Hyaluronic acid levels are increased in complicated parapneumonic pleural effusions

Background and Aim. Hyaluronic acid (HA) is a component of extracellular matrix and may play a role in the pleural inflammation which is implicated in parapneumonic effusions.The aim of the current study was to investigate HA levels in serum and pleura in patients with parapneumonic effusions. Methods. We prospectively studied pleural and serum levels of HA in 58 patients with pleural effusions due to infection (complicated and uncomplicated parapneumonic effusions), malignant effusions and transudative effusions due to congestive heart failure. In addition to HA, TNF-α and IL-1β levels were determined in pleural fluid and serum by ELISA. Results. The median±SD HA levels (pg/ml) in pleural fluid of patients with complicated effusions (39.058±11.208) were significantly increased (p<0.005), compared to those with uncomplicated parapneumonic effusions (11.230±1.969), malignant effusions (10.837±4.803) or congestive heart failure (5.392±3.133). There was no correlation between pleural fluid and serum HA values. Pleural fluid TNF-α levels (146±127 pg/mL) and IL-1β levels (133.4±156 pg/mL) were significantly higher in patients with complicated parapneumonic effusions compared to patients with other types of effusion (p<0.05). No significant association between HA and TNF-α or IL-1β was found. Conclusions. HA may play a significant role in the inflammatory process which characterises exudative infectious pleuritis. Further investigation might reveal whether HA is a useful marker in the management of parapneumonic effusions

One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond.

Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1-42 peptide chain [Aβ1-42] &gt;0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, Aβ1-42, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers

Matrix Metalloproteinases in Respiratory Diseases: From Pathogenesis to Potential Clinical Implications

Matrix metalloproteinases (MMPs) are zinc-endopeptidases responsible for degradation of the extracellular matrix (ECM) components including basement membrane collagen, interstitial collagen, fibronectin, and various proteoglycans, during normal remodeling and repair processes. The turnover and remodeling of ECM must be tightly regulated since excessive or inappropriate expression of MMPs may contribute to the pathogenesis of tissue destructive processes associated with lung inflammation and disease. Despite the fact that our knowledge in the field of MMP biology is rapidly expanding, the role of MMPs in the pathogenesis of lung diseases is still not clear. The aim of the present review is to present the basic principles of MMP biology and, subsequently, to focus on the clinical and experimental evidence related to MMP activity in various lung disorders, including lung cancer, pleural effusions, chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome and interstitial lung diseases

Matrix Metalloproteinase Levels in the Differentiation of Parapneumonic Pleural Effusions

Background: Matrix metalloproteinases (MMPs) have been implicated in the escalation of fibrosis and remodeling which are central to the subsequent progression of a parapneumonic pleural effusion to empyema. Objectives: The aim of this study was the assessment of MMP-2, MMP-8 and MMP-9 in parapneumonic pleural effusions in order to examine their value in the differentiation between uncomplicated and complicated parapneumonic effusions. Methods: The study included 208 consecutive patients with pleural effusions [60 parapneumonic (27 uncomplicated parapneumonic, 17 complicated parapneumonic, 16 empyemas), 24 tuberculous, 89 malignant and 35 transudates]. Concentrations of pleural fluid and serum MMP-2, MMP-8 and MMP-9 were determined by immunoassay. Results: Pleural fluid MMP-8 and MMP-9 levels were higher in complicated parapneumonic effusions or empyema than in uncomplicated effusions, while their serum levels were higher in complicated par apneumonic effusions. MMP-2 levels were higher in uncomplicated than in complicated parapneumonic effusions or empyema. Pleural fluid MMP-2/MMP-9 ratio was the best marker to differentiate complicated from uncomplicated parapneumonic effusions, with a sensitivity of 94.1% and a specificity of 77.8% at a cut-off point of 1.32 (AUC = 0.887). Conclusions: Pleural fluid MMP-2, MMP-8 and MMP-9 may provide useful information for differentiating between uncomplicated and complicated parapneumonic effusions. Copyright (C) 2010 S. Karger AG, Base

ICP-MS/MS-Based Ionomics: A Validated Methodology to Investigate the Biological Variability of the Human Ionome.

