Expression of purinergic P2X7 receptors in subpopulations of peripheral blood mononuclear cells in early-stage of chronic kidney disease.

Chronic kidney disease (CKD) is known as a state of chronic low-grade inflammation, enhancing cardiovascular risk and immunodeficiency. Purinergic signaling has been accepted as a crucial component in the pathogenesis of various diseases, mediating a vast array of biological processes. The P2X7 receptor is one of the important cell surface regulators of several key inflammatory molecules. The aim of the study was to examine the expression of surface P2X7 receptors in subpopulations of peripheral blood mononuclear cells (PBMCs), and to evaluate the promising prognostic markers of inflammation (neutrophil/lymphocyte, Ne/Ly ratio) and cardiovascular risk (monocyte/high density lipoprotein cholesterol, Mo/HDL ratio) in early-stage CKD. The study involved 15 healthy volunteers and 15 non-diabetic patients with CKD stage 2 - 3. PBMCs were isolated from heparinized blood by Ficoll gradient centrifugation. To determine the expression of P2X7 receptors in different subpopulations (CD14+ monocytes, CD3+ T-lymphocytes and CD19+ B-lymphocytes), the cells were stained with FITC-conjugated anti-P2X7. The monocyte, lymphocyte and neutrophil counts were measured in whole blood as a part of routine hemogram. The number of T- and B-lymphocytes was determined by flow cytometry using antibodies anti-CD3-PE and anti-CD19-PE, respectively. The expression of surface P2X7 receptors was 1.4 fold increased in PBMCs of CKD patients compared to healthy volunteers. The expression of P2X7 receptors was 2.1 fold higher in monocytes and 1.5 fold higher in the whole lymphocyte population, with significant increase only in B-cells. The monocyte count, as well as the Ne/Ly and Mo/HDL ratios were also significantly increased. In conclusion, the increased P2X7 receptors expression in monocytes, the monocyte count and the Ne/Ly ratio are manifestations of chronic inflammation already in early stages of CKD. The study also supports recent findings that the Mo/HDL ratio could be used as additional parameter for monitoring cardiovascular risk profile in these patients.

Comparison of iPTH values in serum and plasma samples depending on the time and temperature in patients with chronic kidney disease.

Renal osteodystrophy is a systemic disorder associated with chronic kidney disease (CKD) with abnormal values of biochemical parameters related to bone and mineral metabolism. Assessing renal osteodystrophy subtypes is especially important for diagnostic and therapeutic decision. Management of these disorders includes monitoring of homeostasis of calcium, phosphorus and parathormone (PTH). PTH is a significant regulator of mineral balance and it´s level is used as a surrogate biomarker for the type of underlying renal osteodystrophy. Worldwide, nephrologists rely on KDIGO - Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) to maintain PTH levels within defined narrow range of optimal values for each stage of CKD and adjust such PTH - lowering treatments as active vitamin D sterols or calcimimetics accordingly. PTH is rapidly degraded in vivo, with half life of 5 minutes and it is also unstable in blood samples. Values can differ significantly when samples are not collected in a standard way and when recommended conditions for transport and sample processing are not followed. It is also important to standardize pre-analytic conditions that may influence the variability in PTH results. The goal of the present study was to compare iPTH stability in serum and plasma samples and evaluate possible pre-analytic errors in sample collection, effect of temperature during transportat and storing prior to analysis (Tab. 1, Fig. 1, Ref. 5).

The effect of vitamin D3 supplementation on intracellular calcium and plasma membrane calcium ATPase activity in early stages of chronic kidney disease.

Chronic kidney disease (CKD) is associated with increased concentration of intracellular calcium, which is pathological and may lead to irreversible damage of cell functions and structures. The aim of our study was to investigate the impact of 6 months vitamin D(3) supplementation (14 000 IU/week) on free cytosolic calcium concentration ([Ca(2+)](i)) and on the plasma membrane calcium ATPase (PMCA) activity of patients with CKD stage 2-3. PMCA activity of patients was also compared to that of healthy volunteers. Vitamin D(3) supplementation of CKD patients resulted in the decrease of [Ca(2+)](i) (119.79+/-5.87 nmol/l vs. 105.36+/-3.59 nmol/l, n=14, P<0.001), whereas PMCA activity of CKD patients (38.75+/-22.89 nmol P(i)/mg/h) remained unchanged after vitamin D(3) supplementation (40.96+/-17.74 nmol P(i)/mg/h, n=14). PMCA activity of early stage CKD patients before supplementation of vitamin D(3), was reduced by 34 % (42.01+/-20.64 nmol P(i)/mg/h) in comparison to healthy volunteers (63.68+/-20.32 nmol P(i)/mg/h, n=28, P<0.001). These results indicate that vitamin D(3) supplementation had a lowering effect on [Ca(2+)](i) and negligible effect on PMCA activity in CKD patients.

