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The in vivo antioxidant, anti-inflammatory, and anti-hyperglycemic activities of Salvia splendens extracts (100 mg kg−1d−1 P.O.) in male albino rats were studied. The total 70% methanolic, total aqueous and successive ethyl acetate extracts demonstrated antioxidant and anti-inflammatory activities. The results suggested that S. splendens may have supportive role in controlling diabetic conditions due to the presence of poly-phenolic compounds. [ABSTRACT FROM AUTHOR]

Background: Peripheral artery disease (PAD) is a complication of type 2 diabetes that leads to critical limb ischemia and amputation. We tested whether absent or diminished pedal pulses (ADPPs) predicts subsequent renal functional decline in patients with diabetic chronic kidney disease (CKD). We also examined the association between urinary biomarkers and ADPP as well as worsening CKD. Methods: Using a prospective longitudinal design, we studied 91 patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) from 7 to 146 mL/min/1.73 m2. Baseline pedal pulses were assessed by standardized history and physical examination. The primary endpoint was decline in eGFR >30%. Potential confounders of the relationship between pedal pulses and eGFR were assessed by multivariable logistic regression. Results: Of 91 participants (median age 58 (range 30–83); median eGFR 72.4 ± 33.4 mL/min/1.73 m2), 43% had at least one ADPP. Baseline ADPP associated with increased risk of greater than 30% decline in eGFR (OR= 3.67, p =.004). This association remained significant (OR = 3.09, p =.029) after adjustment for traditional risk factors of renal function decline in diabetic kidney disease (DKD). In addition, urinary endothelin-1 (ET-1) was higher among patients with ADPP (p =.0006) and associated with eGFR decline greater than 30% (adjusted OR = 1.81, p =.035). Conclusions: ADPP is a strong predictor of decline in renal function in type 2 diabetes. Patients with type 2 diabetes and abnormal pedal pulses should be screened for DKD and monitored closely for progression of CKD. [ABSTRACT FROM AUTHOR]

Fenton-reaction initiated in vitro oxidation and in vivo oxidative biotransformation of salicylic acid was investigated by HPLC-UV-Vis method. By means of the developed high performance liquid chromatography (HPLC) method salicylic acid, catechol, and all the possible monohydroxylated derivatives of salicylic acid can be separated. Fenton oxidations were performed in acidic medium (pH 3.0) with two reagent molar ratios: (1) salicylic acid: iron: hydrogen peroxide 1:3:1 and (2) 1:0.3:1. The incubation samples were analysed at different time points of the reactions. The biological effect of elevated reactive oxygen species concentration on the intestinal metabolism of salicylic acid was investigated by an experimental diabetic rat model. HPLC-MS analysis of the in vitro samples revealed presence of 2,3- and 2,5-dihydroxybenzoic acids. The results give evidence for nonenzyme catalysed intestinal hydroxylation of xenobiotics. [ABSTRACT FROM AUTHOR]

Although reactive oxygen species can regulate intracellular signaling pathways, excessive amounts under oxidative stress conditions may cause damage to biomolecules. Hydroxyl radical (˙OH) is a most reactive oxidant that can harm DNA, lipids, and proteins. As the direct determination of ˙OH by highly specialized electron paramagnetic resonance techniques is costly, indirect colorimetric determinations have attracted attention. Salicylic acid has been used both as an in vitro and in vivo probes to detect ˙OH, itself being converted to 2,3-, 2,4-, and 2,5-dihydroxybenzoic acids (DHBA) and catechol, but since 2,5-DHBA may also be generated enzymatically in the cyctochrome P-450 metabolism, 2,3-DHBA is the real marker of oxidative salicylate damage. This work is focused on the development of a selective hydroxyl radical detection assay by modifying a colorimetric nitrite-molybdate method concerning vic-diol determination of 2,3-DHBA among other DHBA isomers. Salicylic acid was hydroxylated to DHBAs and catechol upon the attack of ˙OH produced in a Fenton system. An aliquot from the mixture was oxidized with a nitrite-molybdate(VI) reagent to give an intense red product in alkaline medium with maximal absorbance at 510 nm. The assay was selective to only 2,3-DHBA and catechol among all DHBA isomers. The residual salicylic acid, DHBAs, and catechol were measured using high-performance liquid chromatography (HPLC); the spectrophotometrically measured contents of 2,3-DHBA and catechol were compared with HPLC results. Antioxidants, when present, caused a reduction in the hydroxylation of salicylate probe producing less 2,3-DHBA and catechol, thereby enabling the development of an indirect antioxidant activity assay for colorimetrically measuring ˙OH scavenging ability. [ABSTRACT FROM AUTHOR]

There is increasing evidence for a direct relationship between the vascular system and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate endocan and adhesion molecules such as P-selectin derived from the endothelium and platelets in obese children and adolescents with NAFLD. One hundred obese patients and 40 lean controls were enrolled. The obese subjects were divided into two subgroups based on the presence or absence of fatty liver. Blood samples were assayed for endocan, P-selectin, platelet-derived growth factor (PDGF), intercellular cell adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1. Obese patients with NAFLD presented higher ALT and insulin levels, as well as more profound dyslipidemia when compared with their counterparts without NAFLD. Serum levels of high-sensitivity C-reactive protein, VCAM-1 and ICAM-1 were found increased in both obese groups, regardless of NAFLD. In obese subjects with NAFLD, decreased P-selectin levels (51.6 ± 4.14 ng/mL) were detected as compared with the obese (72.3 ± 4.23) and control (74.2 ± 6.97) subjects. Furthermore, circulating P-selectin levels were closely associated with endocan levels (r = 0.852,p < 0.001). Childhood obesity leads to vascular inflammation and therefore may cause a predisposition to atherosclerosis at an early age. The possible outcome of decreased P-selectin levels with NAFLD development must be further investigated. [ABSTRACT FROM PUBLISHER]

