Mitochondrial depolarisation and oxidative stress in rheumatoid arthritis patients

ObjectivesTo investigate mitochondrial membrane integrity, lipid peroxidation and cytotoxicity in peripheral lymphocytes (PL) from rheumatoid arthritis (RA) patients.Design and methodsSouth African black RA patients (HIV^?) were recruited into the study. Mitochondrial membrane potential (Δψ_m) was analysed in PL using the JC-1 dye distribution assay and flow cytometry. Correlations between Δψ_m and clinical parameters were tested for statistical significance. Cytotoxicity (LDH) and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)) was also determined.ResultsOur findings show significantly elevated levels of cytotoxicity (p = 0.0029) and lipid peroxidation (p = 0.0030) in RA. A significantly higher percentage of circulating PL contained depolarised mitochondria (p = 0.0003) which correlated with disease activity and C-reactive protein levels in patients. Collapse of Δψ_m also negatively correlated to absolute lymphocyte counts (r = ? 0.4041; p = 0.0197).ConclusionThese findings suggest a possible role for mitochondrial membrane alterations in the pathology of RA.     

Assessment of urinary γ-glutamyltransferase and alkaline phosphatase for diagnosis of diabetic nephropathy

BackgroundUrinary biomarkers of tubular damage can be useful for early diagnosis of diabetic nephropathy. Thus, the aim of this study was to test the diagnostic accuracy of the urinary excretion of γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) for diagnosis of diabetic nephropathy (DN).MethodsFasting glucose, fructosamine, serum creatinine, glomerular filtration rate (GFR), serum uric acid, serum albumin, and urinary albumin, creatinine, GGT and ALP were assessed in 74 type 2 diabetic patients without nephropathy and 38 type 2 diabetic patients with nephropathy.ResultsUrinary GGT and ALP were threefold higher in type 2 diabetic patients with nephropathy. Significant correlations were observed between urinary albumin and GGT (r = 0.439, P < 0.001) and urinary albumin and ALP (r = 0.305, P < 0.01). Areas under the curve for GGT and ALP were 0.7696 (P < 0.001) and 0.7233 (P < 0.001), respectively. At a cut-off value of 72 U/g creatinine, GGT demonstrated a sensitivity of 96.0% and a specificity of 52.6%. At a cut-off value of 20 U/g creatinine, ALP demonstrated a sensitivity and specificity of 83.8% and 36.8%, respectively.ConclusionsUrinary GGT and ALP have potential value in the diagnosis of nephropathy in type 2 diabetic patients, but GGT has a slightly higher ability to discriminate nephropathy than ALP.     

Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome

BackgroundIt is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics.MethodsSeventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured.ResultsHS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = ?0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = ?0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic.ConclusionsSimple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition.     

Gamma-glutamyl transferase level predicts the development of hypertension in Hong Kong Chinese

BackgroundPlasma activities of alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase, and γ-glutamyl transferase (GGT) are often increased in cardiometabolic diseases. We investigated if hypertension is associated with increased activities of these plasma markers.MethodsWe included 235 hypertensive and 708 normotensive subjects (mean age 47.3 ± 9.6 and 58.0 ± 10.2 years respectively) from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000–2004 who had drank < 1/week. In the follow-up study in 2005–2008 (CRISPS-3), 126 out of the 708 subjects had developed hypertension.ResultsRaised plasma ALT (OR = 1.22 per SD of log-transformed level, P = 0.045) and GGT (OR = 1.38 per SD of log-transformed level, P = 0.001) levels were associated with hypertension at baseline in CRISPS-2 after adjusting for covariates. Among subjects not on anti-hypertensive medications, plasma ALP, ALT and GGT were related to blood pressure (P < 0.01). In subjects normotensive at CRISPS-2, plasma GGT, but not ALP, ALT and AST, was an independent predictor of new-onset hypertension at CRISPS-3 (OR = 1.38 per SD of log-transformed level, P = 0.020 and OR = 2.68 for 3rd tertile vs. 1st tertile, P = 0.004) after adjusting for covariates.ConclusionsAmong the 4 plasma markers, increased GGT activity is the strongest predictor for existing and new-onset hypertension in Hong Kong Chinese.     

