Nutritional status in relation to adipokines and oxidative stress is associated with disease activity in patients with rheumatoid arthritis

ObjectiveWe assessed whether disease activity was associated with dietary habits, nutritional status, adipokines, and oxidative stress in patients with rheumatoid arthritis.MethodsThe subjects were 37 patients with RA. The assessment of the nutritional status included anthropometric and biochemical parameters. A food-frequency questionnaire and a 3-d diet record to assess dietary intake were used. The serum levels of adipokines and oxidative stress markers in sera and saliva were measured. The disease activity was determined using the 28 Disease Activity Score (DAS28). We divided the subjects into high (DAS28 ≥3.2) and low (DAS28 <3.2) disease activity groups.ResultsThe serum leptin and albumin levels were significantly lower, whereas the inflammatory markers were increased, in the high disease activity group. The dietary intake assessment showed a lower intake of fish oil and a lower ratio of monounsaturated fatty acid intake in the high disease activity group. There was a negative correlation between the DAS28 and the dietary intake of the ratio of monounsaturated fatty acid to total fatty acid intake. The serum oxidative stress marker (reactive oxygen metabolites) showed a positive correlation to the DAS28. The salivary reactive oxygen metabolites also correlated with C-reactive protein and serum reactive oxygen metabolites.ConclusionAltered serum adipokine levels with decreased albumin may reflect the deterioration that is associated with rheumatoid arthritis. An increased oxidative stress was observed in sera and saliva. Intakes of ω-3 polyunsaturated fatty acids, fish oil, and monounsaturated fatty acid seem to affect disease activity and may have beneficial effects by decreasing inflammation.     

Categorical complexities of Plasmodium falciparum malaria in individuals is associated with genetic variations in ADORA2A and GRK5 genes

In the erythrocytes, malaria parasite entry and infection is mediated through complex membrane sorting and signaling processes. We investigated the effects of single-locus and multilocus interactions to test the hypothesis that the members of the GPCR family genes, adenosine A2a receptor (ADORA2A) and G-protein coupled receptor kinase5 (GRK5), may contribute to the pathogenesis of malaria caused by Plasmodium falciparum (Pf) independently or through complex interactions. In a case–control study of adults, individuals affected by Pf malaria (complicated n = 168; uncomplicated n = 282) and healthy controls (n = 450) were tested for their association to four known SNPs in GRK5 (rs2230345, rs2275036, rs4752307 and rs11198918) and two in ADORA2A (rs9624472 and rs5751876) genes with malaria susceptibility, using techniques of polymerase chain reaction-restriction fragment length polymorphisms and direct DNA sequencing. Single-locus analysis showed significant association of 2 SNPs; rs5751876 (OR = 3.2(2.0–5.2); p = 0.0006) of ADORA2A and rs2230345 (OR = 0.3(0.2–0.5); p = 0.0006) of GRK5 with malaria. The mean of the serum creatinine levels were significantly higher in patients with variant GG (p = 0.006) of rs9624472 in ADORA2A gene compared to AA and AG genotypes in complicated Pf malaria cases, with the G allele also showing increased risk for malaria (OR = 1.3(1.1–1.6); p = 0.017). Analyses of predicted haplotypes of the two ADORA2A and the four GRK5 SNPs have identified the haplotypes that conferred risk as well as resistance to malaria with statistical significance. Molecular docking analysis of evolutionary rs2230345 SNP indicated a stable activity of GRK5 for the mutant allele compared to the wild type. Further, generalized multifactor dimensionality reduction to test the contribution of individual effects of the six polymorphisms and higher-order interactions to risk of symptoms/clinical complications of malaria suggested a best six-locus model showing statistical significance. The study provides evidence for the role of ADORA2A and GRK5 that might influence the etiology of malaria infection.     