In this investigation, 14 extra virgin olive oils (EVOOs), produced with Leccino and Raggiola olive cultivars, by a new two-way (2W) decanter were compared with 14 EVOOs produced by means of a conventional three-way (3W) decanter. The 2W EVOOs had higher phenol concentrations, as shown by high-performance liquid chromatography/diode array detection (HPLC-DAD) analysis and yielded a higher extraction of the 3,4-DHPEA-EDA (oleacein), 3,4-DHPEA-EA (oleuropein aglycone) andp-HPEA-EDA (oleocanthal). The concentrations of lignans, (+)-pinoresinol and (+)-1-acetoxypinoresinol, detected by HPLC-FLD equipment, were higher in the 2W EVOOs than they were in EVOOs produced using the 3W system. Total phenols, detected by the Folin–Ciocalteu assay, were lower than those obtained by HPLC, but they significantly correlated (p < 0.05). The antioxidant capacity (ORAC) values of 2W EVOOs were higher than those of 3W EVOOs. In conclusion, the 2W system provided high-quality phenol EVOOs and became an indispensable tool when adverse climatic conditions reduced the olive secoiridoid concentration. [ABSTRACT FROM PUBLISHER]

Chemical speciation of Co(II), Ni(II), Cu(II) and Zn(II) complexes of 2,3-dihydroxybenzoic acid in 0.0-60.0% v/v 1, 2-propanediol-water mixtures maintaining an ionic strength of 0.16 mol dm-3 at 303±0.1 K has been studied pH metrically. The predominant complexes formed are ML, ML2 and ML2H2 for Co(II), Ni(II) and Zn(II) and ML, ML2, ML2H and ML2H2 for Cu(II). Models containing different numbers of species were refined by using the computer program MINIQUAD75. Selection of the best fit chemical models was based on statistical parameters and residual analysis. The trend in variation of complex stability constants with dielectric constant of the medium is explained on the basis of electrostatic and non-electrostatic forces. Distributions of species, formation equilibria and effect of influential parameters on the stability constants have been presented. The possible structures of the various species are elucidated on the basis of the analysis of the pH-metric data. [ABSTRACT FROM AUTHOR]

The tocopherol contents of oils obtained from Ayvalık, Domat and Gemlik olive varieties harvested at different ripening periods were evaluated by high-performance liquid chromatography. α-Tocopherol was the major tocol detected in all the studied olive oil samples. The oils extracted from olive fruits composed of 130.54–180.43 mg kg–1 α-tocopherol, 0.73–1.61 mg kg–1 β-tocopherol and 0.53–2.28 mg kg–1 γ-tocopherol for Ayvalık oil. The α-, β- and γ-tocopherol contents of Domat oil are in the ranges 95.60–125.56, 0.71–2.70 and 0.49–1.25 mg kg–1 at different harvesting periods. The α-, β- and γ-tocopherol contents of Gemlik olive oil are in the ranges 112.59–168.19, 0.94–1.21 and 0.85–2.40 mg kg–1, respectively. There were significant differences between the oils from cultivars grown in different environments. [ABSTRACT FROM PUBLISHER]

Olive oil, an oil rich in monounsaturated fatty acids (MUFCs) and minor constituents including phenolic compounds, is a major component of the Mediterranean diet. The potential health benefits of the Mediterranean diet were highlighted by the seminal Seven Countries Study, and more contemporary research has identified olive oil as a major element responsible for these effects. It is emerging that the phenolic compounds are the most likely candidates accounting for the cardioprotective and cancer preventative effects of extra virgin olive oil (EVOO). In particular, the phenolic compound, hydroxytyrosol has been identified as one of the most potent antioxidants found in olive oil. This review will briefly consider historical aspects of olive oil research and the biological properties of phenolic compounds in olive oil will be discussed. The focus of the discussion will be related to the mechanisms of action of hydroxytyrosol. Studies have demonstrated that hydroxytyrosol induces apoptosis and cell cycle arrest in cancer cells. Further, research has shown that hydroxytyrosol can prevent cardiovascular disease by reducing the expression of adhesion molecules on endothelial cells and preventing the oxidation of low-density lipoprotein (LDL). The molecular mechanisms accounting for these effects are reviewed. [ABSTRACT FROM AUTHOR]

Background: Endothelin-1 (ET-1) is associated with progression of renal disease, acting as a vasoconstrictor and growth factor for mesangial cells. ET-1 and endothelin A receptor (ET-RA) might have a role in the development of diabetic nephropathy (DN). The aims of this study were to determine ET-1 and ET-RA expressions in patients with DN and to correlate these expressions with renal function and proteinuria. Materials and methods: This is a cross-sectional study comprising 13 patients with type 2 diabetes mellitus and DN, 10 patients with proteinuric IgA nephropathy, and 13 samples of normal kidney from tumor nephrectomies. Demographic and selected data were collected from medical charts. The distribution and intensity of ET-1 and ET-RA immunostaining in renal biopsies were determined by immunohistochemistry and these correlated with the estimated glomerular filtration rate (eGFR) and proteinuria. Results: Patients with DN and IgA nephropathy on biopsy had markedly increased staining for ET-1 in endothelial cells of glomerular and peritubular capillaries when compared with controls ( p < 0.001). ET-RA staining was also more intense and more diffuse in DN and IgA nephropathy than in controls ( p == 0.019) and was restricted to tubular epithelial cells. A positive correlation was observed between ET-1 expression and proteinuria ( r == 0.634, p == 0.027), but both ET-1 and ET-RA expressions did not correlate with eGFR. Conclusion: In this preliminary report, the higher expressions of ET-1 and ET-RA found in both DN and IgA nephropathy suggest a potential role for the endothelin system in DN as well as in other nondiabetic glomerular diseases. [ABSTRACT FROM AUTHOR]

The virgin olive oil aroma evaluation has been applied as a quality and authentication control technique. Many analytical procedures have been used to identify and quantify the volatile components that characterize olive oil flavor. Among of them, gas chromatography is the main technique applied for this purpose. This study carries out an extensive and complete review of all the works published, since 30 years ago to the present, that have used gas chromatography technology for olive oil aroma analysis. Special attention has been devoted to the olive oil volatile compounds extraction and concentration techniques and separation and identification methods applied. [ABSTRACT FROM AUTHOR]

