Composition, host responses and clinical applications of bioadhesives.

Bioadhesives are medical devices used to join or seal tissues that have been injured or incised. They have been classified into tissue adhesives, sealants, and hemostatic agents. Bioadhesives such as FloSeal®, CoSeal®, BioGlue®, Evicel®, Tisseel®, Progel™ PALS, and TissuGlu® have been commercialized and used in clinical setting. They can be formulated with natural or synthetic components or a combination of both including albumin, glutaraldehyde, chitosan, cyanoacrylate, fibrin and thrombin, gelatin, polyethylene glycol (PEG), along with urethanes. Each formulation has intrinsic properties and has been developed and validated for a specific application. This review article briefs the mechanisms by which bioadhesives forms adhesion to tissues and highlights the correlation between bioadhesives composition and their potential host responses. Furthermore, clinical applications of bioadhesives and their application-driven requirements are outlined.

OPTICC: A multicentre trial of Occult Pneumothoraces subjected to mechanical ventilation: The final report.

INTRODUCTION: Patients with occult pneumothorax (OPTX) requiring positive-pressure ventilation (PPV) face uncertain risks of tension pneumothorax or chest drainage complications. METHODS: Adults with traumatic OPTXs requiring PPV were randomized to drainage/observation, with the primary outcome of composite "respiratory distress" (RD)). RESULTS: Seventy-five (75) patients were randomized to observation, 67 to drainage. RD occurred in 38% observed and 25% drained (p = 0.14; Power = 0.38), with no mortality differences. One-quarter of observed patients failed, reaching 40% when ventilated >5 days. Twenty-three percent randomized to drainage had complications or ineffectual drains. CONCLUSION: RD was not significantly different with observation. Thus, OPTXs may be cautiously observed in stable patients undergoing short-term PPV when prompt "rescue drainage" is immediately available. As 40% of patients undergoing prolonged (≥5 days) ventilation (PPPV) require drainage, we suggest consideration of chest drainage performed with expert guidance to reduce risk of chest tube complications. LEVEL OF EVIDENCE: Therapeutic study, level II.

Pro-Resolving Effects of Resolvin D2 in LTD4 and TNF-α Pre-Treated Human Bronchi.

Inflammation is a major burden in respiratory diseases, resulting in airway hyperresponsiveness. Our hypothesis is that resolution of inflammation may represent a long-term solution in preventing human bronchial dysfunctions. The aim of the present study was to assess the anti-inflammatory effects of RvD2, a member of the D-series resolving family, with concomitant effects on ASM mechanical reactivity. The role and mode of action of RvD2 were assessed in an in vitro model of human bronchi under pro-inflammatory conditions, induced either by 1 µM LTD4 or 10 ng/ml TNF-α pre-treatment for 48h. TNF-α and LTD4 both induced hyperreactivity in response to pharmacological stimuli. Enhanced 5-Lipoxygenase (5-LOX) and cysteinyl leukotriene receptor 1 (CysLTR1) detection was documented in LTD4 or TNF-α pre-treated human bronchi when compared to control (untreated) human bronchi. In contrast, RvD2 treatments reversed 5-LOX/ß-actin and CysLTR1/ß-actin ratios and decreased the phosphorylation levels of AP-1 subunits (c-Fos, c-Jun) and p38-MAP kinase, while increasing the detection of the ALX/FPR2 receptor. Moreover, various pharmacological agents revealed the blunting effects of RvD2 on LTD4 or TNF-α induced hyper-responsiveness. Combined treatment with 300 nM RvD2 and 1 µM WRW4 (an ALX/FPR2 receptor inhibitor) blunted the pro-resolving and broncho-modulatory effects of RvD2. The present data provide new evidence regarding the role of RvD2 in a human model of airway inflammation and hyperrresponsiveness.

MAG-DPA curbs inflammatory biomarkers and pharmacological reactivity in cytokine-triggered hyperresponsive airway models.