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).

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).

Insulin resistance and vitamin D deficiency in patients with chronic kidney disease stage 2-3.

Vitamin D status and the relationship between serum 25(OH) vitamin D concentrations and the components of insulin resistance were examined in 120 patients with chronic kidney disease stage 2 and 3. Insulin sensitivity/resistance was calculated by the quantitative insulin sensitivity check index (QUICKI). In this analysis, the prevalence of insulin resistance was 42 %. Only 17 % of patients had serum 25(OH) vitamin D concentration in the recommended range (>/=30 ng/ml), 42 % suffered from vitamin D insufficiency and 41 % had moderate vitamin D deficiency. Insulin resistance significantly correlated with serum 25(OH)D and 1,25(OH)(2)D concentrations, renal function and protein excretion rate. Our results support the increasing evidence that vitamin D deficiency may be one of the factors participating in the development of insulin resistance already in the early stages of chronic kidney disease.

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.

Mitochondria and mitochondrial nitric oxide synthase alterations participate in energetical dysbalance, aging and age-related diseases.

Nitric oxide (NO) is a unique mediator of cellular regulations synthesized by nitric oxide synthases (NOS) present in cytoplasm of various cells. An additional Ca-dependent mitochondrial NOS (mtNOS) detected just recently synthesizes also NO inhibiting oxidative phosphorylation, i.e. mitochondrial energy producing metabolic process and protects mitochondria from oxygen radicals. Mitochondrial membrane possesses electrogenic uniporter transporting Ca into mitochondria (stimulation of mtNOS), while Na+/Ca2+ exchanger removes Ca from mitochondria. Mitochondrial disorders with low mtNOS activity participate in accelerated aging and age-related diseases. The direct NO balance determination is outside of the standard clinical facilities; Indirect alternatives, such as insulin resistance determination are accessible. Pharmacotherapy exploits effective therapeutic and preventive measures (NO donors, ACEI inhibitors, etc.) and pharmaceutical approach (development of mitochondriotropic drugs). We suggest, that mitochondrial disorders participate in aging and age related diseases and propose that the early diagnostics, preventive and therapeutic measures could prevent and even correct at least partially the development of age-related diseases (Tab. 4, Ref. 81).

Nitric oxide modulation of metabolic and haemodynamic balance.

Nitric oxide (NO) belongs to signal molecules and modulates notably rapid and dynamic processes. Interests are focused on the decreased NO synthesis by endothelial and mitochondrial nitric oxide synthases with the metabolic (i.e. insulin resistance, diabetes, energetical dysbalance) and vascular (i.e. hypertension, atheroslerosis) consequences. A significant source of NO are NO-donors (i.e. organic nitrates). A number of antihypertensive drugs stimulates NO production or inhibits the production of its antagonists (angiotensin II, catecholamines), other drugs (i.e. glucocorticoids) inhibit NO production. These interferences are targets of an intensive research with the aim of NO dysbalance prevention, hypertension and metabolic dysbalances correction. While the clinical research concentrates on NO and insulin resistance, the molecular biological research concentrates on "mitochondrial medicine" with the ambition to formulate a new theory of aging, carcinoma, and other fundamental biological processes (Fig. 1, Ref. 47).

Cardiovascular risk factors in young Gypsy population.

Lipid and non-lipid cardiovascular risk parameters (cholesterol, HDL- and LDL-cholesterol, triglycerides, homocysteine, C-reactive protein, insulin resistance) and data about blood pressure, smoking, body mass index were assessed in two ethnic groups aged 19-35 years--the Gypsy group (n=122) and the Slovak group (n=137) of two regions with a high density of Gypsy population. In the Gypsy group, the values of triglycerides, atherogenic index, insulin, insulin resistance were significantly increased and the level of HDL-cholesterol was significantly decreased. The risk value of atherogenic index was found in 27 % of Gypsy vs 13 % of majority subjects, and 28 % vs 24 % of subjects had hypertriglyceridemia. Risk value of insulin resistance (HOMA) was presented in 11 % of the Gypsy vs 5 % of the majority group. More obese subjects (20 % vs 8 %), more smokers (55 % vs 25 %) and more subjects with low education (85 % vs 27 %) were recorded in the minority group. The greater occurrence of dyslipidemia, obesity and insulin resistance in young Gypsy subjects is influenced with lifestyle (nutrition /prevalence of animal fat consumption, low consumption of food with low glycemic index and soluble fibre/, smoking, low physical activity) as well as low educational status. (Tab. 2, Ref. 22.).

Folate levels determine effect of antioxidant supplementation on micronuclei in subjects with cardiovascular risk.

