MPO Concentrations Research Articles

Vitamin C Status Is Related to Proinflammatory Responses and Impaired Vascular Endothelial Function in Healthy, College-Aged Lean and Obese Men

Vitamin C supplementation has been suggested to reduce cardiovascular disease risk. However, no studies have examined the relationship between vitamin C status and vascular dysfunction in lean and obese individuals in the absence of supplementation. We examined whether vascular function is interrelated with vitamin C status and inflammation in healthy, college-aged lean and obese men with no history of dietary supplementation. A cross-sectional study was conducted during winter 2008 in lean and obese men aged 21±3 years (n=8/group). Brachial artery flow-mediated dilation (FMD) was measured to determine vascular endothelial function. Plasma antioxidants (vitamin C, vitamin E, and thiols), inflammatory proteins (C-reactive protein [CRP], myeloperoxidase [MPO], and cytokines), and cellular adhesion molecules were measured. Participants also completed 3-day food records on the days preceding their vascular testing. Group differences were evaluated by t tests, and correlation coefficients were determined by linear regression. FMD was 21% lower ( P<0.05) in obese men. They also had 51% lower vitamin C intakes and 38% lower plasma vitamin C concentrations. Obese men had greater plasma concentrations of CRP, MPO, inflammatory cytokines, and cellular adhesion molecules. Participants' CRP and MPO were each inversely related ( P<0.05) to FMD ( r=−0.528 and −0.625) and plasma vitamin C ( r=−0.646 and −0.701). These data suggest that low vitamin C status is associated with proinflammatory responses and impaired vascular function in lean and obese men. Additional study is warranted to determine whether improving dietary vitamin C intakes from food attenuate vascular dysfunction.

Heterogeneity of chronic lung allograft dysfunction: Insights from protein expression in broncho alveolar lavage

Chronic lung allograft dysfunction (CLAD) remains a major risk factor for death after lung transplantation. Previous data suggested that within CLAD at least 2 phenotypes are present: a neutrophilic type (nCLAD or neutrophilic reversible allograft dysfunction [NRAD]), reversible with azithromycin therapy, vs a low neutrophilic type, non-responsive to azithromycin (fibrotic bronchiolitis obliterans syndrome [fBOS]). We aimed to further characterize this dichotomy by measuring multiple proteins in the bronchoalveolar lavage (BAL) fluid of 28 lung recipients. Patients were retrospectively subdivided by the absence or presence of CLAD and subsequently by their response to azithromycin, resulting in 3 groups: 10 stable, 9 responsive (nCLAD/NRAD), and 9 non-responsive (fBOS). Enzyme-linked immunosorbent assay was used to measure 32 different proteins. Protein variations were predominantly present in the nCLAD/NRAD group, whereas no differences were observed in the fBOS group compared with control. MCP-1 (p < 0.01), RANTES (p < 0.05), IL-1β (p < 0.01), IL-8 (p < 0.01), TIMP-1 (p < 0.01), MMP-8 (p < 0.01), MMP-9 (p < 0.01), HGF (p < 0.001), MPO (p < 0.01), and bile acid (p < 0.05) concentrations were upregulated in nCLAD/NRAD compared with fBOS, whereas PDGF-AA (p < 0.05) was downregulated. These data provide further evidence that within CLAD there is a heterogeneity of phenotypes with different mechanisms involved. Further investigation is warranted to unravel the pathophysiology of both phenotypes.

Plasma Myeloperoxidase Predicts Incident Cardiovascular Risks in Stable Patients Undergoing Medical Management for Coronary Artery Disease

