The cytokine network in inflammatory bowel disease (IBD) is a complex, dynamic system that plays an important role in regulating mucosal innate and adaptive immune responses. While several studies have been done to evaluate immunomodulatory profiles in murine IBD, they have been limited to a relatively small number of cytokines that do not take into account its dependency of the interplay of multiple factors, and therefore the diagnostic potential of their cytokine profiles have been inconclusive. Herein we demonstrate a novel approach of comprehensive serum multiplex cytokine profiling to describe the modulation of 16 Th1, Th2, Th17 cytokines and chemokines in both acute and chronic murine models of DSS and TNBS-induced colitis. Distinctive disease-specific cytokine profiles were identified with significant correlations to disease activity and duration of disease. TNBS colitis exhibits heightened Th1-Th17 response (increased IL-12 and IL-17) as the disease becomes chronic. In contrast, DSS colitis switches from a Th1-Th17-mediated acute inflammation (increased TNFα, IL6, IL-17 and KC) to a predominant Th2-mediated inflammatory response (increase in IL-4 and IL-10 and concomitant decrease in TNFα, IL6, IL-17 and KC) in the chronic state. Profiles of multiple cytokines seen systemically were also validated locally in colonic mucosa. Moreover, advanced multivariate analyses identified discriminatory cytokine profiles that can be sufficiently used to distinguish unaffected controls from diseases, and one disease type from another. IL-6 and IL-12 stratified gender-associated disease activity in chronic colitis. Our studies provide insight into disease immunopathogenesis and illustrate the significant potential of utilizing multiplex cytokine profiles and bioinformatics as diagnostic tools in IBD.
Introduction This retrospective cohort study compared clinical and radiographic outcomes of endodontic treatment performed in immature non-vital permanent teeth, by apexification (calcium hydroxide or apical barrier with Mineral Trioxide Aggregate (MTA)), versus revascularization. Methods A comprehensive chart review was performed to obtain a cohort of sequential previously completed cases with recalls. Clinical and radiographic data were collected for 31 treated teeth (19 revascularization and 12 apexification) with an average follow up time of 17 months and a recall rate of 63%. Tooth survival, success rate, and adverse events were analyzed. Changes in radiographic root length, width and area were quantified. Results The majority of treated teeth survived throughout the study period with 30/31 (97%) teeth surviving (18/19 (95%) revascularization, 12/12 apexification). Most cases were also clinically successful with 27/31 (87%) meeting criteria for success, (15/19 (78%) revascularization and 12/12 apexification; non-significant difference). A greater incidence of adverse events was observed in the revascularization group (8/19 (42%) versus 1/12 (11%) in apexification (Risk Ratio= 5.1, p=0.04, 95%CI (0.719, 35.48)). Although more revascularization cases than apexification cases demonstrated an increase in radiographic root area and width, the effect was not statistically significant. Conclusion In this study, revascularization was not superior to other apexification techniques in either clinical or radiographic outcomes. Studies with large subject cohorts, and long follow up periods are needed to evaluate outcomes of revascularization and apexification, while accounting for important co-variants relevant to clinical success.
ObjectiveTo determine if long-term (7 days) infusion of insulin can ameliorate altered protein kinetics in skeletal muscle of severely burned patients and to investigate the hypothesis that changes in protein kinetics during insulin infusion are associated with an increased rate of transmembrane amino acid transport from plasma into the intracellular free amino acid pool. Summary Background DataIn critically ill patients, vigorous nutritional support alone may often fail tb entirely curtail muscle catabolism; insulin stimulates muscle protein synthesis in normal volunteers. MethodsNine patients with severe burns were studied once during enteral feeding alone (control period), and once after 7 days of high-dose insulin. The order of treatment with insulin was randomized.Data were derived from a model based on a primed-continuous infusion of L-[15N]phenylalanine, sampling of blood from the femoral artery and vein, and biopsies of the vastus lateralis muscle. ResultsNet leg muscle protein balance was significantly (p < 0.05) negative during the control period. Exogenous insulin eliminated this negative balance by stimulating protein synthesis approximately 350% (p < 0.01). This was made possible in part by a sixfold increase in the inward transport of amino acids from blood (p < 0.01). There was also a significant increase in leg muscle protein breakdown. The new rates of synthesis, breakdown, and inward transport during insulin were in balance, such that there was no difference in the intracellular phenylalanine concentration from the control period. The fractional synthetic rate of protein in the wound was also stimulated by insulin by approximately 50%, but the response was variable and did not reach significance. ConclusionsExogenous insulin may be useful in promoting muscle protein synthesis in severely catabolic patients. 283
Data indicate that high doses of insulin and glucose can be safely administered to massively burned patients to improve wound matrix formation.
ObjectiveThe authors provide an update on a multidisciplinary approach to the treatment of severely burned patients. A review of studies and clinical trials from the past to the present include fluid resuscitation, sepsis, immune function, hypermetabolism, early excision, wound healing, scar formation, and inhalation injury. Summary Background DataAdvances in treating initial burn shock, infection control, early wound closure, and modulation of the hypermetabolic response have decreased morbidity and mortality in the last two decades. Specialized burn care centers, using a multidisciplinary approach, not only successfully treat large burns and their complications, but provide the necessary rehabilitation and psychological support required for readjustment back into society. ConclusionsThermal injury results in a number of physiologic alterations that can be minimized by adequate fluid resuscitation to maintain tissue perfusion, early excision of burn wounds, and rapid wound coverage. These measures, in combination with antibiotic coverage and nutritional support in the form of early enteral tube feedings, will decrease the hypermetabolic response and the incidence of sepsis that can lead to hemodynamic instability and organ failure. Ongoing clinical trials using anabolic agents (e.g., recombinant human growth hormone) and pharmacologic agents that modulate inflammatory and endocrine mediators (e.g., ibuprofen and propranolol) show promise in the treatment of severe burn injuries.Major burns are relatively common injuries that require multidisciplinary treatment for patient survival and recovery. More than 1 million burn injuries occur annually in the United States. Although most of these burn injuries are minor, 60,000 to 80,000 people require admission to a hospital or to a major burn center for treatment, and 5000 of these patients die each year. In recent years, advances in burn treatment have reduced mortality rates and have improved the quality of life for burn survivors. Improvements have been made in treating initial burn shock, providing appropriate resuscitation, controlling infections, and performing life-saving and scar-reducing surgical interventions. Team efforts by surgeons, nurses, scientists, and a vast array oftherapists are making productive and social lives possible for many burn victims.Thermal injury is associated with anatomic, physiologic, endocrinologic, and immunologic alterations, which require specialized care. Cutaneous injury results
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