Nejvíce citovaný článek - PubMed ID 9292145
Apart from oxygenic photosynthesis, the extent of manganese utilization in bacteria varies from species to species and also appears to depend on external conditions. This observation is in striking contrast to iron, which is similar to manganese but essential for the vast majority of bacteria. To adequately explain the role of manganese in pathogens, we first present in this review that the accumulation of molecular oxygen in the Earth's atmosphere was a key event that linked manganese utilization to iron utilization and put pressure on the use of manganese in general. We devote a large part of our contribution to explanation of how molecular oxygen interferes with iron so that it enhances oxidative stress in cells, and how bacteria have learned to control the concentration of free iron in the cytosol. The functioning of iron in the presence of molecular oxygen serves as a springboard for a fundamental understanding of why manganese is so valued by bacterial pathogens. The bulk of this review addresses how manganese can replace iron in enzymes. Redox-active enzymes must cope with the higher redox potential of manganese compared to iron. Therefore, specific manganese-dependent isoenzymes have evolved that either lower the redox potential of the bound metal or use a stronger oxidant. In contrast, redox-inactive enzymes can exchange the metal directly within the individual active site, so no isoenzymes are required. It appears that in the physiological context, only redox-inactive mononuclear or dinuclear enzymes are capable of replacing iron with manganese within the same active site. In both cases, cytosolic conditions play an important role in the selection of the metal used. In conclusion, we summarize both well-characterized and less-studied mechanisms of the tug-of-war for manganese between host and pathogen.
- Klíčová slova
- iron, manganese, metallostasis, mismetallation, oxidative stress, pathogenesis,
- MeSH
- Bacteria * metabolismus MeSH
- kovy metabolismus MeSH
- kyslík metabolismus MeSH
- mangan * metabolismus MeSH
- železo metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- kovy MeSH
- kyslík MeSH
- mangan * MeSH
- železo MeSH
Approximately half of patients with rheumatoid arthritis (RA) have normal C-reactive protein (CRP) levels. Calprotectin is a promising and likely more specific biomarker of disease activity than conventionally used acute phase reactants. We aimed to analyse the levels of serum calprotectin in RA patients with clinically active disease and with normal/low CRP. A total of 160 RA patients underwent clinical examination (DAS28-ESR and CDAI). The levels of calprotectin were analysed in patients with moderate to high disease activity with normal/low CRP levels and in 32 healthy subjects. The discriminatory capacity of calprotectin to identify clinically active patients in spite of normal/low CRP was assessed using ROC curves. Out of all RA patients, 74/160 (46.3%) were in remission or had low disease activity according to DAS28 and had normal/low CRP levels. However, 51/160 (32%) had normal/low CRP levels despite having moderate to high disease activity. In these patients, calprotectin levels were significantly higher than those in patients who had normal/low CRP and were in remission or showed low disease activity (2.7 ± 1.5 vs. 2.1 ± 1.2 μg/mL, p = 0.043), which differed from those in healthy subjects (2.7 ± 1.5 vs. 1.9 ± 1.2 μg/mL, p = 0.011). The discriminatory capacity for calprotectin to distinguish clinically active vs. inactive disease despite normal/low CRP using AUC of the DAS28 was 0.607 (95% CI 0.503 to 0.711, p = 0.043). The present study demonstrates that calprotectin may reflect inflammatory activity in RA patients where CRP fails to do so.
- Klíčová slova
- C-reactive protein, Calprotectin, Inflammation, Rheumatoid arthritis,
- MeSH
- biologické markery krev MeSH
- C-reaktivní protein analýza MeSH
- krevní sedimentace MeSH
- leukocytární L1-antigenní komplex krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- referenční hodnoty MeSH
- revmatoidní artritida krev MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Finsko MeSH
- Názvy látek
- biologické markery MeSH
- C-reaktivní protein MeSH
- leukocytární L1-antigenní komplex MeSH
BACKGROUND: Calprotectin may be a sensitive biomarker of rheumatoid arthritis (RA) disease activity. OBJECTIVES: In the current study, we investigated whether calprotectin is a better biomarker than CRP for predicting clinical activity and ultrasound parameters in patients with RA. METHODS: A total of 160 patients with RA underwent clinical (swollen joint count-SJC, tender joint count-TJC, Disease Activity Score-DAS28, Clinical Disease Activity Index-CDAI, and simplified Disease Activity Index-SDAI) and ultrasound (German US7) examination. Clinical and laboratory measures were correlated with ultrasound findings using Spearman´s correlation coefficient. Differences in serum calprotectin levels in patients with variable disease activity according to the DAS28-ESR and CDAI scores were assessed using ANOVA. Multivariate regression analysis was used to determine the predictive values of calprotectin, CRP and SJC for CDAI and PD US synovitis scores. RESULTS: Serum calprotectin was significantly associated with DAS28-ESR (r = 0.321, p<0.001), DAS28-CRP (r = 0.346, p<0.001), SDAI (r = 0.305, p<0.001), CDAI (r = 0.279, p<0.001) scores and CRP levels (r = 0.556, p<0.001). Moreover, calprotectin was significantly correlated with GS (r = 0.379, p<0.001) and PD synovitis scores (r = 0.419, p<0.001). The multivariate regression analysis showed that calprotectin is a better predictor of the CDAI score and PD US synovitis than CRP. CONCLUSIONS: The results of this study support an additional role of calprotectin in assessing inflammatory activity in patients with RA.
