Study of the correlations among some parameters of the oxidative status, gelatinases, and their inhibitors in a group of subjects with metabolic syndrome.

Our aim was to examine some parameters of oxidative status, gelatinases, and their inhibitors and to evaluate their interrelationships in subjects with metabolic syndrome (MS). We enrolled 65 MS subjects, subdivided according to the presence or not of diabetes mellitus. We examined lipid peroxidation (expressed as thiobarbituric acid reacting substances, TBARS), protein oxidation (expressed as carbonyl groups), nitric oxide metabolites (NO x ), total antioxidant status (TAS), MMP-2, MMP-9, TIMP-1, and TIMP-2. We found that MS subjects, diabetics and nondiabetics, showed an increase in TBARS, PC, and NO x . A significant decrease in TAS was observed only in nondiabetic MS subjects in comparison with diabetic MS subjects. We observed increased concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2, higher in diabetic subjects. Our data showed a positive correlation between TAS and MMP-2, TAS and MMP-9, and TAS and MMP-9/TIMP-1 and a negative correlation between TBARS and MMP-2 in diabetic MS subjects in the entire group. In MS subjects a prooxidant status and increased levels of gelatinases and their inhibitors are evident although the correlations between oxidative stress and MMPs or TIMPs are controversial and need further investigation.

Calculated whole blood viscosity in non-diabetic subjects with asymptomatic carotid atherosclerosis: How insulin resistance may affect blood viscosity.

BACKGROUND AND OBJECTIVE: Asymptomatic atherosclerosis is an important early marker of vascular damage and, among its risk factors, hemorheological alterations play an important role. PATIENTS AND METHODS: In a cohort of 85 non-diabetic subjects with asymptomatic carotid atherosclerosis (ACA), we have measured whole blood viscosity (cWBV) according to the haematocrit and plasma fibrinogen level. The cWBV distinguish the subgroup of ACA subjects with 3-5 cardiovascular risk factors (CRFs) from that with 1-2 CRFs and the same behavior is present for haematocrit and plasma fibrinogen level. Therefore, we divided the whole group of ACA subjects according to the medians of the four surrogate indexes with an insulin resistance degree of TG/HDL-C, TyG, VAI and LAP. RESULTS: The analysis of the correlation between cWBV and each index of insulin resistance has shown that no correlation is present in the whole group and in the group of ACA subjects with 1-2 CRFs, while in the subgroup with 3-5 CRFs there is a positive correlation between cWBV with TG/HDL-C and TyG at a low degree of statistical significance. CONCLUSIONS: The date underline that subjects with this clinical condition have an unaltered evaluation of the cWBV compared to the other indices.

Leukocyte activation markers and oxidative status in chronic kidney disease.

AIM: In chronic kidney disease (CKD) cardiovascular risk is increased. Oxidative stress is strictly involved in the pathophysiology of this enhanced risk as well as leukocytes' activation. To better elucidate these phaenomena we evaluated some parameters of leukocyte activation and oxidative state on fasting blood samples obtained from CKD patients on conservative or hemodialysis (HD) treatment, compared to those obtained from control subjects. METHODS: We enrolled 41 patients (25 men and 16 women, mean age 64.7 ± 11.1 years) with CKD and 42 patients (21 men and 21 women, mean age 66.83 ± 14.8 years) with CKD on hemodialysis (HD) treatment. Hemodialyzed patients were evaluated before and after a standard HD session. Leukocyte activation was evaluated by determining plasma elastase and myeloperoxidase level employing ELISA methods. Lipid peroxidation was evaluated as thiobarbituric acid-reactive substances (TBARS), total antioxidant status using spectrophotometry. RESULTS: Elastase was higher in CKD on conservative and on HD treatment and its value increased after the HD session. Myeloperoxidase did not show any variation in CKD on conservative and HD treatment while after HD its value was increased. Lipid peroxidation was increased in CKD on conservative and on HD therapy and its value after dialysis showed no significant variation. Total antioxidant status was increased in CKD on HD treatment and significantly decreased after the HD session; no variation between normal controls and CKD subjects on conservative therapy was observed. CONCLUSION: Several aspects derive from these data considering the role of oxidative stress in the cardiovascular events that accompany CKD.

