PMN Elastase Levels Research Articles

Nano-chemically Modified Tetracycline-3 (nCMT-3) Attenuates Acute Lung Injury via Blocking sTREM-1 Release and NLRP3 Inflammasome Activation.

Intratracheal (IT) lipopolysaccharide (LPS) causes severe acute lung injury (ALI) and systemic inflammation. CMT-3 has pleiotropic anti-inflammatory effects including matrix metalloproteinase (MMP) inhibition, attenuation of neutrophil (PMN) activation, and elastase release. CMT-3's poor water solubility limits its bioavailability when administered orally for treating ALI. We developed a nano-formulation of CMT-3 (nCMT-3) to test the hypothesis that the pleiotropic anti-inflammatory activities of IT nCMT-3 can attenuate LPS-induced ALI. C57BL/6 mice were treated with aerosolized IT nCMT-3 or saline, then had IT LPS or saline administered 2 h later. Tissues were harvested at 24 h. The effects of LPS and nCMT-3 on ALI were assessed by lung histology, MMP level/activity (zymography), NLRP3 protein, and activated caspase-1 levels. Blood and bronchoalveolar lavage fluid (BALF) cell counts, PMN elastase, and soluble triggering receptor expressed on myelocytes-1 (sTREM-1) levels, TNF-α, IL-1β, IL-6, IL-18, and BALF protein levels were also measured. LPS-induced ALI was characterized by histologic lung injury (PMN infiltration, alveolar thickening, edema, and consolidation) elevated proMMP-2, -9 levels and activity, increased NLRP-3 protein and activated caspase-1 levels in lung tissue. LPS-induced increases in plasma and BALF levels of sTREM-1, TNF-α, IL-1β, IL-6, IL-18, PMN elastase and BALF protein levels demonstrate significant lung/systemic inflammation and capillary leak. nCMT-3 significantly ameliorated all of these LPS-induced inflammatory markers to control levels, and decreased the incidence of ALI. Pre-treatment with nCMT3 significantly attenuates LPS-induced lung injury/inflammation by multiple mechanisms including: MMP activation, PMN elastase, sTREM-1 release, and NLRP3 inflammasome/caspase-1 activation.

The assessment of electrospun scaffolds fabricated from polycaprolactone with the addition of L-arginine

Polycaprolactone (PCL) was electrospun with the addition of arginine (Arg), an α-amino acid that accelerates the healing process. The efficient needleless electrospinning technique was used for the fabrication of the nanofibrous layers. The materials produced consisted mainly of fibers with diameters of between 200 and 400 nm. Moreover, both microfibers and beads were present within the layers. Higher bead sizes were observed with the increased addition of arginine. The arginine content within the layers as well as the weight of the resultant electrospun materials were enhanced with the increased addition of arginine to the electrospinning solution (1, 5 and 10 wt%). The PCL + 1% Arg nanofibrous layer contained 5.67 ± 0.04% of arginine, the PCL + 5% Arg layer 22.66 ± 0.24% of arginine and the PCL + 10% Arg layer 37.33 ± 0.39% of arginine according to the results of the elemental analysis. A high burst release within 5 h of soaking was recorded for the PCL + 5% and PCL + 10% nanofibrous layers. However, the release rate of arginine from the PCL + 1% Arg was significantly slower, reaching a maximum level after 72 h of soaking. The resulting materials were hydrophobic. Hemocompatibility testing under static conditions revealed no effect on hemolysis following the addition of arginine and the prolongation of the prothrombin time with the increased addition of arginine, thus exerting an influence on the extrinsic and common pathway of coagulation activation. The results of the dynamic hemocompatibility assessment revealed that the numbers of blood cells and platelets were not affected significantly by the various electrospun samples during incubation. The TAT, β-thromboglobulin and SC5-b9 concentrations were characterized by a moderate increase in the PCL group compared to those of the control group. The presence of arginine resulted in a decrease in the investigated hemocompatibility markers. The PMN elastase levels were comparable with respect to all the groups.

Regulation of Salivary Peptidoglycan Recognition Protein 1 in Adolescents.

