Acute effects of ingesting glucose solutions on blood and plasma volume

The change in blood and plasma volume following ingestion of glucose solutions of varying concentrations was estimated in twelve healthy male volunteers. Subjects consumed, within a 5 min period, 600 ml of a solution containing 0, 2, 5 or 10 % glucose with osmolalities of 0 (sd 0), 111 (sd 1), 266 (sd 7) and 565 (sd 5) mOsm/kg, respectively. Blood samples were collected over the course of 1 h after ingestion at intervals of 10 min. After ingestion of the 2 % glucose solution, plasma volume increased from baseline levels at 20 min. Plasma volume decreased from baseline levels at 10 and 60 min after ingestion of the 10 % glucose solution. Heart rate was elevated at 10 and 60 min after ingestion of the 10 % glucose solution and decreased at 30 and 40 min after ingestion of the 2 % glucose solution relative to the average heart rate recorded before drinking. It is concluded that ingestion of hypertonic, energy-dense glucose solutions results in a decrease in plasma and extracellular fluid volume, most likely due to the net secretion of water into the intestinal lumen.     

Postexercise rehydration in man: The effects of osmolality and carbohydrate content of ingested drinks

ObjectiveThis study investigated the effect of the osmolality and carbohydrate content of drinks on their rehydration effectiveness after exercise-induced dehydration.MethodsSix healthy male volunteers were dehydrated by 1.9 ± 0.1% of body mass by intermittent cycle ergometer exercise in the heat before ingesting one of three solutions with different carbohydrate contents and osmolalities over a period of 1 h. Thirty minutes after the cessation of exercise, subjects drank a volume that amounted to 150% (130–150, median [range]) of their body mass loss. Drinks contained 25 mmol/L Na⁺ and 0%, 2%, or 10% glucose with osmolalities of (mean ± SD) 79 ± 4, 193 ± 5, and 667 ± 12 mosm/kg, respectively. Blood and urine samples were collected before exercise, after exercise, and 0, 1, 2, 3, 4, and 6 h after the end of the rehydration period.ResultsSignificantly more of the ingested fluid was retained in the 10% trial (46 ± 9%) than in the 0% trial (27 ± 13%), with 40 ± 14% retained in the 2% trial. Subjects remained euhydrated for 1 h longer in the 10% glucose trial than in the 2% glucose trial. In the 2% glucose trial, plasma volume was elevated immediately after and 1 h after rehydration.ConclusionThis study suggests that, following the rehydration protocol used, hypertonic glucose-sodium drinks may be more effective at restoring and maintaining hydration status after sweat loss than more dilute solutions when the sodium concentration is comparable.     

Function of wild-type or mutant Rac2 and Rap1a GTPases in differentiated HL60 cell NADPH oxidase activation

Studies of neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation in a cell-free system showed that the low molecular-weight guanosine triphosphatase (GTPase) Rac was required, and that Rap1a may participate in activation of the catalytic complex. Full-length posttranslationally modified Rac2 was active, whereas only the 1-166 truncated form of Rap1a was functional in the cell-free system, and thus, clarification of the function of Rap1a and Rac2 in intact human phagocytes is needed to provide further insight into their roles as signal transducers from plasma membrane receptors. In the present studies, oligonucleotide-directed mutagenesis was used to introduce a series of mutations into human rap1a or rac2 in the mammalian expression vector pSR alpha neo. HL60 cells transfected with wild-type or mutated rac2 or rap1a cDNA constructs and control HL60 cells transfected with the pSR alpha neo vector containing no inserted cDNA were selected in G418-containing media, then subclones were isolated. Compared with the parent HL60 cells, each of the stable transfected cell lines differentiated similarly into neutrophil-like cells and expressed comparable levels of NADPH oxidase components p47- phox, p67-phox and gp91-phox. The differentiated vector control cell line produced O2. in response to receptor stimulation at rates that were not significantly different from parent HL60 cells. O2-. production by differentiated cell lines expressing mutated N17 Rap1a or N17 Rac2 dominant-negative proteins was inhibited, whereas O2-. production by the subline overexpressing wild-type Rap1a was increased by fourfold. O2-. production by the differentiated cell line expressing GTPase-defective V12 Rap1a was also significantly inhibited, a finding that is consistent with a requirement for cycling between guanosine diphosphate- and GTP-bound forms of Rap1a for continuous NADPH oxidase activation in intact neutrophils. A model is proposed in which Rac2 mediates assembly of the p47 and p67 oxidase components on the cytosolic face of the plasma membrane via cytoskeletal reorganization, whereas Rap1a functions downstream as the final activation switch involving direct physical interaction with the transmembrane flavocytochrome component of the NADPH oxidase.     