Myeloperoxidase (MPO) concentrations predict adverse clinical outcomes in the setting of acute coronary syndromes and heart failure, but the prognostic role of MPO in stable patients with known atherosclerotic burden is unclear. We examined plasma MPO concentrations and their relationship with prevalent significant coronary artery disease (defined as >50% stenosis in any coronary vessel) and incident major adverse cardiovascular events (MACEs), including death, myocardial infarction, and stroke, in a 3-year prospective follow-up study of 1895 patients undergoing elective coronary angiography. The median plasma MPO concentration was 101 pmol/L (interquartile range 68-187 pmol/L). Patients with plasma MPO concentrations >322 pmol/L (14.6% of population) had increased risk of developing future MACEs [hazard ratio (HR) 1.78, 95% CI 1.33-2.37, P < 0.001], and MPO as a single variable predictor of MACE showed an area under the ROC curve of 0.67. After adjusting for traditional cardiac risk factors, creatinine clearance, B-type natriuretic peptide, and high-sensitivity C-reactive protein (hsCRP), increased MPO concentrations remained significantly associated with incident MACEs over the ensuing 3-year period (HR 1.71; 95% CI 1.27-2.30, P < 0.001). In patients with increased hsCRP, MPO ≤322 pmol/L was associated with lower event rates than observed with MPO >322 pmol/L. Plasma MPO concentrations provide independent prognostic value for the prediction of long-term incident MACEs in a stable, medically managed patient population with coronary artery disease. In individuals with increased hsCRP concentrations, we observed lower risk of incident MACEs when concomitant MPO concentrations were low vs when MPO concentrations were high.

Myeloperoxidase Selectively Binds and Selectively Kills Microbes

Myeloperoxidase (MPO) is reported to selectively bind to bacteria. The present study provides direct evidence of MPO binding selectivity and tests the relationship of selective binding to selective killing. The microbicidal effectiveness of H(2)O(2) and of OCl(-) was compared to that of MPO plus H(2)O(2). Synergistic microbicidal action was investigated by combining Streptococcus sanguinis, a H(2)O(2)-producing microbe showing low MPO binding, with high-MPO-binding Escherichia coli, Staphylococcus aureus, or Pseudomonas aeruginosa without exogenous H(2)O(2), with and without MPO, and with and without erythrocytes (red blood cells [RBCs]). Selectivity of MPO microbicidal action was conventionally measured as the MPO MIC and minimal bactericidal concentration (MBC) for 82 bacteria including E. coli, P. aeruginosa, S. aureus, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus agalactiae, and viridans streptococci. Both H(2)O(2) and OCl(-) destroyed RBCs at submicrobicidal concentrations. Nanomolar concentrations of MPO increased H(2)O(2) microbicidal action 1,000-fold. Streptococci plus MPO produced potent synergistic microbicidal action against all microbes tested, and RBCs caused only a small decrease in potency without erythrocyte damage. MPO directly killed H(2)O(2)-producing S. pyogenes but was ineffective against non-H(2)O(2)-producing E. faecalis. The MPO MICs and MBCs for E. coli, P. aeruginosa, and S. aureus were significantly lower than those for E. faecalis. The streptococcal studies showed much higher MIC/MBC results, but such testing required lysed horse blood-supplemented medium, thus preventing valid comparison of these results to those for the other microbes. E. faecalis MPO binding is reportedly weak compared to binding of E. coli, P. aeruginosa, and S. aureus but strong compared to binding of streptococci. Selective MPO binding results in selective killing.

Plasma level of myeloperoxidase in children with juvenile idiopathic arthritis (a pilot study)

Abstract To examine the plasma levels of MPO in oligoarthritis and polyarthritis subtypes of JIA in comparison with healthy age-matched controls. Thirty-eight JIA patients (25 girls and 13 boys) aged 9.1–11.8 years and 23 healthy controls (8 girls and 15 boys) participated in the study. Twenty-one patients had oligoarthritis (8 with extended oligoarthritis) and 17 had polyarthritis (among them three were seropositive). The plasma concentration of MPO was measured by the ELISA technique (OxisResearchTM, BIOXYTECH® MPO-EIATM, Portland, OR USA). The mean plasma concentration of MPO in the JIA group was significantly higher than in the control group (76.6±24.8 µg/L versus 62.7±15.6 µg/L; p=0.01). Patients with polyarthritis presented a significantly higher mean plasma MPO level than patients with oligoarthritis (81.3±25.6 µg/L and 62.1±27.1 µg/L, respectively; p=0.02). Different subtypes of JIA may have different MPO-related backgrounds. MPO is a new potent inflammatory marker. Patients with polyarthritis have higher mean plasma MPO levels than patients with oligoarthritis and may therefore have an enhanced risk for subclinical oxidative stress-related atherogenic promotion.