Lipoprotein-associated phospholipase A2 activity is associated with coronary artery disease and markers of oxidative stress: a case-control study

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a lipoprotein-bound enzyme that can release atherogenic isoprostanes from esterified phospholipids and that may be involved in inflammation and atherosclerosis. OBJECTIVE: This study investigates the association between Lp-PLA(2) activity and coronary artery disease (CAD) in relation to oxidative stress markers, in particular urinary 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)). DESIGN: We conducted a case-control study in which the cross-sectional relation between Lp-PLA(2) activity, lipoproteins, and oxidative stress markers was determined in 799 patients with angiographically confirmed CAD and 925 healthy controls. RESULTS: Lp-PLA(2) activity was significantly (P < 0.001) higher in CAD cases than in controls (32.9 +/- 0.46 and 29.7 +/- 0.42 nmol . mL(-1) . min(-1), respectively). Both elevated Lp-PLA(2) activity and urinary excretion concentrations of 8-epi-PGF(2alpha) were associated with greater CAD risk (P for trend < 0.001). Odds ratios for the upper quartiles of Lp-PLA(2) activity and 8-epi-PGF(2alpha).excretion were 2.47 (95% CI: 1.79, 3.40) and 2.19 (1.52, 3.15), respectively, after adjustment for sex, age, BMI, blood pressure, smoking and alcohol consumption status, and LDL and HDL cholesterol. When we examined the additive effect of both markers for CAD risk, the relation between 8-epi-PGF(2alpha) and CAD was weakened above the second quartile of Lp-PLA(2) activity. Moreover, Lp-PLA(2) activity was positively correlated with urinary excretion concentrations of 8-epi-PGF(2alpha) in controls (r = 0.277, P < 0.001) and cases (r = 0.202, P < 0.001) and with the tail moment of lymphocyte DNA (r = 0.213, P < 0.001) in controls. CONCLUSION: This study shows an association of elevated Lp-PLA(2) activity with CAD risk in relation to oxidant stress and thus supports a proatherogenic role of Lp-PLA(2).     

Serum beta-glucuronidase activity is inversely associated with plant-food intakes in humans

Beta-glucuronidase hydrolyzes glucuronide moieties from steroids and xenobiotics, such that circulating glucuronyl conjugates can interact with target tissues. In animal models, dietary constituents can alter beta-glucuronidase activity. In humans, serum beta-glucuronidase activity reflects liver enzyme loss during cell turnover, and thus is a surrogate for hepatic beta-glucuronidase. We recruited 83 men and 120 women, who were nonsmokers, 20-40 y of age, with self-reported vegetable and fruit (V&F) intakes of < or = 2.5 or > or = 4.5 servings/d. Diet was assessed by 3-d food record and serum carotenoids were measured as biomarkers of V&F intake (e.g., servings V&F vs. alpha-carotene; r = 0.47, P = 0.0001). Serum beta-glucuronidase activity (Modified Sigma Units/L), determined in blood samples collected on two consecutive days from fasting subjects, was higher in men than women (mean +/- SEM: 20.4 x 10(3) +/- 1.0 x10(3) and 17.0 x 10(3) +/- 0.6 x 10(3), P = 0.002). beta-Glucuronidase activity (adjusted for sex) was inversely associated with intakes of plant protein, fruit, dietary fiber (r = -0.24 to -0.30; P < 0.001), botanical groupings Cucurbitaceae, Rosaceae, and Leguminosae (r = -0.16 to -0.19; P < 0.05), and serum alpha- and beta-carotene and beta-cryptoxanthin (r = -0.18 to -0.26; P < or = 0.01). Activity was not associated with overall vegetable intake. Although these associations are modest, the data suggest that plant foods, particularly constituents of fruits and fiber-containing foods, may influence human beta-glucuronidase activity in a potentially favorable direction.     

