Protein oxidation in chronic kidney disease

An imbalance between oxidative processes and antioxidant systems has been widely demonstrated in chronic kidney diseases (CKD). In this study we enrolled 26 healthy subjects, 27 patients with CKD on conservative treatment (CT-CKD) with various degrees of renal failure, and 31 CKD subjects in haemodialysis treatment (HD-CKD), evaluated before and after a standard haemodialysis session. In each group we measured protein carbonyl groups (PC) as an index of protein oxidation, lipid peroxidation (TBARS) and two plasma markers of leukocyte activation, elastase and myeloperoxidase (MPO). In CT-CKD subjects the PC level was significantly higher than in normal controls, and it was negatively correlated with creatinine clearance. In HD-CKD patients the PC concentration was significantly increased also in comparison with CT-CKD. An increase in TBARS was present both in CT-CKD and in HD-CKD patients, but in HD-CKD patients TBARS were lower than in CT-CKD. Elastase was increased in both CKD groups, while MPO was not different among control and patient groups. In HD-CKD patients the HD session was followed by a further increase in PC, as well as by an increase in elastase and MPO, whereas TBARS did not change. Protein oxidation accelerates the glycation processes and seems to be connected with the chronic inflammatory state detectable in renal failure, although we did not observe any significant correlation between PC level and leukocyte activation markers

Behavior of the total antioxidant status in a group of subjects with metabolic syndrome.

AIM: Our purpose was to examine the total antioxidant status (TAS) in subjects with metabolic syndrome (MS) subdivided according to the presence or not of diabetes mellitus. METHODS: We enrolled 106 subjects (45 women, 61 men) with MS subsequently subdivided in diabetics (14 women, 29 men) and nondiabetics (31 women, 29 men). TAS was obtained using an Assay kit which relies on the ability of plasma antioxidant substances to inhibit the oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline sulfonic acid) to the radical ABTS+. RESULTS: In the group of MS subjects a significant decrease in TAS (p<0.05) in comparison with normal controls was evident. This difference was present between normal subjects and nondiabetic subjects with MS (p<0.001) but not between normal and diabetic subjects with MS. Examining the linear regression among TAS, age, anthropometric profile, blood pressure values and glycometabolic pattern, conflicting data were found. CONCLUSIONS: Although we know that TAS includes several enzymatic and non enzymatic antioxidants, we retain that the difference observed in the two subgroups of subjects with MS must be looked in particular into two pathophysiological aspects regarding bilirubin and uric acid

Nitric oxide metabolites (nitrite and nitrate) in several clinical condition

We determined the concentration of nitric oxide metabolites (NO2-+ NO3-), expressed as NOx, in several clinical conditions. Regarding this, we have examined 25 subjects with arterial hypertension, 41 subjects with chronic kidney disease in conservative treatment, 106 subjects with metabolic syndrome subdivided according to the presence (n=43) or not (n=63) of diabetes mellitus, 48 subjects with obstructive sleep apnea syndrome (OSAS),14 women with systemic sclerosis complicated with Raynaud's phenomenon, 42 dialyzed subjects and 105 young subjects with acute myocardial infarction (AMI). In subjects with arterial hypertension, chronic kidney disease, metabolic syndrome, systemic sclerosis, as well as, in dialyzed and AMI subjects, we found at baseline a NOx increase. In dyalized subjects after a standard dialysis session, we observed a decrease in NOx. The increase in NOx in juvenile AMI was significantly influenced by cigarette smoking and less by cardiovascular risk factors and the extent of coronary lesions; at 3 and 12 months later than the initial event, we observed a decrease of NOx that remains significantly higher than the control group. In subjects with OSAS no difference in NOx was noted in comparison with normal controls, although their subdivision according to the apnea/hypopnea index operates a clear distinction regarding NOx concentration

Behaviour of the plasma concentration of gelatinases and their tissue inhibitors in subjects with venous leg ulcers.

Venous leg ulcers are common in subjects with chronic venous insufficiency. The increased intraluminal pressure causes alteration of the skin microcirculation, leukocyte activation and release of proteolytic enzymes leading to ulceration. An impaired expression and activity of matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) might influence extracellular matrix degradation and deposition in chronic venous ulcers with the failure of the healing process. Our aim was to evaluate plasma concentration of gelatinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in subjects with venous leg ulcers before and after the compression therapy. We enrolled 36 subjects (12 men and 24 women, mean age 67.38 ± 12.7 yrs) with non-infected venous leg ulcers (CEAP C6), which underwent a color Duplex scan examination of the veins and arteries of the inferior limbs and were treated with a multi-layer bandaging system. The ulcer healing was obtained in 23 subjects only (9 men and 14 women). We evaluated, on fasting venous blood, the plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 using ELISA kit, before and after the treatment. We observed a significant increase in plasma concentration of gelatinases and their inhibitors and in MMP-2/TIMP-2 ratio in subjects with leg ulcers in comparison with normal controls. In subjects with healed ulcers we found a decrease in MMP-9 and TIMP-1 levels and in MMP-2/TIMP-2 ratio compared to the baseline values, although higher levels of all the examined parameters in comparison with normal controls. In conclusion, plasma MMPs profile is impaired in subjects with venous leg ulcers and it improves after the healing, persisting anyway altered in respect to healthy controls

Behavior of the total antioxidant status in a group of subjects with metabolic syndrome.