Peptidoglycan recognition protein 1 (PGLYRP1), a member of peptidoglycan recognition proteins, is known to be involved in the proinflammatory response toward bacterial infections. Recently, PGLYRP1 was identified as a ligand for triggering receptor expressed on myeloid cells 1 (TREM-1). Although PGLYRP1 is involved in immune and inflammatory responses, its levels in initial stages of periodontal disease in adolescents are currently unknown. We aimed to investigate salivary levels of PGLYRP1 and its correlation with TREM-1, polymorphonuclear leukocyte elastase (PMN elastase), and an active matrix metalloproteinase 8 (aMMP-8) in adolescents. Whole saliva samples (n = 537) were collected from 15- to 16-y-old adolescents at Kotka Health Center, Finland, prior to periodontal examination, including measurement of periodontal pocket depth (PPD), visible plaque index (VPI), and bleeding on probing (BOP). Adolescents, clustered as periodontally healthy, gingivitis, or subclinical periodontitis, were tested for salivary levels of TREM-1, PGLYRP1, and PMN elastase by enzyme-linked immunosorbent assay and aMMP-8 by a time-resolved immunofluorometric assay (IFMA). Salivary levels of PGLYRP1 and aMMP-8 were significantly higher in adolescents with subclinical periodontitis and gingivitis compared to individuals with healthy periodontium. TREM-1 and PMN elastase levels were higher in adolescents with subclinical periodontitis compared to healthy individuals but did not reach significance. PGLYRP1 correlated positively with BOP, PPD, VPI, aMMP-8, and TREM-1. Elevated PGLYRP1 levels in adolescents with gingivitis and subclinical periodontitis and its positive correlation with TREM-1 and aMMP-8 may indicate an association of PGLYRP1 with initial stages of periodontal disease. Sex and poor oral hygiene but not smoking are also associated with higher levels of PGLYRP1. However, PGLYRP1 has a lower discriminating capacity and is therefore a less reliable marker alone in the diagnosis of initial stages of periodontal disease in adolescents. PGLYRP1, a member of peptidoglycan recognition proteins, is a ligand for TREM-1. Elevated PGLYRP1 levels in adolescents with gingivitis and subclinical periodontitis and its positive correlation with TREM-1 and aMMP-8 may indicate an association of PGLYRP1 with initial stages of periodontal disease. However, it has a lower discriminating capacity and is therefore a less reliable marker alone in the diagnosis of periodontal disease in adolescents.

Correlation of PMN elastase and PMN elastase-to-neutrophil ratio with disease activity in patients with myositis

BackgroundPolymorphonuclear (PMN) elastase plays an important role in a variety of inflammatory disorders. Our aim was to analyse PMN elastase in idiopathic inflammatory myopathies (IIMs) and its association with disease activity.MethodsPMN elastase levels were measured using enzyme-linked immunosorbent assay in serum samples obtained from 74 patients with myositis (58 with dermatomyositis [DM] and 16 with polymyositis [PM]) and 22 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminant capacity of PMN elastase level and PMN elastase-to-neutrophil ratio (ENR) in patients with active and remission myositis. The association of serum PMN elastase level and ENR with disease variables was evaluated in patients with IIMs. The disease specificity of PMN elastase level and ENR was further examined in 60 patients with other systemic autoimmune diseases.ResultsPMN elastase level and ENR were significantly higher in patients with active IIMs, DM, and PM than in patients with remission. ROC curve analysis revealed that PMN elastase level and ENR both outperformed creatine kinase (CK), the currently used laboratory marker, and strongly discriminated patients with active disease and those with remission of IIMs, DM, and PM (area under the ROC curve [AUC] 0.9, 0.9, and 0.88 for PMN elastase; AUC 0.96, 0.96, and 1.0 for ENR; AUC 0.72, 0.70, and 0.80 for CK, respectively). PMN elastase level and ENR were positively correlated with myositis disease activity assessment, CK, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, and erythrocyte sedimentation rate. PMN elastase level and ENR were higher in the anti-PM-Scl positive myositis group than those in the anti-PM-Scl negative myositis group. Nevertheless, PMN elastase was not a specific disease marker for IIMs when compared with other autoimmune diseases.ConclusionsPMN elastase, particularly ENR, were significantly correlated with disease activity and could serve as useful biochemical markers for evaluating the disease activity of patients with IIMs. Thus, they are potentially helpful in monitoring disease progression and guiding treatment.