Leukocyte subtypes, gelatinases, and their tissue inhibitors in a group of subjects with asymptomatic carotid atherosclerosis.

In a cohort of subjects with asymptomatic carotid atherosclerosis (ACA), we have evaluated the neutrophil and lymphocyte count and their ratio (NLR), the gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2). At baseline, no difference was observed between ACA subjects and subject control group regarding neutrophil and lymphocyte count while was evident in ACA subjects a significant increase in MMP-2, MMP-9 and TIMP-2 associated to a significant decrease in TIMP-1. Dividing the ACA according to the number of cardiovascular risk factors (CRFs) we have observed an increase in lymphocyte count in the subgroup with 3-5 CRFs. Evaluating the leukocyte subtypes according to all the surrogate markers of insulin resistance has been noted, in the subgroups that exceed the medians of these markers, a significant increase in neutrophil and lymphocyte count without any variation of the NLR. Effecting the same evaluation for the MMP/TIMP pattern we observed, instead, that the same subgroups tend to show a decrease in MMP-2 and an increase in MMP-9. No difference instead for TIMP-1 and TIMP-2. The abnormality of the MMP/TIMP pattern, bearing in mind the cardiometabolic clustering present in this cohort of ACA subjects, would induce to use drugs able not only to cure the cardiometabolic risk factors but also to influence the MMP/TIMP profile.

An assessment of the hemorheological profile in patients with subclinical carotid atherosclerosis divided in relation to the number of cardiovascular risk factors and different degrees of insulin resistance.

We present a cohort of 100 subjects [43 men and 57 women; median age 66.00(25)] who were tested using carotid ultrasound to identify subclinical carotid atherosclerosis (SCA). We have evaluated the behaviour of whole blood viscosity (WBV) at high (450 s-1) and low (0.51 s-1) shear rates, plasma viscosity (450-1), hematocrit and mean erythrocyte aggregation. When compared to normal control subjects, using the Mann-Whitney test, we observed in SCA patients a significant increase in WBV only. The results were substantial after having divided the SCA subjects according to the cardiovascular risk factors (CRFs) and the degree of insulin resistance; the research was performed using two surrogate indexes such as TG/HDL-C and TyG. With the division carried out according to CRFs, employing the Kruskal-Wallis test, results show a significant increase in WBV (at high and low shear rates), in plasma viscosity, in erythrocyte aggregation and plasma fibrinogen level. Whereas by dividing them into the median of TG/HDL-C and TyG, we noticed a significant increase in WBV (at high and low shear rates) and in erythrocyte aggregation in the two groups with high TG/HDL-C ratio and with high TyG; having found an increased level of plasma fibrinogen in the latter. The data underlines the role of the main hemorheologic aspects in subclinical carotid atherosclerosis being closely correlated to the CRFs and different degrees of insulin resistance.

PCR-RFLP analysis of mitochondrial DNA in tench Tinca tinca.

Polymorphism was detected at ND1, ND6, D-loop and cyt b segments of mtDNA in 105 tench (Tinca tinca L.), using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and five composite haplotypes were identified. The diversity indices and the results of the population comparisons revealed that the identified markers provide a powerful tool for further studies on this species.

Nitric oxide metabolites, leukocyte activation markers and oxidative status in dialyzed subjects.