Genetic variation in stearoyl-CoA desaturase 1 is associated with metabolic syndrome prevalence in Costa Rican adults

Stearoyl-CoA desaturase 1 (SCD1) activity, a key regulator of lipid metabolism, may be associated with the development of metabolic syndrome (MetS). We examined the association of genetic variation in the SCD1 gene with the occurrence of MetS and its five components in a population of Costa Rican adults (n = 2152; mean age, 58 y; range, 18-86 y). Associations of tag single nucleotide polymorphisms (tagSNP) of the SCD1 gene with prevalence of MetS and its five components were analyzed by use of log-Poisson models with robust variance estimates and linear regression models, respectively. The likelihood ratio was used to test potential gene-fatty acid interactive effects with adipose tissue α-linolenic acid. One tagSNP (rs1502593) was significantly associated with an increased prevalence of MetS in the total study sample. Compared with the common homozygous CC genotype, the CT and TT genotypes for rs1502593 were associated with higher prevalence ratios (PR) of MetS for CT vs. CC: [PR = 1.22 (95% CI = 1.03, 1.44)] and for TT vs. CC [PR = 1.24 (95% CI = 1.01, 1.52)]. Among women, we observed borderline positive associations between systolic blood pressure and fasting blood sugar levels and rs1502593 (P = 0.05 and 0.06). Compared to the common haplotype (frequency ≥ 5%) with no minor alleles of SCD1 tagSNP, the other two observed common haplotypes carrying the rs1502593 minor allele were significantly associated with elevated prevalence of MetS. No gene-fatty acid interactive effects were observed. Our results suggest that genetic variation in the SCD1 gene may play a role in the development of MetS.     

Bisphenol A exposure is associated with oxidative stress and inflammation in postmenopausal women

Bisphenol A (BPA) is widely used in the production of polycarbonate plastics and epoxy resins. There is increasing health concerns regarding low-level exposure to BPA among the general population. The aim of this study was to determine the association between BPA exposure with oxidative stress and inflammation in adult populations. A cross-sectional study was conducted. This study included 485 adults (259 men, 92 premenopausal women, and 134 postmenopausal women) living in general communities within large cities. Urinary concentrations of BPA, malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG), white blood cell (WBC) count, and C-reactive protein (CRP) were measured. Multivariate analyses were applied to determine the associations of BPA exposure with oxidative stress and inflammation. The geometric means of urinary BPA for men, premenopausal women, and postmenopausal women were 0.53, 0.61, and 0.58 μg/g cr, respectively. The urinary BPA concentrations were positively associated with MDA, 8-OHdG, and CRP levels in the postmenopausal women; however, such associations did not exist in men and premenopausal women. The findings of this study suggest that BPA exposure would promote oxidative stress and inflammation, in which postmenopausal women are likely to be more susceptible to BPA-induced health effects.     

Lung cancer in humans is not associated with lifetime total alcohol consumption or with genetic variation in alcohol dehydrogenase 3 (ADH3)

Although there is clear evidence that smoking is the primary risk factor for lung cancer, not all variation in disease risk is understood. There is some evidence that alcohol may contribute to risk. We examined lifetime and recent (12-24 mo previous) alcohol consumption in relation to risk of lung cancer in a case-control study in western New York. In addition we examined the alcohol dehydrogenase 3 (ADH3) genotype in relation to lung cancer risk; ADH3 is rate limiting in alcohol metabolism and has a functional polymorphism. We interviewed incident, primary, histologically confirmed lung cancer cases (n = 111) in two counties. Controls were randomly selected from among those residing in the counties, frequency-matched to cases for age and race (n = 1546). Lifetime and recent total alcohol and beverage-specific alcohol consumption as well as relevant confounders were assessed by interview. ADH3 genotype was evaluated by a PCR-restriction fragment length polymorphism assay. Because of the small sample size, power was limited and CI were wide. Residual confounding by smoking remains a concern. Although we found a significant trend for increased risk for beer consumption in the recent period (odds ratio 1.67, 95% CI 0.96-2.92, P for trend = 0.05), chance cannot be ruled out as an explanation. We found no evidence of risk related to lifetime alcohol consumption nor evidence that alcohol dehydrogenase genotype modifies risk related to alcohol and lung cancer.     