Diabetes has been related to changes in vascular responses, mainly an increase in the vasoconstrictor responses and a decrease in the vasodilator responses. The literature has now begun to study the effects of diabetes in the early stages of development; the first studies on these stages indicate that diabetes produces different changes compared to the advanced stages. For that reason, the aim of this work was to evaluate the responses to norepinephrine and dopamine on normotensive and hypertensive rats with 4 weeks of diabetes evolution. The results showed that 4 weeks of diabetes produces a decrease of the vasopressor response to both agents (norepinephrine and dopamine). These results suggest that in the early stages, there are changes that help to decrease the pressor responses and these changes could disappear in the advanced stages. [ABSTRACT FROM AUTHOR]

Background. Diabetic nephropathy (DN) is a severe long-term complication of diabetes characterized by continuous albuminuria, a relentless decline in renal function, and an increased arterial blood pressure. Aims. Our aim was to find out if single nucleotide polymorphisms (SNPs) within the SLC22A1, SLC22A2, and SLC22A3 genes encoding organic cation transporters (OCTs) associate with DN or hypertension. Subjects and methods. We selected 90 SNPs (≈1 SNP/4 kb) in and surrounding SLC22A1, SLC22A2, and SLC22A3 using the HapMap data. The SNPs were tested for association with DN and hypertension in 1,086 unrelated Finnish patients with type 1 diabetes mellitus (T1DM). Eight of the SNPs were genotyped in 1,252 additional Finnish patients to verify the findings. Results. We detected nominal evidence of association ( P < 0.05) between the SLC22A2 (SNPs rs653753, rs596881, and rs316019) and SLC22A3 (SNPs rs376563, rs2048327, rs2457576, and rs1567438) genes and DN and hypertension in Finnish men with T1DM. We were not, however, able to replicate the associations, and none of them reached the significance limit adjusted for multiple testing ( P < 0.00009). Conclusions. There was no clear association between the SLC22A1, SLC22A2, and SLC22A3 genes and DN or hypertension. Although several SLC22A2 and SLC22A3 SNPs indicated association, lack of association was evident after the replication study. [ABSTRACT FROM AUTHOR]

Background. Postmenopausal metabolic changes increase cardiovascular risk and impair quality of life (QoL). Despite this, few reports have addressed the association of these changes with female sexuality. Objective. To determine the association between the metabolic syndrome (METS), and its components, and female sexuality. Methods. Data of sexually active postmenopausal women who participated in a METS screening program who filled out the menopause-specific quality of life questionnaire (MENQOL) were assessed. Specifically the sexual domain of the MENQOL was analyzed in regard to mean total and item scores (decreased libido, vaginal dryness, and sexual avoidance). Criteria of the Third Adult Treatment Panel (ATP III) were used to identify women with the METS. Results. Two hundred six women fulfilled inclusion criteria. Mean age of participants was 54 ± 6.9 years (median: 54 years). Prevalence of the METS in this sexually active postmenopausal series was 39.8%. About 52.9% of them presented abdominal obesity, 35.4% hypertension, 55.8% high triglycerides, 17.5% hyperglycemia, and 59.7% decreased high density lipoprotein cholesterol (HDL-C). Women with the METS as compared with those without the syndrome displayed no significant differences in MENQOL sexual scorings (total or of its composing items). Equally there were also no score differences among those presenting any of the five components of the METS, except women with hyperglycemia who significantly displayed a higher total sexual domain score (5.6 ± 2.1 vs. 4.8 ± 2.3, p < 0.05) in association to a higher mean score in the decreased libido item (6.0 ± 2.3 vs. 4.8 ± 2.6, p < 0.01). After controlling for several confounding factors, logistic regression confirmed that women with hyperglycemia were significantly at higher risk for presenting decreased libido (higher item score, OR 2.4, CI 95%: 1.0–5.7, p < 0.05) and more impaired sexuality (higher total MENQOL sexual domain score: OR, 2.5, CI 95%: 1.1–5.4, p < 0.05). Conclusion. Despite the limitations of this study, as assessed with the MENQOL, hyperglycemia in postmenopausal women screened for the METS was associated to a negative impact in sexuality. More research is warranted in this regard. [ABSTRACT FROM AUTHOR]

Oxidative stress has been related increasingly to the onset and/or progression of a growing number of human diseases. However, large studies on supplementation with anti-oxidants for prevention or treatment of different pathologies have yielded contradictory and mostly negative results, as documented by numerous meta-analyses and clinical trials. Here we analyze in detail the findings of these studies and discuss major aspects that, in our opinion, are likely to be responsible for these confounding data. With the belief that a clear correlation between disease and oxidative stress is far from being proven for most pathological conditions, our argument focuses on the following points: i) choice of biomarker(s) and/or the biological system(s) for the analyses; ii) pitfalls in pre-analytical and analytical methods for assessing oxidative stress; and iii) scientific misconduct. Eventually, suggestions aiming to obtain more convergent results on this topic are provided. [ABSTRACT FROM AUTHOR]

Insulin is a vascular hormone, able to influence vascular cell responses. In this review, we consider the insulin actions on vascular endothelium and on vascular smooth muscle cells (VSMC) both in physiological conditions and in the presence of insulin resistance. In particular, we focus the relationships between activation of insulin signalling pathways of phosphatidylinositol-3 kinase (PI3-K) and mitogen-activated protein kinase (MAPK) and the different vascular actions of insulin, with a particular attention to the insulin ability to activate the pathway nitric oxide (NO)/cyclic GMP/PKG via PI3-K, owing to the peculiar relevance of NO in vascular biology. We also discuss the insulin actions mediated by the MAPK pathway (such as endothelin-1 synthesis and secretion and VSMC proliferation and migration) and by the interactions between the two pathways, both in insulin-sensitive and in insulin-resistant states. Finally, we consider the influence of free fatty acids, cytokines and endothelin on vascular insulin resistance. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to determine whether whole body hyperthermia (WBH) could reduce oxidative stress in the striatum produced by 3-nitropropionic acid (3-NP), a mitochondrial toxin that irreversibly inhibits succinate dehydrogenase (SDH), causing impairment of energy metabolism, oxidative stress and a selective degeneration of striatal cells. Methods: Rats were subjected to WBH (42°C) or normothermia control conditions for 30 min and then treated with 3-NP. Striatum samples were processed and the levels of protein carbonyl groups, biogenic amines, Hsp72 and salicylate hydroxylation (to probe the hydroxyl radical (OH•) intervention) were determined. Results: WBH significantly reduced oxidative stress in the striatum of animals treated with 3-NP, as judged by reductions in protein carbonyl and salicylate hydroxylation derivative levels, whereas striatal Hsp72 expression was significantly increased. The groups treated with 3-NP presented an increased in the dopamine (DA) derivatives 2,3-dihydroxyphenylacetic acid (DOPAC) and norepinephrine (NE) concentration, whereas the striatal relation DOPAC/DA concentration indicate a reduced dopamine turnover. Conclusions: These studies show, for the first time, that a heat shock pretreatment can ameliorate the oxidative stress produced by a metabolic toxin (3-NP) capable of impairing energy supply and produce selective striatal degeneration. These data contribute to a better understanding of the potential for thermal stress to modulate the type of oxidative stress usually present in neurodegenerative disorders associated with metabolic defects. [ABSTRACT FROM AUTHOR]

