Global gene expression patterns in the post-pneumonectomy lung of adult mice

<p>Abstract</p> <p>Background</p> <p>Adult mice have a remarkable capacity to regenerate functional alveoli following either lung resection or injury that exceeds the regenerative capacity observed in larger adult mammals. The molecular basis for this unique capability in mice is largely unknown. We examined the transcriptomic responses to single lung pneumonectomy in adult mice in order to elucidate prospective molecular signaling mechanisms used in this species during lung regeneration.</p> <p>Methods</p> <p>Unilateral left pneumonectomy or sham thoracotomy was performed under general anesthesia (n = 8 mice per group for each of the four time points). Total RNA was isolated from the remaining lung tissue at four time points post-surgery (6 hours, 1 day, 3 days, 7 days) and analyzed using microarray technology.</p> <p>Results</p> <p>The observed transcriptomic patterns revealed mesenchymal cell signaling, including up-regulation of genes previously associated with activated fibroblasts (Tnfrsf12a, Tnc, Eln, Col3A1), as well as modulation of Igf1-mediated signaling. The data set also revealed early down-regulation of pro-inflammatory cytokine transcripts and up-regulation of genes involved in T cell development/function, but few similarities to transcriptomic patterns observed during embryonic or post-natal lung development. Immunohistochemical analysis suggests that early fibroblast but not myofibroblast proliferation is important during lung regeneration and may explain the preponderance of mesenchymal-associated genes that are over-expressed in this model. This again appears to differ from embryonic alveologenesis.</p> <p>Conclusion</p> <p>These data suggest that modulation of mesenchymal cell transcriptome patterns and proliferation of S100A4 positive mesenchymal cells, as well as modulation of pro-inflammatory transcriptome patterns, are important during post-pneumonectomy lung regeneration in adult mice.</p

Growth factor-enriched autologous plasma improves wound healing after surgical debridement in odontogenic necrotizing fasciitis: a case report

<p>Abstract</p> <p>Background</p> <p>Odontogenic necrotizing fasciitis of the neck is a fulminant infection of odontogenic origin that quickly spreads along the fascial planes and results in necrosis of the affected tissues. It is usually polymicrobial, occurs frequently in immunocompromised patients, and has a high mortality rate.</p> <p>Case presentation</p> <p>A 69-year old Mexican male had a pain in the maxillar right-canine region and a swelling of the submental and submandibular regions. Our examination revealed local pain, tachycardia, hyperthermia (39°C), and the swelling of bilateral submental and submandibular regions, which also were erythematous, hyperthermic, crepitant, and with a positive Godet sign. Mobility and third-degree caries were seen in the right mandibular canine. Bacteriological cultures isolated <it>streptococcus pyogenes </it>and <it>staphylococcus aureus</it>. The histopathological diagnosis was odontogenic necrotizing fasciitis of the submental and submandibular regions. The initial treatment was surgical debridement and the administration of antibiotics. After cultures were negative, the surgical wound was treated with a growth factor-enriched autologous plasma eight times every third day until complete healing occurred.</p> <p>Conclusions</p> <p>The treatment with a growth factor-enriched autologous plasma caused a rapid healing of an extensive surgical wound in a patient with odontogenic necrotizing fasciitis. The benefits were rapid tissue regeneration, an aesthetic and a functional scar, and the avoidance of further surgery and possible complications.</p

Effects of retinoic acid on compensatory lung growth

<p>Abstract</p> <p>Background</p> <p>We investigated the effect of Retinoic acid in the growth of contralateral lung after pneumonectomy.</p> <p>Methods</p> <p>Twentyone adult male Wistar albino rats from the same colony were used. They were divided into three groups (Group A, B and C). Group A undergone only left posterolateral thoracotomy. In Group B and C, the rats were subjected to left posterolateral thoracotomy and left pneumonectomy. In Group C, rats were given intraperitoneal Retinoic acid during the operation and continued to be given everyday postoperatively. Rats were sacrificed on the 10^thday and their total body, right lung weights and right lung volumes were measured.</p> <p>Results</p> <p>The volume and weight indices of the lung were found to be higher in Group C. In histopathological examination, there was a reduction in the mean number of alveoli in Group B and C. A significant rise in the mean dimension and average wall thickness of the alveolar structure were determined in Group C.</p> <p>Conclusion</p> <p>Retinoic acid contributes to the compensatory growth of the residual lung tissue.</p

