Short-term use of an exposed polypropylene barrier in the preservation of alveolar bone after extraction: randomized clinical trial.

This study was performed to evaluate the short-term preservation of alveolar bone volume with or without a polypropylene barrier and exposure of the area after extractions. Thirty posterior tooth extraction sockets were distributed randomly to a control group (n=15; extraction and suture) and a barrier group (n=15; extraction, barrier, and suture). All sutures and barriers were removed 10 days postoperatively. Cone beam computed tomography scans taken with the aid of a tomographic guide were obtained preoperatively, immediately postoperative, and at 120 days postoperative. A visual analysis of the coronal sections of the alveolus was performed, and vertical loss in the mesial, distal, buccal, and lingual bone ridges and horizontal thickness were evaluated. The mean vertical loss after extraction did not differ significantly between the control and barrier groups (Student t-test: mesial P= 0.989, buccal P= 0.997, lingual/palatal P= 0.070, distal P= 0.107). The mean vertical loss at 120 days postoperative did not differ significantly between the control (0.65 mm) and barrier (0.52 mm) groups (P> 0.05), with an effect size of 0.13 mm. At 120 days, the barrier group presented a mean resorption in thickness (0.45 mm) that was significantly lower than that in the control group (0.76 mm) (P= 0.021), with an effect size of 0.31 mm. The polypropylene barrier reduced the horizontal resorption in sockets of posterior teeth after extraction.

Perspectives of the International Society for Cell & Gene Therapy Gastrointestinal Scientific Committee on the Intravenous Use of Mesenchymal Stromal Cells in Inflammatory Bowel Disease (PeMeGi).

Inflammatory bowel disease (IBD), namely, Crohn's disease and ulcerative colitis, remains a grievous and recalcitrant problem incurring significant human and health care costs, even in consideration of the growing incidence. Initial goals of care aimed to achieve the induction and maintenance of clinical remission. The advent of novel treat-to-target approaches using patient stratification, early introduction of immunosuppressants and rapid escalation to biologics or early use of combination therapy has refocused the goals of care toward the achievement of mucosal healing. This is in an attempt to preserve intestinal function, decrease hospitalization and surgery rates and improve the quality of life of affected patients. Cellular therapeutics for the treatment of IBD offers an unprecedented opportunity to change the current paradigm from single-targeted to systems-targeted therapy, trying to dampen the whole inflammatory cascade instead of a only molecule. Therefore, as we move forward, the importance of designing informative and possibly adaptive trial designs, standardizing methodologies, harmonizing goals of therapy and evaluating methods cannot be underemphasized. In this article, we review the current literature on the application of mesenchymal stromal cells for the treatment of IBD in an effort to establish a consensus on designing efficient and consistent clinical trials for the intravenous use of this cellular therapy in IBD.

DNA microarray analysis of gene expression in alveolar epithelial cells in response to TNFalpha, LPS, and cyclic stretch.

Recent evidence suggests that alveolar epithelial cells (AECs) may contribute to the development, propagation, and resolution of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Proinflammatory cytokines, pathogen products, and injurious mechanical ventilation are important contributors of excessive inflammatory responses in the lung. In the present study, we used cDNA microarrays to define the gene expression patterns of A549 cells (an AEC line) in the early stages of three models of pulmonary parenchymal cell activation: cells treated with tumor necrosis factor-alpha (TNFalpha) (20 ng/ml), lipopolysaccharide (LPS, 1 microg/ml), or cyclic stretch (20% elongation) for either 1 h or 4 h. Differential gene expression profiles were determined by gene array analysis. TNFalpha induced an inflammatory response pattern, including induction of genes for chemokines, inflammatory mediators, and cell surface membrane proteins. TNFalpha also increased genes related to pro- and anti-apoptotic proteins, signal transduction proteins, and transcriptional factors. TNFalpha further induced a group of genes that may form a negative feedback loop to silence the NFkappaB pathway. Stimulation of AECs with mechanical stretch changed cell morphology and activated Src protein tyrosine kinase. The combination of TNFalpha plus stretch enhanced or attenuated expression of multiple genes. LPS decreased microfilament polymerization but had less impact on NFkappaB translocation and gene expression. Results from this study indicate that AECs can tailor their response to different stimuli or/and combination of stimuli and subsequently play an important role in acute inflammatory responses in the lung.