The relationship between insulin-like growth factor-1 and metabolic syndrome, independent of adiponectin

BackgroundInsulin-like growth factor-1 (IGF-1) is associated with obesity and aging, and was recently linked to metabolic syndrome (MetS) and insulin resistance. However, little is known about the relationship between IGF-1 and adiponectin (adiponectin), another marker of MetS.MethodsWe measured the plasma IGF-1 and adiponectin levels of 3099 subjects (1869 males, 55.9 ± 10.8 y). We applied the Korean-modified International Diabetes Foundation (k-IDF) criteria for determination of, and risk assessment for, MetS.ResultsK-IDF criteria-based MetS occurred in 37.0% (n = 1146) of patients. IGF-1 (91.5 vs. 97.3 ng/ml, p < 0.001) and adiponectin (3.95 vs. 4.23 μg/ml, p < 0.001) were significantly lower in MetS patients than without MetS. Lower IGF-1 was associated with increasing numbers of MetS abnormalities, independent of adiponectin (p for trend < 0.001, F = 12.615, p < 0.001 in ANCOVA). MetS prevalence in individuals with both high IGF-1 and adiponectin levels (6.7%, n = 206) was significantly lower than in other groups. Both high IGF-1 and adiponectin group was associated with reduced MetS risk after adjusting for other confounding factors (OR 0.694, 95% CI 0.493–0.977, p = 0.036).ConclusionsIGF-1 was associated with MetS independent of adiponectin in our study. The independent relationship between IGF-1 and MetS provides insight into the pathophysiologic mechanisms of MetS.     

Lipid, protein, DNA oxidation and antioxidant status in rheumatoid arthritis

ObjectivesTo investigate lipid, protein, DNA oxidation and antioxidant status in blood and synovial fluid of rheumatoid arthritis (RA) patients and to determine the importance of oxidative stress parameters in reflecting disease activity.Design and methods20 RA patients and 15 healthy controls were included. Lipid peroxidation (thiobarbituric acid reactive substances (TBARS), lipid hydroperoxide, and conjugated diene), protein oxidation (carbonyl and thiol), DNA oxidation (8-OHdG) and antioxidant status markers (glutathione (GSH), glutathione peroxidase (GSH Px), superoxide dismutase (CuZn SOD), and catalase) were determined in blood and synovial fluid.ResultsTBARS (p < 0.001), lipid hydroperoxide (p < 0.001), conjugated diene (p < 0.001), carbonyl (p < 0.001) and 8-OHdG (p < 0.01) levels were significantly higher; thiol (p < 0.01) and GSH levels (p < 0.01) and GSH Px (p < 0.001) and CuZn SOD (p < 0.01) activities were significantly lower in blood of RA patients. TBARS (p < 0.001), lipid hydroperoxide (p < 0.001), conjugated diene (p < 0.01), carbonyl (p < 0.001) and 8-OHdG (p < 0.05) levels were significantly higher, catalase activity (p < 0.001) significantly lower in synovial fluid of RA patients.ConclusionsIncreased lipid, protein and DNA oxidation markers and impaired antioxidant status confirm the role of oxidative stress in the pathogenesis of RA. Lipid peroxidation markers can serve as surrogate markers for disease activity.     