Delayed activation of quiescent donor hematopoietic stem cells in the host marrow cavity by anti-host monoclonal antibody

To understand the mechanisms controlling hematopoietic engraftment in untreated, normal recipients, we investigated the fate of parental, donor hematopoietic stem cells after apparent graft failures in unconditioned F1 hybrid recipient mice. By administering an anti-host H- 2K monoclonal antibody, which targets host cells but spares the donor, we found that chimerism could be induced by delayed conditioning in animals with apparent graft failure. Engraftment kinetics in the host were followed by typing individual colony forming unit-- granulocyte/macrophage (CFU-GM) colonies for their origin and showed that parental cells, which were otherwise virtually absent, become promptly detectable within the marrow cavity after antibody administration. Marrow transfers to secondary hosts suggested that parental stem cells were present in the marrow of the untreated recipients. These findings establish that the elimination of all parental cells cannot account for the absence of peripheral blood chimerism in the unconditioned F1 hybrid recipient. Thus, viable and functional donor stem cells, which remain quiescent in the host marrow, can be activated by a selective conditioning regimen and can rescue an apparent graft failure. The selective activation in vivo of marked stem cells in an unirradiated microenvironment may be a useful system to study the regulation of cellular proliferation within the marrow cavity.     

The Relevance of Health Education to Health Activation and Self-care

Contemporary medical care is a valuable but incomplete approach to health. The individual is coming to be recognized by many providers and consumers of health care alike as the primary health care resource, and individual behaviors and lifestyles are now recognized as the principle determinants of health. A new trend toward health activation is emerging which emphasizes self-care and self-help. This movement is transforming the traditionally passive patient into an active, informed and effective participant in health care and health promotion. The recent interest in programs designed to enhance self-care skills is extremely relevant to health education in the schools and the community. The prime justification of health education has traditionally been one of promoting individual responsibility for generating and maintaining health. Integration of health education concepts may have an overall effect of enhancing health in the United States.     

Inhibition of calcineurin phosphatase activity in adult bone marrow transplant patients treated with cyclosporine A

In vitro studies have demonstrated that cyclosporine A (CsA) acts by inhibiting the phosphatase activity of calcineurin, an important mediator of T-cell activation. The relationship of CsA administration in vivo, calcineurin activity, and graft-versus-host disease (GVHD) has yet to be studied. The calcineurin activities of mononuclear cells isolated from 62 bone marrow transplant recipients and 12 normal volunteers were determined and analyzed with respect to administration of CsA, presence or absence of CsA in plasma, and presence or absence of GVHD. Of 62 patients, 33 were taking CsA and 29 were not. Early posttransplant (< 100 days), the calcineurin activity of patients on CsA was significantly lower than that of patients not on CsA (P = .0004) and than that of normal volunteers (P < .0001). Similarly, late posttransplant (> 100 days), the calcineurin activity of patients taking CsA was inhibited compared with normal volunteers (P < .05). The calcineurin activity of patients with acute GVHD who were taking CsA was lower than that of patients on CsA without acute GVHD matched for time posttransplant (P = .02). Calcineurin activity in patients on CsA with chronic GVHD was similar to those without chronic GVHD on drug. In conclusion, calcineurin activity is significantly suppressed by in vivo administration of CsA. The lower calcineurin activity of patients on CsA with acute GVHD suggests that CsA-resistant GVHD is not the result of inadequate suppression of calcineurin activity. These data suggest that if inhibition of calcineurin is the only physiologic target of CsA administration, simply increasing doses of CsA or treatment with other inhibitors of calcineurin, such as FK506, would not be expected to ameliorate GVHD.