Serum polymorphonuclear leukocyte elastase enzyme level in neonatal sepsis

Objective The aim of this study is to evaluate the clinical importance of polymorphonuclear leukocyte (PMN) elastase level in neonatal sepsis. Background Neonatal sepsis is defined as a clinical syndrome of bacteremia with systemic signs and symptoms of infection in the first 4 weeks of life. When pathogenic bacteria gain access into the bloodstream, they may cause overwhelming infection without much localization (septicemia) or may be predominantly localized to the lung (pneumonia) or the meninges. Patients and methods This prospective study was performed on 60 newborns, which included 30 newborns with positive clinical sepsis score and 30 healthy neonates matched for age, sex, and weight as a control group. Blood samples for blood culture, routine biochemistry, whole blood count, immature neutrophil: total neutrophil ratio, C-reactive protein, and PMN elastase were taken. Antibiotics were commenced after the blood specimens were collected. Second blood samples for sepsis markers were obtained from the patient only on the fourth day of treatment. Results In our study, we found that respiratory distress was the most common clinical presentation (86.7%) in neonates with sepsis followed by poor activity (83.3%) and jaundice (40%). PMN elastase levels in neonates with sepsis were highly significantly increased compared with controls. Overall, 100% of patients had a positive PMN elastase test result, and PMN elastase has a sensitivity of 96% and positive predictive value of 86% in prediction of sepsis. The sensitivity of C-reactive protein in detecting sepsis was 77%, specificity was 93%, positive predictive value was 87%, and negative predictive value was 14%. Conclusion These findings indicate that PMN elastase level is a major indicator for the early diagnosis of sepsis in newborns.

A Study of the effect of Octreotide and N-acetylcysteine on inflammatory and prognostic parameters in severe acute pancreatitis in rats

Acute pancreatitis (AP) is a common emergency presentation and can be disabling. There is significant morbidity and mortality associated with AP, and it places a considerable burden on the healthcare system. Octreotide and N-acetylcysteine have been shown to have a protective effect in induced severe acute pancreatitis in rats. This study aim to clarify the protective potential effect of these two medications on the prognostic and inflammatory parameters in severe acute pancreatitis in rats. 40 adult male rats were allocated to five groups (n=8), control group, AP group, octreotide group, NAC group, combination group. Rats with severe acute pancreatitis have significant (p>0.05) higher levels of lipase, PMN elastase, urea, IL-1s and significant (p>0.05) lower levels of TAC as compared with control group. Rats treated by octreotide and NAC have significant lower levels of lipase, PMN elastase, urea, IL-1s and significant (p>0.05) higher levels of TAC as compared with AP group. Furthermore octreotide has antioxidant and anti-inflammatory activity better than NAC. Prognostic markers are possible predictors of outcome, we found that PMN elastase is a good early predictor and start to peak in the first hours of the disease faster than urea, they are positively correlated with the severity of the disease also the protective effects of Octreotide treated group were more than those carried out in NAC treated group.

Human semen hyperviscosity: prevalence and effects on physical and biochemical semen parameters in subfertile Egyptian men

Background Semen hyperviscosity (SHV) is a condition that can markedly impair the physical and chemical characteristics of seminal fluid, which leads to an adverse impact on sperm function. The aim of this study was to assess the prevalence of SHV in infertile Egyptian men and to evaluate its effects on physical and biochemical semen parameters, and also to identify any correlation between SHV and infections or inflammation of the genital tract. Participants and methods Semen samples were studied for 300 infertile men; of these, 225 men had normal semen viscosity and were excluded from the study. Seventy-five men with SHV were selected and included in this study. In addition, 25 fertile men with completely normal semen parameters who had recently fathered children were included as a control group. All participants underwent seminal analysis and measurement of seminal plasma fructose, ascorbic acid, calcium, and zinc, in addition to a peroxidase test and polymorphonuclear granulocyte elastase (PMN elastase). Results Our study showed that the prevalence of SHV was 25% in infertile Egyptian men. Sperm motility and sperm vitality, in addition to fructose, ascorbic acid, calcium, and zinc levels, were significantly reduced, whereas PMN elastase levels were significantly increased in samples with hyperviscosity (P Conclusion Our results showed that hyperviscosity seems to be the result of infection or inflammation in 75% in our cases and hyperviscosity seems not to be because of a single pathogenic factor, but rather because of several (biochemical, enzymatic, and genetic) factors that act in synergy. These factors should be studied further.