Glutathione is an intracellular antioxidant that often becomes depleted in pathologies with high oxidative loads. We investigated the provision of cysteine for glutathione synthesis to the human erythrocyte (red blood cell; RBC). Almost all plasma cysteine exists as cystine, its oxidized form. In vitro, extracellular cystine at 1.0 mM sustained glutathione synthesis in glutathione-depleted RBCs, at a rate of 0.206 ± 0.036 μmol (L RBC)-1min-1 only 20% of the maximum rate obtained with cysteine or N-acetylcysteine. In plasma-free solutions, N-acetylcysteine provides cysteine by intracellular deacetylation but to achieve maximum rates of glutathione synthesis by this process in vivo, plasma N-acetylcysteine concentrations would have to exceed 1.0 mM, which is therapeutically unattainable. 1H-NMR experiments demonstrated that redox exchange reactions between NAC and cystine produce NAC-cysteine, NAC-NAC and cysteine. Calculations using a mathematical model based on these results showed that plasma concentrations of N-acetylcysteine as low as 100 μM, that are attainable therapeutically, could potentially react with plasma cystine to produce ∼50 μM cysteine, that is sufficient to produce maximal rates of glutathione synthesis. We conclude that the mechanism of action of therapeutically administered N-acetylcysteine is to reduce plasma cystine to cysteine that then enters the RBC and sustains glutathione synthesis. [ABSTRACT FROM AUTHOR]

Virgin olive oil is a unique oil that can be consumed directly without any refining process. This particularity is due to the exceptional quality and flavour formed by the presence of more than 100 volatile compounds. Nine new hybrids obtained by controlled crossing of the Chemlali and seven ancient Mediterranean varieties cultivated in the same orchard under identical agronomic and pedoclimatic conditions were characterised by their main volatile compounds quantified by dynamic headspace-gas chromatography-MS. More than 40 volatile compounds from the main chemical groups, aldehydes, alcohols, ketones and esters, were identified by GC-MS and confirmed by their Linear Retention Index (LRI). Compounds produced from the lipoxygenase pathway were studied to determine the genetic potential and the influence on each crossing. Finally, Ward's method test and Pearson PCA analysis were used to check the ability of the volatiles to cluster the varietal virgin olive oils according to their genetics origin. [ABSTRACT FROM AUTHOR]

The Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular disease, and certain types of cancer. The apparent health benefits have been partially attributed to the dietary consumption of virgin olive oil by Mediterranean populations. Most recent interest has focused on the biologically active phenolic compounds naturally present in virgin olive oils. Studies (human, animal, in vivo and in vitro) have shown that olive oil phenolics have positive effects on certain physiological parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet and cellular function, and antimicrobial activity. Presumably, regular dietary consumption of virgin olive oil containing phenolic compounds manifests in health benefits associated with a Mediterranean diet. This paper summarizes current knowledge on the physiological effects of olive oil phenolics. Moreover, a number of factors have the ability to affect phenolic concentrations in virgin olive oil, so it is of great importance to understand these factors in order to preserve the essential health promoting benefits of olive oil phenolic compounds. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction plays an important role in the pathogenesis of hypertension. Other risk factors of atherosclerosis also affect its development. The aim of the study was to assess nitric oxide metabolites concentration (nitrites and nitrates Nox) and endothelin (ET-1) in plasma and cyclic 3,5-guanosine monophosphate (cGMP) in 24 h-urine collection in patients with noncomplicated hypertension without risk factors of atherosclerosis and in hypertensive patients with coronary artery disease (CAD). Sixty-eight subjects were included in the study (44 men, 24 women), aged 47 ± 76 years, allotted into four groups: I - controls (18 clinically healthy subjects); II - 12 subjects with hypertension without risk factors of atherosclerosis; III - 16 subjects with hypertension and risk factors of atherosclerosis; and IV - 22 subjects with hypertension and CAD. Plasma NOx concentration was determined using the Greiss method, plasma ET-1 by ELISA, and urine cGMP using the immunoenzymatic method. Plasma NOx concentration was 14.00 ± 6.88 μmol/L in group I, in group II - 18.62 ± 5.84 μmol, in group III - 9.96 ± 4.72 μmol/L, and in group IV - 8.78 ± 3.72 μmol/L. Statistically significant differences were between groups I and III (p < 0.05) and I and IV (p < 0.04) and groups II and III (p < 0.01) and II and IV (p < 0.01). The concentration of cGMP in 24 h urine collection was in group I - 40 ± 24 pmol/L; in group II - 54 ± 41 pmol/L; in group III - 38 ± 32 pmol/L; and in group IV - 42 ± 36 pmol/L. There were no significant differences between the groups. Plasma ET-1 concentration was 3.86 ± 0.52 pg/mL in group I, in group II - 4.05 ± 0.71 pg/mL, in group III - 4.22 ± 0.79 pg/mL and in group IV - 4.38 ± 0.75 pg/mL. Statistically significant differences were between group I and III (p < 0.05), I and IV (p < 0.03), and between group II and IV (p < 0.04). Endothelial dysfunction was not found in hypertensive patients without a family history of cardiovascular diseases and without other risk factors of atherosclerosis. Deterioration of endothelial function was observed in patients with hypertension with risk factors of atherosclerosis. It was most pronounced in those with CAD. [ABSTRACT FROM AUTHOR]

