Speckle tracking can detect subclinical myocardial dysfunction in rheumatoid arthritis patients.

INTRODUCTION: Patients with rheumatoid arthritis (RA) have shorter life expectancy and their risk of cardiovascular death is more than 50 % higher than the rest of the population. Early myocardial dysfunction in RA patients may be detectable sooner using speckle­tracking echocardiography. METHOD: Cross-sectional study enrolled 55 patients with RA (mean age 44.1 years) without known cardiovascular disease and 31 healthy controls. All subjects underwent a standard echocardiographic examination: indexed left ventricular mass, left ventricle ejection fraction, isovolumic contraction and relaxation times (IVCT and IVRT), mitral valve inflow curve (E/A), septal mitral annular motion (e'), and E/e' ratio as well as the speckle tracking assessment of left ventricle longitudinal, radial and circular strain and strain rate. RESULTS: In standard echocardiographic examination RA patients exhibited higher indexed left ventricle mass (96.36±20.90 g/m2 vs 95.84±21.86 %, p=0.013), lower ejection fraction (64.84±3.87 % vs 67.10±3.87 %, p=0.011) and prolonged IVCT (61.51±9.30 ms vs 53.71±8.95 ms, p=0.001). Diastolic dysfunction was demonstrated by prolonged IVRT (81.62±9.56 ms vs 74.58±12.02 ms, p=0.007) as well as by higher E/e' ratio (8.21±1.76 vs 7.21±1.52, p=0.009). Speckle­tracking method detected lower global longitudinal epicardial strain (-19.51 % vs -21.46 %, p=0.049). Radial, circular, and transversal strains and strain rates were same in both groups. Global longitudinal epicardial strain correlated with IVCT and IVRT, disease duration, and markers of myocardial damage NTproBNP. CONCLUSIONS: Standard echocardiographic assessment of myocardial function is examiner- and angle-dependent method with considerable limitations for evaluation of minimal subclinical changes. Speckle-tracking echocardiography significantly revealed incipient myocardial dysfunction in RA patients without overt cardiovascular diseases. This correlates with clinical RA characteristics and markers of cardiac damage (Tab. 4, Ref. 48).

The effect of bioactive complex of quercetin, selenium, catechins and curcumin on cardiovascular risk markers in healthy population after a two month consumption.

BACKGROUND: Nutrition is an important factor in prevention of degenerative age-related diseases. Health benefits of the functional food - cereal selenized onion biscuits with bioactive complex such as selenium in organic form, quercetin (onion), curcumin (curcuma) and catechins (green tea) were evaluated. METHODS: In a group of randomly selected 50 apparently healthy men, aged 30-50 years, the levels of total cholesterol, HDL-cholesterol, C-reactive protein (hs-CRP), homocysteine (HCy) and its nutritional determinants (methionine, vitamin B12, folic acid, cysteine, vitamin B6) and asymmetric dimethylarginine (ADMA) were measured and the LDL cholesterol and atherogenic index was calculated before and after a 2-month consumption period and after a 2-month wash-out period. RESULTS: The significant reduction of total cholesterol, LDL-cholesterol, atherogenic index, HCy and ADMA was found after onion biscuit consumption. Alternative pathway for HCy degradation using betaine as methyl donor is probably a sole argument for reduced HCy value at the significantly reduced concentrations of the methionine, folic acid, cysteine and vitamin B6. Value of hs-CRP was non-significantly reduced after biscuit consumption. CONCLUSION: The results of improved lipid profile, significantly reduced values of HCy and ADMA document a beneficial effect of cereal biscuit with selenized onion, curcuma and green tea in prevention of cardiovascular disease (Tab. 2, Ref. 19).

Supplementation-induced change in muscle carnosine is paralleled by changes in muscle metabolism, protein glycation and reactive carbonyl species sequestering.

