Uric Acid: The Oxidant-Antioxidant Paradox

Uric acid, despite being a major antioxidant in the human plasma, both correlates and predicts development of obesity, hypertension, and cardiovascular disease, conditions associated with oxidative stress. While one explanation for this paradox could be that a rise in uric acid represents an attempted protective response by the host, we review the evidence that uric acid may function either as an antioxidant (primarily in plasma) or pro-oxidant (primarily within the cell). We suggest that it is the pro-oxidative effects of uric acid that occur in cardiovascular disease and may have a contributory role in the pathogenesis of these conditions.     

Superiority of total white blood cell count over other leukocyte differentials for predicting long-term outcomes in patients with non-ST elevation acute coronary syndrome

Abstract

Context: Leukocytes have been found to be the predictor of outcome following acute coronary syndrome (ACS).

Objective: We sought to determine the relationship between leukocyte differentials and developing major adverse cardiac events (MACE) in patients with non-ST elevation ACS (NSTE-ACS).

Materials and methods: A total of 490 consecutive patients were enrolled, and MACE incidence was evaluated at long-term follow-up period.

Results: Total white blood cell (WBC) was higher in subjects occurring MACE. Moreover, elevated total WBC, ≥7.5?×?10³/µL, independently predicted MACE.

Discussion and conclusion: Elevated admission total WBC can predict long-term MACE in NSTE-ACS patients better than other differentials.     

Urinary desmosine as a biomarker in acute lung injury

Acute lung injury (ALI) is a complex disorder associated with an acute inflammatory response thought to contribute to tissue injury. Desmosine, a cross-linking amino acid present in elastin, is released during matrix degradation and cleared by the kidney. Results from animal models and human disease studies have suggested that ALI is associated with the release of desmosine, resulting in increased urinary desmosine. A radioimmunoassay was used to monitor urinary desmosine levels over 10 days in ten patients with ALI. The concentration of desmosine was measured with and without acid hydrolysis. Baseline urinary desmosine was increased in two of ten patients. The concentration of desmosine at baseline did not appear to be related to age, gender, neutrophil elastase (NE)/α₁-antiprotease complex concentration or P_aO₂/F_iO₂ ratio. No meaningful changes in desmosine levels were noted after removal from mechanical ventilation. Baseline desmosine concentrations did not appear to correlate with the risk of death. The limited sensitivity, predictive correlations and dynamic modulation would suggest that urine desmosine has a limited role as a biomarker for ALI. Hydrolysis of urine samples appears necessary for optimal measurement of urine desmosine.     

Development of an expert system for the integration of biomarker responses in mussels into an animal health index

Biomarkers on sentinel organisms are utilised worldwide in biomonitoring programs. However, the lack of effective interpretational capacity has hampered their uptake for use for assessment of risk in environmental management. The aim of the present study was to develop and test an objective decision-support or expert system capable of integrating biomarker results into a five-level health-status index. The expert system is based on a set of rules derived from available data on responses to natural and contaminant-induced stress of marine mussels. Integration of parameters includes: level of biological organization; biological significance; mutual inter-relationship; and qualitative trends in a stress gradient. The system was tested on a set of biomarker data obtained from the field and subsequently validated with data from previous studies. The results demonstrate that the expert system can effectively quantify the biological effects of different levels of pollution. The system represents a simple tool for risk assessment of the harmful impact of contaminants by providing a clear indication of the degree of stress syndrome induced by pollutants in mussels.     

Th1/Th2/Th17/Treg cytokines in Guillain–Barré syndrome and experimental autoimmune neuritis

Guillain–Barré syndrome (GBS) is an immune-mediated acute inflammatory disorder in the peripheral nervous system (PNS) of humans characterized by inflammatory infiltration and damage to myelin and axon. Experimental autoimmune neuritis (EAN) is a useful animal model for GBS. Although GBS and EAN have been widely studied, the pathophysiological basis of GBS/EAN remains largely unknown. Immunocompetent cells together with cytokines produced by various cells contribute to the inflammatory process of EAN by acting as mediators or effectors. Both GBS and EAN have hitherto been attributed to T helper (Th)1 cells-mediated disorders, however, some changes in GBS and EAN could not be explained by the pathogenic role of Th1 cells and a disturbance of the Th1/Th2 balance, which has previously been considered to be important for the homeostatic maintenance of the immune responses and to explain the adaptive immunity and autoimmune diseases. The Th1/Th2 paradigm in autoimmune diseases has been greatly challenged in recent years, with the identification of a particular T cell subset Th17 cells. Studies on the associations between Th17 cells/cytokines and GBS/EAN are reviewed. But some of them occasionally yield conflicting results, indicating an intricate network of cytokines in immune response.     