Dietary supplementation with 11trans- and 12trans-18:1 and oxidative stress in humans

BACKGROUND: High consumption of trans fat has been associated with high oxidative stress in humans, which could increase the risk of the development or acceleration of several diseases, such as atherosclerosis, cancer, and type 2 diabetes. OBJECTIVE: Several urinary and blood biomarkers of oxidative stress [8-iso-prostaglandin-F(2alpha) (PGF(2alpha)), 15-keto-dihydro-PGF(2alpha), and 7,8-dihydro-8-oxo-2'-deoxy-guanosine in urine and alpha-,beta-,gamma-,delta-tocopherol, and retinol in plasma] were monitored to evaluate the oxidative stress induced by dietary supplementation of 11trans- and 12trans-18:1 isomers in humans during a 6-wk intervention. DESIGN: After a 14-d adaptation period free of trans fatty acid supplementation (baseline), the test group (n = 12) received 3.0 g 11trans-18:1/d and 3.0 g 12trans-18:1/d (Sigma 6.0 g/d), and the control group (n = 12) consumed a control oil free of trans fatty acids and conjugated linoleic acids for 6 wk. RESULTS: The postintervention concentration of urinary 8-iso-PGF(2alpha) (free radical-induced lipid peroxidation) in the test group was significantly higher than baseline and significantly higher than that observed in the control group. The concentrations of 15-keto-dihydro-PGF(2alpha) (cyclooxygenase-mediated inflammatory response indicator) and 7,8-dihydro-8-oxo-2'-deoxy-guanosine (oxidative DNA damage) were not affected by the 11trans- and 12trans-18:1 supplementation. CONCLUSIONS: Although an increase in urinary 8-iso-PGF(2alpha) was observed and the effects of prolonged high (ie, >5.0 g/d) consumption of trans fat could be relevant to the development of disease, the mean intakes of 11trans- and 12trans-18:1 in Europeans are estimated to be significantly below the amounts administered in this study (ie, 6.0 g/d); such low intakes could minimize the possible risk of detrimental effects on human health.     

Mitochondrial variations in the MT-ND4 and MT-TL1 genes are associated with male infertility

Mitochondrial gene mutations have been reported to be associated with sperm motility and the quality of semen. The aim of this study was to investigate whether the two mitochondrial genes (MT-ND4 and MT-TL1) are involved in Chinese male infertility. A total of 97 asthenospermia patients and 80 fertile controls were recruited in this case-control study. Genomic DNA were extracted from the sperm of all participants. Two mitochondrial DNA genes (MT-ND4 and MT-TL1) were amplified by using polymerase chain reaction (PCR) with the gene-specific primers and sequenced on an ABI 3730XL DNA sequencer. For the MT-ND4 gene, we found a total of 64 and 54 nucleotide substitutions in patients and controls, respectively, with no discrepancy in the mutation rates (66.0% vs. 67.5%, p>0.05). However, one mutation (g.11084A>G, p.T109A) leading to an amino acid substitution in a highly conserved residue and predicted to be deleterious was detected only in the cases. For another gene MT-TL1, a novel mutation (g.3263C>T) near the anticodon TAA was identified in an asthenospermia patient and was absent from normal controls. However, the mutation positions in the cases varied from the controls and one highly conserved mutation (g.11084A>G, p.T109A) which was not found in the controls and probably caused damage to the protein structure might contribute to asthenospermia. For another gene MT-TL1, a highly conservative novel mutation which is located closely next to the anticodon also might contribute to asthenospermia. Our result suggests that the MT-ND4 and MT-TL1 genes might be associated with Chinese male infertility.

