Irreversible and permanent damage develop immediately adjacent to the region of reduced cerebral blood perfusion in stroke patients. Currently, the proven thrombolytic treatment for stroke, tissue plasminogen activator, is only effective when administered within 3 h after stroke. These disease characteristics should be taken under consideration in developing any therapeutic intervention designed to widen the narrow therapeutic range, especially cell-based therapy. Over the past several years, our group and others have characterized the therapeutic potential of human umbilical cord blood cells for stroke and other neurological disorders using in vitro and vivo models focusing on the cells' ability to differentiate into nonhematopoietic cells including neural lineage, as well as their ability to produce several neurotrophic factors and modulate immune and inflammatory reaction. Rather than the conventional cell replacement mechanism, we advance alternative pathways of graft-mediated brain repair involving neurotrophic effects resulting from release of various growth factors that afford cell survival, angiogenesis, and anti-inflammation. Eventually, these multiple protective and restorative effects from umbilical cord blood cell grafts may be interdependent and act in harmony in promoting therapeutic benefits for stroke.
Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual bloodderived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells.
Introduction Neurological disorders are routinely characterized by loss of cells in response to an injury or a progressive insult. Stem cells could therefore be useful to treat these disorders. Sources of data Pubmed searches of recent literature. Areas of agreement Stem cells exhibit proliferative capacity making them ideally suited for replacing dying cells. However, instead of cell replacement therapy stem cell transplants frequently appear to work via neurotrophic factor release, immunomodulation and upregulation of endogenous stem cells. Areas of controversy and areas timely for developing research Many questions remain with respect to the use of stem cells as a therapy, the answers to which will vary depending on the disorder to be treated and mode of action. Whereas the potential tumorigenic capability of stem cells is a concern, most studies do not support this notion. Further determination of the optimal cell type, and whether to perform allogeneic or autologous transplants warrant investigation before the full potential of stem cells can be realized. In addition, the use of stem cells to develop disease models should not be overlooked.
Background: The quantitative effect of strong electrolytes, pCO 2 , and plasma protein concentration in determining plasma pH and bicarbonate concentrations can be demonstrated with the physicochemical approach. Plasma anion gap (AG) and strong ion gap (SIG) are used to assess the presence or absence of unmeasured anions.Hypotheses: The physicochemical approach is useful for detection and explanation of acid-base disorders in horses with colitis. AG and SIG accurately predict hyperlactatemia in horses with colitis.Animals: Fifty-four horses with acute colitis and diarrhea. Methods: Retrospective study. Physicochemical variables were calculated for each patient. ROC curves were generated to analyze sensitivity and specificity of AG and SIG for predicting hyperlactatemia.Results: Physicochemical interpretation of acid-base events indicated that strong ion metabolic acidosis was present in 39 (72%) horses. Mixed strong ion acidosis and decreased weak acid (hypoproteinemia) alkalosis was concomitantly present in 17 (30%) patients. The sensitivity and specificity of AG and SIG to predict hyperlactatemia (L-lactate > 5 mEq/L) were 100% (95% CI, 66.4-100; P < .0001) and 84.4% (95% CI, 70.5-93.5 P < .0001). Area under the ROC curve for AG and SIG for predicting hyperlactatemia was 0.95 (95% CI, 0.86-0.99) and 0.93 (95% CI, 0.83-0.99), respectively.Conclusion and Clinical relevance: These results emphasize the importance of strong ions and proteins in the maintenance of the acid-base equilibria. AG and SIG were considered good predictors of clinically relevant hyperlactatemia.
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