Carnosine is a performance-enhancing food supplement with a potential to modulate muscle energy metabolism and toxic metabolites disposal. In this study we explored interrelations between carnosine supplementation (2 g/day, 12 weeks) induced effects on carnosine muscle loading and parallel changes in (i) muscle energy metabolism, (ii) serum albumin glycation and (iii) reactive carbonyl species sequestering in twelve (M/F=10/2) sedentary, overweight-to-obese (BMI: 30.0+/-2.7 kg/m2) adults (40.1+/-6.2 years). Muscle carnosine concentration (Proton Magnetic Resonance Spectroscopy; 1H-MRS), dynamics of muscle energy metabolism (Phosphorus Magnetic Resonance Spectroscopy; 31P-MRS), body composition (Magnetic Resonance Imaging; MRI), resting energy expenditure (indirect calorimetry), glucose tolerance (oGTT), habitual physical activity (accelerometers), serum carnosine and carnosinase-1 content/activity (ELISA), albumin glycation, urinary carnosine and carnosine-propanal concentration (mass spectrometry) were measured. Supplementation-induced increase in muscle carnosine was paralleled by improved dynamics of muscle post-exercise phosphocreatine recovery, decreased serum albumin glycation and enhanced urinary carnosine-propanal excretion (all p<0.05). Magnitude of supplementation-induced muscle carnosine accumulation was higher in individuals with lower baseline muscle carnosine, who had lower BMI, higher physical activity level, lower resting intramuscular pH, but similar muscle mass and dietary protein preference. Level of supplementation-induced increase in muscle carnosine correlated with reduction of protein glycation, increase in reactive carbonyl species sequestering, and acceleration of muscle post-exercise phosphocreatine recovery.

Short term oxidative DNA damage by hyperbaric oxygenation in patients with chronic leg ulcers.

INTRODUCTION: Hyperbaric oxygen therapy (HBO) is successfully used for the treatment of a variety of conditions and diseases. HBO therapy can be valuable for treating selected cases of hypoxic diabetic leg ulcers and chronic venous insufficiency. Exposure to high concentration of oxygen is known to induce damage to cells, possibly due to an increased oxygen radical production. Reactive oxygen species also cause DNA damage. METHOD: The Comet assay method has been used to determine DNA damage. Number of DNA strand breaks obtained by the single cell gel electrophoresis in nucleuses of lymphocytes was isolated from venous blood. Nucleuses of lymphocytes were incubated by bacterial repair endonucleases, which detect and remove damaged parts of DNA (SBs, FPG, AlcA, ENDO, and H2O2). MATERIAL: 27 patients were investigated in this study; diabetes mellitus was diagnosed in 15 of them, and chronic venous insufficiency in 12. They were exposed in average 27 times in a hyperbaric chamber to a pressure of 2.5-3ATA of 100 % oxygen. Lymphocytes were isolated from venous blood before treatment and at different time after treatment (24 hours, 7 days, 14 days, 6 weeks). RESULTS AND CONCLUSION: Results of DNA damage evaluation at different time periods suggest there are no significant changes if compared to initial DNA damage values. HBO treatment can be used as adjuvant treatment because no significant risk is manifested with this therapy (Tab. 1, Fig. 7, Ref. 52).

Selected biomarkers of age-related diseases in older subjects with different nutrition.

BACKGROUND: The nutritionists introduce on the base of epidemiological and clinical studies that appropriately planned vegetarian diets are healthful, and may provide health benefits in the prevention and treatment of certain diseases. Aging belongs to the main risks of cardiovascular disease. METHODS: Markers of age-related diseases (cardiovascular, metabolic syndrome, diabetes) were assessed in two nutritional groups of older apparently healthy non-obese non-smoking women aged 60-70 years, 45 vegetarians (lacto-ovo-vegetarians and semi-vegetarians) and 38 non-vegetarians (control group on a traditional mixed diet, general population). RESULTS: Vegetarian values of total cholesterol, LDL-cholesterol, triacylglycerols, C-reactive protein, glucose, insulin and insulin resistance are significantly reduced. Non-vegetarian average values of total cholesterol, LDL-cholesterol and C-reactive protein are risk. Vegetarians have a better antioxidative status (significantly increased vitamin C, lipid-standardized vitamine E and beta-carotene plasma concentrations). CONCLUSION: Favourable values of cardiovascular risk markers in older vegetarian women document a beneficial effect of vegetarian nutrition in prevention of this disease as well as the vegetarian diet can be an additional factor in therapy. Vegetarians suffer from mild hyperhomocysteinemia; it is due to the lower vitamin B12 concentration. Vitamin B12 supplements are inevitable for the hyperhomocysteinemia prevention (Tab. 2, Ref. 26).