Overview of high-frequency ventilation modes, clinical rationale, and gas transport mechanisms.

HFV has been demonstrated to be a safe and effective way to ventilate and oxygenate patients, both short- and long-term, when used by experienced practitioners. It has carved out a niche in the specific management of respiratory problems in children and neonates; however, as understanding of the variables that independently contribute to VILI evolves, it is becoming clear that this mode of ventilation may be suited to the goals of lung protection. In addition, it is accepted also that initial assessment of HFV as a lung-protective strategy has failed to take into consideration significant variables that have been shown to be important in animal studies. This may have caused this mode of ventilation to be over looked as a possible strategy in the management of patients with severe lung disease. A number of trials are underway using ventilatory approaches based on current concepts of VILI, including improved CMV strategies. It is hoped that the results of these studies will identify the future role for HFV in the clinical setting.

Invited review: mechanisms of ventilator-induced lung injury: a perspective.

Despite advances in critical care, the mortality rate in patients with acute lung injury remains high. Furthermore, most patients who die do so from multisystem organ failure. It has been postulated that ventilator-induced lung injury plays a key role in determining the negative clinical outcome of patients exposed to mechanical ventilation. How mechanical ventilation exerts its detrimental effect is as of yet unknown, but it appears that overdistension of lung units or shear forces generated during repetitive opening and closing of atelectatic lung units exacerbates, or even initiates, significant lung injury and inflammation. The term "biotrauma" has recently been elaborated to describe the process by which stress produced by mechanical ventilation leads to the upregulation of an inflammatory response. For mechanical ventilation to exert its deleterious effect, cells are required to sense mechanical forces and activate intracellular signaling pathways able to communicate the information to its interior. This information must then be integrated in the nucleus, and an appropriate response must be generated to implement and/or modulate its response and that of neighboring cells. In this review, we present a perspective on ventilator-induced lung injury with a focus on mechanisms and clinical implications. We highlight some of the most recent findings, which we believe contribute to the generation and propagation of ventilator-induced lung injury, placing a special emphasis on their implication for future research and clinical therapies.

Expression of the Fanconi anemia gene FAC in human cell lines: lack of effect of oxygen tension.

Fanconi anemia (FA) is a recessively inherited disease characterized by bone marrow failure, congenital anomalies, chromosomal instability and hypersensitivity to crosslinking agents. Some of the cellular defects of FA are known to be responsive to the ambient oxygen concentration. We examined the responsiveness of the FA complementation group C (FAC) gene to changes in oxygen concentration using two types of human cell lines, hypoxia-responsive Hep3B hepatoma cells and Epstein-Barr virus-immortalized lymphoblasts (normal and FA complementation groups B and C). Although the expression of erythropoietin in Hep3B cells was induced in response to the hypoxia-mimicking agent CoCl2, there was no concomitant induction in FAC expression as assessed by mRNA levels and immunoprecipitable protein, and no detectable change in the cytoplasmic location of the FAC polypeptide as determined by indirect immunofluorescence. In human lymphoblasts we examined the effect of oxygen (0.1% -95% O2) on cell proliferation and FAC expression. FA lymphoblasts had a normal sensitivity to the cytostatic effect of hyperoxia, while in both control and FA lymphoblasts FAC mRNA levels were unaffected by oxygen. Our results indicate that ambient oxygen is not a regulator of the FAC gene.

Fanconi anemia revisited: old ideas and new advances.

This review summarizes both historical and more recent data on the clinical, cellular and genetic features of Fanconi anemia (FA), a rare autosomal recessive disorder. FA patients are characterized by pancytopenia, congenital malformations, growth delay and an increased susceptibility to the development of malignancies, particularly acute myelogenous leukemia. FA cells show chromosomal fragility, slow growth and increased sensitivity to DNA crosslinking agents. FA can be caused by defects in any one of at least four genes. Two general hypotheses have been proposed to explain the underlying defect: loss of a DNA repair function or of a step in the defense toward oxygen toxicity. After many attempts to clone the FA genes, the first one, that defective in group C, has been cloned by complementation of the increased sensitivity of FA(C) cells to mitomycin C and diepoxybutane. This gene (FACC) codes for a novel protein and is ubiquitously expressed. Mutations in various FA(C) patients that cause loss of function have been identified. The review concludes by suggesting directions for future research in FA.