Gamma-glutamyltransferase, alanine transaminase and aspartate transaminase levels and the diagnosis of gestational diabetes mellitus

ObjectivesTo evaluate gamma-glutamyltransferase (GGT), alanine transaminases (ALT) and aspartate transaminases (AST) levels and prevalent gestational diabetes mellitus (GDM).Design and methodsRandom plasma glucose, GGT, ALT and AST and the 50-g glucose challenge test were done on antenatal women followed by diagnostic 3-point 75-g oral glucose tolerance test within two weeks. GDM was diagnosed by ADA (2011) criteria.ResultsThe GDM rate was 12.2% (319/2610). Mean GGT level was higher in GDM women, 18 ± 12 vs. 16 ± 11 IU/L; P = 0.03. The risk for GDM was higher for women in the highest GGT quartile band compared to the lowest: RR 1.35 95%CI 1.0–1.8; P = 0.04. However, after adjustment for confounders, GGT was no longer associated with GDM. There was no correlation between ALT and AST levels and GDM.ConclusionsLiver transaminases do not predict GDM in contrast to type 2 diabetes.     

Carotid intima media thickness is related positively to plasma pre ß-high density lipoproteins in non-diabetic subjects

BackgroundLipid-poor or lipid-free high density lipoprotein (HDL) particles, designated pre ß-HDL, stimulate removal of cell-derived cholesterol to the extracellular compartment, which is an initial step in the reverse cholesterol transport pathway. Pre ß-HDL levels may be elevated in subjects with established cardiovascular disease. We determined the relationship of carotid intima media thickness (IMT), a marker of subclinical atherosclerosis, with pre ß-HDL in subjects without clinically manifest cardiovascular disease.MethodsIMT and plasma pre ß-HDL, assayed by crossed immuno-electrophoresis, were determined in 70 non-diabetic subjects (aged 56 ± 9 years; non-smokers only; 27 women).ResultsIMT was correlated positively with pre ß-HDL, both expressed as plasma apolipoprotein (apo) A-I concentration (r = 0.271, p = 0.023) and as% of apo A-I (r = 0.341, p = 0.004). In contrast, IMT was correlated inversely with HDL cholesterol (r = ? 0.253, p = 0.035). IMT was also related positively to pre ß-HDL after adjustment for age, sex, systolic blood pressure (in apoA-I concentration, ß = 0.203, p = 0.043; in% of plasma apoA-I, ß = 0.235, p = 0.023). IMT remained associated with pre ß-HDL after additional adjustment for either body mass index, plasma glucose, cholesterol, triglycerides, HDL cholesterol, apoA-I and apoB.ConclusionSubclinical atherosclerosis may relate to higher plasma pre ß-HDL independently of apoA-I and HDL cholesterol levels.     

Plasma ceruloplasmin as a biomarker for obesity: a proteomic approach

ObjectivesThis study aimed to investigate new biomarkers of obesity particularly in relation with inflammation-associated proteins using protein differential display techniques.Design and methodsComparison of protein expression in plasma between non-obese (n = 109, body mass index, BMI < 25 kg/m²) and obese (n = 32, BMI ≥ 25 kg/m²) groups was carried out using two-dimensional gel electrophoresis (2-DE) analysis. ELISA was also performed for validation.ResultsAmong six differentially expressed protein spots, ceruloplasmin (Cp) and fibrinogen were over-expressed in obese group. Plasma Cp levels were significantly higher in obese group than non-obese group (34.0 ± 8.6 vs. 41.3 ± 12.7 mg/dL, p < 0.001) and positively correlated with age (r = 0.253, p < 0.005), BMI (r = 0.265, p < 0.001) and hsCRP (r = 0.385, p < 0.001). In stepwise multiple linear regression analysis, plasma Cp along with hsCRP were found predictors for obesity (adjusted β-coefficient = 0.266, p < 0.01).ConclusionElevated plasma Cp levels were significantly associated with obesity, which may be suggested to be a marker of obesity.     

Does non-alcoholic fatty liver impair alterations of plasma lipoproteins and associated factors in metabolic syndrome?