Leukocyte Counts, Myeloperoxidase, and Pregnancy-Associated Plasma Protein A as Biomarkers for Cardiovascular Disease: Towards a Multi-Biomarker Approach

We evaluated leukocyte counts and levels of CRP, fibrinogen, MPO, and PAPP-A in patients with stable and unstable angina pectoris, acute myocardial infarction, and healthy controls. All biomarkers were analyzed again after 6 months. Leukocyte counts and concentrations of fibrinogen, CRP, MPO, and PAPP-A were significantly increased in patients with acute myocardial infarction. Leukocyte counts and concentrations of MPO were significantly increased in patients with unstable angina pectoris compared with controls. After 6 months, leukocyte counts and MPO concentrations were still increased in patients with acute myocardial infarction when compared to controls. Discriminant analysis showed that leukocyte counts, MPO, and PAPP-A concentrations classified study group designation for acute coronary events correctly in 83% of the cases. In conclusion, combined assessment of leukocyte counts, MPO, and PAPP-A was able to correctly classify acute coronary events, suggesting that this could be a promising panel for a multibiomarker approach to assess cardiovascular risk.

Abstract 5650: Interactions Between the Endogenous NO Synthase Inhibitor Asymmetric Dimethylarginine and the Leukocyte-derived Hemoprotein Myeloperoxidase

Background: ADMA and the NO oxidizing leukocyte-derived hemoprotein MPO are associated with cardiovascular diseases. ADMA and MPO per se coincide with increased oxidative stress and induction of inflammatory responses. Furthermore, the enzymes responsible for ADMA homeostasis (i.e. dimethylarginine dimethylaminohydrolase, DDAH) are regulated in a redox-sensitive fashion. Therefore, the aim of the study was to investigate whether there is an interaction between ADMA and MPO resulting in increased leukocyte (PMN) activation and reduced NO bioavailability. Methods: To test a direct leukocyte activating effect of ADMA, isolated human PMN were subjected to ADMA, SDMA, and fMLP -an inductor of NADPH oxidase activity- to determine PMN degranulation (MPO activity, MPO and elastase levels) and leukocyte superoxide production. NO synthase and DDAH activity was measured by GC-MS and LC-MS/MS, respectively. In vivo, the effect of chronic ADMA (250 μ mol/kg/d; 28 days) treatment on MPO concentrations was induced by osmotic minipumps in C57 mice. To test the effect of MPO on DDAH1 and -2 gene expression, taqman rtPCR technique was performed in liver and kidney tissue of MPO knockout mice. The effect of MPO on DDAH activity in vitro was studied using a recombinant DDAH enzyme. Results: ADMA and fMLP incubation -but not SDMA- significantly increased superoxide production, PMN degranulation and MPO release. Furthermore, ADMA but not SDMA was able to impair NO synthesis of PMN and enhanced PMN’s adhesion to cultured HUVECs in vitro. In vivo, chronic treatment with ADMA resulted in a significant increase of plasma MPO concentrations in C57 mice in contrast to vehicle-treated controls. DDAH1 gene expression was markedly increased in liver and kidney tissue of MPO knockout mice compared to C57 controls. In vitro, MPO and its product HOCl were able to impair recombinant DDAH activity, whereas inactivated MPO was not. Summary and conclusions: ADMA profoundly activates PMN resulting in increased degranulation and MPO release, superoxide production, and impaired NO synthesis. MPO modulates DDAH expression and impairs DDAH activity. Our data revealed a two-way interaction between the ADMA and MPO pathway, which may open a new avenue for treatment of cardiovascular disease.

Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory disease associated with premature atherosclerosis. We hypothesized that mediators of inflammation associated with atherosclerosis in other populations (interleukin-6 [IL-6], tumor necrosis factor alpha [TNFalpha], serum amyloid A [SAA], vascular endothelial growth factor, neutrophil count, IL-1alpha, E-selectin, intercellular adhesion molecule 1 [ICAM-1], myeloperoxidase [MPO], matrix metalloproteinase 9, and vascular cell adhesion molecule 1) would be increased and associated with the severity of coronary atherosclerosis in patients with RA. Clinical variables, concentrations of inflammatory mediators, and coronary artery calcification were measured in 169 patients with RA and 92 control subjects. Differences in concentrations of inflammatory mediators were compared using median quantile regression. The relationship of inflammatory mediators with the severity of coronary calcification in RA and control subjects was examined using proportional odds logistic regression, allowing for interaction with disease status. Models were adjusted for traditional cardiovascular risk factors. Median serum concentrations of IL-6, SAA, ICAM-1, E-selectin, TNFalpha, and MPO and peripheral blood neutrophil count were higher in patients with RA than controls (all P < 0.05), independent of Framingham risk score and diabetes mellitus (DM). IL-6 (main effect odds ratio [OR] 1.72; 95% confidence interval [95% CI] 1.12, 2.66) and TNFalpha (main effect OR 1.49; 95% CI 1.16, 1.90) concentrations were significantly associated with higher amounts of coronary calcium, independent of Framingham risk score and DM, and such main effects significantly differed from controls (P = 0.001 and 0.03 for interaction, respectively). TNFalpha and IL-6 are significantly associated with the severity of subclinical atherosclerosis, independent of Framingham risk score, in RA.

Biochemical Markers for Determining Vulnerable Atherosclerotic Plaque in Stenotic Patient: Biochemical Markers Study of Myeloperoxidase (MPO), Matrix Metallo-Proteinase-9 (MMP-9), Secretory Phospholipase A2 (SPLA2) and CD40 Ligand

BACKGROUND: Thrombus is a main cause of cardiac death. Therefore identifying which coronary artery plaque is vulnerable to rupture is a critical step for cardiac intervention to prevent future cardiac events. Systemic biochemical markers are used for predicting rupture of coronary plaque or identifying stenotic coronary artery plaque(s) vulnerable to rupture.METHODS: Blood samples of 2x24 locations (2x10 controls, 2x12 stable plaques and 2x2 unstable plaques) of 13 patients to undergo stent placement were taken from an artery which showed no stenosis (control), 70% or more stenosis of stable plaques and unstable plaques, respectively. The blood samples were taken by using microcatheter distally and proximally. Concentrations of MPO, MMP-9, SPLA2 and CD40L of each sample were assayed.RESULTS: Concentration of MMP-9 in unstable coronary artery plaque (94.7+14.4 ng/ml) significantly increased compared with that of stable coronary artery plaque (71.0+67.8 ng/ml, p=0.024). SPLA2 concentration significantly decreased in unstable coronary artery plaque (45.9+14.0 pg/ml) compared with that of stable coronary artery plaque (80.9+39.3 pg/ml, p=0.015). Nine of ten studied subjects showed an average of 14.5% (range: 0.0-28.8%) decrease of the SPLA2 concentration in stable plaques compared with that of the non-stenotic coronary artery.CONCLUSION: MMP-9 increased in unstable coronary artery plaque compared with that of stable coronary plaque. Unstable coronary artery plaques absorbed SPLA2 from the vasculars more than the stable plaques and control plaques. MMP-9 and SPLA2 may be used as markers of stability of a plaque in coronary artery in relation to its rupture potential.KEYWORDS: stable and unstable plaque, myeloperoxidase, matrix metalloproteinase-9, secretory phospholipase A2, CD40 Ligand

Expression of toll-like receptor 2/4 on alveolar macrophage in the model of total hepatic ischemia/reperfusion injury in mice

Objective: To explore the expression and meaning of Toll-like receptor 2/4 in alveolar macrophage during the process of total hepatic ischemia in mice. Methods: BALB/c mice were used in a model of total hepatic ischemia/reperfusion. Alveolar Macrophage were collected at the time point of 1h, 6h and 12h by the means of bronchoalveolar lavage (BAL), and its TLR2/4 mRNA and protein were detected with Flow Cytometry and Real-time PCR. The level of TNF in BAL fluid were measured. The concentration of MPO, the ratio of wet/dry and lung histological scores were used to assess the degrees of lung injuries. Results: At the three time points of hepatic ischemia reperfusion, the expression of TLR2/4 protein of and mRNA were up-regulated and the level of TLR2 was on the rise continually. TLR4 at the time of 6 h reached the peak value (P<0.01). The level of TNF-2 in BAL fluid reached the highest point at the time of 6 h (P<0.01). The ratio of wet/dry rose continually during hepatic ischemia reperfusion. After 1 h, the level of MPO increased rapidly. Then it reached the peak value during the period of 6 h to 12 h. Conclusion: TLR2/4 on the mice of alveolar macrophage were activated in the process of hepatic ischemia/reperfusion and involved in the injury of lung.