Bronchial inflammation contributes to a sustained elevation of airway hyperresponsiveness (AHR) in asthma. Conversely, omega-3 fatty acid derivatives have been shown to resolve inflammation in various tissues. Thus, the effects of docosapentaenoic acid monoacylglyceride (MAG-DPA) were assessed on inflammatory markers and reactivity of human distal bronchi as well as in a cultured model of guinea pig tracheal rings. Human bronchi were dissected and cultured for 48 h with 10 ng/mL TNF-α or IL-13. Guinea pig tracheas were maintained in organ culture for 72 h which was previously shown to trigger spontaneous AHR. All tissues were treated with increasing concentrations of MAG-DPA (0.1, 0.3, and 1 µmol/L). Pharmacomechanical reactivity, Ca2+ sensitivity, and western blot analysis for specific phosphoproteins and transcription factors were performed to assess the effects of both cytokines, alone or in combination with MAG-DPA, on human and guinea pig airway preparations. Although 0.1 µmol/L MAG-DPA did not significantly reduce inflammatory biomarkers, the higher concentrations of MAG-DPA (0.3 and 1 µmol/L) blunted the activation of the TNF-α/NF κB pathway and abolished COX-2 expression in human and guinea pig tissues. Moreover, 0.3 and 1 µmol/L MAG-DPA consistently decreased the Ca2+ sensitivity and pharmacological reactivity of cultured bronchial explants. Furthermore, in human bronchi, IL-13-stimulated phosphorylation of CPI-17 was reversed by 1 µmol/L MAG-DPA. This effect was further amplified in the presence of 100 µmol/L aspirin. MAG-DPA mediates antiphlogistic effects by increasing the resolution of inflammation, while resetting Ca2+ sensitivity and contractile reactivity.

Right upper lobe lung cancer: Resection through left anterior mediastinotomy.

There is sparse information concerning approaches to metachronous lung cancer in patients who had a previous pneumonectomy for lung carcinoma. We describe the case of a 55-year-old woman who underwent a left pneumonectomy for lung carcinoma. Four years later, a radiological examination revealed a hypermetabolic nodule in the right upper lobe, which was located in the left hemithorax because of right lung hyperinflation and a mediastinal shift to the left. Wedge resection was carried out through a left anterior mediastinotomy. We believe that an anterior mediastinotomy represents a valuable option for the management of recurrent lung cancer after previous surgery.

Resolvin E1 normalizes contractility, Ca2+ sensitivity and smooth muscle cell migration rate in TNF-α- and IL-6-pretreated human pulmonary arteries.

Pulmonary hypertension (PH) is a rare disease in which pathophysiology is characterized by an increase in proinflammatory mediators, chronic endothelial dysfunctions, and a high migration rate of smooth muscle cells (SMC). Over the course of the last decade, various treatments have been proposed to relax the pulmonary arteries, none of which have been effective in resolving PH. Our hypothesis is that artery-relaxing drugs are not the long-term solution, but rather the inhibition of tissue inflammation, which underlies human pulmonary artery (HPA) dysfunctions that lead to abnormal vasoconstriction. The goal of the present study was to assess the anti-inflammatory effects of resolvin E1 (RvE1) with concomitant effects on SMC migration and on HPA reactivity. The role and mode of action of RvE1 and its precursor, monoacylglyceride eicosapentaenoic acid were assessed on HPA under proinflammatory conditions, involving a combined pretreatment with 10 ng/ml TNF-α and 10 ng/ml IL-6. Our results show that TNF-α and IL-6 treatment induced hyperreactivity and Ca(2+) hypersensitivity in response to pharmaco-mechanical stimuli, including 80 mM KCl, 1 µM phorbol 12-13-dibutyrate, and 30 nM U-46619. Furthermore, the proinflammatory treatment increased the migration rate of SMC isolated from HPA. The phosphorylation level of regulatory contractile proteins (CPI-17, MYPT-1), and proinflammatory signaling pathways (c-Fos, c-Jun, NF-κB) were also significantly increased compared with control conditions. Conversely, 300 nM RvE1 was able to normalize all of the above abnormal events triggered by proinflammation. In conclusion, RvE1 can resolve human arterial hyperreactivity via the resolution of inflammatory markers.