Chemokines, MMP-9 and PMN elastase in spontaneous sputum of sulfur mustard exposed civilians: Sardasht-Iran Cohort Study

Chemokines play an important role in acute and chronic pulmonary diseases. The aim of this study was to evaluate the levels of chemokines, MMP-9, and PMN elastase in spontaneous sputum and serum of patients 20 years after SM exposure. In context of Sardasht-Iran Cohort Study (SICS) 40 male volunteers with a history of SM exposure in June 1987 and complain of excessive sputum were recruited. The volunteers were clinically examined and their history was collected by internists. Sputum and serum levels of IL-8, fractalkine, MCP-1, RANTES, MMP-9, and PMN elastase were measured using ELISA kits (R&D System). Spirometries were performed on all the participants. Sputum level of fractalkine was significantly lower in the hospitalized group (N=16, Median=1.05; IQR=0.41-2.62) than non-hospitalized group (N=18, 4.031; IQR=0.947-8.203) (p=0.042). However, serum levels of fractalkine were higher in the hospitalized group (Mean±SD=2.08±5.09) than in the non-hospitalized (Mean±SD=0.53±0.87) group (T-test, p=0.03). Serum levels of PMN-elastase were also higher in the hospitalized group (Mean±SD; 64,794.43±26,820.08) than in the non-hospitalized group (Mean±SD=44,049.33±17,675.85) (p=0.017). There was no relationship between the cytokines and the studied factors in sputum and the GOLD classification, but the serum levels of fractalkine and MMP-9 were significantly higher in the more severe (grades 3-4) group. There was no significant correlation between sputum and serum levels of measured inflammatory mediators and pulmonary complications in the patients who were exposed to SM 20 years earlier. Pathophysiologic process involved in SM induced pulmonary problems might be different from those in other chronic pulmonary diseases such as COPD and asthma.

The volatile anesthetic sevoflurane inhibits activation of neutrophil granulocytes during simulated extracorporeal circulation

Extracorporeal circulation (ECC) is an essential tool for the execution of cardiac operations. However, ECC is also associated with undesirable side effects. These include the induction of a systemic inflammatory response associated with leukocyte activation and cytokine release as well as potentially life-threatening complications. The volatile anesthetic sevoflurane has been reported to exert anti-ischemic and anti-inflammatory effects. We therefore investigated whether sevoflurane modulates the ECC-triggered inflammatory response.Heparinized human blood was circulated for 90min in a normothermic (37°C) ex vivo ECC circuit. An air–oxygen mixture was administered via an oxygenator in controls (n=5). Sevoflurane (2vol.%) was added to the gas mixture in a second group (n=5). At baseline and after 30, 60 and 90min of ECC, blood samples were taken. In each sample whole blood counts were determined. Expression of the activation-indicating Mac-1 receptor on granulocytes and monocytes as well as leukocyte–platelet aggregate formation was measured in flow cytometry. Levels of the granulocyte activation marker PMN-elastase and of the cytokines IL-1β, IL-8 and TNF-α were analyzed using ELISA.ECC induced significant increases in Mac-1 expression on granulocytes (p<0.001) and PMN-elastase release (p<0.001). Sevoflurane decreased granulocyte Mac-1 expression during ECC (p<0.05) and inhibited the ECC-induced PMN-elastase release (p<0.05). Sevoflurane had no effect on whole blood cell counts, leukocyte–platelet aggregate formation and cytokine release during ECC.Sevoflurane inhibits granulocyte activation during ex vivo ECC and therefore has the potential to decrease the ECC-triggered inflammatory response. This promising finding warrants further investigation under clinical conditions.