HSP60, oxidative stress parameters and cardiometabolic risk markers in hypertensive and normotensive Slovak females.

BACKGROUND: The aim of our study was to analyse the relationships between hypertension, HSP60, oxidative stress, lipid profile and cardiometabolic risk in 126 females with arterial hypertension (AHW) and 39 normotensive females (AH-). RESULTS: Females with AH+ were significantly older and more frequently suffered from ischemic heart disease, angina pectoris, prior MI, abdominal obesity, obesity, metabolic syndrome and diabetes mellitus. On the other hand, normotensive females smoked significantly more often. Plasma levels of HSP60 were similar in both AH+ and AH- groups. However, hypertensive females exhibited almost two times lower values of oxidative glutation and lower levels of carbonyl protein, but significantly higher levels of homocysteine. In normotensive females, the total glutathione was the only parameter predicting females with the plasma level of HSP60 = 60 ng/ml. The independent predictors in hypertensive females were angina pectoris, triglycerides and the mean arterial pressure (MAP). MAP had also a borderline significance in normotensive females suggesting an association between HSP60 and blood pressure. MAP formed a J shaped curve with HSP60. CONCLUSION: Results suggest the association of blood pressure and heart shock protein 60 Kda in form of the J curve (Tab. 11, Fig. 3, Ref. 29).

MCP-1 -2518 A/G gene polymorphism is associated with blood pressure in ischemic heart disease asymptomatic subjects.

Monocyte chemoattractant protein-1 (MCP-1), one of the key inflammatory chemokines, plays an important role in the initiation of atherosclerosis, and represents a risk for coronary artery disease and myocardial infarction. A recent animal study showed that MCP-1 gene might be a candidate gene for salt-sensitive hypertension in Dahl salt sensitive rats. This effect has not been yet studied in asymptomatic humans. We tested the MCP-1 -2518 A/G single nucleotide polymorphism (SNP) in 66 hypertensive ischemic heart disease asymptomatic subjects. Inflammatory markers, classic risk factors and absolute cardiovascular risk (SCORE system) were also investigated in these subjects. Our results showed that both, systolic and diastolic values of blood pressure were associated with MCP-1 -2518 A/G SNP at the level of both, genotype and allele frequencies. Subjects with mutant G allele had higher levels of both values of blood pressure, systolic (p = 0.035) and diastolic (p = 0.040) than subjects with allele A. Statistically significantly higher levels of both values of blood pressure, systolic (p = 0.037) and diastolic (p = 0.021) were found also in IHD asymptomatic subjects with AG and GG genotypes. Subjects with AG and GG genotypes had also an increased absolute cardiovascular risk (1.62% vs 3.17%; p = 0.004) and an increasing trend for elevated plasma level of high-sensitive CRP (2.858 vs 2.062 mg/l; p = 0.076). We did not find any significant correlation between the serum level of MCP-1 and blood pressure. To our best knowledge, this is the first study concerning the association between MCP-1 polymorphism and arterial blood pressure in IHD asymptomatic subjects. These results indicate that the expression of MCP-1 may be increased before the onset of hypertension but further observations from larger cohorts are needed to confirm this finding (Tab. 6, Ref. 41).

Evaluation of alternative calculation methods for determining LDL cholesterol.

BACKGROUND: Due to limitations of the Friedewald formula, alternative methods for calculating low-density lipoprotein cholesterol (LDL-C) were suggested. We evaluated utility of these methods. METHODS: Ninety three subjects free of coronary heart disease were considered. LDL-C was measured by the homogeneous method, and calculated by the Friedewald formula LDL-C = TC-HDL-(TG/2.2) (LDL1) and alternative formulas LDL-C = 0.41 TC - 0.32 TG + 1.70 apoB - 0.27 (LDL2) and LDL-C = 0.94 TC - 0.94 HDL - 0.435 TG (LDL3). RESULTS: All three formulas underestimated the measured LDL-C, both in the whole group and in subgroups according to TG levels (TG < 1.7 and in a range of 1.7-4.5 mmol/l, p < 0.001 for all). We found significantly higher bias for all three formulas in subjects with 1.7 < or = TG < 4.5 mmol/l levels. The Friedewald formula showed the lowest assay bias in all the groups investigated. The mean absolute bias for LDL1 was 7.6%, 18.3% for LDL2 and 13.6% for LDL3, respectively. Linear regression analysis showed correlation of calculated LDL-C values with the direct method in the range of r = 0.82 - 0.90 (p < 0.0001 for all, except of LDL2 in 1.7 < or = TG < 4.5 mmol/l group where p = 0.0011). CONCLUSIONS: The Friedewald formula seems to be a better estimator of LDL-C in our study than the other two alternative formulas; however, it underestimated the LDL-C levels.