Reversal of IL-13-induced inflammation and Ca(2+) sensitivity by resolvin and MAG-DHA in association with ASA in human bronchi.

The aim of this study was to investigate the effects of resolvin D1 (RvD1), as well as the combined treatment of docosahexaenoic acid monoglyceride (MAG-DHA) and acetylsalicylic acid (ASA), on the resolution of inflammation markers and Ca(2+) sensitivity in IL-13-pretreated human bronchi (HB). Tension measurements performed with 300 nM RvD1 largely abolished (50%) the over-reactivity triggered by 10 ng/ml IL-13 pretreatment and reversed hyper Ca(2+) sensitivity. Addition of 300 nM 17(S)-HpDoHE, the metabolic intermediate between DHA and RvD1, displayed similar effects. In the presence of 100 µM ASA (a COX inhibitor), the inhibitory effect of 1 µM MAG-DHA on muscarinic tone was further amplified, but not in the presence of Ibuprofen. Western blot analysis revealed that the combined treatment of MAG-DHA and ASA upregulated GPR-32 expression and downregulated cytosolic TNFα detection, hence preventing IκBα degradation and p65-NFκB phosphorylation. The Ca(2+) sensitivity of HB was also quantified on ß-escin permeabilized preparations. The presence of ASA potentiated the inhibitory effects of MAG-DHA in reducing the Ca(2+) hypersensitivity triggered by IL-13 by decreasing the phosphorylation levels of the PKC-potentiated inhibitor protein-17 regulatory protein (CPI-17). In summary, MAG-DHA combined with ASA, as well as exogenously added RvD1, may represent valuable assets against critical AHR disorder.

Proresolving Action of Docosahexaenoic Acid Monoglyceride in Lung Inflammatory Models Related to Cystic Fibrosis.

Cystic fibrosis (CF) is a hereditary, chronic disease of the exocrine glands, characterized by the production of viscid mucus that obstructs the pancreatic ducts and bronchi, leading to infection and fibrosis. ω3 fatty acid supplementations are known to improve the essential fatty acid deficiency as well as reduce inflammation in CF. The objective of this study was to determine the effects of docosahexaenoic acid monoacylglyceride (MAG-DHA) on mucin overproduction and resolution of airway inflammation in two in vitro models related to CF. Isolated human bronchi reverse permeabilized with CF transmembrane conductance regulator (CFTR) silencing (si) RNA and stable Calu3 cells expressing a short hairpin (sh) RNA directed against CFTR (shCFTR) were used. Lipid analyses revealed that MAG-DHA increased DHA/arachidonic acid (AA) ratio in shCFTR Calu-3 cells. MAG-DHA treatments, moreover, resulted in a decreased activation of Pseudomonas aeruginosa LPS-induced NF-κB in CF and non-CF Calu-3 cells. Data also revealed a reduction in MUC5AC, IL-6, and IL-8 expression levels in MAG-DHA-treated shCFTR cells stimulated, or not, with LPS. Antiinflammatory properties of MAG-DHA were also investigated in a reverse-permeabilized human bronchi model with CFTR siRNA. After MAG-DHA treatments, messenger RNA transcript levels for MUC5AC, IL-6, and IL-8 were markedly reduced in LPS-treated CFTR siRNA bronchi. MAG-DHA displays antiinflammatory properties and reduces mucin overexpression in Calu-3 cells and human bronchi untreated or treated with P. aeruginosa LPS, a finding consistent with the effects of resolvinD1, a known antiinflammatory mediator.

Resolvin D1 reverses reactivity and Ca2+ sensitivity induced by ET-1, TNF-α, and IL-6 in the human pulmonary artery.