We here describe the development, validation and application of a quantitative methodology for the simultaneous determination of 29 elements in human serum using state-of-the-art inductively coupled plasma triple quadrupole mass spectrometry (ICP-MS/MS). This new methodology offers high-throughput elemental profiling using simple dilution of minimal quantity of serum samples. We report the outcomes of the validation procedure including limits of detection/quantification, linearity of calibration curves, precision, recovery and measurement uncertainty. ICP-MS/MS-based ionomics was used to analyze human serum of 120 older adults. Following a metabolomic data mining approach, the generated ionome profiles were subjected to principal component analysis revealing gender and age-specific differences. The ionome of female individuals was marked by higher levels of calcium, phosphorus, copper and copper to zinc ratio, while iron concentration was lower with respect to male subjects. Age was associated with lower concentrations of zinc. These findings were complemented with additional readouts to interpret micronutrient status including ceruloplasmin, ferritin and inorganic phosphate. Our data supports a gender-specific compartmentalization of the ionome that may reflect different bone remodelling in female individuals. Our ICP-MS/MS methodology enriches the panel of validated "Omics" approaches to study molecular relationships between the exposome and the ionome in relation with nutrition and health

Hyaluronic acid levels are increased in complicated parapneumonic pleural effusions

Background and Aim. Hyaluronic acid (HA) is a component of extracellular matrix and may play a role in the pleural inflammation which is implicated in parapneumonic effusions.The aim of the current study was to investigate HA levels in serum and pleura in patients with parapneumonic effusions. Methods. We prospectively studied pleural and serum levels of HA in 58 patients with pleural effusions due to infection (complicated and uncomplicated parapneumonic effusions), malignant effusions and transudative effusions due to congestive heart failure. In addition to HA, TNF-α and IL-1β levels were determined in pleural fluid and serum by ELISA. Results. The median±SD HA levels (pg/ml) in pleural fluid of patients with complicated effusions (39.058±11.208) were significantly increased (p<0.005), compared to those with uncomplicated parapneumonic effusions (11.230±1.969), malignant effusions (10.837±4.803) or congestive heart failure (5.392±3.133). There was no correlation between pleural fluid and serum HA values. Pleural fluid TNF-α levels (146±127 pg/mL) and IL-1β levels (133.4±156 pg/mL) were significantly higher in patients with complicated parapneumonic effusions compared to patients with other types of effusion (p<0.05). No significant association between HA and TNF-α or IL-1β was found. Conclusions. HA may play a significant role in the inflammatory process which characterises exudative infectious pleuritis. Further investigation might reveal whether HA is a useful marker in the management of parapneumonic effusions

Matrix Metalloproteinase Levels in the Differentiation of Parapneumonic Pleural Effusions

Background: Matrix metalloproteinases (MMPs) have been implicated in the escalation of fibrosis and remodeling which are central to the subsequent progression of a parapneumonic pleural effusion to empyema. Objectives: The aim of this study was the assessment of MMP-2, MMP-8 and MMP-9 in parapneumonic pleural effusions in order to examine their value in the differentiation between uncomplicated and complicated parapneumonic effusions. Methods: The study included 208 consecutive patients with pleural effusions [60 parapneumonic (27 uncomplicated parapneumonic, 17 complicated parapneumonic, 16 empyemas), 24 tuberculous, 89 malignant and 35 transudates]. Concentrations of pleural fluid and serum MMP-2, MMP-8 and MMP-9 were determined by immunoassay. Results: Pleural fluid MMP-8 and MMP-9 levels were higher in complicated parapneumonic effusions or empyema than in uncomplicated effusions, while their serum levels were higher in complicated par apneumonic effusions. MMP-2 levels were higher in uncomplicated than in complicated parapneumonic effusions or empyema. Pleural fluid MMP-2/MMP-9 ratio was the best marker to differentiate complicated from uncomplicated parapneumonic effusions, with a sensitivity of 94.1% and a specificity of 77.8% at a cut-off point of 1.32 (AUC = 0.887). Conclusions: Pleural fluid MMP-2, MMP-8 and MMP-9 may provide useful information for differentiating between uncomplicated and complicated parapneumonic effusions. Copyright (C) 2010 S. Karger AG, Base