We have investigated the effect of modest supplementation with alpha-tocopherol (100 mg/day), beta-carotene (6 mg/day), vitamin C (100 mg/day) and selenium (50 microg/day) on oxidative stress and chromosomal damage, and the influence of methylenetetrahydrofolate reductase (MTHFR) genotype on these end-points. Subjects were two groups of middle-aged men differing in cardiovascular risk; 46 survivors of myocardial infarction before age 50 and 60 healthy controls. They were randomly divided into equal groups to receive antioxidants or placebo for 12 weeks. Twenty-eight patients and 58 controls completed the intervention. Micronucleus levels in peripheral lymphocytes and changes seen after intervention were studied in relation to the MTHFR C677T genotype, basal homocysteine and plasma folate levels. Ferric reducing ability of plasma and concentration of malondialdehyde were measured to assess the antioxidant effect of supplementation. There was no association of micronuclei with folate, homocysteine or malondialdehyde levels before supplementation. Micronucleus frequencies and plasma folate levels did not vary significantly with MTHFR genotype. Homocysteine levels in subjects with the TT variant genotype were significantly higher compared with CT or CC (P = 0.001), especially in subjects with low folate (P = 0.012). In the placebo control group an increase in micronuclei (P = 0.04) was detected at the end of the intervention period. This effect was not seen in the supplemented group. In antioxidant-supplemented myocardial infarction survivors we found an increase in the ferric reducing ability of plasma (P < 0.001) and a decrease in malondialdehyde (P = 0.001). Micronucleus frequency showed a decrease, strongest in subjects with normal folate levels (P = 0.015). In subjects with low folate levels, a high correlation was found between micronuclei after supplementation and homocysteine, both before (r = 0.979, P = 0.002) and after supplementation (r = 0.922, P = 0.009). Thus, folate deficiency may amplify the effect of other risk factors such as elevated homocysteine levels or variant MTHFR genotype, as well as influencing the ability of antioxidant supplementation to protect against genetic damage.

Calcitriol load test in postmenopausal osteoporosis: a pilot study.

BACKGROUND: Calcium and vitamin D balance is of critical importance in both, prevention and treatment of osteoporosis. The evaluation of this balance is difficult under steady state conditions, therefore the effect of a single oral calcitriol load in postmenopausal women with osteopenia/osteoporosis was used. METHODS: Mineral and hormone concentrations were determined under basal conditions and after the administration of a single 0.5 microg calcitriol dose (Rocaltrol, Roche). RESULTS: Single oral calcitriol dose was administered to 36 postmenopausal women. Increased calciuria (p < 0.001) and calcium fractional excretion (p < 0.001) 24 hours after drug administration indicated kidney participation in calcium homeostasis. Urinary calcium excretion after the calcitriol load correlated with basal urinary calcium excretion (r = 0.772; p < 0.001). On the basis of calciuric response, women could be separated to responders and non-responders; in responders, increase in calciuria was >1.0 mmol/d, while in non-responders < 1.0 mmol/d (p < 0.001). Neither plasma calcium nor plasma 25-hydroxycholecalciferol concentrations increased after the calcitriol load. Both basal (r = -0.361; p < 0.03) and calcitriol stimulated urinary calcium excretion correlated inversely with age (r = -0.425; p < 0.01). No significant changes in measured mineral and hormone parameters were found in women with osteopenia in comparison to women with osteoporosis, with the exception of plasma intact parathormone concentration, which was significantly higher in osteoporotic women (p < 0.05) and significantly decreased (p < 0.001) after the calcitriol load. CONCLUSION: Postmenopausal women suffered from calcium and vitamin D imbalance which could be elucidated by a simple calcitriol test. The reference range, significance and differentiation from other abnormalities are to be defined in an extensive study. (Tab. 4, Ref. 19.).

[Vitamin D: synthesis, metabolism, regulation, and an assessment of its deficiency in patients with chronic renal disease]. / Vitamin D: syntéza, metabolizmus, regulácie a hodnotenie deficitu u pacientov s chronickým ochorením obliciek.

The main source of vitamin D in a man is its synthesis in human skin. 7-Dehydrocholesterol converts into cholecalciferol--vitamin D3--as a result of UV radiation. Cholecalciferol hydroxylates in liver into 25-hydroxyvitamin D3 [25(OH)D, calcidiol], which concentration in blood is a relevant indicator of the total of vitamin D in a human body. 25(OH)D hydroxylates in kidneys into 1,25-dihydroxyvitamin D3 [1,25(OH)2D, calcitriol], which is considered an active metabolite of vitamin D. Epidemiological studies showed high prevalence of low concentrations of 25(OH)D especially in older population and people with chronic diseases. 25(OH)D concentrations were defined at which rise parathormone levels, increases bone conversion, impairs bone mineralization and develops osteomalacia. Based on these results a deficiency of vitamin D was defined. Patients with chronic renal disease experience development of serious bone impairments described as renal osteodystrophy. These disorders are caused by secondary hyperparathyroidism which develops as a result of mineral metabolism impairment, especially of hypocalemia, 25(OH)D deficiency, and insufficient synthesis of 1,25(OH)2D. Presently published guidelines K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification define processes of vitamin D supplementation, particularly 1,25(OH)2D according to a degree of renal disease. Early prevention and treatment of hypovitaminosis D is a treatment goal in order to reduce or stop development of secondary hyperparathyroidism with its consequences for bone metabolism.