Pulmonary hypertension (PH) is a rare and progressive disease characterized by an inflammatory status and vessel wall remodeling, resulting in increased pulmonary artery resistance. During the last decade, treatments have been proposed; most of them target the endothelial pathways that stimulate smooth muscle cell relaxation. However, PH remains associated with significant morbidity. We hypothesized that inflammation plays a crucial role in the severity of the abnormal vasoconstriction in PH. The goal of this study was to assess the effects of resolvin D1 (RvD1), a potent anti-inflammatory agent, on the pharmacological reactivity of human pulmonary arteries (HPAs) via an in vitro model of induced hyperreactivity. The effects of RvD1 and monoacylglyceride compounds were measured on contractile activity and Ca(2+) sensitivity developed by HPAs that had been pretreated (or not) under proinflammatory conditions with either 10 ng/ml TNF-α or 10 ng/ml IL-6 or under hyperreactive conditions with 5 nM endothelin-1. The results demonstrated that, compared with controls, 24-h pretreatment with TNF-α, IL-6, or endothelin-1 increased reactivity and Ca(2+) sensitivity of HPAs as revealed by agonist challenges with 80 mM KCl, 1 µM serotonin (5-hydroxytryptamine), 30 nM U-46619, and 1 µM phorbol 12,13-dibutyrate. However, 300 nM RvD1 as well as 1 µM monoacylglyceride-docosapentaenoic acid monoglyceride strongly reversed the overresponsiveness induced by both proinflammatory and hyperreactive treatments. In pretreated pulmonary artery smooth muscle cells, Western blot analyses revealed that RvD1 treatment decreased the phosphorylation level of CPI-17 and expression of transmembrane protein member 16A while increasing the detection of G protein-coupled receptor 32. The present data demonstrate that RvD1, a trihydroxylated docosahexaenoic acid derivative, decreases induced overreactivity in HPAs via a reduction in CPI-17 phosphorylation and transmembrane protein member 16A expression.

Lipoxin generation is related to soluble epoxide hydrolase activity in severe asthma.

RATIONALE: Severe asthma is characterized by airway inflammatory responses associated with aberrant metabolism of arachidonic acid. Lipoxins (LX) are arachidonate-derived pro-resolving mediators that are decreased in severe asthma, yet mechanisms for defective LX biosynthesis and a means to increase LXs in severe asthma remain to be established. OBJECTIVES: To determine if oxidative stress and soluble epoxide hydrolase (sEH) activity are linked to decreased LX biosynthesis in severe asthma. METHODS: Aliquots of blood, sputum, and bronchoalveolar lavage fluid were obtained from asthma subjects for mediator determination. Select samples were exposed to t-butyl-hydroperoxide or sEH inhibitor (sEHI) before activation. Peripheral blood leukocyte-platelet aggregates were monitored by flow cytometry, and bronchial contraction was determined with cytokine-treated human lung sections. MEASUREMENTS AND MAIN RESULTS: 8-Isoprostane levels in sputum supernatants were inversely related to LXA4 in severe asthma (r = -0.55; P = 0.03) and t-butyl-hydroperoxide decreased LXA4 and 15-epi-LXA4 biosynthesis by peripheral blood leukocytes. LXA4 and 15-epi-LXA4 levels were inversely related to sEH activity in sputum supernatants and sEHIs significantly increased 14,15-epoxy-eicosatrienoic acid and 15-epi-LXA4 generation by severe asthma whole blood and bronchoalveolar lavage fluid cells. The abundance of peripheral blood leukocyte-platelet aggregates was related to asthma severity. In a concentration-dependent manner, LXs significantly inhibited platelet-activating factor-induced increases in leukocyte-platelet aggregates (70.8% inhibition [LXA4 100 nM], 78.3% inhibition [15-epi-LXA4 100 nM]) and 15-epi-LXA4 markedly inhibited tumor necrosis factor-α-induced increases in bronchial contraction. CONCLUSIONS: LX levels were decreased by oxidative stress and sEH activity. Inhibitors of sEH increased LXs that mediated antiphlogistic actions, suggesting a new therapeutic approach for severe asthma. Clinical trial registered with www.clinicaltrials.gov (NCT 00595114).

Occult pneumothoraces in critical care: a prospective multicenter randomized controlled trial of pleural drainage for mechanically ventilated trauma patients with occult pneumothoraces.

