Current Issue : April - June Volume : 2013 Issue Number : 2 Articles : 6 Articles
Acute lung injury (ALI) describes one or more initiating assaults either directly to the lungs or systemically that, if not\r\ntreated in a timely manner, ultimately progresses to the development of acute respiratory distress syndrome (ARDS) a\r\ncondition which is characterized by atelectasis, pulmonary hypertension, and an intense, overwhelming inflammatory\r\nresponse that leads to obliterating pulmonary fibrosis and ultimately respiratory failure. The long-term complications\r\nassociated with ALI/ARDS can be subverted if the fibrotic phase of the disease is suppressed; therefore, it is essential\r\nto control inflammation in such a way that endogenous self-protection mechanisms are maintained while not allowing\r\nescalating inflammatory damage to occur in the local environment of the lungs. Current treatment strategies focus on\r\noptimal ventilator management and treatment of the underlying condition. Cell-based approaches are an attractive\r\noption for directed therapeutic intervention for ALI/ARDS. In particular, mesenchymal stem cells (MSCs) from bone\r\nmarrow, adipose, umbilical cord, and lung tissue as well as induced pluripotent stem (iPS) cells have been shown to\r\nfacilitate lung repair in several animal models of ALI. The exact mechanism(s) by which these cells accomplish this\r\nfeat are as yet unknown; however, mounting evidence suggests that they possess potent immunomodulatory and anti-\r\nmicrobial capabilities which diminish the injury-induced inflammatory responses and reduce infection-mediated ALI,\r\nrespectively, in these various models. Both direct delivery of stem cells to the lung and systemic administration have\r\nbeen somewhat effective, suggesting that stem cells utilize paracrine mechanisms, at least in part, to perform these\r\nfunctions. Aside from their endogenous ability to suppress inflammation and infection, gene-modified MSCs and iPS\r\ncells have recently been used as vehicles for carrying anti-inflammatory agents to the lung. Taken together, stem cell\r\ntherapy is a promising alternative to current therapeutic intervention for ALI/ARDS....
Supplementation with n-3 polyunsaturated fatty acids, both in dietary in vivo studies, as well as in vitro tissue culture models, has anti-proliferative effects on tumor cells. In the current study, the role of p53-dependent growth inhibition by docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, is examined. Previous work has established that DHA is capable of growth inhibitory effects independent of p53 mutational status in colon carcinomas, however, one of the same studies showed an increase in the number of apoptotic cells (measured by Annexin V-FITC) only in the DHAtreated cells of the colon carcinoma with wildtype p53. To determine the potential role of p53 on the growth inhibition observed with DHA treatment of the human colon carcinomas COLO-205 (wildtype p53) and WiDr (mutant p53, His 237) and the human lung adenocarcinomas A549 (wildtype p53) and H441 (mutant p53, codon 158), p53-specific siRNA�s and a chemical inhibitor of p53, pifithrin-a, were employed in vitro. Significant increases in the number of DHA-treated cells by p53 siRNA or pifithrin-a addition were observed only in the COLO-205 and A549 cell lines expressing wildtype p53, and these correlated with a reduction in the percentage of apoptotic and necrotic cells. This data confirms a role for p53-dependent growth inhibition with DHA treatment....