Inclusion of fiber in the diet has been linked to the prevention of a range of illnesses and conditions. This review contains several ideas about the possible benefits of dietary fiber intake in patients with metabolic syndrome. The principal beneficial effects of a fiber-rich diet in these patients are: prevention of obesity, improved glucose levels, and control of the profile of blood lipids. We now also know that dietary fiber may favor the control of arterial blood pressure. Animal experiments have also shown the benefit of different types of fiber on these variables. Of particular relevance are the studies using obese Zucker rats, which present similar anomalies to those seen in patients with metabolic syndrome. There is therefore a growing interest in discovering new sources of natural fiber. Some of these different kinds of fiber may then be used as functional ingredients to obtain foods with properties that are beneficial to health. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) associates with excess cardiovascular (CV) morbidity and mortality. Hypertension, a highly prevalent entity in RA, has been associated with the endothelin-1 (ET-1) gene locus (EDN1) in some groups, such as Afro-Caribbean, the obese, and in low-renin states, but not in the general population as a whole. High levels of plasma ET-1 have been observed in RA. This study evaluated the potential association of EDN1 gene locus and serum ET-1 levels with hypertension in patients with RA. Genomic DNA and serum samples were collected from 397 well-characterized RA patients; DNA was also available from 401 local general population controls without RA. To explore the overall relevance of EDN1, two suitable single-nucleotide polymorphisms (SNPs), rs1800541 and rs5370, were selected and haplotype analysis was performed. Both SNPs were identified using real-time polymerase chain reaction (PCR) and melting curve analysis. Genetic analysis was related to hypertension as dichotomous trait and to blood pressure indices as continuous variables. Serum endothelin levels were also assessed in the RA patients. No genotype or haplotype differences were observed between RA and control subjects. Within RA, logistic regression analysis of each SNP separately revealed a threefold increase in the adjusted odds of being hypertensive of rs5370 TT homozygotes compared to GG homozygotes (OR = 2.89, 95%CI: 1.02 to 8.19). After adjustment for multiple potential confounders, haplotype analysis revealed an additive effect of the rs1800541-rs5370 T-T haplotype on hypertension (OR = 2.96, 95%CI: 1.28 to 6.86; p = .011), systolic blood pressure (SBP) (β = 6.75 ± 2.57 mm Hg; p = .009), and pulse pressure (PP) (β = 4.37 ± 2.12 mm Hg; p = .040). There was an increased prevalence of raised ET-1 levels amongst hypertensive RA patients, whereas a similar trend was observed for T-T haplotype carriers. RA patients who carry the rs1800541-rs5370 T-T EDN1 haplotype appear more likely to be hypertensive with an increased SBP and PP. These findings, if replicated in future studies, could be used as a screening tool for RA patients at increased hypertension, and thus cardiovascular, risk. [ABSTRACT FROM AUTHOR]

The two possibilities to explain the pathogenic basis of stiff-person syndrome (SPS) are intrathecal sensitization of GAD65-reactive CD4+T cells and synthesis of GAD65-specific autoantibodies within the CNS [Rakocevic et al., Arch. Neurol. 61: 902-904, 2004]; and peripheral antigen sensitization followed by CNS antigen recognition by autoantibodies that cross the blood-brain barrier. Antigen-specific CD4+ T cells are essential for the generation of high-affinity autoantibodies [Lanzavecchia, Nature 314: 537-539, 1985], but there is no evidence of cellular infiltration in the CNS of SPS patients [Warich-Kirches et al., Clin. Neuropathol. 16: 214-219, 1997; Ishizawa et al., Acta Neuropathol.(Berl) 97: 63-70, 1999]. This review discusses the possible role of autoantibodies and autoreactive T cells specific to neuronal antigens in SPS pathogenesis. [ABSTRACT FROM AUTHOR]

Reduced glutathione (L-γ-glutamyl-L-cysteinyl-glycine, GSH) is the prevalent low-molecular-weight thiol in mammalian cells. It is formed in a two-step enzymatic process including, first, the formation of γ-glutamylcysteine from glutamate and cysteine, by the activity of the γ-glutamylcysteine synthetase; and second, the formation of GSH by the activity of GSH sythetase which uses γ-glutamylcysteine and glycine as substrates. While its synthesis and metabolism occur intracellularly, its catabolism occurs extracellularly by a series of enzymatic and plasma membrane transport steps. Glutathione metabolism and transport participates in many cellular reactions including: antioxidant defense of the cell, drug detoxification and cell signaling (involved in the regulation of gene expression, apoptosis and cell proliferation). Alterations in its concentration have also been demonstrated to be a common feature of many pathological conditions including diabetes, cancer, AIDS, neurodegenerative and liver diseases. Additionally, GSH catabolism has been recently reported to modulate redox-sensitive components of signal transduction cascades. In this manuscript, we review the current state of knowledge on the role of GSH in the pathogenesis of human diseases with the aim to underscore its relevance in translational research for future therapeutic treatment design. [ABSTRACT FROM AUTHOR]

The effect of sulfur dioxide (SO2) on hippocampus antioxidant status, lipid peroxidation and learning and memory was investigated in diabetic rats. A total of 40 rats were divided into four equal groups: Control (C), SO2 + C (SO2), diabetic (DM) and SO2 + D (DMSO2). Experimental diabetes mellitus (DM) was induced by i.v injection of alloxan with a dose of 50 mg/kg body weight. Ten ppm SO2 was administered to the rats in the sulfur dioxide groups in an exposure chamber. Exposure occurred 1 h/d, 7 d/wk, for 6 wk; control rats were exposed to filtered air during the same time periods. SO2 exposure, while markedly increasing Cu-Zn Superoxide dismutase activity, significantly decreased glutathione peroxidase activity in diabetic and non-diabetic groups compared with the C group; hippocampus catalase activity was unaltered. Hippocampus thiobarbituric acid reactive substances (TBARS) were found to be elevated in all experimental groups with respect to control group. The active avoidance training results indicated that diabetic condition has been associated with learning and memory impairment. SO2 exposure caused deficits of learning and memory. Diabetes mellitus-induced impairment of learning and memory were potentiated by SO2 exposure. These findings suggest that exposure to SO2 by increasing lipid peroxidation, can change antioxidant enzyme activities and can elevated intensity of deficits of learning and memory in diabetic rats. [ABSTRACT FROM AUTHOR]