Diagnostic accuracy of biomarkers of oxidative stress in parapneumonic pleural effusions

P&gt;Background The imbalance between oxidants and antioxidants is referred to as oxidative stress and has been associated with various respiratory disorders. The aim of this study was the assessment of 8-isoprostane (8-iso-PGF(2 alpha)) and Cu/Zn superoxide dismutase (Cu/Zn SOD) in exudative pleural effusions in order to examine the diagnostic accuracy of these markers in the differentiation between complicated and uncomplicated parapneumonic effusions. Methods The study included 214 consecutive patients with pleural effusions [68 parapneumonic (31 uncomplicated parapneumonic, 20 complicated parapneumonic, 17 empyemas), 24 tuberculous, 88 malignant and 34 transudates]. 8-Isoprostane and Cu/Zn SOD were determined by ELISA in pleural fluid and serum. Results Parapneumonic effusions were characterized by higher pleural fluid 8-isoprostane levels compared to transudative, malignant and tuberculous effusions. Pleural fluid Cu/Zn SOD levels were lower in transudates, while serum levels were higher in transudative compared to all exudative pleural effusions. Both pleural fluid 8-isoprostane and Cu/Zn SOD were higher in complicated parapneumonic effusions and empyemas compared to uncomplicated parapneumonic effusions. Pleural fluid 8-isoprostane was the most accurate test to differentiate between complicated and uncomplicated parapneumonic pleural effusions with a sensitivity of 100% and a specificity of 58 center dot 1% at a cut-off point of 35 center dot 1 (AUC = 0 center dot 848). Conclusions Pleural fluid 8-isoprostane and Cu/Zn SOD may provide useful information for the differentiation between uncomplicated and complicated parapneumonic effusions and empyemas

Residual Pleural Thickening Is Related to Vascular Endothelial Growth Factor Levels in Parapneumonic Pleural Effusions

Background: Many patients with pneumonia develop pleural effusions. Pleural fluid vascular endothelial growth factor (VEGF) levels are known to be elevated in complicated parapneumonic effusion and seem to play a major role in the fibrotic process in the pleura. Objectives: To test whether VEGF levels in pleural effusions of infectious origin correlate with the residual pleural thickening. Methods: VEGF levels were measured in the pleural fluid of 45 patients with pleural effusion of infectious origin. Patients were reassessed 3 months after hospital discharge and residual pleural thickening (RPT) was recorded using a simple chest radiograph. Results: Pleural fluid VEGF was higher in empyemas compared to simple parapneumonic and complicated parapneumonic effusions. RPT was higher in patients with empyemas compared to simple parapneumonic effusions. Patients with RPT > 2 mm had higher pleural fluid LDH and pleural fluid to serum LDH ratio, lower glucose and pH and higher VEGF levels. However, patients with RPT >= 10 mm differed only in pleural fluid VEGF levels. Pleural fluid VEGF levels correlated to RPT and to pleural fluid pH. VEGF presented moderate performance for the prediction of RPT 3 months after hospital discharge. Its performance was comparable to that of pleural fluid glucose and pH for the development of a radiologically significant RPT > 2 mm, whereas it was the only statistically significant predictor of a clinically significant RPT >= 10 mm. Conclusion: VEGF levels are elevated in complicated parapneumonic effusions and empyemas compared to simple parapneumonic effusions and are a significant predictor for the development of clinically significant RPT. Copyright (C) 2009 S. Karger AG, Base