Acute Pancreatitis Hypertonic Saline Increases Heat Shock Proteins 70 and 90 and Reduces Neutrophil Infiltration in Lung Injury

Objectives: Acute pancreatitis (AP) protease release induces lung parenchymal destruction via matrix metalloproteinases (MMPs), a neutrophil (polymorphonuclear leukocyte)-dependent process. Recent studies in hemorrhagic shock revealed that hypertonic saline (HTS) has an anti-inflammatory effect and can inhibit a variety of neutrophil functions. The aim of this study was to determine whether HTS and its actions in the pathway of neutrophil migration, MMPs, and heat shock proteins (HSPs) are effective in protecting the lung from injury associated with AP. Methods: We determined neutrophil infiltration and expressions of MMPs and HSPs in the lung tissue after AP induced by retrograde infusion of 2.5% of sodium taurocholate. Results: Animals submitted to AP that received HTS compared with those who received normal saline presented with increased HSP70 and HSP90 expressions and reduced myeloperoxidase levels and MMP-9 expression and activity. Conclusions: Our data raised the hypothesis that a sequence of HTS lung protection events increases HSP70 and HSP90, inhibiting infiltration of neutrophils and their protease actions in the lung.

Effects of chronic L-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation

The importance of lung tissue in asthma pathophysiology has been recently recognized. Although nitric oxide mediates smooth muscle tonus control in airways, its effects on lung tissue responsiveness have not been investigated previously. We hypothesized that chronic nitric oxide synthase (NOS) inhibition by N-omega-nitro-L-arginine methyl ester (L-NAME) may modulate lung tissue mechanics and eosinophil and extracellular matrix remodeling in guinea pigs with chronic pulmonary inflammation. Animals were submitted to seven saline or ovalbumin exposures with increasing doses (1 similar to 5 mg/ml for 4 wk) and treated or not with L-NAME in drinking water. After the seventh inhalation (72 h), animals were anesthetized and exsanguinated, and oscillatory mechanics of lung tissue strips were performed in baseline condition and after ovalbumin challenge (0.1%). Using morphometry, we assessed the density of eosinophils, neuronal NOS (nNOS)- and inducible NOS (iNOS)-positive distal lung cells, smooth muscle cells, as well as collagen and elastic fibers in lung tissue. Ovalbumin-exposed animals had an increase in baseline and maximal tissue resistance and elastance, eosinophil density, nNOS- and iNOS-positive cells, the amount of collagen and elastic fibers, and isoprostane-8-PGF(2 alpha) expression in the alveolar septa compared with controls (P < 0.05). L-NAME treatment in ovalbumin-exposed animals attenuated lung tissue mechanical responses (P < 0.01), nNOS- and iNOS-positive cells, elastic fiber content (P < 0.001), and isoprostane-8-PGF(2 alpha) in the alveolar septa (P < 0.001). However, this treatment did not affect the total number of eosinophils and collagen deposition. These data suggest that NO contributes to distal lung parenchyma constriction and to elastic fiber deposition in this model. One possibility may be related to the effects of NO activating the oxidative stress pathway.

Acute and Chronic Effects of Epicardial Radiofrequency Applications Delivered on Epicardial Coronary Arteries