AIMS: Our purpose was to evaluate, in a group of 42 end-stage renal disease patients who regularly undergo hemodialysis, some indexes of leukocyte activation, nitric oxide metabolites (NOx) and other parameters that reflect the oxidative stress before and after a standard hemodialysis session. METHODS: Elastase and myeloperoxidase (MPO) were determined by means of ELISA. The NO production was evaluated by a micromethod which measures the concentration of NOx. The oxidation of polyunsaturated fatty acids was evaluated in plasma by detection of thiobarbituric acid-reactive substances (TBARS). Total antioxidant status (TAS) was obtained using spectrophotometry. RESULTS: At baseline, we observed an increase of elastase, NOx, TBARS and TAS, without any variation of MPO. After the dialysis session, we found an increase in elastase and MPO, a decrease in NOx and TAS and no variation in TBARS. No modification occurred after subdividing the patients in two subgroups. CONCLUSIONS: Our data confirm the involvement of leukocytes and oxidative stress in hemodialysis patients.

Haemorheological profile in congenital afibrinogenemia and in congenital dysfibrinogenemia: A clinical case report.

Although the inherited quantitative and qualitative disorders of fibrinogen are rare, in the course of time patients may develop complications including episodes of arterial and venous thrombosis. It can be useful to complete the laboratory assessment of these clinical conditions with the evaluation of the haemorheological profile. The data obtained from this study showed that congenital afibrinogenemia was characterized by a primary plasma hypoviscosity, whereas congenital dysfibrinogenemia by a primary plasma hyperviscosity. Both these haemorheological alterations may concur, with different mechanisms, to the pathogenesis of thrombotic vascular complications.

Erythrocyte deformability and hemorheological profile in multiple myeloma.

The hemorheological profile in multiple myeloma (MM) has been extensively studied. Our investigation regarded the behavior of whole-blood viscosity, plasma viscosity and erythrocyte deformability in MM. We enrolled 24 MM patients; 13 of them had been recently diagnosed and were at the initial stage of therapy, 6 were on consolidation/conservation therapy and 5 had achieved a complete remission. On fasting venous blood we evaluated whole-blood and plasma viscosity at high and low shear rates, haematocrit, the ratios between whole-blood viscosity (at high and low shear rate) and haematocrit×100, the ratio between plasma viscosity at low and high shear rate and the erythrocyte deformability examined by using laser diffractometry and expressed as elongation index. A significant increase in plasma viscosity at low shear rate and a marked decrease in haematocrit were observed in MM patients compared with normal controls. Also the ratio between the high shear rate whole-blood viscosity and haematocrit ×100 and the ratio between the low and high shear rate plasma viscosity were significantly increased in MM patients. A significant decrease in erythrocyte deformability, especially at low shear stresses, was found. We discuss some hypotheses that might explain the behavior of red blood cell deformability in MM, considering that its impairment, in addition to the increase of plasma viscosity, can alter the microcirculatory flow in these patients.

Hemorheological parameters in Monoclonal Gammopathy of Undetermined Significance (MGUS).

There is scarcity of information about the hemorheological pattern in subjects with Monoclonal Gammopathy of Undetermined Significance (MGUS). This preliminary research is focused on the behaviour of whole-blood and plasma viscosity, haematocrit and erythrocyte deformability in the above clinical condition. We enrolled 21 MGUS subjects (10 women and 11 men; mean age 66.4 ± 11.6 years). In fasting venous blood we examined whole-blood and plasma viscosity at high and low shear rates, haematocrit, the ratios between whole-blood viscosity (at high and low shear rate) and haematocrit × 100, the ratio between plasma viscosity at low and high shear rate, and the erythrocyte deformability expressed as elongation index. By comparing normal controls to MGUS subjects a significant increase in whole-blood viscosity at high shear rate and in plasma viscosity at low shear rate were observed. In MGUS subjects the ratios between the high and low shear rate blood viscosity and haematocrit × 100, as well as the ratio between the low and high shear rate plasma viscosity were significantly higher. In MGUS subjects a marked decrease in erythrocyte deformability was also observed. The alteration of the hemorheological profile found in these subjects might be involved in the pathogenesis of thromboembolic events, which occur with a high frequency in MGUS.

Impairment of plasma nitric oxide availability in senescent healthy individuals: apparent involvement of extracellular superoxide dismutase activity.