Abbreviations: MT-ND4: mitochondrially encoded NADH dehydrogenase 4; MT-TL1: mitochondrially encoded tRNA leucine 1 (UUA/G); PCR: polymerase chain reaction; OXPHOS: mitochondrial oxidative phosphorylation; ATP: adenosine triphosphate; mtDNA: mitochondrial DNA; SNPs: single nucleotide substitutions; AD: alzheimer’s disease; PD: parkinson’s disease; MELAS: mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; ROS: reactive oxygen species     

Genetic variation in genes associated with arsenic metabolism: glutathione S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans

Individual variability in human arsenic metabolism has been reported frequently in the literature. This variability could be an underlying determinant of individual susceptibility to arsenic-induced disease in humans. Recent analysis revealing familial aggregation of arsenic metabolic profiles suggests that genetic factors could underlie interindividual variation in arsenic metabolism. We screened two genes responsible for arsenic metabolism, human purine nucleoside phosphorylase (hNP), which functions as an arsenate reductase converting arsenate to arsenite, and human glutathione S-transferase omega 1-1 (hGSTO1-1), which functions as a monomethylarsonic acid (MMA) reductase, converting MMA(V) to MMA(III), to develop a comprehensive catalog of commonly occurring genetic polymorphisms in these genes. This catalog was generated by DNA sequencing of 22 individuals of European ancestry (EA) and 24 individuals of indigenous American (IA) ancestry. In (Italic)hNP(/Italic), 48 polymorphic sites were observed, including 6 that occurred in exons, of which 1 was nonsynonymous (G51S). One intronic polymorphism occurred in a known enhancer region. In hGSTO1-1, 33 polymorphisms were observed. Six polymorphisms occurred in exons, of which 4 were nonsynonymous. In contrast to hNP, in which the IA group was more polymorphic than the EA group, in hGSTO1-1 the EA group was more polymorphic than the IA group, which had only 1 polymorphism with a frequency > 10%. Populations representing genetic admixture between the EA and IA groups, such as Mexican Hispanics, could vary in the extent of polymorphism in these genes based upon the extent of admixture. These data provide a framework in which to conduct genetic association studies of these two genes in relevant populations, thereby allowing hNP and hGSTO1-1 to be evaluated as potential susceptibility genes in human arsenicism.     

Increase in maternal adiposity and poor lipid profile is associated with oxidative stress markers during pregnancy

ObjectiveThis study aimed to evaluate changes in maternal adiposity and lipid profile and to correlate these parameters with Deoxyribonucleic acid (DNA) damage and total antioxidant capacity (TAC) levels among pregnant women.MethodThis was a longitudinal study which took place in Kelantan state, Malaysia. Fasting blood samples of 159 healthy pregnant women were collected in second and third trimesters from April 2010 until October 2011. Maternal total body fat was assessed using bioimpedance analysis method.ResultsWhen compared to data in second trimester, pregnant women in third trimester showed significantly higher levels of total body fat (p < 0.001), total cholesterol (p < 0.001), triglyceride (p < 0.001), LDL-C (p = 0.001), DNA damage (p < 0.001) and TAC (p < 0.001) but a lower level of HDL-C (p < 0.001). Maternal adiposity and lipid profile were positively and consistently correlated with DNA damage in second and third trimesters. Significant and positive correlations of triglyceride with TAC levels were noted in both periods indicating compensatory action against increased oxidative stress.ConclusionNormal pregnancy is associated with marked changes in lipid metabolism, prooxidant and antioxidant status. Dyslipidemia-associated oxidative stress was demonstrated with advancing gestational age. Appropriate preventive and compensatory measures should be practiced to minimize the effect of oxidative stress throughout pregnancy.     

Selenium inadequacy is not associated with oxidative stress in child and adolescent acute lymphocytic leukemia survivors