Background-Epicardial coronary injury is by far the most feared complication of epicardial ablation. Little information is available regarding the chronic effects of delivering radiofrequency in the vicinity of large coronary vessels, and the long-term impact of this approach for mapping and ablation on epicardial vessel integrity is poorly understood. Therefore, the aim of this study was to characterize the acute and chronic histopathologic changes produced by in vivo epicardial pulses of radiofrequency ablation on coronary artery of porcine hearts. Methods and Results-Seven pigs underwent a left thoracotomy. The catheter was sutured adjacent to the left anterior descending artery and left circumflex artery, and 20 pulses of radiofrequency energy were applied. Radiofrequency lesions located no more than 1 mm of the vessel were used for this analysis. Three animals were euthanized 20 days (acute phase) after the procedure and 4 animals after 70 days (chronic phase). The following parameters were obtained in each vessel analyzed: (1) internal and external perimeter; (2) vessel wall thickness; (3) tunica media thickness, and (4) tunica intima thickness. The presence of adipose tissue around the coronary arteries, the distance between the artery and the epicardium, and the anatomic relationship of the artery with the coronary vein was also documented for each section. Sixteen of 20 (80%) sections analyzed, showed intimal thickening with a mean of 0.18 +/- 0.14 mm compared with 0.13 +/- 0.16 mm in the acute phase (P=0.331). The mean tunica media thickness was 0.25 +/- 0.10 mm in the chronic phase animals compared with 0.18 +/- 0.03 mm in the acute phase animals (P=0.021). A clear protective effect of pericardial fat and coronary veins was also present. A positive correlation between depth of radiofrequency lesion and the degree of vessel injury expressed as intimal and media thickening (P=0.001) was present. A negative correlation was identified (r = -0.83; P=0.002) between intimal thickening and distance between epicardium and coronary artery. Conclusions-In this porcine model of in vivo epicardial radiofrequency ablation in proximity to coronary arteries leads to acute and chronic histopathologic changes characterized by tunica intima and media thickening, with replacement of smooth muscle cells with extracellular matrix, but no significant stenosis was observed up to 70 days after the ablation. The absence of acute coronary occlusion or injury does not preclude subsequent significant arterial damage, which frequently occurs when epicardial radiofrequency applications are delivered in close vicinity to the vessels. (Circ Arrhythm Electrophysiol. 2011;4:526-531.)

Use of SVM Methods with Surface-Based Cortical and Volumetric Subcortical Measurements to Detect Alzheimer`s Disease

Here, we examine morphological changes in cortical thickness of patients with Alzheimer`s disease (AD) using image analysis algorithms for brain structure segmentation and study automatic classification of AD patients using cortical and volumetric data. Cortical thickness of AD patients (n = 14) was measured using MRI cortical surface-based analysis and compared with healthy subjects (n = 20). Data was analyzed using an automated algorithm for tissue segmentation and classification. A Support Vector Machine (SVM) was applied over the volumetric measurements of subcortical and cortical structures to separate AD patients from controls. The group analysis showed cortical thickness reduction in the superior temporal lobe, parahippocampal gyrus, and enthorhinal cortex in both hemispheres. We also found cortical thinning in the isthmus of cingulate gyrus and middle temporal gyrus at the right hemisphere, as well as a reduction of the cortical mantle in areas previously shown to be associated with AD. We also confirmed that automatic classification algorithms (SVM) could be helpful to distinguish AD patients from healthy controls. Moreover, the same areas implicated in the pathogenesis of AD were the main parameters driving the classification algorithm. While the patient sample used in this study was relatively small, we expect that using a database of regional volumes derived from MRI scans of a large number of subjects will increase the SVM power of AD patient identification.

Alternatives for parallel Krylov subspace basis computation

Numerical methods related to Krylov subspaces are widely used in large sparse numerical linear algebra. Vectors in these subspaces are manipulated via their representation onto orthonormal bases. Nowadays, on serial computers, the method of Arnoldi is considered as a reliable technique for constructing such bases. However, although easily parallelizable, this technique is not as scalable as expected for communications. In this work we examine alternative methods aimed at overcoming this drawback. Since they retrieve upon completion the same information as Arnoldi's algorithm does, they enable us to design a wide family of stable and scalable Krylov approximation methods for various parallel environments. We present timing results obtained from their implementation on two distributed-memory multiprocessor supercomputers: the Intel Paragon and the IBM Scalable POWERparallel SP2. (C) 1997 by John Wiley & Sons, Ltd.

Finite element analysis of mechanical properties in discontinuously reinforced metal matrix composites with ultrafine microstructure

This investigation focused on the finite element analyses of elastic and plastic properties of aluminium/alumina composite materials with ultrafine microstructure. The commonly used unit cell model was used to predict the elastic properties. By combining the unit cell model with an indentation model, coupled with experimental indentation measurements, the plastic properties of the composites and the associated strengthening mechanism within the metal matrix material were investigated. The grain size of the matrix material was found to be an important factor influencing the mechanical properties of the composites studied. (C) 1997 Elsevier Science S.A.