To verify the potential involvement of the age-dependent modifications of EC-SOD activity in the impairment of plasma NO availability with advancing age, 40 healthy men divided into 4 age groups for the purpose of comparison (young: 27.4 +/- 1.5 years; middle: 50.8 +/- 2.2, years; old: 70.0 +/- 1.8 years; very old: 86.1 +/- 1.1 years) were enrolled in this study. Plasma samples were used for measurements of the stable end-product nitrite/nitrate (NOx), as an expression of NO availability, EC-SOD activity, thiobarbituric acid reactive substances (TBARS) as a marker of lipid peroxidation, low density lipoprotein (LDL) copper-mediated oxidation in vitro and total antioxidant capacity (TEAC). Our results indicated a significant age-related progressive decrease of plasma NOx content and EC-SOD activity and their values were positively correlated (r = 0.713, p < 0.001). Increased TBARS amount together with reduced lag time for in vitro oxidation of LDL and decreased content of TEAC were observed with advancing age. Finally, EC-SOD values were negatively correlated with plasma TBARS values (r = -0.855, p < 0.001). Findings of the present study suggest that the decrease of antioxidant defence strategies play a primary role by compromising NO availability in normally aged individuals, particularly through a progressive decrease of EC-SOD activity.

[Chronic exposure to styrene and psychiatric symptomatology: a case-control descriptive study]. / Esposizione cronica a stirene e sintomatologia psichiatrica: studio descrittivo caso-controllo.

BACKGROUND: Although the acute psychiatric consequences exerted by Styrene and other aromatic hydrocarbons are abundantly described, the effects produced by a low-dosages chronic exposure are not known, in spite of the wide employment in the field of industrial production. The aim of this study is to evaluate the psychiatric symptoms in a group of subjects exposed to styrene in comparison with a control group, not exposed to the substance. SUBJECTS AND METHODS: Twenty two qualified workers, divided into 11 subjects in charge of welding and resin tapping exposed to styrene, and 11 not exposed to neurotoxic substances, were evaluated through the Symptom Check List Revised (SCL-90-R), a scale for the global self-evaluation of psychiatric symptomatology. RESULTS: The statistical tests, herein utilized, showed a significant prevalence for the dimensions somatization and psychoticism in the exposed subjects to styrene as compared to the non-exposed subjects. CONCLUSIONS: The results of this study, although limited by the paucity of the sample, emphasize the importance of an early diagnosis and evaluation of the clinical predictors in subjects exposed to styrene. The relatively low concentration levels of styrene in the working area of the subjects exposed underlines the opportunity to arrange preventive evaluation strategies for a prompt intervention in those cases with a clear syndromic presentation.

Behaviour of the neutrophil to lymphocyte ratio in young subjects with acute myocardial infarction.

In the last years the neutrophil to lymphocyte ratio (NLR) has been examined in cardiovascular disorders and in particular in coronary artery disease and acute myocardial infarction (AMI). Now we examined this parameter in subjects with juvenile myocardial infarction at the initial stage and after 3 and 12 months. We enrolled 123 young subjects (112 men and 11 women, mean age 39.4 ± 5.8 yrs) with AMI. The time interval between the AMI onset and the investigation was 13 ± 7 days. The mean value of NLR observed in young AMI subjects was significantly increased compared to normal controls (N = 1.817 ± 0.711; young AMI subjects = 2.376 ± 0.873, p <  0.0001). NLR does not discriminate STEMI (2.427 ± 0.878) and non STEMI (2.392 ± 0.868) or diabetics (2.604 ± 1.000) and non diabetics (2.324 ± 0.853), but it differentiates smokers (2.276 ± 0.853) and non smokers (2.837 ± 1.072). NLR at the initial stage is not correlated with the number of cardiovascular risk factors or with the extent of the coronary disease. In this study we found a significant decrease of neutrophil count at 3 and 12 months later AMI without any significant variation of lymphocyte and consequently we observed a decrease in NLR at these two intervals of time in comparison with the initial stage. Despite some limitations present in this study, it is interesting to underline that also in juvenile myocardial infarction this low-cost haematological marker may be considered together with other inflammatory indicators.