This study aimed to further analyse the potential role of oxidative stress in children and adolescents with type 1 diabetes at clinical onset, during disease progression and when early microvascular complications ( + DC) appeared. Compared with age-matched controls, diabetic patients had greater oxidative damage to lipids, proteins and DNA demonstrated by analysis of plasma and erythrocyte malondialdehyde, carbonyl proteins and leukocyte 8-hydroxy-deoxyguanosine, all of which were significantly raised at onset, decreased during the first 1.5 years of evolution and rose progressively thereafter. Plasma lipid levels were significantly associated with lipid and protein oxidation products. Erythrocyte glutathione and glutathione-peroxidase activity were significantly decreased with the lowest values at onset and in + DC sub-groups. Insulin therapy in the first year improved metabolic and oxidant-antioxidant status and, consequently, hyperglycaemia-derived biomolecular oxidative damage. Diabetes-associated hyperlipidaemia is related to lipid and protein oxidation, thereby supporting the concept of glucotoxicity and lipotoxicity being inter-related. The overall increase in lipid, protein and DNA oxidative damage in diabetic patients with microangiopathy could be pathogenetically relevant in the early development of diabetes-related complications. [ABSTRACT FROM AUTHOR]

Diabetes mellitus has assumed epidemic proportions in most parts of the world, and it is a major source of morbidity in developed countries. In addition, in several instances, diabetes is associated with a variety of metabolic abnormalities, including abdominal obesity, insulin resistance, hypertension, dyslipidemia, and hyperglycemia. There is considerable evidence that hyperglycemia causes the generation of reactive oxygen species (ROS), ultimately leading to increased oxidative stress in a variety of tissues. In the absence of an appropriate compensatory response by the endogenous antioxidants, such as vitamins C and E, catalase, glutathione, and superoxide dismutase, oxidative stress dominates, resulting in the activation of stress-sensitive intracellular signaling pathways. One of the major consequences is the generation of gene products that cause cellular damage and are ultimately responsible for the late complications of diabetes. The ability of antioxidants to protect against the effects of hyperglycemia in vitro, along with the clinical benefits often reported following antioxidant therapy, supports a causative role of oxidative stress in mediating and/or worsening these abnormalities. This review will focus on the critical assessment of the literature as it relates to the association between oxidative stress and diabetes, followed by the role of oxidative stress in the complications of type 2 diabetes mellitus. Finally, a review of the use of the antioxidant vitamin E will be provided in diabetic patients by assessing and evaluating some of the clinical trials in the literature. [ABSTRACT FROM AUTHOR]

The work evaluated the use of a bioreactor for the enzymatic transesterification of oilseed. Rhizopus oryzae resting-cells, isolated from Foeniculum vulgare Fennel, were used as a biocatalyst. The bioreactor consisted of two glass-jacketed flasks, interconnected by a circuit using isooctane as a solvent, which was recirculated with the help of a peristaltic pump. The system enabled the extraction and hydrolysis of triacylglycerides (TAG), and the subsequent esterification of the free fatty acids formed (FFA). Esterification was carried out by the addition of alcohol using a peristaltic pump. This reactive extraction of vegetable oil was optimized for sunflower seeds using 4-hydroxymethyl-2,2-dimethyl-1,3-dioxolane (solketal) as alcohol. Subsequently, a variety of oil seeds and alcohols were tested. Final ester conversions ranged from 84 to 98% depending on the alcohol and the oilseed used. [ABSTRACT FROM AUTHOR]

There is evidence that oxidative stress might be implicated in promoting a state of systemic inflammation in diabetic patients. Understanding the role of reactive oxygen species in the inflammatory response in diabetes becomes essential in finding preventive treatments. Pioglitazone is a new oral antidiabetic agent with potent antioxidant and anti-inflammatory properties. The drug is a high affinity ligand of peroxisome proliferator-activated receptor gamma. This receptor seems to be involved in the control of inflammation by modulating the production of inflammatory mediators. In the present study, the changes in some markers of enhanced oxidative stress and in the level of pro-inflammatory interleukin-6 (IL-6) were examined in plasma of diabetic rabbits after 4 and 8 weeks of pioglitazone treatment. Ascorbic acid (AA) concentration and total antioxidant status (TAS) in plasma of diabetic animals were diminished and significantly elevated after pioglitazone treatment (p [ABSTRACT FROM AUTHOR]

In patients on chronic hemodialysis the prevalence of atherosclerosis is increased and is by far the leading cause of morbidity and mortality. Endothelin-1, an endothelium-derived peptide with vasoconstrictive and mitogenic effects on vascular smooth muscles, is involved in the pathogenesis of atherosclerosis. The aim of the present study was to investigate the time course of plasma endothelin-1 levels during a hemodialysis session and to explore the influence of preexisting type 2 diabetes mellitus. Forty-five clinically stable hemodialysis patients (21 females, 24 males; mean age 62 ± 12 years) were evaluated. Patients with type 2 diabetes (n = 11) were compared with the group of patients without diabetes (n = 34). Relative blood volume (BV) changes (hemoglobinometry) and blood pressure (BP) was measured. Samples were taken before, every hour during, and after hemodialysis. Plasma endothelin-1 levels were measured by enzyme-linked immunoassay (ELISA) and results were corrected according to hemoconcentration. Hemodialysis with an ultrafiltration of 2215 ± 952 mL was performed. Total BV at the end of hemodialysis was 89.3% ± 8.3% of the pretreatment volume. Plasma endothelin-1 was enhanced in hemodialysis patients compared to normal subjects and increased from 1.28 ± 0.47 before to 1.44 ± 0.54 pg/mL (ref. 0.3–0.9) at the end of hemodialysis ( p [ABSTRACT FROM AUTHOR]