Influence of Suture on Peripheral Nerve Regeneration and Collagen Production at the Site of Neurorrhaphy: An Experimental Study

BACKGROUND: Restoration of nerve continuity and effective maintenance of coaptation are considered fundamental principles of end-to-end peripheral nerve repair. OBJECTIVE: To evaluate the influence of the number of stitches on axonal regeneration and collagen production after neurorrhaphy. METHODS: Thirty male Wistar rats were equally divided into 3 groups and were all operated on with the right sciatic nerve exposed. In 2 groups, the nerve was sectioned and repaired by means of 3 (group B) or 6 (group C) epineurium sutures with 100 monofilament nylon. One group (group A) was used as a control. Each animal from groups B and C underwent electrophysiological evaluation with motor action potential recordings before nerve section and again at an 8-week interval after neurorrhaphy. Nerve biopsy specimens were used for histomorphometric assessment of axonal regeneration and quantification of collagen at the repair site. RESULTS: Animals from group C had significantly lower motor action potential conduction velocities compared with control animals (P = .02), and no significant difference was seen between groups B and C. Parameters obtained from morphometric evaluation were not significantly different between these 2 groups. Type I collagen and III collagen in the epineurium were significantly higher in group C than in either the control group (P = .001 and P = .003) or group B (P = .01 and P = .02). No differences were identified for collagen I and III in the endoneurium. CONCLUSION: Using 6 sutures for nerve repair is associated with worse electrophysiological outcomes and higher amounts of type I and III collagen in the epineurium compared with control. Neurorraphy with 6 stitches is also related to a significant increase in epineurium collagen I and III compared with 3-stitch neurorraphy.

Sensory phenomena in obsessive-compulsive disorder and tic disorders: A review of the literature

Introduction: A variety of subjective experiences have been reported to be associated with the symptom expression of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). First described in TS patients, these subjective experiences have been defined in different ways. There is no consensus in the literature on how to best define subjective experiences. This lack of consensus may hinder the understanding of study results and prevents the possibility of including them in the search for etiological factors associated with OCD and TS. Methods: The objective of this article was to review the descriptions of subjective experiences in the English-language literature from 1980-2007. This meta-analytic review was carried out using the English-language literature from 1980-2007 available on MEDLINE, PsycINFO, and the Cochrane Library databases using the following search terms: premonitory urges, sensory tics, ""just-right"" perceptions, sensory phenomena, sensory experiences, incompleteness, ""not just-right"" phenomena, obsessive-compulsive disorder and TS, including OCD and/or TS, in all combination searches. We also searched for the references cited in each article previously found that referred to the aforementioned terms. Thirty-one articles were included in the study. Results: Subjective experiences, in particular, the sensory phenomena, were important phenotypic variables in the characterization of the tic-related OCD subtype and were more frequent in the early-onset OCD subtype. There is a paucity of studies using structured interviews to assess sensory phenomena, their epidemiology and the etiological mechanisms associated with sensory phenomena. Conclusion: The current review provides some evidence that sensory phenomena can be useful to identify more homogenous subgroups of OCD and TS patients and should be included as important phenotypic variables in future clinical, genetic, neuroimaging, and treatment-response studies.