BACKGROUND: Patients with an occult pneumothoraces (OPTXs) may be at risk of tension pneumothoraces (TPTXs) without drainage or pleural drainage complications if treated. METHODS: Adults with traumatic OPTXs and requiring positive-pressure ventilation (PPV) were randomized to pleural drainage or observation (one side only enrolled if bilateral). All subsequent care and method of pleural drainage was per attending physician discretion. The primary outcome was a composite of respiratory distress (RD) (need for urgent pleural drainage, acute/sustained increases in O2 requirements, ventilator dysynchrony, and/or charted respiratory events). RESULTS: Ninety severely injured patients (mean [SD], Injury Severity Score [ISS], 33 [11]) were studied at four centers: Calgary (55), Toronto (27), Quebec (6), and Sherbrooke (3). Forty were randomized to tube thoracostomy, and 50 were randomized to observation. The risk of RD was similar between the observation and tube thoracostomy groups (relative risk, 0.71; 95% confidence interval, 0.40-1.27). There was no difference in mortality or intensive care unit (ICU), ventilator, or hospital days between groups. In those observed, 20% required subsequent pleural drainage (40% PTX progression, 60% pleural fluid, and 20% other). One observed patient (2%) undergoing PPV at enrollment had a TPTX, which was treated with urgent tube thoracostomy without sequelae. Drainage complications occurred in 15% of those randomized to drainage, while suboptimal tube thoracostomy position occurred in an additional 15%. There were three times (24% vs. 8%) more failures and more RDs (p = 0.01) among those observed with OPTXs requiring sustained PPV versus just for an operation, which increases threefold after a week in the ICU (p = 0.07). CONCLUSION: Our results suggest that OPTXs may be safely observed in hemodynamically stable patients undergoing PPV just for an operation, although one third of those requiring a week or more of ICU care received drainage, and TPTXs still occur. Complications of pleural drainage remain unacceptably high, and future work should attempt to delineate specific factors among those observed that warrant prophylactic drainage. LEVEL OF EVIDENCE: Therapeutic study, level III.

Relationship between bradykinin-induced relaxation and endogenous epoxyeicosanoid synthesis in human bronchi.

Epoxyeicosanoids (EETs) are produced by cytochrome P-450 epoxygenase; however, it is not yet known what triggers their endogenous production in epithelial cells. The relaxing effects of bradykinin are known to be related to endogenous production of epithelial-derived hyperpolarizing factors (EpDHF). Because of their effects on membrane potential, EETs have been reported to be EpDHF candidates (Benoit C, Renaudon B, Salvail D, Rousseau E. Am J Physiol Lung Cell Mol Physiol 280: L965-L973, 2001.). Thus, we hypothesized that bradykinin (BK) may stimulate endogenous EET production in human bronchi. To test this hypothesis, the relaxing and hyperpolarizing effects of BK and 14,15-EET were quantified on human bronchi, as well as the effects of various enzymatic inhibitors on these actions. One micromolar BK or 1 µM 14,15-EET induced a 45% relaxation on the tension induced by 30 nM U-46619 [a thromboxane-prostanoid (TP)-receptor agonist]. These BK-relaxing effects were reduced by 42% upon addition of 10 nM iberiotoxin [a large-conductance Ca(2+)-sensitive K(+) (BK(Ca)) channel blocker], by 27% following addition of 3 µM 14,15-epoxyeicosa-5(Z)-enoic acid (an EET antagonist), and by 32% with 3 µM N-methanesulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH, an epoxygenase inhibitor). Hence, BK and 14,15-EET display net hyperpolarizing effects on airway smooth muscle cells that are related to the activation of BK(Ca) channels and ultimately yielding to relaxation. Data also indicate that 3 µM MS-PPOH reduced the hyperpolarizing effects of BK by 43%. Together, the present data support the current hypothesis suggesting a direct relationship between BK and the production of EET regioisomers. Because of its potent anti-inflammatory and relaxing properties, epoxyeicosanoid signaling may represent a promising target in asthma and chronic obstructive pulmonary disease.

Anti-cancer effects of a new docosahexaenoic acid monoacylglyceride in lung adenocarcinoma.