Surfactant phospholipid metabolism

Pulmonary surfactant is essential for life and is composed of a complex lipoprotein-like mixture that lines the inner surface of the lung to prevent alveolar collapse at the end of expiration. The molecular composition of surfactant depends on highly integrated and regulated processes involving its biosynthesis, remodeling, degradation, and intracellular trafficking. Despite its multicomponent composition, the study of surfactant phospholipid metabolism has focused on two predominant components, disaturated phosphatidylcholine that confers surface-tension lowering activities, and phosphatidylglycerol, recently implicated in innate immune defense. Future studies providing a better understanding of the molecular control and physiological relevance of minor surfactant lipid components are needed. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism.     

Serum malondialdehyde levels,myeloperoxidase and catalase activities in patients with nephrotic syndrome

Abstract

Objectives

Some studies have indicated the pathophysiological importance of reactive oxygen species (ROS) in patients with nephrotic syndrome. Myeloperoxidase (MPO) is a leukocyte-derived enzyme-generating ROS that has been proposed to exert a wide array of pro-atherogenic effects throughout all stages of the atherosclerotic process. The aim of this study was to investigate the serum malondialdehyde (MDA) levels, MPO and catalase activities in patients with adult nephrotic syndrome.

Patients and Methods

Twenty-four patients with nephrotic syndrome and 24 healthy controls were enrolled. Serum MPO activity, catalase activity, and MDA levels were assessed.

Results

Serum MPO activity and MDA levels were signi?cantly higher in patients with nephrotic syndrome than controls (both, P < 0.001), while catalase activity was signi?cantly lower (P < 0.001). Serum catalase activity was found to be significantly correlated with MPO activity (r = ?0.417, P = 0.003) and MDA levels (r = ?0.532, P = 0.007). The serum MDA levels were also found to be significantly correlated with MPO activity (r = 0.419, P = 0.003).

Conclusions

We concluded that serum MPO activity and oxidative stress were increased and that serum catalase activity was decreased in patients with adult nephrotic syndrome. In addition, these results indicate that increased MPO activity is associated with an oxidant–antioxidant imbalance that may contribute to atherosclerosis in patients with adult nephrotic syndrome.     

Cystatin C,a novel urinary biomarker for sensitive detection of acute kidney injury during haemorrhagic fever with renal syndrome

To explore the value of cystatin C for evaluating acute kidney injury (AKI) in haemorrhagic fever with renal syndrome (HFRS), the concentrations of cystatin C in serum and urine samples from HFRS patients were determined. The serum and urinary cystatin C concentrations significantly increased in HFRS patients compared with normal controls (p?<?0.001). In the acute phase of HFRS, urinary cystatin C increased to higher levels than serum creatinine, especially in severe or critical cases in the oliguric stage. Furthermore, higher levels of urinary cystatin C in the acute phase positively correlated with increased severity of the subsequent kidney injury. In conclusion, urinary cystatin C is a more sensitive clinical marker for AKI in HFRS, which may enable us to initiate treatment measures as early as possible.     

A real‐time eco‐evolutionary dead‐end strategy is mediated by the traits of lineage progenitors and interactions with colony invaders

Evolutionary dead‐end strategies are characterized by short‐term productivity benefits and long‐term evolutionary costs. Here, I detail a real‐time dead‐end strategy associated with the behavioural traits of lineage progenitors in the social spider Anelosimus studiosus. Specifically, colony lineages founded by docile spiders were eight times more likely to suffer extinction, despite their superior reproductive output. However, when inquilines were experimentally removed from progenitor colonies, differences in extinction probability among lineages vanished. Similarly, among lineages founded by purely docile or aggressive individuals, the descendants of lineages with the highest reproductive output suffered the lowest survivorship, whereas lineages founded by a mixture of docile/aggressive lacked such a trade‐off. Finally, lineages with shorter progenitor‐descendant distances gained more inquilines and their descendants had lower survivorship, relative to more diffuse lineages. Overall, this study demonstrates how the traits of lineage progenitors and species interactions can unite to determine the fates of entire lineages.