AIM: Our purpose was to examine the total antioxidant status (TAS) in subjects with metabolic syndrome (MS) subdivided according to the presence or not of diabetes mellitus. METHODS: We enrolled 106 subjects (45 women, 61 men) with MS subsequently subdivided in diabetics (14 women, 29 men) and nondiabetics (31 women, 29 men). TAS was obtained using an Assay kit which relies on the ability of plasma antioxidant substances to inhibit the oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline sulfonic acid) to the radical ABTS+. RESULTS: In the group of MS subjects a significant decrease in TAS (p<0.05) in comparison with normal controls was evident. This difference was present between normal subjects and nondiabetic subjects with MS (p<0.001) but not between normal and diabetic subjects with MS. Examining the linear regression among TAS, age, anthropometric profile, blood pressure values and glycometabolic pattern, conflicting data were found. CONCLUSIONS: Although we know that TAS includes several enzymatic and non enzymatic antioxidants, we retain that the difference observed in the two subgroups of subjects with MS must be looked in particular into two pathophysiological aspects regarding bilirubin and uric acid

Matrix metalloproteinases in metabolic syndrome.

Metabolic syndrome is commonly accompanied by an elevated cardiovascular risk with high morbidity and mortality. The alterations of the arterial vasculature begin with endothelial dysfunction and lead to micro- and macrovascular complications. The remodeling of the endothelial basal membrane, that promotes erosion and thrombosis, has a multifactorial pathogenesis that includes leukocyte activation, increased oxidative stress and also an altered matrix metalloproteinases (MMPs) expression. MMPs are endopeptidases which degrade extracellular matrix proteins, such as collagen, gelatins, fibronectin and laminin. They can be secreted by several cells within the vascular wall, but macrophages are determinant in the atherosclerotic plaques. Their activity is regulated by tissue inhibitors of MMP (TIMPs) and also by other molecules, such as plasmin. MMPs could be implicated in plaque instability predisposing to vascular complications. It has been demonstrated that an impaired MMP or TIMP expression is associated with higher risk of all-cause mortality. A large number of studies evaluated MMPs pattern in obesity, diabetes mellitus, arterial hypertension and dyslipidemia, all of which define metabolic syndrome according to several Consensus Statement (i.e. IDF, ATP III, AHA). However, few research have been carried out on subjects with metabolic syndrome. The evidences of an improvement in MMP/TIMP ratio with diet, exercise and medical therapy should encourage further investigations with the intent to contrast the atherosclerotic process and to reduce morbidity and mortality of this kind of patients

Obstructive Sleep Apnea Syndrome: Links Betwen Pathophysiology and Cardiovascular Complications

Purpose: The prevalence of obstructive sleep apnea syndrome (OSAS) is increasing, especially in the middle-aged population. OSAS is associated with an elevated risk of cardiovascular morbidity and mortality. Arterial hypertension is often the first consequence of OSAS, but the most severe complications are coronary artery disease, stroke and arrhythmias. The aim of this review was to analyze the several mechanisms involved in the development of the cardiovascular events, such as endothelial dysfunction accompanied by a pro-inflammatory and pro-oxidant status, hemorheological alterations, hypercoagulability and imbalance between matrix metalloproteases and their inhibitors. Source: A search on PubMed was carried out using the following terms: obstructive sleep apnea syndrome; endothelial dysfunction; oxidative stress; inflammation; rheology; matrix metalloproteases. Principal findings: OSAS severity strongly influenced cardiovascular risk factors and, furthermore, it was correlated with the incidence of fatal and non-fatal events. Conclusions: The treatment with continuous positive airways pressure (cPAP) is the gold standard for OSAS and was able to positively influence all the pathophysiological mechanisms responsible for cardiovascular diseases. Long-term cPAP improved endothelial function and hemorheology, reduced oxidative stress and inflammation, and decreased the levels of metalloproteases

Exercise in obesity management

Obesity is considered a global epidemic by the World Health Organization in both developed and developing countries. It is associated with a higher risk of cardiovascular disease, diabetes mellitus, cancer and other clinical conditions. Visceral fat is the major responsible for metabolic complications, such as insulin-resistance, and it acts as an endocrine organ producing adipokines involved in lipidic and glycaemic metabolism. TNF-α and IL-6, produced by adipose tissue, increase NADPH oxidase activity activating protein kinase C and NFκB leading to an higher oxidative stress. The obesity management includes physical activity: aerobic training improves lipid profile and insulin sensitivity while resistance training increases lean body mass and basal metabolism and has beneficial effects on bone mineral density and glucose tolerance. An exercise program should include 30 to 45 minutes of moderate intensity activity performed 3 to 5 days a week. Weight loss is also associated with lower blood pressure and improved oxidative status, confirmed by reduced oxidative stress markers and increased antioxidant protection. An inverse association between indicators of systemic inflammation and physical activity has been demonstrated, so exercise training may reduce endothelial damage and cardiovascular risk

Protein Oxidation in Metabolic Syndrome

Purpose: Oxidative stress plays a pivotal role in the pathogenesis of the metabolic syndrome and in the progression of its complications. Carbonylated proteins are a stable marker of severe oxidative stress because damage to the protein structure is irreversible and may cause an inhibition of their enzymatic activity or an increased susceptibility to proteolysis. There are few data regarding protein oxidation in metabolic syndrome, although elevated levels of carbonyl groups are often detected in subjects with obesity, diabetes mellitus, hypertension or dyslipidemia, well-known components of the metaboic syndrome. In particular, obesity, insulin resistance and diabetes mellitus are frequently associated with increased protein carbonylation. A relationship between insulin resistance, protein oxidative stress and inflammation has also been suggested as well as protein oxidation products are correlated with overexpression of resistin, TNF-α and IL-6. Conclusion: Therapeutic interventions based on lifestyle modifications and pharmacological agents in order to correct all the main risk factors influence oxidative stress and protein carbonylation