MPO and Cytokines in the Serum of Cancer Patients in the Context of Candida Colonization and Infection

This study investigated the immunological factors, such as neutrophils number, the level of myeloperoxidase and IL-12, IL-10, TNF-α, IFN-γ, that additionally might correlate with increased susceptibility to Candida infections in cancer patients. A total of 105 cancer patients were evaluated. Patients were examined twice for Candida colonization and presence of Candida antigen and DNA in bloodstream. Serum concentrations of MPO and selected cytokines were quantified by ELISA. The values for myeloperoxidase were decreased in Candida-colonized as well as deep-infected cancer patients groups, compared to healthy persons. In the group of patients suspected of deep candidiasis, we observed significantly elevated level of IFN-γ compared to control. In the group of Candida-colonized patients, the concentrations of IL-12, TNF- α and IFN-γ were significantly heightened when compared to control.MPO deficiency seems to be one of the important risk factor for deep candidiasis independently of the neutrophil count. The disturbances in cytokines levels in cancer patients group can be connected with underlying cancer disease, its treatment as well as Candida infection. The decreased level of TNF-α, in particular may be connected with Candida invasion.

A protective effect of the synthetic coumarine derivative Cloricromene against DNB-colitis in the rat

Biologic therapies, namely antibodies against tumor necrosis factor-α (TNF- α) or its receptors, have been recently introduced for the treatment of patients with inflammatory bowel disease (IBD). In the present study the effects of cloricromene, an agent with known antithrombotic actions and with demonstrated anti-TNF- α activity were investigated in a rat model of experimental colitis induced with dinitrobenzenesulphonic acid (DNB)/ethanol. We investigated three experimental groups: (i) sham-colitis with vehicle-treatment (controls, n = 6), (ii) colitis with vehicle-treatment (saline, 0.1 ml s.c., daily) (DNB-V, n = 7), (iii) colitis with cloricromene-treatment (10 mg/kg/day s.c.; DNB-C, n = 8). After 7 days, the weight gain, colon wet weight, macroscopic damage score, coagulation parameters, colon mucosal myeloperoxidase activity (MPO), and tissue concentrations of TNF- α and of macrophage inhibitory peptide-2 (MIP-2) were assessed. The macroscopic damage scores, colon wet weights, and tissue MIP-2 levels were significantly increased in untreated and in cloricromene-treated rats compared with controls. Cloricromene treatment was associated with a minor body weight loss (p < 0.025) and significantly reduced tissue concentrations of MPO and TNF-α (p < 0.02, both). Blood coagulation parameters were not affected by treatment. In the DNB-model treatment with cloricromene effectively reduces tissue levels of TNF- α and of myeloperoxidase, whereas MIP-2 concentrations were not influenced. Blood coagulation parameters remained unchanged indicating safety of treatment. Since biological therapies frequently fail to improve disease course of IBD, other therapies with similar targets should be further investigated.

A neurokinin 1 receptor antagonist reduces an ongoing ileal pouch inflammation and the response to a subsequent inflammatory stimulus.

