Since the lung is repeatedly subjected to injury by pathogens and toxicants, maintenance of pulmonary homeostasis requires rapid repair of its epithelial surfaces. Ciliated bronchiolar epithelial cells, previously considered as terminally differentiated, underwent squamous cell metaplasia within hours after bronchiolar injury with naphthalene. Expression of transcription factors active in morphogenesis and differentiation of the embryonic lung, including ␤-catenin, Foxa2, Foxj1, and Sox family members (Sox17 and Sox2), was dynamically regulated during repair and redifferentiation of the bronchiolar epithelium after naphthalene injury. Squamous cells derived from ciliated cells spread beneath injured Clara cells within 6-12 h after injury, maintaining the integrity of the epithelium. Dynamic changes in cell shape and gene expression, indicating cell plasticity, accompanied the transition from squamous to cuboidal to columnar cell types as differentiation-specific cell markers typical of the mature airway were restored. Similar dynamic changes in the expression of these transcription factors occurred in ciliated and Clara cells during regeneration of the lung after unilateral pneumonectomy. Taken together, these findings demonstrate that ciliated epithelial cells spread and transdifferentiate into distinct epithelial cell types to repair the airway epithelium. Keywords: naphthalene; lung injury; transcription; pneumonectomy; bronchioleThe respiratory tract has an extensive cell surface that is directly exposed to inhaled gases, particles, and pathogens. A complex epithelium lines the airways, mediating gas exchange, mucociliary clearance, host defense, and surfactant homeostasis to maintain lung sterility and stability. While the adult lung is not mitotically active, respiratory epithelial cells can proliferate rapidly after injury to maintain lung structure and function.Models in which relatively rare subsets of nonciliated respiratory epithelial cells located in unique environments play critical roles in lung repair have been proposed (1-5). Krause and coworkers have provided evidence that extrapulmonary, bone marrow-derived cells migrate to the lung, contributing to the repair of the respiratory epithelium after injury (6). From a stochastic view, however, models in which rare progenitor cells account for the rapid and extensive repair of the lung are not compatible with the observed short period of proliferation and rapid restoration of epithelial surfaces that is observed after catastrophic injury caused by infection or toxicants. Rather, the remarkable repair capacity of the lung is more consistent with a model in (Received in original form August 30, 2005 and in final form September 30, 2005) This study was supported by NIH HL56387 (J.A.W.) and HL61646 (J

activation is a key initiation signal for acute lung ischemia-reperfusion injury.

Pulmonary ischemia-reperfusion (IR) injury entails acute activation of alveolar macrophages followed by neutrophil sequestration. Although proinflammatory cytokines and chemokines such as TNF-alpha and monocyte chemoattractant protein-1 (MCP-1) from macrophages are known to modulate acute IR injury, the contribution of alveolar epithelial cells to IR injury and their intercellular interactions with other cell types such as alveolar macrophages and neutrophils remain unclear. In this study, we tested the hypothesis that following IR, alveolar macrophage-produced TNF-alpha further induces alveolar epithelial cells to produce key chemokines that could then contribute to subsequent lung injury through the recruitment of neutrophils. Cultured RAW264.7 macrophages and MLE-12 alveolar epithelial cells were subjected to acute hypoxia-reoxygenation (H/R) as an in vitro model of pulmonary IR. H/R (3 h/1 h) significantly induced KC, MCP-1, macrophage inflammatory protein-2 (MIP-2), RANTES, and IL-6 (but not TNF-alpha) by MLE-12 cells, whereas H/R induced TNF-alpha, MCP-1, RANTES, MIP-1alpha, and MIP-2 (but not KC) by RAW264.7 cells. These results were confirmed using primary murine alveolar macrophages and primary alveolar type II cells. Importantly, using macrophage and epithelial coculture methods, the specific production of TNF-alpha by H/R-exposed RAW264.7 cells significantly induced proinflammatory cytokine/chemokine expression (KC, MCP-1, MIP-2, RANTES, and IL-6) by MLE-12 cells. Collectively, these results demonstrate that alveolar type II cells, in conjunction with alveolar macrophage-produced TNF-alpha, contribute to the initiation of acute pulmonary IR injury via a proinflammatory cascade. The release of key chemokines, such as KC and MIP-2, by activated type II cells may thus significantly contribute to neutrophil sequestration during IR injury.