Semen characteristics and inflammatory mediators in infertile men with different clinical diagnoses

This study was aimed at investigating whether semen characteristics in different clinical diagnoses of infertility are associated with PMN elastase, IL-6, IL-8, IL-1beta and TNFalpha levels detected in seminal plasma. Sixty-eight patients were divided into groups according to their clinical diagnosis: idiopathic infertility (group I), varicocele with infections (group II), varicocele (group III), infections (group IV), controls (group V). Physical examination and scrotal Eco-color Doppler was used to detect the varicocele. Patients with positive bacteriological semen analysis were considered as having an infection of the male reproductive tract. Samples were examined by light microscopy and transmission electron microscopy (TEM). TEM data were quantified with a mathematical formula furnishing a fertility index and the percentage of sperm apoptosis, immaturity and necrosis. PMN elastase/alpha1-PI complex levels were determined by ELISA and IL-6, IL-8, IL-1beta, TNFalpha by Bio-Plex Cytokine assay. Sperm concentration (I-II: p < 0.005; III-IV: p < 0.0001), motility (I-IV: p < 0.0001) and the fertility index (I: p < 0.005; II-IV: p < 0.0001) were significantly lower in the groups vs. controls, whereas sperm pathologies, except for apoptosis, were significantly higher in group I and apoptosis and necrosis were higher in group III. An increase in immaturity (p < 0.005) with a decrease in necrosis (p < 0.005) were observed in group III vs. group IV. Significantly higher levels of inflammatory mediators were detected in groups III and IV vs. controls. Despite a broad relationship among different inflammatory mediators, no correlation was found among them and the semen parameters, including indices from TEM analysis. In conclusion, patients with idiopathic infertility showed altered semen quality and normal levels of inflammatory mediators. Genitourinary infection and varicocele induced an inflammatory effect which could play a detrimental role in spermatogenesis, revealed by a decrease in sperm motility and the fertility index, concomitant with an increase in immaturity mainly in varicocele and necrosis in infection.

Clinical relevance of polymorphonuclear (PMN‐) elastase determination in semen and serum during infertility investigation

The polymorphonuclear (PMN) elastase is secreted by activated granulocytes and is widely used as a marker of male accessory gland infection. However, the clinical value of routine determination of seminal plasma (SP) PMN elastase in asymptomatic patients during infertility investigation has not clearly been established and not much is known about the significance of PMN-elastase levels in serum as a potential biochemical determinant associated with infection/inflammation of the male genital tract. This prospective study included a total of 221 asymptomatic males from unselected subfertile couples, to evaluate the relationship of (i) serum and (ii) same-day SP PMN elastase concentrations with established semen quality parameters, including sperm functional capacity, local antisperm antibodies (ASA), seminal leucocytes, and the outcome of semen cultures including typical sexually transmitted disease pathogens, and a potential association with patients' medical history and results of clinical andrological examination. Furthermore, couples were followed up for subsequent fertility (controlled for female infertility factors). The concentrations of PMN elastase in serum and in SP were not significantly related to semen quality [with regard to microscopic (e.g. count, motility, morphology) as well as biochemical parameters, and also to local ASA of the IgG- or IgA-class]. There was no strong relationship with sperm functional capacity. No significant relationship with the outcome of the microbial screening was found. PMN-elastase levels in serum and SP were not significantly correlated and there was no association with subsequent fertility. Therefore, the value of routine determination of PMN elastase in semen and/or serum samples, particularly when used as a single parameter to screen for subclinical infection/inflammation in males under infertility investigation is limited.