Ileal pouch-anal anastomosis (IPAA) is an excellent surgical option for patients with chronic ulcerative colitis (CUC) requiring colectomy; however, persistent episodes of ileal pouch inflammation, or pouchitis, may result in debilitating postoperative complications. Because considerable evidence implicates substance P (SP) as an inflammatory mediator of CUC, we investigated whether SP participates in the pathophysiology of pouchitis. With the use of a rat model of IPAA that we developed, we showed that ileal pouch MPO levels and neurokinin 1 receptor (NK-1R) protein expression by Western blot analysis were significantly elevated 28 days after IPAA surgery. In situ hybridization and immunohistochemistry showed that the increase in NK-1R protein expression was localized to the lamina propria and epithelia of pouch ileum. The intraperitoneal administration of the NK-1R antagonist (NK-1RA) CJ-12,255 for 4 days, starting on day 28, was effective in reducing MPO levels. Starting on day 28, animals with IPAA were given 5% dextran sulfate sodium (DSS) in their drinking water for 4 days, which caused histological and physical signs of clinical pouchitis concomitant with significant increases in ileal pouch MPO concentrations as well as NK-1R protein expression by Western blot analysis. In situ hybridization and immunohistochemistry showed that the increase in NK-1R protein expression was especially evident in crypt epithelia of pouch ileum. When the NK-1RA was administered 1 day before starting DSS and continued for the duration of DSS administration, the physical signs of clinical pouchitis and the rise in MPO were prevented. These data implicate SP in the pathophysiology of pouchitis and suggest that NK-1RA may be of therapeutic value in the management of clinical pouchitis.

Neutrophil and eosinophil granule proteins as markers of response to local prednisolone treatment in distal ulcerative colitis and proctitis

OBJECTIVE: The pathophysiological role of neutrophil and eosinophil granulocytes in relation to steroid enema treatment was studied in patients with distal ulcerative colitis and proctitis. METHODS: The rectal release of the neutrophil (myeloperoxidase, MPO), and eosinophil (eosinophilic cationic protein, ECP and eosinophil peroxidase, EPO) granule constituents were measured in 11 patients using intraluminal segmental perfusion of the rectum. The released amounts of MPO, ECP, and EPO in the perfusion fluids were determined by radioimmunoassays before and during prednisolone enema treatment and related to clinical, endoscopical, and histopathological data in addition to treatment outcome. RESULTS: Clinical activity and particularly endoscopic activity correlated well with intraluminal MPO concentrations both before and during treatment. At the end of the study, eight of 11 patients fulfilled predefined response criteria; all responding patients had significant decrease of MPO concentrations ( p < 0.01). This decline of MPO concentration was seen after 7 days of treatment ( p < 0.05) in the response group and often occurred before clinical improvement. There was a nonsignificant trend toward a decrease in the concentrations of ECP and EPO at the end of treatment in responders. CONCLUSIONS: In patients with distal ulcerative colitis and proctitis, neutrophil activation determined, as a release of MPO is an early marker of treatment response. Eosinophil activation measured as a release of ECP and EPO correlates with endoscopic activity, but the relationship to treatment outcome is less clear.

Neutrophil and eosinophil granule proteins as markers of response to local prednisolone treatment in distal ulcerative colitis and proctitis.

The pathophysiological role of neutrophil and eosinophil granulocytes in relation to steroid enema treatment was studied in patients with distal ulcerative colitis and proctitis. The rectal release of the neutrophil (myeloperoxidase, MPO), and eosinophil (eosinophilic cationic protein, ECP and eosinophil peroxidase, EPO) granule constituents were measured in 11 patients using intraluminal segmental perfusion of the rectum. The released amounts of MPO, ECP, and EPO in the perfusion fluids were determined by radioimmunoassays before and during prednisolone enema treatment and related to clinical, endoscopical, and histopathological data in addition to treatment outcome. Clinical activity and particularly endoscopic activity correlated well with intraluminal MPO concentrations both before and during treatment. At the end of the study, eight of 11 patients fulfilled predefined response criteria; all responding patients had significant decrease of MPO concentrations (p < 0.01). This decline of MPO concentration was seen after 7 days of treatment (p < 0.05) in the response group and often occurred before clinical improvement. There was a nonsignificant trend toward a decrease in the concentrations of ECP and EPO at the end of treatment in responders.

Study on pathogenetic role of myeloperoxidase, tumor necrosis factor alpha, interferon gamma in chronic airway infection with Pseudomonas aeruginosa