ObjectiveAcute lymphocytic leukemia (ALL) and its subsequent treatment may provoke increased oxidative stress. The aim of this study was to investigate the antioxidant status of children and adolescents who had received ALL therapy, and to test the hypothesis that selenium (Se) inadequacy is correlated with reduced defenses against oxidative stress in this population.MethodsThis case–control study involved 24 patients between ages 5 and 13 y who had been treated successfully for ALL (ALL group) and 60 children of similar age and socioeconomic background with no clinical history of leukemia (control group). Dietary intake of Se was evaluated by the 24-h recall method, and the concentrations of Se in plasma, erythrocytes, and urine determined. Antioxidant status was assessed by analysis of the oxidative stress markers, namely, superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), α-tocopherol, and 8-oxo-deoxyguanosine (8-oxo-dG).ResultsThere were no between-group differences with respect to plasma (P = 0.122), erythrocyte (P = 0.202), urinary (P = 0.608), or dietary (P = 0.757) levels of Se. GPx activity was significantly (P < 0.001) reduced in the ALL group compared with the control group, whereas SOD activity and MDA concentrations were similar. The concentrations of α-tocopherol and 8-oxo-dG were significantly increased in the ALL group compared with the control group (P < 0.001 and P = 0.031, respectively).ConclusionAll participants were Se inadequate, but such inadequacy was not correlated with reduced defenses against oxidative stress. However, individuals of the ALL group were with increased oxidative stress compared with the control group, possibly due to previous disease and to intensive polychemotherapy.     

Genetic variation in IL28RA is associated with the outcomes of HCV infection in a high-risk Chinese population

Hepatitis C virus (HCV) infection varies in the outcomes depending on both viral and host factors. This study aims to investigate the association of single-nucleotide polymorphisms (SNPs) of IFNAR2, IL10RB, and IL28RA genes with susceptibility to HCV infection and resolution. Genotyping of IFNAR2, IL10RB, and IL28RA gene polymorphisms were performed using TaqMan® method from 552 patients with sero-positive anti-HCV and 421 uninfected controls. The distribution of IFNAR2 and IL10RB genotypes among the control, persistent infection, and spontaneous clearance groups did not differ. However, IL28RA-rs10903035 A allele was over-represented in persistent infection group when compared with uninfected controls and spontaneous clearance group, respectively (OR = 1.54, 95%CI = 1.23–1.92, P = 0.004; OR = 1.42, 95%CI = 1.12–1.81, P = 0.016), and AA genotype had a significant increased risk of persistent infection in different strata except for the females subgroup (P < 0.05). IL28RA-rs11249006 GG genotype showed reduced susceptibility to persistent HCV infection (OR = 0.53, 95%CI = 0.31–0.91, P = 0.044), and the protective effect was significantly different among subgroups stratified by age and likely source of infection (P < 0.05). Besides, AG genotype had a significant negative effect on spontaneous clearance of HCV among young subjects (aged ?40) and patients infected with viral genotype-1 (P < 0.05). Stratified analysis also showed that IL10RB-rs2834167 AG genotype was associated with an increased risk of persistent HCV infection in females, and GG genotype was associated with an increased risk of persistent HCV infection in females and patients with viral genotype non-1 (P < 0.05). Haplotype analysis showed that IL28RA rs10903035-rs11249006 haplotype GG played a protective effect for HCV infection (OR = 0.21, 95%CI = 0.13–0.36, P < 0.001; OR = 0.20, 95%CI = 0.12–0.34, P < 0.001). This study indicates that two SNPs in IL28RA are correlated with susceptibility to HCV infection and spontaneous viral clearance, which implicates a primary role of IL28RA in the outcomes of HCV infection.     

Increased influence of genetic variation on PON1 activity in neonates

PON1 (paraoxonase-1) detoxifies organophosphates by cleavage of active oxons before they have a chance to inhibit cholinesterases. The corresponding gene PON1 has common polymorphisms in both the promoter (-909, -162, -108) and the coding region (L55M, Q192R). The five PON1 genotypes were determined for maternal blood (n= 402) and cord blood (n= 229) as part of a study of the effects of organophosphate pesticide exposure on infant growth and neurodevelopment. PON1 enzymatic activities were determined for a majority of subjects. The population contained Caucasians, Caribbean Hispanics, and African Americans. PON1 activity was strongly dependent upon the promoter alleles in both maternal and cord blood. For example, PON1 activities for position -108CC, CT, and TT mothers were 146, 128, and 109 arylesterase U/mL (analysis of variance, p< 0.0001), whereas the same PON1 activities for the respective cord bloods were 49.0, 32.4, and 23.2 U/mL (p < 0.0001). Compared with adults, neonates had lower PON1 activity, implying reduced capacity to detoxify organophosphates. In addition there was a larger difference in activity between genotype groups in neonates than in adults. Because the five polymorphisms in PON1 occur in a short stretch of DNA, they were tested for linkage disequilibrium (LD). Significant LD was found among all three promoter polymorphisms as well as between promoter polymorphisms and L55M, with the strongest LD for Caucasians and the weakest for African Americans. The Caribbean Hispanics fall between these two groups. Surprisingly, significant LD also was observed between the promoter polymorphisms and C311S in PON2. LD between the promoter polymorphisms and Q192R was not significant.     