BackgroundHepatic steatosis (HS) is closely associated to metabolic syndrome (MS). Both, VLDL-triglyceride oversecretion and intrahepatic deposits, can take place. We evaluated VLDL characteristics, CETP, hepatic lipase (HL), IDL and small dense LDL (sdLDL), in patients with HS associated to MS.MethodsWe studied 3 groups matched by age and sex: 25 MS patients with HS (diagnosed by ultrasonography), 25 MS patients without HS and 25 healthy controls. Main measurements were: lipid profile, free fatty acids, VLDL composition, VLDL size by HPLC, CETP and HL activities, IDL-cholesterol and sdLDL-cholesterol.ResultsPatients with HS presented higher triglyceride levels, HOMA-IR and free fatty acids, VLDL mass and VLDL-apoB (p < 0.05). No differences in VLDL composition were observed. MS groups presented higher proportion of large VLDL than controls (p < 0.05). HS group showed higher CETP than controls (p = 0.01) and almost higher than MS without HS (p = 0.06). CETP correlated with VLDL-cholesterol content, r = 0.48, p < 0.005. The increase in sdLDL-cholesterol correlated with CETP (r = 0.47) and HL (r = 0.56), independent of insulin resistance (p < 0.003).ConclusionDespite intrahepatic fat, patients with HS secreted higher number of VLDL particles. CETP would have a remodeling action on VLDL in circulation, enriching it in cholesterol and also favoring, together with HL, the formation of sdLDL.     

Effects of endurance and endurance–strength exercise on biochemical parameters of liver function in women with abdominal obesity

IntroductionObesity is a risk factor of nonalcoholic fatty liver disease. Although the standard therapy for obesity involves physical exercise, well-planned studies of the changes in liver function in response to different exercise intensities in obese subjects are scarce. The aim of the present study was to examine a question of how does exercise mode affect the liver function.Material and methods44 women with abdominal obesity were randomized into two exercise groups: endurance (group A) and endurance-strength (group B). Women in each group exercised for 60 min 3 times/week for a 3-month period. Markers of liver function: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) activities, and bilirubin levels were quantified.ResultsWe found significant differences in ALT (p < 0.01) and AST (p < 0.05) activities between group A and B after training exercise. Blood ALT and AST tended to decrease in group B, increase in group A. Significant reduction in serum GGT level after exercise in both groups was observed (p < 0.001, group A; p < 0.01, group B). Neither endurance nor endurance-strength exercise led to changes in serum ALP activity and total or direct bilirubin level. However, endurance-strength training resulted in significant decreases in serum indirect bilirubin (p < 0.05). Strong positive correlations between serum indirect bilirubin and body mass (r = 0.615; p = 0.0085) and BMI (r = 0.576; p = 0.0154) were found after endurance-strength exercise (group B).ConclusionThe mode of exercise does matter: endurance-strength exercise led to a greater improvement, compared to endurance exercise, in the liver function in women with abdominal obesity.     

Association between serum retinol-binding protein 4 and small dense low-density lipoprotein cholesterol levels in young adult women

BackgroundSerum retinol-binding protein 4 (RBP4) and small dense low-density lipoprotein (sdLDL) have been suggested to be associated with insulin resistance, but no information is available on the relationship between RBP4 and sdLDL.MethodsWe determined serum RBP4, sdLDL-cholesterol, and other metabolic variables on 38 young women, aged 19–29 years. The homeostatic model assessment of insulin resistance (HOMA-IR) was used for the estimation of insulin resistance.ResultsIn simple regression analyses, RBP4 levels had significant correlations with total cholesterol (r = 0.354, P = 0.029), LDL-cholesterol (r = 0.396, P = 0.014), and sdLDL-cholesterol (r = 0.510, P = 0.001) levels. The sdLDL-cholesterol levels also correlated significantly with total cholesterol (r = 0.402, P = 0.012), LDL-cholesterol (r = 0.627, P < 0.001) and triglycerides (r = 0.449, P = 0.005). Stepwise multiple regression analyses showed only sdLDL-cholesterol (β coefficient (ß) = 0.510, P = 0.001) level was a significant independent predictor of RBP4 levels (adjusted R² = 0.240), whereas RBP4 (ß = 0.289, P = 0.026) level was one of major factors affecting sdLDL-cholesterol levels (adjusted R² = 0.519). There was no significant association of HOMA-IR with RBP4 or sdLDL levels.ConclusionsWe showed an independent linkage between serum RBP4 and sdLDL-cholesterol levels in young adult women. These findings may contribute to understanding of lipoprotein metabolisms involved in diabetes and cardiovascular disease.     