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite advances in research, diagnosis and treatment, lung cancer remains a highly lethal disease, often diagnosed at advanced stages and with a very poor prognosis. Therefore, new strategies for the prevention and treatment of lung cancer are urgently needed. The aim of the present study was to determine the anti-tumorigenic effects of docosahexaenoic acid monoacylglyceride (MAG-DHA), a newly patented DHA derivative in lung adenocarcinoma. Our results demonstrate that MAG-DHA treatments decreased cell proliferation and induced apoptosis in A549 human lung carcinoma cells whereas MAG-DHA treatment did not induce apoptosis of normal bronchial epithelial BEAS-2B cells. MAG-DHA decreased NFκB activation leading to a reduction in COX-2 expression level in both A549 cells and lung adenocarcinoma tissues. Furthermore, MAG-DHA treatment increased PTEN expression and activation concomitant with a decrease in AKT phosphorylation levels and enhanced apoptosis. Oral administration of MAG-DHA significantly reduced tumor growth in a mouse A549 xenograft model. Lastly, MAG-DHA markedly decreased COX-2 and enhanced PTEN protein expression in tumor tissue sections. Altogether, these data provide new evidence regarding the mode of action of MAG-DHA and strongly suggest that this compound could be of clinical interest in cancer treatment.

Huge malignant solitary fibrous tumor of the pleura.

INTRODUCTION: Solitary fibrous pleural tumors are rare mesenchymal tumors that can be mistaken for mesothelioma. A positive staining of vimentin, negative staining of cytoplasmic keratin, and expression of the CD34 antigen can confirm their diagnosis. These tumors should be surgically excised although they are benign because they have malignant potential and tendency for recurrence. PATIENTS AND METHODS: We present here a 63-year-old patient who had an inconclusive biopsy of a huge right intrathoracic lesion. Further testing after radical surgical resection revealed a malignant solitary fibrous pleural tumor. Surgery was complicated with injury of the thoracic duct. Patient was re-operated upon for ligation of the thoracic duct. He is doing well with no recurrence after 18 months of follow-up. CONCLUSION: In conclusion, definitive treatment for solitary fibrous tumor is radical surgical resection with close follow-up for the recurrences. Follow-up of this tumor is essential especially when it showed malignant features on pathological examination.

Group A Streptococcus causing descending necrotizing mediastinitis: report of a case and literature review.

BACKGROUND: Descending necrotizing mediastinitis is a serious condition with few cases reported in the literature. Surgical treatment is controversial and may include wound exploration, local drainage, and even mediastinal debridement approached by thoracotomy. METHODS: Description of a case of descending mediastinitis caused by group A Streptococcus as a complication of thyroidectomy. RESULTS: Aggressive debridement was required for source control and treatment of septic shock. CONCLUSION: Post-thyroidectomy descending necrotizing mediastinitis is a rare and dangerous infection. It should be treated aggressively with appropriate cervical and mediastinal drainage combined with optimum medical care.

Concentration- and time-dependent effects of enoxaparin on human adenocarcinomic epithelial cell line A549 proliferation in vitro.

Non-small cell lung cancer (NSCLC) is a major health problem. Surgery is the only potential curative treatment, in spite of the high recurrence and mortality rates. Low molecular weight heparins (LMWH) have been suggested to have a positive impact on the outcome of various cancers, mainly attributed to their anticoagulant properties; yet a direct antineoplastic effect has not been excluded. We thought to evaluate the direct effect of the LMWH enoxaparin on the human lung adenocarcinomic epithelial cell line A549 and to determine potential antiproliferative and antimetastatic effects that could guide future trials. A549 cells were cultured with different concentrations of enoxaparin (1-30 U/mL). Cell counting was performed at 24, 48, and 72 h. Detection of c-Myc protein and CD44 protein was performed by electrophoresis and Western blotting. Statistical analysis was performed using paired Student's t tests. Cell counts were decreased with increasing concentrations and time of exposure to enoxaparin. This corresponds to decreased expression of c-Myc and CD44. In conclusion, enoxaparin displayed a direct dose and exposure duration dependent suppressor effect on A549 cell proliferation and the expression of both c-Myc and CD44 in vitro, suggesting reduced proliferative and metastatic potentials of these cells.