The redox state of glutathione in erythrocytes of individuals with Down syndrome.

BACKGROUND: The redox state of glutathione has been used as indicator for the redox environment of the cell. OBJECTIVES: To investigate relationships between the redox environments, the SOD activity, total antioxidant status and the oxidation stress markers production (MDA and lipofuscin). METHODS: Individuals with Down syndrome and age-matched healthy controls were enrolled into a study. Some parameters of oxidative stress in serum were determined: reduced glutathione, oxidized glutathione, redox potential of this couple (Eh), activity of superoxide dismutase in the red blood cells as well as malondialdehyde and lipofuscin. RESULTS: In the group of persons with DS statistically significant decrease in the GSH concentration was found, however, no differences in the GSSG concentration versus controls was observed. The redox potential values for couple GSH/GSSG are a statistically significantly increased in DS individuals compared to controls. CONCLUSION: In this study we highlighted the different ways of view at the role of GSH in metabolism of persons with DS. It is useful to look at the GSH and GSSG concentrations separately as well as at redox potential value, which influence total redox state of organism (Tab. 2, Fig. 3, Ref. 30) Full Text (Free, PDF) www.bmj.sk.

Nutritional determinants of plasma homocysteine.

The total Hcy, methionine, vitamin B12, folic acid and vitamin B6 blood concentrations were measured in apparently healthy adult subjects aged 20-30 years with three types of nutrition - 52 normal weight subjects of general population on traditional mixed diet (non-vegetarians), 52 normal weight vegetarians and 24 overweight and obese non-vegetarians. In the groups with lower methionine intake (vegetarians, normal weight non-vegetarians; methionine intake 0.45-2.12 g/day), Hcy values are dependent on vitamin B12 and folic acid. Vegetarian Hcy concentration is significantly increased and hyperhomocysteinemia was found in 35% of vegetarians vs 10% of non-vegetarians. Elevated Hcy values in vegetarians are the consequence of vitamin B12 deficiency - 31% of vegetarians with deficient serum values vs 2% of non-vegetarians (vitamin is not contained in plant food). Non-vegetarians are more deficient in folic acid (8% vs 0% in vegetarians) due to of lower consumption of food rich in folic acid (vegetables, whole grain products, pulses, seeds). The results suggest that in healthy population, a correct nutritional regime with an optimal intake of nutritional Hcy determinants is crucial for the maintenance of Hcy concentration in normal range and for the prevention of hyperhomocysteinemia (Tab. 2, Fig. 2, Ref. 27). Full Text (Free, PDF) www.bmj.sk.

Vitamin C protective plasma value.

The relationship of plasma concentration and intake of vitamin C was measured in a randomly selected group of 368 apparently healthy adult subjects of two nutritional regimens: traditional mixed diet (general population, n=187) and vegetarians (n=181). The condition of protective plasma concentration over 50 micromol/l (50.3-89.4 micromol/l), the value of which reduces the risk of free radical disease, was found in 87 subjects from the general population group, in whom the average vitamin C intake was 124.2 mg per day in range of 92-181. The recommended dietary allowance for this group in amount of 77 mg of vitamin C daily was calculated from current Slovak recommendations being in amount of 80 mg per day for men and 75 mg for women. Previous epidemiological studies as well as the presented results show that approximately a half of Slovak general population have vitamin C deficient (below 23 micromol/l) or suboptimal (23-50 micromol/l) plasma concentrations with insufficient antioxidative protection. Significantly higher plasma vitamin C concentrations in comparison to non-vegetarians were observed in the vegetarian group. Protective concentrations were noted in 88% of vegetarians vs 46% of non-vegetarians. The significantly reduced values of products of oxidative damage of DNA (DNA breaks with oxidised purines and oxidised pyrimidines), lipids (conjugated dienes of fatty acids, malondialdehyde) and proteins (carbonyls) were found in subjects with plasma vitamin C concentrations being over 50 micromol/l vs. below 50 micromol/l. The data emphasize the role of vitamin C in free radical disease prevention under the condition of protective, antioxidative concentrations. The results of general population group document the need to revise the recommended dietary allowance for vitamin C as well as to change the nutritional habits including regular consumption of fruit and vegetables several times daily (Tab. 3, Ref. 28).