- MeSH
- C-reaktivní protein metabolismus MeSH
- dospělí MeSH
- kohortové studie MeSH
- leukocytární L1-antigenní komplex krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- revmatoidní artritida krev diagnostické zobrazování patologie MeSH
- ultrasonografie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- C-reaktivní protein MeSH
- leukocytární L1-antigenní komplex MeSH
OBJECTIVE: Clinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation. METHODS: Seventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0-1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves. RESULTS: The total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58-67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 μg/mL, p<0.005). Using ultrasound-defined remission criteria, calprotectin had an AUC of 0.692, p<0.05 using DAS28-ESR remission criteria and an AUC of 0.712, p<0.005 using DAS28-CRP remission criteria. Calprotectin correctly distinguished ultrasound remission from subclinical activity in 70% of patients. CRP (AUC DAS28-ESR = 0.494, p = NS; AUC DAS28-CRP = 0.498, p = NS) had lower and insignificant discriminatory capacity. CONCLUSION: The present study demonstrates the potential of calprotectin to distinguish RA patients in both clinical and ultrasound-defined remission from patients in clinical remission but with residual subclinical disease activity.
- MeSH
- C-reaktivní protein analýza MeSH
- dospělí MeSH
- leukocytární L1-antigenní komplex krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- revmatoidní artritida krev diagnostické zobrazování MeSH
- reziduální nádor MeSH
- senioři MeSH
- ultrasonografie MeSH
- zánět krev diagnostické zobrazování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- C-reaktivní protein MeSH
- leukocytární L1-antigenní komplex MeSH
INTRODUCTION: Calprotectin, a heterodimeric complex of S100A8/9 (MRP8/14), has been proposed as an important serum biomarker that reflects disease activity and structural joint damage in rheumatoid arthritis (RA). The objective of this cross-sectional study was to test the hypothesis that calprotectin is associated with clinical and ultrasound-determined disease activity in patients with RA. METHODS: A total of 37 patients with RA (including 24 females, a mean disease duration of 20 months) underwent a clinical examination and 7-joint ultrasound score (German US-7) of the clinically dominant hand and foot to assess synovitis by grey-scale (GS) and synovial vascularity by power Doppler (PD) ultrasound using semiquantitative 0-3 grading. The levels of serum calprotectin and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined at the time of the ultrasound assessment. We analysed the relationship between serum calprotectin level, traditional inflammatory markers, and ultrasound-determined synovitis. RESULTS: The levels of serum calprotectin were significantly correlated with swollen joint count (r = 0.465, p < 0.005), DAS28-ESR (r = 0.430, p < 0.01), ESR (r = 0.370, p < 0.05) and, in particular, CRP (r = 0.629, p < 0.001). Calprotectin was significantly associated with GS (r = 0.359, p < 0.05) and PD synovitis scores (r = 0.497, p < 0.005). Using multivariate regression analysis, calprotectin, adjusted for age and sex, was a better predictor of PD synovitis score (R(2) = 0.765, p < 0.001) than CRP (R(2) = 0.496, p < 0.001). CONCLUSIONS: The serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of RA disease activity. These results suggest that calprotectin might be superior to CRP for monitoring ultrasound-determined synovial inflammation in RA patients.
- MeSH
- biologické markery krev MeSH
- C-reaktivní protein metabolismus MeSH
- dospělí MeSH
- krevní sedimentace MeSH
- leukocytární L1-antigenní komplex krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- průřezové studie MeSH
- reprodukovatelnost výsledků MeSH
- revmatoidní artritida krev diagnóza diagnostické zobrazování MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- stupeň závažnosti nemoci MeSH
- synovitida krev diagnóza diagnostické zobrazování MeSH
- ultrasonografie dopplerovská metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- C-reaktivní protein MeSH
- leukocytární L1-antigenní komplex MeSH
BACKGROUND: The role of glucan in the stimulation of immune reactions is well established. In our report, we focused on the effects of orally administered glucan on nonspecific immunity of children with chronic respiratory problems. MATERIALS AND METHODS: We measured the levels of albumin, lysozyme. C-reactive protein (CRP) and calprotectin in the saliva of 60 children ages 8-12 years and evaluated the effects of 30-day treatment with 100 mg/d oral dose of glucan. RESULTS: We found a significant increase in the production of lysozyme, CRP and calprotectin in glucan-treated children. CONCLUSIONS: Short-term oral application of natural immunomodulator β-glucan significantly stimulated mucosal immunity of children with chronic respiratory problems.
- Klíčová slova
- Glucan, children, lysozyme, mucosal immunity, saliva,
- Publikační typ
- časopisecké články MeSH