Mesenchymal stem cells are able to differentiate in various cell lineages and they have shown immunomodulatory properties in vitro, altering the cytokine secretion profile of T helper, T effector and dendritic cells and stimulating natural killer cells towards an anti-inflammatory and tolerant phenotype. In vivo they prolong skin allograft survival and may decrease graft-versus-host disease after hematopoietic stem cell transplants. In this work we studied the effects of mesenchymal stem cell treatment in an allogeneic heterotopic heart-lung transplant model.\r\n \r\nThe following experimental groups were formed: A) Control B) Immunosuppressive therapy (Cyclosporine A) C) Mesenchymal stem-cell intravenous infusion D) Mesenchymal stem-cell infusion plus immunosuppressive treatment.\r\n \r\nThe infusion of mesenchymal stem cells improved the mean graft survival up to 14.5�±3.7 days with respect to the control group (3�±0.6 days). Treatment with Cyclosporine A plus mesenchymal stem cells (group D) produced a mean survival time of 18.25�±4.9 days, and was not significantly different to the results for group B (21.75�±3.5 days). Furthermore, in the immunosuppressive treatment and the mesenchymal stem cell treatment, histological analysis revealed a reduction in the grade of rejection in heart and lung grafts. This decrease was most significant in group D.\r\n \r\nIn conclusion, mesenchymal stem cells alone or in combination with Cyclosporine A were able to prolong graft survival time. These data suggest that, in vivo, mesenchymal stem cells retain their ability, already shown in vitro, to suppress lymphocyte activation and proliferation....
Parenchymal lung diseases are the main cause of persistent pulmonary hypertension of the newborn (PPHN).We aimed to assess\r\nthe non cardiac conditions associated to PPHN in the newborn and the survival rate over the last 15 years, at our center. A\r\nretrospective chart review of the neonates admitted for PPHN from 1996 to 2010 was performed. New therapies were introduced\r\nin 2003, and the survival rates between two periods (1996ââ?¬â??2002 and 2003ââ?¬â??2010) were compared. Out of 6750 newborns, 78 (1.1%)\r\nhad the diagnosis of PPHN of non cardiac cause. The most prevalent causes were associated to pulmonary hypoplasia (30.7%),\r\ninfection (24.3%), and aspiration syndromes (15.3%). Many other causes were identified in 33.3%. The overall survival rate was\r\n68%. There was a significant difference on survival rates between the two periods (1996ââ?¬â??2002 = 63.8% and 2003ââ?¬â??2010 = 71.4%,\r\nP = 0.04). Our study showed a myriad of non cardiac aetiologies for PPHN of the newborn, most of them related to lung disease\r\nor lung hypoplasia.We observed an improvement in survival rate since 2003, which was associated to the use of new therapies....
Surfactant protein-C (SP-C) is a lung cell specific protein whose expression is identified from the earliest stages of mammalian lung development in a subset of developing epithelial cells and in the alveolar type II cell in the mature lung. Although SP-C gene expression is not critical and protein function is not necessary for the normal developing morphological patterning of the lung, studies of SP-C protein mutations and SP-C deficiency have revealed critical roles of SP-C in the maintenance and function of the preterm and mature lung during various forms of intrinsic or extrinsic lung injury. This review summarizes studies using in vitro experimental approaches, in vivo modeling in transgenic mice, and analysis of human disease pathogenesis. Collected data reveal an essential role for SP-C singly and in combination with other lung proteins, in maintenance of lung structure and pulmonary function of the immature and mature lung....
Background. Oxygen uptake efficiency slope (OUES) is a reproducible, objective marker of cardiopulmonary function. OUES is\r\nreported as being relatively independent of exercise intensity. Practical guidance and criteria for reporting OUES from submaximal\r\ntests has not been established. Objective. Evaluate the use of respiratory exchange ratio (RER) as a secondary criterion for reporting\r\nOUES. Design. 100 healthy volunteers (53 women) completed a ramped treadmill protocol to exhaustive exercise. OUES was\r\ncalculated from data truncated to RER levels from 0.85 to 1.2 and compared to values generated from full test data. Results. Mean\r\n(sd) OUES from full test data and data truncated to RER 1.0 and RER 0.9 was 2814 (718), 2895 (730), and 2810 (789) mL/min\r\nper 10-fold increase in VE, respectively. Full test OUES was highly correlated with OUES from RER 1.0 (r = 0.9) and moderately\r\ncorrelated with OUES from RER 0.9 (r = 0.79). Conclusion. OUES values peaked in association with an RER level of 1.0. Submaximal\r\nOUES values are not independent of exercise intensity. There is a significant increase in OUES value as exercise moves\r\nfrom low to moderate intensity. RER can be used as a secondary criterion to define this transition....
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