Products of DNA, protein and lipid oxidative damage in relation to vitamin C plasma concentration.

Oxidative stress plays an important role in the pathogenesis of numerous chronic age-related free radical-induced diseases. Improved antioxidant status minimizes oxidative damage to DNA, proteins, lipids and other biomolecules. Diet-derived antioxidants such as vitamin C, vitamin E, carotenoids and related plant pigments are important in antioxidative defense and maintaining health. The results of long-term epidemiological and clinical studies suggest that protective vitamin C plasma concentration for minimum risk of free radical disease is higher than 50 micromol/l. Products of oxidative damage to DNA (DNA strand breaks with oxidized purines and pyrimidines), proteins (carbonyls) and lipids (conjugated dienes of fatty acids, malondialdehyde) were estimated in a group of apparently healthy adult non-smoking population in dependence on different vitamin C plasma concentrations. Under conditions of protective plasma vitamin C concentrations (>50 micromol/l) significantly lower values of DNA, protein and lipid oxidative damage were found in comparison with the vitamin C-deficient group (<50 micromol/l). The inhibitory effect of higher fruit and vegetable consumption (leading to higher vitamin C intake and higher vitamin C plasma concentrations) on oxidation of DNA, proteins and lipids is also expressed by an inverse significant correlation between plasma vitamin C and products of oxidative damage. The results suggest an important role of higher and frequent consumption of protective food (fruit, vegetables, vegetable oils, nuts, seeds and cereal grains) in prevention of free radical disease.

Hyperosmotic environment blunts effectivity of ischemic preconditioning against ischemia-reperfusion injury and improves ischemic tolerance in non-preconditioned isolated rat hearts.

Several studies have shown that diabetes mellitus modulates heart resistance to ischemia and abrogates effectivity of cardioprotective interventions, such as ischemic preconditioning (IP). The aim of this study was to evaluate whether the effect of hyperglycemic conditions on the severity of ischemia-reperfusion (I/R) injury in preconditioned and non-preconditioned hearts (controls, C) is related to changes in osmotic activity of glucose. Experiments were performed in isolated rat hearts perfused according to Langendorff exposed to 30-min coronary occlusion/120-min reperfusion. IP was induced by two cycles of 5-min coronary occlusion/5-min reperfusion, prior to the long-term I/R. Hyperosmotic (HO) state induced by an addition of mannitol (11 mmol/l) to a standard Krebs-Henseleit perfusion medium significantly decreased the size of infarction and also suppressed a release of heart fatty acid binding protein (h-FABP - biomarker of cell injury) from the non-IP hearts nearly to 50 %, in comparison with normoosmotic (NO) mannitol-free perfusion. However, IP in HO conditions significantly increased the size of infarction and tended to elevate the release of h-FABP to the effluent from the heart. The results indicate that HO environment plays a cardioprotective role in the ischemic myocardium. On the other hand, increased osmolarity, similar to that in the hyperglycemic conditions, may play a pivotal role in a failure of IP to induce cardioprotection in the diabetic myocardium.

C-reactive protein and nutrition.

High sensitivity C-reactive protein (hsCRP) is a proven method to better predict the cardiovascular risk and target therapeutic interventions. Serum concentrations of hsCRP were measured in an adult apparently healthy population aged 19-75 years of different nutrition: a vegetarian group (lacto- and lacto-ovo-vegetarians who consumed plant food, dairy products and eggs) and a group of non-vegetarians (general population) on traditional mixed diet. The average hsCRP concentration was significantly reduced in the vegetarian group (0.72 +/- 0.07 vs 1.62 +/- 0.12 mg/l) with no risk values >3 mg/l vs 14 % in non-vegetarians. In non-vegetarians, a positive linear correlation of hsCRP values and age (r=0.35, p<0.001) was recorded vs horizontal trend line in vegetarians. Low and age independent concentration of hsCRP in vegetarians is the consequence of a long-term consumption of fruits and vegetables. These food commodities are important sources of dietary salicylates as well as other anti-inflammatory compounds (Tab. 1, Fig. 1, Ref. 15).