The outer wall of small airways is a major site of remodeling in fatal asthma

Background: Structural and inflammatory changes in asthma involve both the large and small airways, with involvement of the distal lung being related to disease severity. We have previously shown that changes in the extracellular matrix (ECM) composition of the distal lung are associated with loss of alveolar attachments in patients with fatal asthma. However, major ECM elements, such as collagen I and fibronectin and their regulators, have not been addressed at the distal level. Objective: We sought to evaluate ECM remodeling in the distal lungs of asthmatic patients. Methods: Using immunohistochemistry and image analysis, we determined the content of collagen I and III, fibronectin, and matrix metalloproteinases; (MMPs) 1, 2, and 9 and tissue inhibitors of metalloproteinase (MMPs) 1 and 2 in the large and small airways and lung parenchyma of 24 patients with fatal asthma and compared the results with those of 11 nonasthmatic control subjects. Protein content was defined as the area of positive staining divided by basement membrane or septum length. Results: We observed increased collagen I and decreased collagen III content in the small airways of asthmatic patients compared with that seen in control subjects. Greater fibronectin and MMP-1, MMP-2, and MMP-9 content was observed at the outer area of the small airways in asthmatic patients. NIMP content was also increased in the peribronchiolar parenchyma in asthmatic patients. In contrast, TIMP expression was only increased in the large airways of asthmatic patients compared with that seen in control subjects. Conclusions: The outer area of the small airways is a major site of ECM remodeling in fatal asthma, potentially contributing to functional changes and the loss of airway-parenchyma interdependence observed in patients with fatal asthma. (J Allergy Clin Immunol 2009;123:1090-7.)

Prognostic relevance of TTF-1 and MMP-9 expression in advanced lung adenocarcinoma

Background: The thyroid transcription factor-1 (TTF-1) is a tissue-specific transcription factor that Could playan important role in cell differentiation and morphogenesis of lung tumors. Matrix metalloproteinase-9 (MMP-9) is a protease commonly expressed in non-small cell lung cancer, conferring angiogenic and metastatic potential. Methods: We assessed TTF-1 and MMP-9 tumor expression by immunohistochemistry in 51 patients with lung adenocarcinoma, stage 11113 or IV, treated with platinum regimens. A bicategorical prognostic model was obtained using the Kaplan-Meier method, COX regression, and conjunctive consolidation. Results: The median expression of TTF-1 was 30.0% (range: 0-85.9%). All tumors expressed MMP-9 (median: 78.7%: range: 15.2-96.1%). Median survival was 41.6 weeks, with estimated 1- and 2-year survival rates of 45.0% and 22.0%, respectively. Poor performance status (Karnofsky scale) - hazards ratio(HR): 1.03. 95% confidence interval (CI): 1.01-1.06: low TTF-1 expression (<40%) - FIR: 4.00, 95% CI: 1.75-9.09: and high MMP-9 expression (>= 80%) - HR: 2.82, 95% CI: 1.30-6.08 were independent prognostic factors. Patients could be stratified in three death risk groups according to markers expression: low risk (high TTF-1 and low MMP-9; median survival: 127.6 weeks), intermediate risk (low TTF-1 OF high MMP-9; median survival: 39.0 weeks): and high risk (low TTF-1 and high MMP-9: median survival: 16.4 weeks). Conclusion: TTF-1 and MMP-9 tumor expression as detected by immunohistochemistry may allow identification of different, clinically meaningful, prognostic groups of advanced lung adenocarcinoma patients treated with platinum regimens. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Different strains of mice present distinct lung tissue mechanics and extracellular matrix composition in a model of chronic allergic asthma

The impact of genetic factors on asthma is well recognized but poorly understood. We tested the hypothesis that different mouse strains present different lung tissue strip mechanics in a model of chronic allergic asthma and that these mechanical differences may be potentially related to changes of extracellular matrix composition and/or contractile elements in lung parenchyma. Oscillatory mechanics were analysed before and after acetylcholine (ACh) in C57BL/10, BALB/c, and A/J mice, subjected or not to ovalbumin sensitization and challenge. In controls, tissue elastance (E) and resistance (R), collagen and elastic fibres` content, and alpha-actin were higher in A/J compared to BALB/c mice, which, in turn, were more elevated than in C57BL/10. A similar response pattern was observed in ovalbumin-challenged animals irrespective of mouse strain. E and R augmented more in ovalbumin-challenged A/J [E: 22%, R: 18%] than C57BL/10 mice [E: 9.4%, R: 11 %] after ACh In conclusion, lung parenchyma remodelled differently yielding distinct in vitro mechanics according to mouse strain. (C) 2008 Elsevier B.V. All rights reserved.