OBJECTIVEPerception of perioperative pain is influenced by various psychological factors. The aim of this study was to determine the impact of catastrophizing, anxiety, and depression on in-hospital opioid consumption, pain scores, and quality of recovery in adults who underwent spine surgery.METHODSPatients undergoing spine surgery were enrolled in this study, and the preoperatively completed questionnaires included the verbal rating scale (VRS), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), and Oswestry Disability Index (ODI). Quality of recovery was assessed using the 40-item Quality of Recovery questionnaire (QoR40). Opioid consumption and pain scores according to the VRS were recorded daily until discharge.RESULTSOne hundred thirty-nine patients were recruited for the study, and 101 completed the QoR40 assessment postoperatively. Patients with higher catastrophizing scores were more likely to have higher maximum pain scores postoperatively (estimate: 0.03, SE: 0.01, p = 0.02), without increased opioid use (estimate: 0.44, SE: 0.27, p = 0.11). Preoperative anxiety (estimate: 1.18, SE: 0.65, p = 0.07) and depression scores (estimate: 1.06, SE: 0.71, p = 0.14) did not correlate with increased postoperative opioid use; however, patients with higher preoperative depression scores had lower quality of recovery after surgery (estimate: −1.9, SE: 0.56, p < 0.001).CONCLUSIONSCatastrophizing, anxiety, and depression play important roles in modulating postoperative pain. Preoperative evaluation of these factors, utilizing a validated tool, helps to identify patients at risk. This might allow for earlier psychological intervention that could reduce pain severity and improve the quality of recovery.

Here we investigate the biochemical, molecular, and cellular changes directed toward blood pressure homeostasis that occur in the endocrine branch of the reninangiotensin system of mice having one angiotensinogen gene inactivated. No compensatory up-regulation of the remaining normal allele occurs in the liver, the main tissue of angiotensinogen synthesis. No significant changes occur in expression of the genes coding for the angiotensin converting enzyme or the major pressormediating receptor for angiotensin, but plasma renin concentration in the mice having only one copy of the angiotensinogen gene is greater than twice wild-type. This increase is mediated primarily by a modest increase in the proportion of renal glomeruli producing renin in their juxtaglomerular apparatus and by four times wild-type numbers of renin-producing cells along afferent arterioles of the glomeruli rather than by upregulating renin production in cells already committed to its synthesis.

After pneumonectomy, the remaining lung increases in size. This process is referred to as compensatory lung growth. Various pathways likely play important roles in this growth response. The molecular mechanisms involved in compensatory lung growth, however, remain poorly understood. Hypoxia-induced mitogenic factor (HIMF), also called FIZZ1 or RELM-alpha, possesses mitogenic, vasoconstrictive, angiogenic, and antiapoptotic effects. In this study, we examined the expression of HIMF in mouse lung after pneumonectomy to test the hypothesis that HIMF expression is upregulated during compensatory lung growth. Results showed that HIMF is upregulated from Day 1 after pneumonectomy and peaking at Day 7 in the lung. HIMF upregulation is temporally and spatially related to lung cell proliferation, as demonstrated by expression of proliferating cell nuclear antigen. Immunohistochemical staining and in situ hybridization showed that upregulated HIMF protein and mRNA are mainly distributed in airway epithelium, alveolar type II cells, and endothelial cells of the pulmonary vessels. Intratracheal instillation of recombinant HIMF resulted in widespread cell proliferation, including airway epithelium, alveolar type II cells, and cells in the alveolar septa. These results indicate a new role for HIMF in compensatory lung growth, which is that HIMF may act as a lung-specific growth factor and participate in lung regeneration after pneumonectomy.

SEER sonorheometry demonstrates significant correlation with ROTEM for determining Clot Stiffness and assessing Fibrinogen Contribution. SEER sonorheometry results can provide valuable information about the coagulation status in patients undergoing cardiac surgery using CPB.

Kidney morphogenesis is accomplished by the coordinated interaction of molecular signals that culminate in the production of an organ that is architecturally and functionally ready for extrauterine, free life. In humans, nephrogenesis is completed before birth. However the kidney continues to mature both from a functional and anatomical point of view. Throughout its development, the kidney is susceptible to a variety of injurious agents. This brief review considers the basic mechanisms of kidney organogenesis and functional maturation. To illustrate some concepts, the renal alterations caused by interference with a normal regulatory system, the renin-angiotensin system is discussed.