Systemic hyperinsulinemia induces enhancement of endothelium-dependent vasodilation of healthy subjects. During systemic infusion of insulin, endothelium-dependent vasodilation may be improved through a decrease in the concentration of free fatty acids. To explore the direct effect of continued insulin on the vascular endothelium, the authors infused insulin in the brachial artery for 4 h and measured the effect on endothelium-dependent vasodilation in the human forearm. Thirty-six experiments were performed in healthy subjects, mean age 47.7 ± 1.1 years. Endothelium-dependent and -independent vasodilatation was studied during intra-arterial infusion of serotonin and sodium nitroprusside (SNP), respectively. Forearm blood flow was measured by plethysmography. Intra-arterial insulin was infused for 240 min at a constant rate and blood flow was measured hourly during stimulation of endothelium-dependent and-independent vasodilation. NG-monomethyl-L-arginine (L-NMMA) was coinfused to test the degree of nitric oxide (NO)-mediated vasodilation. Insulin infusion for 60 min enhanced serotonin-induced vasodilation by 37% compared to vehicle, p = ⋅ 016. This increase was maintained for 4 h and was blocked by L-NMMA. The SNIP response was increased by insulin but the increment was inhibited by L-NMMA. Four hours of local forearm hyperinsulinemia causes a sustained increase in endothelium dependent vasodilation in resistance vessels, which is mediated by NO. [ABSTRACT FROM AUTHOR]

In essential hypertension (EH) patients, blood pressure can modify serum concentrations of some soluble forms of cell adhesion molecules (CAM), e.g., soluble E-selectin (sE-selectin) and soluble vascular cell adhesion molecule-1 (sVCAM-1). The objective of this study was to compare the serum levels of these CAMs in compensated (CH) and non-compensated (NCH) EH patients. Our findings show that sE-selectin and sVCAM-1 levels are higher in EH patients than normotensive subjects (sVCAM-1: 796 ± 52 vs. 605 ± 24 ng/mL, p < 0.0001, and sE-selectin: 71 ± 21 vs. 48 ± 14 ng/mL, p < 0.0001). Serum concentrations of both CAMs was higher in NCH patients than CH patients. High arterial blood pressure (ABP) may therefore increase the production of cell adhesion molecules, probably through endothelial activation. [ABSTRACT FROM AUTHOR]

Many growth factors are implicated in the pathogenesis of proliferative diabetic retinopathy. Alteration of growth factors and their receptors in diabetes has been shown in both experimental and clinical studies. Sustained hyperglycemia resulting from long-standing diabetes leads to several biochemical abnormalities that consequently result in retinal hypoxia. Retinal oxygenation state regulates various growth factors that promote angiogenesis in order to meet the oxygen demands of the tissue. However, unregulated expression of these growth factors and induction of complex cascades leading to augmentation of other proangiogenic factors, which may not be regulated by tissue oxygenation, leads to uncontrolled retinal neovascularization and blindness in diabetic patients. [ABSTRACT FROM AUTHOR]

We are applying a dynamic systems biology approach to the development of several phenolic phytochemicals in food-grade plants as ingredients for functional food applications. Phenolic antioxidant phytochemicals from food-grade plants will be an important part of a healthy diet in a global population that is projected to reach 9 billion in the next 50 years. Such phytochemicals are being targeted for designing conventional foods with added health benefits (functional foods). Such value-added foods are needed for dietary support to manage major oxidation-linked diseases, such as diabetes, cardiovascular disease, arthritis, cognition diseases and cancer. Plants produce phenolic metabolites as a part of growth, developmental and stress-adaptation response. These stress and developmental-modulated phenolic phytochemicals can be targeted for the design of functional foods. In order to design consistent food-grade phytochemical profiles for safety and clinical relevancy, novel tissue culture and bioprocessing technologies have been developed. The strategy for designing these phenolic phytochemicals is based on the model that phenolic metabolites in plants are efficiently produced through an alternative mode of metabolism that links proline synthesis to activity of the pentose-phosphate pathway. Using the proline-linked pentose-phosphate pathway model, techniques have been developed to isolate high phenolic clonal lines of food-grade plants from single heterozygous seeds. Further, using the same model, elicitation concepts and techniques have been applied to over-produce phenolic metabolites in seeds and sprouts. In both clonal and seed sprout systems, exogenous treatment of phenolic phytochemicals from a non-target species elicited endogenous stimulation of phenolic synthesis and, potentially, an antioxidant response. From these investigations, a hypothetical model has been proposed in which the proline-linked pentose-phosphate pathway is critical for modulating... [ABSTRACT FROM AUTHOR]

The diabetic state confers an increased propensity to accelerated atherogenesis. In addition to the established risk factors, there is evidence for increased oxidative stress and inflammation in diabetes. Increased oxidative stress is manifested by increased lipid peroxidation (e.g. increased F 2 -isoprostanes) and increased DNA damage. Evidence for increased inflammation includes increased monocyte superoxide and pro-inflammatory cytokine release (IL-1, IL-6, and TNF-α), increased monocyte adhesion to endothelium and increased levels of plasma C-reactive protein, the prototypic marker of inflammation. Most importantly, alpha tocopherol therapy, especially at high doses, clearly shows a benefit with regards to LDL oxidation, isoprostanes and a decrease in inflammatory markers such as C-reactive protein, pro-inflammatory cytokines and PAI-1 levels. Thus, it appears that, in diabetes, alpha tocopherol therapy could emerge as an additional therapeutic modality. [ABSTRACT FROM AUTHOR]

Endothelin (ET) peptides perform several physiological, vascular, and nonvascular functions and are widely distributed in a number of tissues. They are altered in several disease processes including diabetes. Alteration of ETs have been demonstrated in organs of chronic diabetic complications in both experimental and clinical studies. The majority of the effects of ET alteration in diabetes are due to altered vascular function. Furthermore, ET antagonists have been shown to prevent structural and functional changes induced by diabetes in animal models. This review discusses the contribution of ETs in the pathogenesis and the potential role of ET antagonism in the treatment of chronic diabetic complications. [ABSTRACT FROM AUTHOR]