Erythrocyte deformability, plasma lipid peroxidation and plasma protein oxidation in a group of OSAS subjects.

Considering that obstructive sleep apnea syndrome (OSAS) is usually associated with endothelial dysfunction, atherosclerosis and cardiovascular disorders, our aim was to examine the erythrocyte deformability and the oxidative status in a group of OSAS subjects. We consecutively enrolled 48 subjects with OSAS defined after a 1-night cardiorespiratory sleep study, subsequently subdivided according to the apnea/hypopnea index (AHI) value in two subgroups: Low (L = 21 subjects with AHI<30) and High (H = 27 subjects with AHI>30). We evaluated the erythrocyte deformability, expressed as elongation index (EI) and the parameters of the oxidative status, such as lipid peroxidation (expressed as thiobarbituric acid-reactive substances - TBARS) and protein oxidation (measured as carbonyl groups - PC). In the entire group and in the two subgroups of OSAS subjects we found a decreased erytrocyte deformability at all shear stresses, not correlated with the plasmatic oxidative stress nor with the polysomnographic parameters. Lipid peroxidation was increased in the whole group and in the H subgroup of OSAS while protein oxidation showed a different trend. As in OSAS the osmotic fragility and the metabolism of the red cells seem to be not impaired, the oxidative damage to the red cell membrane proteins might be responsible for the reduced erythrocyte deformability. This rheological alteration, in addition to the increase in whole blood and plasma viscosity and to the erythrocyte hyperaggregation, could influence the microcircolatory profile in OSAS subjects.

Pathophysiological and clinical aspects of malnutrition in chronic renal failure.

Kidney diseases are the ninth leading cause of death in the USA. In these patients cardiovascular mortality is greater than in the general population. This observation, not completely explained by the so-called 'traditional' cardiovascular risk factors, lead the authors to postulate other 'emerging' ones found in chronic renal failure patients. Among these new findings, nutritional status, considered as the balance existing between nutrient requirements and intakes, plays an important role for the development of cardiovascular diseases. In fact several nutritional parameters are widely known as pathophysiological determinants of cardiovascular disturbances, which are based on accelerated atherosclerosis, due especially to enhanced oxidative stress and endothelial dysfunction. Chronic renal failure is a clinical condition that from many points of view seems to be a chronic inflammatory state, and many studies confirm this observation. This influences nutritional status especially in dialysis patients. Malnutrition is related in turn to accelerated atherosclerosis thus leading to a postulated 'malnutrition, inflammation, atherosclerosis' (MIA) syndrome in which malnutrition, inflammation and atherosclerosis contribute to an elevated cardiovascular mortality rate. The present review explores this issue, first by describing epidemiological aspects of malnutrition in chronic renal failure patients and then by analysing the specific biochemical and metabolic features of these patients.

Polymorphonuclear leukocyte integrins in deep venous thrombosis.

The polymorphonuclear leukocytes (PMN) have a role in the pathophysiology of deep venous thrombosis (DVT). We examined the phenotypical expression of PMN beta(2M)-integrins (CD ll a, CDll b, CD 11c) in a group of 19 subjects with leg DVT. PMN cells were incubated with fluorescent monoclonal antibodies against CD11a, CD11b, CD11c, and the evaluation was made by flow cytofluorimetry. The same integrins were determined after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). In DVT subjects, at baseline, the phenotypical expression of CD11b was decreased and that of CD11c increased when compared with normal controls. In normal subjects PMN activation with PMA and fMLP led to a constant increase of all PMN adhesion molecules, while in DVT subjects the CDl l a did not show any change. These data might have therapeutical applications, especially with the aim of preventing post-thrombotic deterioration of vein function.