Small dense LDL cholesterol is a robust therapeutic marker of statin treatment in patients with acute coronary syndrome and metabolic syndrome

BackgroundSmall dense low-density lipoprotein (sd-LDL) is an atherogenic LDL subfraction and often increased in metabolic syndrome (MetS). This study aimed to determine whether sd-LDL cholesterol (sd-LDL-C) is a therapeutic marker of statin treatment in patients with acute coronary syndrome (ACS) and MetS.MethodsWe examined 71 patients with ACS and 50 non-ACS subjects with normal coronary arteries (controls). The patients with ACS were treated with life-style modifications (n = 36) or those plus 20 mg atorvastatin daily (n = 35) for 6 months. We measured sd-LDL-C by a novel detergent-based homogenous assay and calculated buoyant LDL-C (b-LDL-C).ResultsThe patients with ACS had higher sd-LDL-C than did the controls (30 ± 14 vs. 22 ± 8 mg/dl, p < 0.001). Furthermore, sd-LDL-C was higher in the patients with ACS and MetS (n = 31) than in those without MetS (n = 40) (35 ± 17 vs. 27 ± 11 mg/dl, p < 0.05). Atorvastatin reduced LDL-C and sd-LDL-C by 31% (102 ± 23 to 70 ± 28 mg/dl, p < 0.0001) and 24% (29 ± 15 to 22 ± 13 mg/dl, p < 0.01). The reduction in sd-LDL-C by atorvastatin was 5.5-fold greater in the patients with ACS and MetS than in those without MetS (p < 0.001). Contrary, that in b-LDL-C was similar between the groups.Conclusionssd-LDL-C is a superior therapeutic marker of statin treatment in patients with ACS and MetS.     

Emesis and gastrointestinal problems during radiotherapy: A comparison of performance of daily activities between patients experiencing nausea and patients free from nausea

Purpose of the researchTo describe the experiences of nausea, vomiting and gastrointestinal problems during radiotherapy, and to compare patients experiencing nausea with patients not experiencing nausea regarding performance in daily activities, sleeping and eating capacity.Methods and sampleA cross-sectional sample of 131 Swedish radiotherapy patients answered a questionnaire regarding the preceding week of radiotherapy. Mean age was 63 years (standard deviation 12.1) and 56% were women. The radiotherapy fields were breast (35%), abdomen/pelvis (15%), prostate/bladder (21%), head/neck (10%) and other (8%).Key resultsThe patients experiencing nausea within the observed week (n = 31) had, compared to the patients not experiencing nausea (n = 100), lower ability in daily activities in general (p = 0.001), in shopping (p = 0.014), walking (p = 0.007) and social interaction (p = 0.007). Of the patients with nausea 48% had seldom woken up rested and 34% were not able to eat as much as they used to. Corresponding figures for nausea free patients were 27% (not significant; ns) and 16% (ns). Six (5%) experienced vomiting, 15 (12%) diarrhoea, 23 (18%) constipation and 52 (40%) any gastrointestinal symptoms. Forty seven (90%) were negatively bothered by the experienced gastrointestinal symptoms.ConclusionsThe fourth of patients experiencing nausea during radiotherapy had lower ability to perform daily activities than the three quarters of patients who were free from nausea. Few patients vomited while 40% experienced gastrointestinal symptoms during the observed week of radiotherapy. This implies that health care professionals could consider identifying nauseous patients that possibly need support in nausea-reduction and in daily activities during radiotherapy.     