Arterial and interstitial remodelling processes in non-specific interstitial pneumonia: systemic sclerosis versus idiopathic

Aims: To compare septal and vascular matrix remodelling, vascular occlusion, Pulmonary function tests and survival between two groups: one with idiopathic non-specific interstitial pneumonia (NSIP) and one with NSIP associated with systemic sclerosis (SSc). Methods and results: Pulmonary biopsy specimens were examined from 40 patients, 22 with NSIP and 18 with NSIP associated with SSc. The content of septal collagen and elastic fibres, as well as the elastic fibres in the vascular interstitium, were higher in the SSc group (P = 0.01, P = 0.001 and P < 0.0001, respectively). Among pulmonary function tests. the diffusing capacity for carbon monoxide/alveolar volume was affected to a greater extent in the SSc group (59%) of the predicted value in SSc and 97% in the idiopathic group). There were no differences in collagen content of the vascular interstitium, arterial occlusion, or survival between the two groups. Conclusions: Although the fibrotic process is more intense in the SSc group. it, does not affect the prognosis of these patients. Because the elastotic process is higher in the SSc group, this might suggest that autoimmune inflammatory mechanisms affecting the elastic fibre system play a greater role in the pathogenesis and pulmonary remodelling process of SSc NSIP than in idiopathic NSIP.

Extracellular matrix components and regulators in the airway smooth muscle in asthma

There is an intimate relationship between the extracellular matrix (ECM) and smooth muscle cells within the airways. Few studies have comprehensively assessed the composition of different ECM components and its regulators within the airway smooth muscle (ASM) in asthma. With the aid of image analysis, the fractional areas of total collagen and elastic fibres were quantified within the ASM of 35 subjects with fatal asthma (FA) and compared with 10 nonfatal asthma (NFA) patients and 22 nonasthmatic control cases. Expression of collagen I and III, fibronectin, versican, matrix metalloproteinase (MMP)-1, -2, -9 and -12 and tissue inhibitor of metalloproteinase-1 and -2 was quantified within the ASM in 22 FA and 10 control cases. In the large airways of FA cases, the fractional area of elastic fibres within the ASM was increased compared with NFA and controls. Similarly, fibronectin, MMP-9 and MMP-12 were increased within the ASM in large airways of FA cases compared with controls. Elastic fibres were increased in small airways in FA only in comparison with NFA cases. There is altered extracellular matrix composition and a degradative environment within the airway smooth muscle in fatal asthma patients, which may have important consequences for the mechanical and synthetic functions of airway smooth muscle.

Oral tolerance attenuates changes in in vitro lung tissue mechanics and extracellular matrix remodeling induced by chronic allergic inflammation in guinea pigs

Oral tolerance attenuates changes in in vitro lung tissue mechanics and extracellular matrix remodeling induced by chronic allergic inflammation in guinea pigs. J Appl Physiol 104: 1778-1785, 2008. First published April 3, 2008; doi:10.1152/japplphysiol.00830.2007.-Recent studies emphasize the presence of alveolar tissue inflammation in asthma. Immunotherapy has been considered a possible therapeutic strategy for asthma, and its effect on lung tissue had not been previously investigated. Measurements of lung tissue resistance and elastance were obtained before and after both ovalbumin and acetylcholine challenges. Using morphometry, we assessed eosinophil and smooth muscle cell density, as well as collagen and elastic fiber content, in lung tissue from guinea pigs with chronic pulmonary allergic inflammation. Animals received seven inhalations of ovalbumin (1-5 mg/ml; OVA group) or saline (SAL group) during 4 wk. Oral tolerance (OT) was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st inhalation (OT1 group) or after the 4th (OT2 group). The ovalbumin-exposed animals presented an increase in baseline and in postchallenge resistance and elastance related to baseline, eosinophil density, and collagen and elastic fiber content in lung tissue compared with controls. Baseline and post-ovalbumin and acetylcholine elastance and resistance, eosinophil density, and collagen and elastic fiber content were attenuated in OT1 and OT2 groups compared with the OVA group. Our results show that inducing oral tolerance attenuates lung tissue mechanics, as well as eosinophilic inflammation and extracellular matrix remodeling induced by chronic inflammation.