Deep venous thrombosis: behaviour of the polymorphonuclear leukocyte integrin pattern at baseline and after in vitro activation.

In a group of 18 subjects with acute deep venous thrombosis (DVT), evidenced by clinical examination and echo-color-Doppler, we examined the phenotypical expression of the polymorphonuclear leukocyte (PMN) beta2-integrins (CD11a, CD11b, CD11c, CD18), obtained by using a flow cytofluorimeter. The evaluation was performed before and after in vitro activation (prolonged for 5 and 15 minutes) with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). In DVT subjects, at baseline, the phenotypical expression of CD11b was decreased and that of CD11c was increased when compared with normal controls; no difference was found in CD11a and CD18 expression. In normal subjects PMN activation with both activators led to a constant increase of all PMN adhesion molecules; in DVT subjects CD11b, CD11c and CD18 increased, while CD11a expression did not show any change. These data indicate the presence of a functional alteration in circulating PMN cells from patients with DVT.

Membrane fluidity, membrane lipid pattern, and cytosolic Ca2+ content in platelets from a group of type II diabetic patients with macrovascular complications.

OBJECTIVE: To evaluate platelet membrane fluidity and some platelet metabolic parameters in type II diabetic patients with macrovascular complications. RESEARCH DESIGN AND METHODS: In a group of 21 type II diabetic patients with macrovascular complications, we evaluated platelet membrane fluidity [marking intact resting platelets with the fluorescent probe 1,4-(trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH)], platelet membrane lipid pattern (cholesterol:phospholipid [C:PL] ratio and individual phospholipids), and platelet cytosolic Ca2+ content (marking intact resting platelets with the fluorescent probe Fura 2AM). RESULTS: Platelet membrane fluidity is decreased in type II diabetic patients with macrovascular complications compared with normal subjects (P < 0.001). Platelet membrane C:PL ratio and cytosolic Ca2+ content do not discriminate normal subjects from diabetic patients, and for individual phospholipids, only phosphatidylethanolamine is decreased in diabetic patients compared with control subjects (P = 0.051). In normal subjects, the polarization degree of TMA-DPH is related to phosphatidylserine (P < 0.05) and phosphatidylcholine (P < 0.05), and in diabetic patients the polarization degree of TMA-DPH is related to C:PL ratio (P < 0.05) and sphyngomyelin (P < 0.05). CONCLUSIONS: In type II diabetic patients with macrovascular complications, we observed an abnormality of platelet membrane fluidity, which may contribute to platelet functional alteration present in this clinical condition.

Analysis of the correlations between oxidative stress, gelatinases and their tissue inhibitors in the human subjects with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is commonly associated with endothelial dysfunction, atherosclerosis and cardiovascular disorders. On the basis of this observation, our aim was to examine the oxidative status and the matrix metalloproteases (MMP) profile in a group of subjects with OSAS. We enrolled 48 subjects with OSAS defined after a 1-night cardiorespiratory sleep study, who were subsequently subdivided in two subgroups according to the severity of OSAS (low grade = L-OSAS; high grade= H-OSAS). We measured the parameters of oxidative stress, such as lipid peroxidation, protein oxidation, total antioxidant status (TAS), nitric oxide metabolites (NOx), and the plasma concentrations of the gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2). We found a significant impairment of oxidative status in H-OSAS compared to L-OSAS and higher plasma levels of MMP-9 and TIMP-1 in H-OSAS compared to L-OSAS. In this study we observed a positive correlation between TBARS and MMP-9, a positive correlation between PC and MMP-9, and a negative correlation between NOx and MMP-9, especially in the whole group of OSAS subjects. These data underline how strong interrelationships among some parameters of the oxidative stress, in particular those reflecting lipid peroxidation, protein oxidation and NOx, and MMP-9 are evident in OSAS subjects. All these information may be useful in the clinical practice keeping in mind the cardiovascular complications generally accompanying the obstructive sleep apnea syndrome.