Serum vascular adhesion protein-1 is higher in subjects with early stages of chronic kidney disease

ObjectivesAn increased level of serum vascular adhesion protein-1 (VAP-1) has been found in patients with diabetes mellitus and vascular disorders. This study examined whether serum VAP-1 levels are associated with chronic kidney disease (CKD).Design and methodsWe included 262 subjects aged 30 and above with fasting plasma glucose level < 7 mmol/L checked within 1 year. First morning urine specimens were collected. Microalbuminuria was defined if urinary albumin-to-creatinine ratio ≥ 30 μg/mg creatinine. The glomerular filtration rate (GFR) was estimated. CKD stages were defined according to the suggestions of the National Kidney Foundation. Serum VAP-1 levels were analyzed by immunofluorometric assay.ResultsSerum VAP-1 levels were positively associated with the urinary albumin-to-creatinine ratio ( r = 0.29, p < 0.0001) and negatively associated with estimated GFR (r = ?0.24, p =  0.0001). Subjects with CKD stage 2 (N =  51) and stage 3 (N =  91) had significantly higher levels of serum VAP-1 than those without CKD (p =  0.0003 and p =  0.035, adjusted for age and gender, respectively). A high serum VAP-1 level was associated with the presence of CKD (OR 1.63 for 1 SD increase of VAP-1, p =  0.018), adjusting for age, sex, and smoking. Ordered logit models revealed that high serum VAP-1 levels correlated with advanced stages of CKD.ConclusionsSerum levels of VAP-1 are associated with the severity of kidney damage or stages of kidney disease. The true mechanism which links the serum VAP-1 and CKD remains to be elucidated in further studies.     

Glycated albumin is independently associated with estimated glomerular filtration rate in nondiabetic patients with chronic kidney disease

BackgroundGlycated albumin (GA) may contribute to diabetic nephropathy, but the clinical significance of GA in patients with chronic kidney disease (CKD) is unknown.MethodsPatients were classified with the NKF/DOQI classification system as mild (stage I, II), moderate (stage III), or advanced CKD (stage IV). Those undergoing dialysis or with CKD stage V were excluded. GA was measured using the Lucica TM GA-L assay kit. The relationship between GA and renal dysfunction was analyzed in patients with or without diabetes.ResultsA total of 187 subjects were enrolled. GA values in those with normal, mild, moderate and advanced CKD were 18.4 ± 1.4%, 18.4 ± 3.1%, 19.0 ± 3.8%, 20.4 ± 6.4%, respectively, in diabetic patients (N = 67, p = 0.5), and were 14.1 ± 1.9%, 14.2 ± 2.2%, 15.9 ± 1.9%, 15.0 ± 1.7%, respectively, in nondiabetic patients (N = 120, p = 0.004). GA value was negatively correlated to eGFR in nondiabetic patients (r = ?0.35, p < 0.001) but not in diabetic patients (r = ?0.11, p = 0.39). In the adjusted model, GA is independently correlated to eGFR only in nondiabetic subjects.ConclusionsIncreased GA concentrations are independently associated with renal dysfunction in nondiabetic patients with CKD.     

Identification of local angiogenic and inflammatory markers in the menstrual blood of women with endometriosis

The aim of this study was to evaluate the presence of myeloperoxidase (MPO), N-acetyl-β-D-glucosaminidase (NAG), tumor necrosis factor alpha (TNF-α) and vascular endothelial growth factor (VEGF) in peripheral and menstrual blood in women with (n = 10) and without (n = 7) endometriosis. NAG and MPO activities were evaluated by enzymatic methods, whereas TNF-α and VEGF by immunoassay. No significant differences were found for these markers, neither in menstrual nor in peripheral blood between groups. Menstrual blood NAG (P = 0.039) and MPO (P = 0.0117) activities in the endometriosis group were significantly higher than in peripheral blood. NAG and MPO presented positive linear correlation in peripheral (P = 0.07; r = 0.641) and menstrual blood (P = 0.01; r = 0.603). These findings point to the existence of an increased local inflammatory activity in women with endometriosis.     