Elevated Serum Concentrations of Polymorphonuclear Neutrophilic Leukocyte Elastase in Systemic Sclerosis: Association with Pulmonary Fibrosis

To determine the serum concentrations and clinical association of polymorphonuclear neutrophilic leukocyte (PMN) elastase in patients with systemic sclerosis (SSc). Serum PMN elastase levels from 21 patients with limited cutaneous SSc (lSSc) and 32 with diffuse cutaneous SSc (dSSc) were examined by ELISA. Serum PMN elastase levels were elevated in patients with SSc, especially dSSc, compared to healthy controls. SSc patients with elevated serum PMN elastase levels had more frequent presence of pulmonary fibrosis, arthritis, contracture of phalanges, and diffuse pigmentation. Anticentromere antibody was detected less frequently in SSc patients with elevated serum PMN elastase levels than in controls. Consistently, serum PMN elastase levels also correlated positively with serum levels of KL-6 and surfactant protein-D, serological markers for pulmonary fibrosis. Serum PMN elastase levels were also associated with levels of serum 8-isoprostane, an oxidative stress marker in SSc. Serum PMN elastase levels were elevated in patients with SSc, and it was more prominent in patients with pulmonary fibrosis, suggesting that serum PMN elastase is a novel serological marker for SSc-related pulmonary fibrosis.

Age-related changes in seminal polymorphonuclear elastase in men with asymptomatic inflammation of the genital tract

To investigate age-related inflammatory events in the male genital tract. In a total of 4265 randomly collected patients attending the andrological outpatient clinic of the Center for Dermatology and Andrology, University of Giessen, Germany, ejaculate volume, pH-value, sperm concentration, total and progressive sperm motility, concentration of polymorphonuclear (PMN) elastase, number of peroxidase-positive cells and fructose were measured and correlated with patient's age. While ejaculate volume, motility and fructose all correlated negatively with age, sperm concentration, PMN elastase and the pH-value showed a positive correlation. The prevalence of male genital tract inflammation (as defined by PMN elastase > 250 ng/mL) and its severity increased significantly. PMN elastase did not correlate with sperm motility. Fructose as a marker of seminal vesicle function showed a significant negative relationship with the PMN elastase levels, the number of peroxidase-positive cells and sperm motility. The significant increases of PMN-elastase levels as marker of male genital tract inflammation in older men appear to be indicative of age-related changes in local immunoregulatory mechanisms. Because there is no association of PMN elastase with sperm motility, a direct inhibitory effect of this enzyme can be excluded.

Increased Pericardial Fluid Level of Matrix Metalloproteinase-9 Activity in Patients With Acute Myocardial Infarction Possible Role in the Development of Cardiac Rupture

In an animal model of acute myocardial infarction (AMI), deletion of matrix metalloproteinase (MMP)-9 results in suppression of the development of cardiac rupture. The present study sought to clarify how myocardial MMP-9 activity is related to the pathophysiologies of AMI and cardiac rupture in humans. Levels of interleukin-8 (IL-8), polymorphonuclear leukocyte (PMN) elastase, monocyte chemotactic protein-1 (MCP-1) and MMP activity were measured in the pericardial fluid obtained from 28 patients with angina pectoris (AP group) and 16 patients with AMI (AMI group) undergoing cardiac surgery. In the AMI group, 5 were complicated with ventricular septal perforation (VSP) and the remaining 11 were not (non-VSP). Levels of IL-8, PMN elastase, MMP-2 and MMP-9 activity were all higher in the AMI group than in the AP group. In the AMI group, all levels other than MMP-2 activity were further elevated in cases with VSP compared with those in the non-VSP group. There was no significant difference in MCP-1 among the groups Markers of neutrophil activation in the infarcted cardiac tissue seem to be elevated in AMI. Highly elevated levels of MMP-9 activity, which may be derived from neutrophils, and PMN elastase may be related to the pathophysiology of VSP or cardiac rupture in AMI.

Early cellular brain damage and systemic inflammatory response after cardiopulmonary resuscitation or isolated severe head trauma: a comparative pilot study on common pathomechanisms