Production of human monoclonal autoantibodies to glutamic acid decarboxylase M r 65,000 (GAD 65 ), characterization of their isotype, binding affinity, V region sequences and competition with autoantibodies in patients' sera is described. Lymphocytes from a patient with Addison's disease who had GAD 65 autoantibodies without diabetes were immortalised and fused to a mouse/human hybridoma. In addition, mouse monoclonal antibodies to GAD 65 were produced using standard techniques. F(ab′) 2 s from our monoclonals and the GAD6 mouse monoclonal were used in competition with intact monoclonals and sera from diabetic patients for binding to 125 I-labelled GAD 65 (amino acids 46-586). Reactivities of the human monoclonals with GAD 65,000/67,000 M r chimeras were also studied. Variable region genes of human monoclonals were sequenced and analysed. The human monoclonals ( n =3) had affinity constants for GAD 65 of 2.2×10 9 , 5.8×10 9 , 1.3×10 10 mol/l -1 ; affinities of the mouse monoclonals ( n =5) ranged from 1.1×10 8 to 5.4×10 10 mol/l -1 . The binding of each of the human monoclonals was inhibited by GAD6 F(ab′) 2 and the binding of GAD6 antibody was inhibited by the human monoclonal F(ab′) 2 s suggesting that the epitopes for these antibodies were overlapping. Studies with GAD 65 /GAD 67 chimeras indicated that the human monoclonals reacted with C-terminal epitopes. The human monoclonals, GAD6 and 3/5 mouse monoclonals inhibited serum autoantibody binding to 125 I-labelled GAD 65 . Overall, the human monoclonals were of high affinity, reacted with C-terminal epitopes and showed evidence of antigen driven maturation; they represented only a proportion of the repertoire of autoantibodies to GAD 65 in the donor's serum and in the sera of patients with type-1 diabetes. [ABSTRACT FROM AUTHOR]

Hypertension and obesity are risk factors for coronary heart diseases in adults. In turn, childhood overweight and high blood pressure increase the risk of subsequent obesity and hypertension in adulthood. Human obesity is characterized by profound alterations of hemodynamic and metabolic states. Whether these alterations involve sympathetic nervous system control on cardiac function is controversial. We report the results of our study, conducted in a sample of obese adolescents by using power spectral analysis of heart rate variability. An increase in sympathetic tone coupled with a reduction in vagal tone was found. This allowed us to hypothesize that autonomic nervous system changes depend on the time course of obesity development. It is still unclear if treatment of obesity in adolescence prevents subsequent autonomic imbalance and hypertension. [ABSTRACT FROM AUTHOR]

To evaluate oxidative stress in type I diabetes mellitus, two antioxidant enzymes in erythrocytes, copper-zinc superoxide dismutase (SOD EC 1.15.1.1.) and seleno-dependent glutathione peroxidase (GSH-Px; EC 1.11.19), and two indexes of peroxidation in plasma, thiobarbituric acid reactive substances (TBARS) and organic hydroperoxides (OHP), were measured in 118 patients with insulin-dependent diabetes mellitus (IDDM), classified in accordance with the presence or absence of vascular complications and the degree of metabolic control established by the HbA1c level. Ninety healthy subjects made up the control group. According to our results, plasmatic TBARS and OHP concentrations are significantly higher in diabetics than in controls, and these differences are accentuated in diabetic people with vascular disorders. The GSH-Px activity was significantly reduced in diabetic patients with poor and medium metabolic control in relation to the control group, regardless of the existence or absence of vascular disorders. No differences in SOD activity between diabetic and control groups were found. A significant positive correlation between TBARS and HPO (r=0.683, p<0.001) was found in both the control and diabetic groups. Among the lipid parameters studied, there were only significantly positive correlations between TBARS and total cholesterol; TBARS and tryglicerides; OHP and total cholesterol and OHP and tryglicerides. Positive correlations between TBARS and HbA1c and between OHP and and HbA[sub 1c], and negative correlations between GSH-Px and HbA[sub 1c] and between SOD and HbA1c were also found. The multiple regression analysis shows that TBARS and HPO correlate negatively with GSH-Px. There was no significant correlation with SOD. [ABSTRACT FROM AUTHOR]

Reviews aspects of past, present and future potential of oxidants and antioxidants in clinical medicine. Observation that antioxidants help to defend against cellular lipid peroxidation and lipofuscin and ceroid pigment formation; Epidemiological and clinical intervention information; Development of a new, comprehensive model for viewing oxidants and antioxidants in clinical context.

PURPOSE. To examine the effect of elevated extracellularglucose, thus simulating diabetes, on migration, adhesion and proliferationof SV40 transformed human corneal epithelial (HCE) cells. METHODS. HCE cells were maintained in serum supplemented media containing5 mM, 17.5 mM or 38 mM D-glucose. Cell migration was determined using Blindwell chambers fitted with fibronectin/collagen I coated filters. In adhesionexperiments, cells were allowed to adhere to extracellular matrix protein-coatedwells for 90 min at 37°C. Non-adherent cells were removed by washing,then the fluorochrome calcein-AM was added to quantitate the number of attachedcells. Proliferation was determined by plating the cells at low density, thenquantitating viable cells with calcein-AM 5 to 7 days later. RESULTS. Raising extracellular glucose from 5 mM to 17.5 mM significantlyincreased cell migration by 42%. When glucose was further raised to 38 mM,migration was not significantly different from that in 5 mM glucose. Adhesionto fibronectin and collagen I (but not IV) was significantly increased (62%and 32% respectively) when cells were cultured in 17.5 mM glucose. Similarly,proliferation was increased by 44%. Adhesion and proliferation tended to bedecreased at 38 mM compared to 17.5 mM glucose, but not significantly so.In the presence of 5 mM glucose and mannitol (12.5 mM or 33 mM), neither migration,adhesion nor proliferation were significantly different from that in 5 mMglucose alone. CONCLUSION. Elevated extracellular glucose modulates migration, adhesionand proliferation of HCE cells. The effects are dependent on the concentrationof glucose and are not due to changes in osmolality since mannitol failedto produce similar results. Our in vitro findings suggest that high-glucoseeffects may directly contribute to the etiology of impaired corneal woundhealing in diabetes. [ABSTRACT FROM AUTHOR]