Sperm head defects and disturbances in spermatozoal chromatin and DNA integrities in idiopathic infertile subjects: Association with cigarette smoking

ObjectivesTo evaluate sperm chromatin and DNA integrities in idiopathic infertile men and determine the possible association(s) of cigarette smoking on oxidative stress markers, antioxidant capacity and semen quality.Subjects and methodsSemen samples from men referring to the andrology laboratory were categorized into 3 groups: fertile non-smokers (n = 16), infertile non-smokers (n = 36), and infertile smokers (n = 34). Semen analysis was performed according to WHO criteria. The percentage of sperm DNA fragmentation index (%DFI) and the percentage of sperm with abnormally high DNA stainability (HDS%; immature spermatozoa) were determined by SCSA using the metachromatic properties of acridine orange. Lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels in seminal plasma and spermatozoa were measured by spectrophotometric assays.ResultsThe classical semen parameters were negatively correlated with lipid peroxidation in spermatozoa; motility and morphology were negatively correlated with %DFI (p < 0.05). HDS% was also negatively correlated with above markers except for morphology (r = ? 0.352, p = 0.081). DFI% and HDS% were significantly higher in the infertile smokers group than in infertile non-smokers (p = 0.032; p = 0.001 respectively). Cigarette smoking was significantly associated with DFI%, HDS%, TBARS and the fraction of “round-headed” sperm (r = 0.796, p = 0.0001; r = 0.371, p = 0.033; r = 0.606, r = 0.591, p = 0.001 respectively), and decreased SOD levels (r = ? 0.545).ConclusionDFI%, HDS% and round-head sperms are increased in idiopathic infertile men; this increase is associated with cigarette smoking. These defects may be attributed to increased oxidative stress and insufficient scavenging antioxidant enzymes in the seminal fluid of infertile patients.     

Serum nitric oxide metabolites in subjects with metabolic syndrome

ObjectivesEvidence are available showing that higher nitric oxide production is associated with metabolic disorders. The aim of this study was to determine serum nitric oxide metabolites (NO_x) concentration in subjects with metabolic syndrome (MetS).Design and methodsIn a cross-sectional study, NO_x was measured in 3505 subjects, aged 20–94 years, using the Griess reaction. After excluding subjects taking medications for hypertension and dyslipidemia, data for 3148 subjects were analyzed.ResultsThere was a direct association between the numbers of metabolic risk factors and serum NO_x values in both genders (p for trend < 0.05). After multivariable adjustment, serum NO_x concentration was significantly higher in subjects with MetS [(31.9 (29.4–34.6) vs. 29.8 (27.6–32.1), p < 0.01) or type 2 diabetes (34.6 (31.3–38.2) vs. 30.2 (27.9–32.6), p < 0.001) as compared to their corresponding controls.ConclusionsHigher NO_x concentrations in subjects with MetS and type 2 diabetes support the existing hypothesis that NO overproduction affects insulin's metabolic actions.     

Plasma concentrations but not serum concentrations of brain-derived neurotrophic factor are related to pro-inflammatory cytokines in patients undergoing major abdominal surgery

ObjectivesTo investigate peripheral brain-derived neurotrophic factor (BDNF) concentrations in the perioperative period, their relationship with transforming growth factor-β1 (TGF-β1 tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-6 genetics.Design and methodsProspective, observational study. BDNF, TGF-β1, IL-6 and TNF-α were analysed at baseline (T0), 5 h (T1), 24 h (T2) and 5 days (T3) after surgery, in 21 patients. The IL-6 ? 174 G/C polymorphism was genotyped.ResultsSerum BDNF concentrations decreased (P = 0.048), correlated with TGF-β1 (r = 0.610 at T1, r = 0.493 at T2, r = 0.554 at T3). Plasma BDNF concentrations raised (P = 0.049), correlated with IL-6 and TNF-α at T1 (r = 0.495 and r = 0.441, respectively). BDNF response was predictable from TNF-α and IL-6 concentrations and the IL-6 ? 174 G/C genotype.ConclusionSerum and plasma BDNF concentrations could relate to platelet activation and inflammatory response, respectively. IL-6 genetics played a role in the BDNF acute response.