High-fructose feeding of streptozotocin-diabetic rats is associated with increased cataract formation and increased oxidative stress in the kidney

We examined the effects of high-fructose (FR) feeding on the development of diabetic complications in the lens and the kidney of streptozotocin (STZ)-diabetic rats. Male Wistar Furth rats were treated with one of two doses of STZ (HIGH STZ, 55 mg/kg body weight; MOD STZ, 35 mg/kg body weight) or vehicle alone (SHAM) and were then assigned to a control (CNTL) or 400 g FR/kg diet for 12 weeks. At the end of the study, body weight, plasma glucose and insulin concentrations differed among STZ groups (HIGH v. MOD v. SHAM, P < 0.001) but did not differ due to diet. Plasma FR concentrations were significantly higher in FR-fed v. CNTL-fed groups (P < 0.0001) and in HIGH-STZ groups v. MOD-STZ and SHAM groups (P < 0.0004 and P < 0.0001 respectively). Focal length variability of the lens, a quantitative measure of cataract formation, was increased in the HIGH STZ, FR group compared with the HIGH STZ, CNTL group (P < 0.01). The concentration of H2O2 in kidney microsomes was significantly higher in HIGH STZ, FR rats v. HIGH STZ, CNTL rats (P < 0.01). Micro-albuminuria was not observed in any of the groups examined, and there was no evidence of extensive histological damage in the kidney from any rats. Under conditions of severe hyperglycaemia, high FR intake promotes the development of cataracts in the lens of the eye, and results in increased concentrations of substances indicative of oxidative stress in the kidney. Although FR has been suggested as a carbohydrate source for diabetics, a high FR diet coupled with hyperglycaemia produces effects that may promote some of the complications associated with diabetes.     

Genetic variation associated with ischemic heart failure: a HuGE review and meta-analysis

The ischemic etiology of heart failure is an independent prognostic factor associated with worse long-term outcome. Recent evidence indicates a role for genetic susceptibility to ischemic heart failure. The authors systematically reviewed all known case-control studies that investigated the association between genetic variants and ischemic heart failure. Twenty-two articles, which examined 24 gene polymorphisms, were identified. In 22 polymorphisms, the variant form had a functional effect. Twenty-two polymorphisms were variants of genes involved in the maladaptive neurohormonal activation. Seven polymorphisms (ACE I/D, AGT M235T, ADRA2C Del322-325, ADRB2 Arg16Gly, ADRB2 Gln27Glu, EDN1 Lys198Asn, VEGF G-405C) showed a significant association in individual studies. Five polymorphisms (ACE I/D, ADRB1 Arg389Gly, ADRB2 Arg16Gly, ADRB2 Gln27Glu, TNF G308A) were examined by more than one study, and meta-analyses were performed. The meta-analyses showed no significant sign of heterogeneity. In all settings, there was no significant association, except for polymorphism ADRB2 Arg16Gly under a recessive model (fixed-effects odds ratio = 1.32, 95% confidence interval: 1.05, 1.65). Taking into account that ischemic heart failure is a complex disease with multifactorial etiology, a minor contributing pathogenetic role of the investigated gene polymorphisms cannot be totally excluded. Case-control studies that investigate gene-gene and gene-environment interactions might further elucidate the genetics of ischemic heart failure.