 fmole mg protein−1) comparable with that of other β3-adrenoceptor agonists. These results suggest that lipid mobilizing factor induces lipolysis through binding to a β3-adrenoceptor

    Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids

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    The aim of the study was to assess the total energy expenditure (TEE), resting energy expenditure (REE) and physical activity level (PAL) in home-living cachectic patients with advanced pancreatic cancer. The influence of an energy and protein dense oral supplement either enriched with or without the n-3 fatty acid eicosapentaenoic acid (EPA) and administered over an 8-week period was also determined. In total, 24 patients were studied at baseline. The total energy expenditure was measured using doubly labelled water and REE determined by indirect calorimetry. Patients were studied at baseline and then randomised to either oral nutritional supplement. Measurements were repeated at 8 weeks. At baseline, REE was increased compared with predicted values for healthy individuals (1387(42) vs 1268(32) kcal day-1, P=0.001), but TEE (1732(82) vs 1903(48) kcal day-1, P=0.023) and PAL (1.24(0.04) vs 1.50) were reduced. After 8 weeks, the REE, TEE and PAL of patients who received the control supplement did not change significantly. In contrast, although REE did not change, TEE and PAL increased significantly in those who received the n-3 (EPA) enriched supplement. In summary, patients with advanced pancreatic cancer were hypermetabolic. However, TEE was reduced and this was secondary to a reduction in physical activity. The control energy and protein dense oral supplement did not influence the physical activity component of TEE. In contrast, administration of the supplement enriched with EPA was associated with an increase in physical activity, which may reflect improved quality of life

    On-farm practices for the safe use of wastewater in urban and peri-urban horticulture

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    The drafting of this handbook was initiated in October 2007, in Ghana, by Ines Beernaerts, in the framework of the FAOKNUST project on “Evaluation of non-treatment options for maximizing public health benefits of WHO guidelines governing the use of wastewater in urban vegetable production in Ghana”. The Farmer Field School (FFS) approach was introduced in the FAO-KNUST project and materialized in this handbook to enhance the experimental learning of the (peri-) urban farmers. The best practices described in this handbook were designed and field-tested in a project funded by the CGIAR Challenge Program on Water and Food (CPWF) under the coordination of the Kwame Nkrumah University of Science and Technology (KNUST) and the International Water Management Institute (IWMI). This initiative was taken to enable the project to go beyond research and ensure the sustainability of the results

    The relationship of air pollution and surrogate markers of endothelial dysfunction in a population-based sample of children

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    <p>Abstract</p> <p>Background</p> <p>This study aimed to assess the relationship of air pollution and plasma surrogate markers of endothelial dysfunction in the pediatric age group.</p> <p>Methods</p> <p>This cross-sectional study was conducted in 2009-2010 among 125 participants aged 10-18 years. They were randomly selected from different areas of Isfahan city, the second large and air-polluted city in Iran. The association of air pollutants' levels with serum thrombomodulin (TM) and tissue factor (TF) was determined after adjustment for age, gender, anthropometric measures, dietary and physical activity habits.</p> <p>Results</p> <p>Data of 118 participants was complete and was analyzed. The mean age was 12.79 (2.35) years. The mean pollution standards index (PSI) value was at moderate level, the mean particular matter measuring up to 10 μm (PM<sub>10</sub>) was more than twice the normal level. Multiple linear regression analysis showed that TF had significant relationship with all air pollutants except than carbon monoxide, and TM had significant inverse relationship with ozone. The odds ratio of elevated TF was significantly higher in the upper vs. the lowest quartiles of PM<sub>10</sub>, ozone and PSI. The corresponding figures were in opposite direction for TM.</p> <p>Conclusions</p> <p>The relationship of air pollutants with endothelial dysfunction and pro-coagulant state can be an important factor in the development of atherosclerosis from early life. This finding should be confirmed in future longitudinal studies. Concerns about the harmful effects of air pollution on children's health should be considered a top priority for public health policy; it should be underscored in primordial and primary prevention of chronic diseases.</p

    B and T lymphocyte attenuator mediates inhibition of tumor-reactive CD8+ T cells in patients after allogeneic stem cell transplantation.

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    Allogeneic stem cell transplantation (allo-SCT) can cure hematological malignancies by inducing alloreactive T cell responses targeting minor histocompatibility antigens (MiHA) expressed on malignant cells. Despite induction of robust MiHA-specific T cell responses and long-term persistence of alloreactive memory T cells specific for the tumor, often these T cells fail to respond efficiently to tumor relapse. Previously, we demonstrated the involvement of the coinhibitory receptor programmed death-1 (PD-1) in suppressing MiHA-specific CD8(+) T cell immunity. In this study, we investigated whether B and T lymphocyte attenuator (BTLA) plays a similar role in functional impairment of MiHA-specific T cells after allo-SCT. In addition to PD-1, we observed higher BTLA expression on MiHA-specific CD8(+) T cells compared with that of the total population of CD8(+) effector-memory T cells. In addition, BTLA's ligand, herpes virus entry mediator (HVEM), was found constitutively expressed by myeloid leukemia, B cell lymphoma, and multiple myeloma cells. Interference with the BTLA-HVEM pathway, using a BTLA blocking Ab, augmented proliferation of BTLA(+)PD-1(+) MiHA-specific CD8(+) T cells by HVEM-expressing dendritic cells. Notably, we demonstrated that blocking of BTLA or PD-1 enhanced ex vivo proliferation of MiHA-specific CD8(+) T cells in respectively 7 and 9 of 11 allo-SCT patients. Notably, in 3 of 11 patients, the effect of BTLA blockade was more prominent than that of PD-1 blockade. Furthermore, these expanded MiHA-specific CD8(+) T cells competently produced effector cytokines and degranulated upon Ag reencounter. Together, these results demonstrate that BTLA-HVEM interactions impair MiHA-specific T cell functionality, providing a rationale for interfering with BTLA signaling in post-stem cell transplantation therapies
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