This study was performed to demonstrate the pathogenetic role of mucoid-alginate produced by Pseudomonas aeruginosa in relation to immuno-interaction in host cells. The obtained results are as follows. 1. Clinical Observation The concentration of MPO, TNF alpha, and IFN gamma in peripheral blood of 37 cases of chronic airway infection were observed. The cases were divided into the groups with mucoid strain positive (21 cases) and negative (16 cases), and each group was also divided into subgroups with active clinical symptom and without. High concentration of serum IFN gamma was shown in the group of mucoid strain positive cases (0.10 +/- 0.08 IU/ml in healthy volunteers group, 0.54 +/- 0.56 IU/ml in mucoid group with symptom: p < 0.01, 0.09 +/- 0.15 IU/ml in mucoid group without symptom, 0.13 +/- 0.13 IU/ml in non-mucoid group with symptom, 0.09 +/- 0.13 IU/ml in non-mucoid group without symptom). But plasma concentrations of MPO and serum concentrations of TNF alpha were not increased in all groups, except MPO in non-mucoid group with symptom. It indicates that IFN gamma has a characteristic role in chronic airway infection with mucoid Pseudomonas aeruginosa (P. aeruginosa). 2. Experimental Observation One hundred twenty-two of alginate-immunized mice were made by 5 times of intraabdominal injection with purified alginate extracted from mucoid P. aeruginosa PT-1252. 4 x 10(6) CFU/body of mucoid P. aeruginosa PT-1252 or 20 micrograms/body of purified alginate was intubated per trachea into the immunized mice, and changes in mean fluorescence intensity (MFI) of MPO and TNF alpha on neutrophils and IFN gamma on CD3 positive lymphocytes in BALF were observed. MFI of MPO (99.7 +/- 16.5-->177.0 +/- 23.1: p < 0.001) and TNF alpha (59.2 +/- 13.3-->197.0 +/- 62.0: p < 0.001) were increased on day 2 and they were kept up till on day 30 in P. aeruginosa group. But in alginate group they were temporally decreased on day 2, and they were gradually increased (MPO: 99.7 +/- 16.5-->212.6 +/- 12.1: p < 0.001, TNF alpha: 59.2 +/- 13.3-->162.4 +/- 30.9: p < 0.01). The temporally decrease of MPO and TNF alpha on day 2 in alginate group may suggest that a large amount of alginate inhibits neutrophils chemotaxis. MFI of IFN gamma in P. aeruginosa was also increased (110.0 +/- 32.9-->198.3 +/- 23.0: p < 0.01) on day 2 and it was gradually decreased on day 30 (156.0 +/- 13.8). In alginate group, MFI of IFN gamma in BALF was increased on day 5 (110.0 +/- 32.9-->201.0 +/- 49.3: p < 0.001) and kept a high level till day 30 (223.0 +/- 57.5: p < 0.01). In morphological, the moderate grade of lymphocytes infiltration observed in intersitial area of lung tissue on both groups of P. aeruginosa and alginate intubation mice. The findings was continuously seen from day 5 through day 30. The lymphocytes infiltration appeared in lung tissue can be though as an result of immuno-interaction with IFN gamma positive lymphocytes and mucoid-alginate. Inferences are drawn from the clinical results and the experimental ones that the CD3 positive IFN gamma lymphocytes expressed by immunological interaction with mucoid-alginate and the IFN gamma lymphocytes (Th1 like cells) plays an important role on advancement of chronic airway infection with mucoid P. aeruginosa.

鼻アレルギーに対するオキサトミドの効果

Oxatomide was administered to 27 patients with allergic rhinitis and serum concentrations of MPO and arylsulfatase B were measured to determine its effectiveness. Oxatomide was effective in reducing nasal symptoms. It did not affect the serum concentrations of MPO or arylsulfatase B. No side effects were noted in the present study.