The use of the Airtraq® optical laryngoscope for routine tracheal intubation in high-risk cardio-surgical patients

<p>Abstract</p> <p>Background</p> <p>The Airtraq^®optical laryngoscope (Prodol Ltd., Vizcaya, Spain) is a novel disposable device facilitating tracheal intubation in routine and difficult airway patients. No data investigating routine tracheal intubation using the Airtaq^®in patients at a high cardiac risk are available at present. Purpose of this study was to investigate the feasibility and hemodynamic implications of tracheal intubation with the Aitraq^®optical laryngoscope, in high-risk cardio-surgical patients.</p> <p>Methods</p> <p>123 consecutive ASA III patients undergoing elective coronary artery bypass grafting were routinely intubated with the Airtraq^®laryngoscope. Induction of anesthesia was standardized according to our institutional protocol. All tracheal intubations were performed by six anesthetists trained in the use of the Airtraq^®prior.</p> <p>Results</p> <p>Overall success rate was 100% (n = 123). All but five patients trachea could be intubated in the first attempt (95,9%). 5 patients were intubated in a 2nd (n = 4) or 3rd (n = 1) attempt. Mean intubation time was 24.3 s (range 16-128 s). Heart rate, arterial blood pressure and SpO₂were not significantly altered. Minor complications were observed in 6 patients (4,8%), i.e. two lesions of the lips and four minor superficial mucosal bleedings. Intubation duration (p = 0.62) and number of attempts (p = 0.26) were independent from BMI and Mallampati score.</p> <p>Conclusion</p> <p>Tracheal intubation with the Airtraq^®optical laryngoscope was feasible, save and easy to perform in high-risk patients undergoing cardiac surgery. In all patients, a sufficient view on the vocal cords could be obtained, independent from BMI and preoperative Mallampati score.</p> <p>Trial Registration</p> <p>DRKS 00003230</p

Angiogenesis gene expression in murine endothelial cells during post-pneumonectomy lung growth

Although blood vessel growth occurs readily in the systemic bronchial circulation, angiogenesis in the pulmonary circulation is rare. Compensatory lung growth after pneumonectomy is an experimental model with presumed alveolar capillary angiogenesis. To investigate the genes participating in murine neoalveolarization, we studied the expression of angiogenesis genes in lung endothelial cells. After left pneumonectomy, the remaining right lung was examined on days 3, 6, 14 and 21days after surgery and compared to both no surgery and sham thoracotomy controls. The lungs were enzymatically digested and CD31+ endothelial cells were isolated using flow cytometry cell sorting. The transcriptional profile of the CD31+ endothelial cells was assessed using quantitative real-time polymerase chain reaction (PCR) arrays. Focusing on 84 angiogenesis-associated genes, we identified 22 genes with greater than 4-fold regulation and significantly enhanced transcription (p <.05) within 21 days of pneumonectomy. Cluster analysis of the 22 genes indicated that changes in gene expression did not occur in a single phase, but in at least four waves of gene expression: a wave demonstrating decreased gene expression more than 3 days after pneumonectomy and 3 sequential waves of increased expression on days 6, 14, and 21 after pneumonectomy. These findings indicate that a network of gene interactions contributes to angiogenesis during compensatory lung growth

Egr-1 Regulates Autophagy in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear. Methodology and Principal Findings: Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3b, LC3B, Atg4, Atg5/12, Atg.7). Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1-1- mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema. Conclusions: We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury. © 2008 Chen et al