Surgical management of sternoclavicular joint infection.

OBJECTIVE: Sternoclavicular joint (SCJ) infections are rarely encountered and their management is not well standardised. We reviewed our experience with the management of this condition in order to evaluate the role of surgery in the management of the SCJ infection and to provide an algorithm for its treatment. METHODS: It is a multicentre study in which we retrospectively reviewed the data files of the patients who were referred to us for surgical management of SCI infection. RESULTS: From March 2003 to June 2009, 14 patients (12 men and two women) were treated surgically for infected SCJ. No patients were found in the paediatric age group. Mean age was 49.8 years with a range between 26 and 77 years. All patients were symptomatic. The prevalent symptom was either anterior chest wall swelling (21%) or pain (29%); while 50% of them presented with both swelling and pain. Associated risk factors were elicited in 12 patients (86%) while it could not be identified in two patients (14%). These risk factors were in the form of drug addiction in three patients, diabetes mellitus (DM) in four, chronic renal failure (CRF) in three patients and two patients had both DM and CRF. Surgical management was performed in all patients in the form of either incision and drainage in two patients (14%); or SCJ curettage in three patients (21%), while resection of the SCJ was done in nine patients (62%). Mean postoperative hospital stay period (PHS) was 8.1 days (range: 5-30 days). All of them are alive and free of symptoms in follow-up. CONCLUSION: Surgery was found to be curative with good results for those patients with SCJ infection that did not respond to a full course of intravenous antibiotic therapy. Surgical options include incision and drainage, curettage or SCJ resection. The type of surgical procedure depends on the radiological findings, presentation, severity of the infection and intra-operative findings. In our experience, complex muscle flap reconstruction was not necessary following SCJ resection.

17,18-epoxyeicosatetraenoic acid targets PPARγ and p38 mitogen-activated protein kinase to mediate its anti-inflammatory effects in the lung: role of soluble epoxide hydrolase.

This study sought to assess putative pathways involved in the anti-inflammatory effects of 17,18-epoxyeicosatetraenoic acid (17,18-EpETE), as measured by a decrease in the contractile reactivity and Ca(2+) sensitivity of TNF-α-pretreated human bronchi. Tension measurements performed in the presence of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a soluble epoxide hydrolase (sEH)-specific inhibitor, demonstrated that 17,18-EpETE reduced the reactivity of TNF-α-pretreated tissues. The overexpression of sEH detected in patients with asthma and TNF-α-treated bronchi contributed to the maintenance of hyperresponsiveness in our models, which involved intracellular proinflammatory cascades. The inhibition of peroxisome proliferator-activated receptor (PPAR)γ by GW9662 abolished 17,18-EpETE + AUDA-mediated anti-inflammatory effects by inducing IκBα degradation and cytokine synthesis, indicating that PPARγ is a molecular target of epoxy-eicosanoids. Western blot analysis revealed that 17,18-EpETE pretreatment reversed the phosphorylation of p38 mitogen-activated protein kinase (p38-MAPK) induced by TNF-α in human bronchi. The Ca(2+) sensitivity of human bronchial explants was also quantified on ß-escin permeabilized preparations. The presence of SB203580, a p38-MAPK inhibitor, reversed the effect induced by epoxy-eicosanoid in the presence of AUDA on TNF-α-triggered Ca(2+) hypersensitivity by increasing the phosphorylation level of PKC Potentiated Inhibitor Protein-17 (CPI-17) regulatory protein. Moreover, PPARγ ligands, such as rosiglitazone and 17,18-EpETE, decreased the expression of CPI-17, both at the mRNA and protein levels, whereas this effect was countered by GW9662 treatment in TNF-α-treated bronchi. These results demonstrate that 17,18-EpETE is a potent regulator of human lung inflammation and concomitant hyperresponsiveness, and may represent a valuable asset against critical inflammatory bronchial disorder.