Impaired PI3K/Akt signaling as a potential cause of failure to precondition rat hearts under conditions of simulated hyperglycemia.

The aim of the study was to evaluate the impact of simulated acute hyperglycemia (HG) on PI3K/Akt signaling in preconditioned and non-preconditioned isolated rat hearts perfused with Krebs-Henseleit solution containing normal (11 mmol/l) or elevated (22 mmol/l) glucose subjected to ischemia-reperfusion. Ischemic preconditioning (IP) was induced by two 5-min cycles of coronary occlusion followed by 5-min reperfusion. Protein levels of Akt, phosphorylated (activated) Akt (P-Akt), as well as contents of BAX protein were assayed (Western blotting) in cytosolic fraction of myocardial tissue samples taken prior to and after 30-min global ischemia and 40-min reperfusion. In "normoglycemic" conditions (NG), IP significantly increased P-Akt at the end of long-term ischemia, while reperfusion led to its decrease together with the decline of BAX levels as compared to non-preconditioned hearts. On the contrary, under HG conditions, P-Akt tended to decline in IP-hearts after long-term ischemia, and it was significantly higher after reperfusion than in non-preconditioned controls. No significant influence of IP on BAX levels at the end of I/R was observed under HG conditions. It seems that high glucose may influence IP-induced activation of Akt and its downstream targets, as well as maintain persistent Akt activity that may be detrimental for the heart under above conditions.

Influence of age on activities of antioxidant enzymes and lipid peroxidation products in erythrocytes and neutrophils of Down syndrome patients.

Thirty-seven individuals with Down syndrome (DS) were divided into four age categories: (i) 1 to < 6 years, (ii) 6 to < 13 years, (iii) 13 to < 20 years, and (iv) over 20 years. Activities of antioxidant enzymes found in individual age categories were different, but the differences between age groups were not statistically significant. We confirmed significantly higher activities of Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase (GPx) in blood cells of people with DS as compared to 35 controls, which consisted, for the first time, of siblings of children with DS. No significant differences were found in activities of catalase and glutathione reductase in DS vs. controls. A significant difference was observed in serum concentration of malondialdehyde (MDA) in DS vs. controls (8.39 +/- 0.34 micromol/l vs. 7.34 +/- 0.27 micromol/l; p = .021) and concentration of MDA in erythrocytes of individuals with DS between the third and fourth age group (p = .05). In DS persons, an elevated ratio of SOD to catalase plus GPx with respect to the controls in all age categories was found, suggesting oxidative imbalance, potentially contributing to accelerated aging observed in these persons.

Malondialdehyde, lipofuscin and activity of antioxidant enzymes during physical exercise in patients with essential hypertension.

DESIGN: To clarify the role of oxidative damage in essential hypertension, levels of lipid peroxidation products (malondialdehyde and lipofuscin) and activity of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) were examined during a short period of physical exercise. PATIENTS AND METHODS: We studied 11 male patients with mild to moderate essential hypertension in World Health Organization classes I or II and 10 healthy male controls. Physical exercise was performed on a bicycle ergometer at graded intensities of 1.0, 1.5 and 2.0 W/kg body weight Plasma concentrations of lipofuscin, malondialdehyde, epinephrine, norepinephrine, insulin, free fatty acids and glucose were determined. Superoxide dismutase activity was analysed in erythrocytes and glutathione peroxidase activity in whole blood. RESULTS: Concentrations of lipofuscin and malondialdehyde were significantly elevated in hypertensive patients. Superoxide dismutase activity was not different between groups, while glutathione peroxidase activity was significantly decreased in hypertensive subjects. During exercise, the concentration of malondialdehyde and antioxidant enzyme activities increased significantly in both groups. No differences were found in absolute increases between the normotensive and hypertensive subjects. The levels of glucose, insulin and free fatty acids were similar in both groups. Basal concentrations of catecholamines and also the exercise-induced increases were lower in hypertensive patients. CONCLUSIONS: Our results indicate increased oxidative damage in patients with essential hypertension, which might be caused by a decrease in the activity of glutathione peroxidase. The ability of superoxide dismutase and glutathione peroxidase to respond to increased production of reactive oxygen species during a short period of physical exercise was not impaired in hypertensive subjects.