Severe neurological deficits are common characteristics of patients surviving cardiopulmonary resuscitation (CPR) or isolated severe head trauma (SHT). For comparative evaluation of underlying pathomechanisms, 22 patients with out-of-hospital cardiac arrest and successful CPR as well as 10 patients with SHT were included in our prospective study. Circulating S-100B was determined as an indicator of cellular brain damage. Interleukin-8 (IL-8), soluble E-selectin (sE-selectin) and polymorphonuclear (PMN-) elastase were measured as markers of systemic inflammation following whole body ischaemia and reperfusion injury. Venous blood samples were drawn on scene (median time 11.0 min after starting basic life support) and in the intensive care unit (median time 12.5 h thereafter) in CPR patients and at admission to hospital (median time 43.8 min after trauma) and approx. 12 h later in SHT patients. Biochemical parameters in these samples were compared with specimens taken from 20 healthy volunteers. Initial median S-100B levels of the CPR and SHT patients were both significantly increased compared with the controls. Twelve hours later, significant falls in S-100B revealed no differences between the two patient groups, but did not reach control values. Median IL-8 and sE-selectin levels entry to the study were elevated in both patient groups compared with controls and showed further rises within the following 12 h. Finally, increased initial median levels of PMN-elastase revealed significant differences between the patient groups and between patients and controls. Twelve hours later, median PMN-elastase values were equally elevated in the CPR and SHT subjects. Our preliminary data suggest similar pathomechanisms occurring after both CPR and SHT. Both clinical entities seem to be associated with early transient cellular brain damage as shown by prolonged rapidly increasing and subsequent fall in S-100B serum levels. In contrast, the prolonged elevation of circulating IL-8, sE-selectin and PMN-elastase may indicate a very similar systemic inflammatory response by endothelial cells and neutrophils initiated by ischaemia and reperfusion injury in both conditions. Further studies should be carried out to determine the cause and the prognostic value of these biochemical parameters in relation to long-term neurological outcome.

Blood polymorphonuclear leukocyte activation in atherosclerosis: effects of aspirin.

The aim of the study was to demonstrate an activation of polymorpho-nuclear leukocytes (PMNs) in chronic progressive atherosclerosis (ATH). A group of patients with ATH, and a group of ATH patients under aspirin (ASA) therapy were compared with control persons without atherosclerotic alterations (healthy controls). Each group comprised 15 male age-matched subjects. The following inflammatory parameters related to PMN activities were measured: the polymorphonuclear leukocyte (PMN) blood count; blood PMN migration and reactive oxygen species release in vitro; the blood levels of PMN elastase, malondialdehyde, antibodies to oxidized LDL and soluble ICAM-1. In ATH patients, the PMN blood counts and the share of blood PMNs migrating upon platelet activating factor and leukotriene B4 stimulation were significnatly above the values of the healthy controls, while the other parameters were not significantly altered. ASA treatment attenuated the inflammatory response and reduced the differences between ATH and the healthy controls. It can be concluded that, in patients with chronic progressive atherosclerosis, PMNs are involved in the inflammatory process underlying the disease.

Evidence for Early Bacteremia/Endotoxemia and Inflammatory Responses after Trauma – Hemorrhage and Complement Activation in a Nonhuman Primate Model

There is criticism that the major line of evidence regarding posttraumatic inflammatory response and bacterial translocation has mainly come from experiments in rodents. The aim of this study was therefore to investigate the very early bacteremia/endotoxemia and inflammatory response in nonhuman primates. Six baboons were subjected to hemorrhagic shock (40 mm Hg mean arterial pressure) preceded by infusion of zymosan-activated plasma (to simulate trauma-associated complement activation) followed by reinfusion for 1 h. Measurements of complement and granulocyte (PMN) activation, cytokines of the inflammatory network, soluble cytokine receptors, and bacteria/endotoxin translocation (BT) were performed. There were significantly increased levels of PMN elastase, interleukin-6, and soluble tumor necrosis factors (TNF) receptors, but not of TNF. BT was evident from positive blood cultures, and from trendwise increased endotoxin plasma levels. Early liver damage was shown from elevated glutathione S-transferase (GST) plasma levels. Complement activation and hemorrhagic shock lead to an early inflammatory response together with bacteremia/endotoxemia as evidence of translocation from the gut already during the shock period in subhuman primates.

Respiratory dysfunction after cardiac surgery: effects of avoiding cardiopulmonary bypass and the use of bilateral internal mammary arteries.