Redox Chemistry and [Au (CN)2 -] in the Formation of Gold Metabolites

The role of hypochlorite ion, which can be generated by the enzyme myleoperoxidase, in the biochemistry of gold(I) anti-arthritic drugs was investigated. Sodium hypochlorite (OCl−) directly and rapidly oxidizes AuSTm, Au(CN)2-, AuSTg (gold thioglucose) and auranofin (Et3PAuSATg). The resulting gold(III) species were detected by an Ion Chromotography Ion-Pairing technique that was developed to distinguish gold(I) and gold(III). Formation of Au(III) was also demonstrated spectrophotometrically after the conversion to AuCl4−. The reactions of AuSTm, AuSTg, and auranofin are complex and gold(III) appears only after the initial oxidation of the thiolate (and phosphine) ligands. The enzymatic reaction, using MPO with H2O2 and Cl− as substrates, leads to slow oxidation of Au(CN)2-, AuSTm or AuSTg. The extent and rate of reaction depend on the concentrations of MPO, H2O2, and Au(I). The continued presence of Au(I) during the initial stages of reaction (oxidation of the thiolates in AuSTm and AuSTg) and the conversion to Au(III) in the latter stages of the reaction were demonstrated. Au(CN)2-, a gold metabolite, binds tightly to serum albumin. Unlike other gold(I) complexes, aurocyanide reacts almost negligibly at Cys-34 via ligand exchange. Instead, there is a strong association (K1 = 5.5 × 104 and K2 = 7.0 × 103; n1 = 0.8 and n2 = 3) of intact Au(CN)2-. The full extent of binding is revealed only by equilibrium methods such as NMR or ultrafiltration; the bound gold dissociates extensively on conventional gel-exclusion columns and partially on Penefesky spun columns. The immunological and pharmacological significance of these results are discussed.

Anaphylatoxin C5a Production During Short-Term Submaximal Dynamic Exercise in Man

We studied the effects of short-term submaximal exercise on the plasma levels of myeloperoxidase ([MPO]) and C5a anaphylatoxin ([C5a]), taken as specific markers of polymorphonuclear neutrophil (PMN) and complement activation, respectively. Eleven young, healthy male volunteers were subjected to a constant-load concentric exercise on a cycle ergometer (20 min at 80% maximal oxygen uptake). Mean resting MPO and C5a concentrations were 437 +/- 113 and 0.47 +/- 0.21 ng/ml, respectively. During exercise, [MPO] and [C5a] increased significantly (p < 0.001) towards respective peak values of 649 +/- 131 and 1.3 +/- 0.6 ng/ml. A rapid decrease of both [MPO] and [C5a] was observed during recovery. The similar time course of [MPO] and [C5a] changes and the highly significant relationship between these two variables (r = 0.651; p < 0.001) argues for the possible involvement of the complement anaphylatoxin C5a in the process of PMN degranulation. During exercise, the number of circulating PMN increased (+80%; p < 0.001) and remained practically unchanged up to 20 minutes of recovery. As [MPO] and PMN count were not significantly related (r = 0.2; p < 0.1), we concluded that the activation of PMN was independent of their mobilization.

Examination of comparative rare earth element complexation behavior using linear free-energy relationships

The comparative behavior of rare earth formation constants, L β n ( M), where M a trivalent rare earth element (REE), has been assessed using compilations of rare earth-organic ligand stability constants. Linear free-energy relationships of the form log L β n ( M) = I n ( M) + S n ( M) log Lβ n (Gd), where I n ( M) and S n ( M) are constants, are used to quantitatively describe the relative magnitudes of Lβ n ( M) for rare earth complexation by a given ligand L. Our characterizations provide a means of estimating formation constants for the entire suite of rare earths when formation constants Lβ n ( M) = ML n M 3+ −1 [ L] − n ) have been determined experimentally for at least one element. We have used the results of our analyses to calculate rare earth phosphate stability constants for the entire suite of rare earths. Estimated stability constants for each rare earth have been used to assess the relative importance of phosphate complexes, carbonate complexes, and hydrolyzed rare earths in groundwaters. Speciation calculations for representative groundwater environments indicate a strong dependence of Speciation on REE atomic number and pH. Between pH 7 and 9, heavy REE complexes, MPO 4 0, can be important compared to MCO 3 + and M( CO 3) 2 −. The complexes M( PO 4) 2 3− become significant at higher phosphate concentrations than those considered in our model groundwater. For the light REEs at pH ≤9, the concentrations of MCO 3 + complexes can exceed the concentrations of MPO 4 0 complexes. For pH ≤ 6, M 3+ concentrations exceed the concentrations of complex ions. Phosphate complexes exhibit an insignificant role in REE Speciation in seawater. Using3 ×10 3 as a carbonate/phosphate ion concentration ratio representative of seawater ([ CO 3 2− [PO 4 3−] ≈310 3 ) calculations indicate that, for all rare earths, [MCO 3 +] [MPO 4 0] 100, and [CeCO 3 + [CePO 4 0] ≈ 450.