Influence of food restriction on dopamine receptor densities, catecholamine concentrations and dopamine turnover in chicken brain.

To investigate further a putative role of dopamine in control of food restriction-induced behavioural stereotypies, chickens were fed during rearing on either a daily restricted ration recommended by a breeding company, twice the recommended restricted ration, or ad libitum food. They were killed at 60 days of age and their excised brains were dissected into six regions and homogenized. Densities of dopamine D1 and D2 receptors were assessed, after first estimating binding parameters for [3H]SCH 23390 (D1) and [3H]spiperone (D2) in chicken brain homogenates. Specific binding of both ligands was highest in basal telencephalon. Concentrations of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were also highest in basal telencephalon, whereas noradrenaline and adrenaline levels were highest in diencephalon. Dopamine concentration in basal telencephalon and noradrenaline concentration in diencephalon were increased significantly in response to food restriction, but no effect of feeding treatment was found in dopamine turnover, adrenaline levels, or D1 and D2 receptor densities in any brain region studied. The observed changes in brain catecholamine levels are consistent with roles for dopaminergic and adrenergic mechanisms in the control of food restriction-induced behavioural stereotypies in chickens.

Modulation of rat testicular LH/hCG receptors by membrane lipid fluidity.

The specific binding of [125I]hCG to rat testicular membrane preparations was investigated as a function of membrane fluidity changed by lipids. Membrane fluidity was measured either by fluorescence depolarization of diphenylhexatriene or ESR spectra of I(1,14), I(12,3) and CAT 16 incorporated into the membrane. Incubation of membrane with cholesteryl-hemisuccinate increased both the rigidity of membrane lipids and the specific binding of [125I]hCG. A similar rigidifying action of saturated fatty acids was, however, not accompanied by increased accessibility of LH/hCG receptors. Treatment of testicular membranes with unsaturated fatty acids enhanced membrane fluidity but specific binding of the gonadotropin disappeared. In spite of the increase of LH/hCG receptors in cell membranes treated with cholesteryl-hemisuccinate, Leydig cells showed decreased sensitivity to cAMP response to LH stimulation. The results indicate that newly exposed LH/hCG receptors are not coupled with the adenylate cyclase system.

Circulating advanced glycation end product levels in rats rapidly increase with acute renal failure.

BACKGROUND: Advanced glycation end products (AGEs) are formed on proteins and peptides slowly during aging, and they accumulate in circulation and tissues in diabetes and chronic renal failure. Except for nonenzymatic glycation, enhanced oxidative/carbonyl stress is supposed to participate in their formation. The kidney plays a key role in disposal of AGEs, particularly AGE-peptides. We assumed that even a short time combination of enhanced oxidative/carbonyl stress and a lack of renal function should result in elevation of circulating AGE levels. METHOD: To verify this hypothesis, two models of acute renal failure in rats, bilateral nephrectomy and bilateral ureteral ligation, were employed, and the data were compared with those of sham-operated animals. RESULTS: AGE levels determined fluorimetrically or as carboxymethyllysine concentration rose by a factor of three within 48 hours. Enhanced levels of malondialdehyde and lipofuscin pointed to an enhanced oxidative/carbonyl stress. Activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase were not compromised, or were even elevated, respectively. Total antioxidant status increased, probably as a consequence of an accumulation of indols and benzoic acid derivatives, uremic toxins with scavenging capacities, as shown for hippurate. CONCLUSIONS: Evidence was given that circulating AGEs in the model of acute renal failure in rats undergo a substantial rise within a short time period. A source of increased AGEs is not clear, since except for the lack of the kidney function, accelerated synthesis of AGEs under enhanced oxidative/carbonyl stress as well as liberation of AGEs from tissues due to protein catabolism might be anticipated. If AGEs accumulate in acute renal failure in humans, their contribution to acute toxicity, or of the development of the complications later, might be of importance.