The quantitative contribution of cardiopulmonary bypass (CPB) to respiratory dysfunction after cardiac surgery is not documented and the effect of the use of bilateral internal mammary artery (IMA) grafts is not clear. One hundred and seventy-five patients undergoing CABG with (CPB, n=150) and without (NOCPB, n=25) CPB were studied. PMN elastase (as a marker of the systemic inflammatory response) and serial arterial oxygen (paO(2)) and carbon dioxide (paCO(2)) tension, alveolar arterial oxygen (AaO(2)) gradient and percent saturation were measured. The CPB group was subdivided into three groups by the number of IMA grafts used: 0IMA (n=12), 1IMA (n=82) and 2IMA (n=51). The NOCPB group was younger, had significantly better preoperative blood gases, received fewer grafts and had lower PMN elastase levels than the CPB group. In both groups maximum respiratory dysfunction occurred at 48 h (paO(2), percentage saturation and Aa gradient all P<0.001 versus baseline) with partial recovery by 5 days. The percentage decline and subsequent recovery in all blood gas parameters was near identical in the CPB and NOCPB groups. Amongst the three IMA groups the percentage changes in all blood gas parameters were similar, as was the duration of postoperative ventilation and time to discharge. There was no correlation between blood gas parameters at 48 h with age, CPB time, blood loss, duration of ventilation or peak PMN elastase level. Changes in postoperative gas exchange are similar in patients undergoing CABG with and without CPB even although PMN elastase levels indicate that CPB produces a more marked inflammatory response. The use of 2IMA compared with 1IMA does not increase respiratory dysfunction.

Effects of antidepressant treatments on polymorphonuclear elastase levels in patients with depression

Background: We have previously reported that severe depression is associated with immunological and inflammatory alterations and these alterations may be showed easily by polymorphonuclear elastase (PMNE) measurements. The purpose of the present study is to show how PMN elastase levels change before and after antidepressant treatment. Methods: Fifty-five patients with depression (40 with major depression [MD], 15 with dysthymic disorder [DD]) were included in the study. Blood samples were drawn prior to drug treatment, and 3 months after the treatment. Severity of depression was measured by 24-item Hamilton depression rating scale (HDRS). Results: There was a positive correlation between ΔPMNE levels and ΔHDRS in patients with MD, but not in patients with DD. Twenty-eight patients were given moclobemide, and 27 patients were given imipramine. It was seen that PMN elastase levels were significantly reduced after 3-month antidepressant treatment period only in patients with MD. Conclusion: These findings suggest that PMNE activity is a state dependent parameter and improvement of depressive symptoms due to antidepressant treatment may lead to decrement of PMNE levels. Clinical implication and limitations: PMN elastase measurements may be used as a sensitive biological marker to follow the time-course of the disease activity in patients with major depression.

Polymorphonuclear leukocyte functions as predictive markers for infections after organ transplantation.

Infectious complications are still a major cause of morbidity and mortality after organ transplantation, and early therapy would certainly reduce the risk associated with severe infections. We therefore investigated the significance of polymorphonuclear leukocyte (PMN) functional tests as predictive markers for infection in transplant patients under immunosuppressive therapy in a longitudinal study. In 41 patients, blood PMN migration and reactive oxygen species release, the blood levels of PMN elastase, malondialdehyde, neopterin, sICAM-1 and sVCAM-1, and urine neopterine were measured in 3- and 4-day intervals after liver-, kidney-, kidney-pancreas-, and heart and lung transplantation. PMN migration was determined in whole blood and estimated by the amount of PMNs to penetrate into a membrane filter upon FMLP stimulation. Three groups of patients were formed according to their postoperative course. Group I patients (n = 23) had no or only minor local infection, group II patients (n = 11) had infections with distinct systemic involvement, and group III patients (n = 7) developed sepsis. A first elastase-level of over 100 mg/L after surgery, followed by a drop in the amount of blood PMNs ready to migrate, on FMLP stimulation, to below 12 %, turned out to be a marker for impending infection, whereas all other parameters tested were not predictive. In six of seven group III patients, this marker became positive (sensitivity 85.7 %) up to 15 days before clinical manifestation of sepsis. In group I (largely uneventful recovery) only one of 23 patients was positive (specificity 95.6 % ), whereas group II patients were in between (4 of 11 positive). By this method it seems possible to diagnose severe infections in the pre-clinical phase, which may help prevent them if treatment is begun promptly.