[Intensive vitamin D supplementation in the treatment of osteoporosis]. / Intenzifikovaná suplementácia vitamínom D v liecbe osteoporózy.

Vitamin D deficiency is not possible to correct with the nutritional vitamin D doses in postmenopausal women with decreased bone mineral density. The aim of study was to evaluated the effectivity and safety of 15,000 IU/week vitamin D administrated in 52 postmenopausal women with osteopenia or osteoporosis. Patients were divided into two groups. Treated group was supplemented by calcium 0.5 g/d and 25-hydroxycholecalciferol 15,000 IU/week and control group was supplemented by calcium and placebo for two months. Plasma calcium concentration did not change in the vitamin D treated group while it decreased (p < 0.001) in the control group. Neither calciuria nor fractional excretion of calcium changed during the treatment period. Plasma inorganic phosphate concentration did not change in any group, but urinary inorganic phosphate excretion increased in the vitamin D treated group (p < 0.001). The starting 25-hydroxycholecalciferol plasma concentrations were almost at the deficiency range in both groups. The 25-hydroxycholecalciferol plasma concentration increased substantially (p < 0.001) in the treated group, but it remained at the starting level in control group during the treatment period. Similar plasma concentration increase (p < 0.001) was apparent also in 1.25-dihydroxycholecalciferol. Plasma intact parathormone concentration did not change in the vitamin D treated patients, while it increased (p < 0.01) in the control group. None of the vitamin D treated women suffered from hypercalcemia and mild hypercalciuria was observed in one patient. In conclusion, the study presents an evidence on the effectiveness and safety of 15,000 IU/week 25-hydroxycholecalciferol dosage schedule.

Lipid peroxidation and nutrition.

Levels of conjugated dienes of fatty acids (first peroxidation product) in relation to their substrates and promotors (triacylglycerols, homocysteine, iron) as well as to their inhibitors (essential antioxidative vitamins) were assessed in a vegetarian group (n=24) and compared with subjects on a mixed diet (traditional nutrition, n=24). Positive significant linear correlation between conjugated dienes and triacylglycerols, homocysteine, iron as well as inverse relationship between conjugated dienes and vitamin E, vitamin C, beta-carotene were observed in pooled groups. Lipid peroxidation risk in vegetarians seems to be caused predominantly by hyperhomocysteinemia, whereas in a mixed diet group this was due to a higher supply of substrates or risk iron values. The incidence of only 8 % of risk conjugated diene values in vegetarians in contrast to 42 % in the group with traditional diet indicates that vegetarians have a better antioxidative status as a consequence of regular consumption of protective food.

Insulin resistance in kidney disease patients with mild to moderate kidney disease.

BACKGROUND: Insulin resistance is a very early sign of atherosclerosis and an increased risk of cardiovascular morbidity and mortality. Insulin resistance detection by the fasting plasma insulin and glucose determination enables early detection, follow-up, treatment and the search for accelerating factors in kidney disease patients threatened by atherosclerosis. PATIENTS AND METHODS: Insulin resistance was evaluated by the Quantitative Insulin Sensitivity Check Index from fasting glucose and insulin plasma concentrations in 66 kidney disease patients with a mild to moderate decrease in kidney function. RESULTS: Forty patients were insulin sensitive and 26 suffered from insulin resistance. These groups of patients did not differ significantly in age, gender, clearance of creatinine and cholesterol concentrations. However, patients with insulin resistance suffered from increased BMI (p < 0.001), fasting plasma glucose (p < 0.01), insulin (p < 0.001) and triglyceride (p < 0.01) concentrations. Insulin resistance correlated with BMI (r = -0.417, p < 0.001) and with plasma triglycerides concentration (r = -0.307, p < 0.01). The absent relationship between insulin resistance and age (r = -0.154, NS) or creatinine clearance (r = -0.061, NS) suggests the need for screening of insulin resistance even in young patients with mild kidney function reduction. CONCLUSION: A considerable number of renal patients in the early stages of kidney function reduction suffers from insulin resistance. They need to improve their life style and take medication (i.e. antihypertensive drugs) improving insulin sensitivity and to omit medications which harm it. (Fig. 2, Tab. 1, Ref. 20.)

[Nephrogenic metabolic acidosis]. / Nefrogénna metabolická acidóza.

Metabolic acidosis is a major risk factor of kidney disease progression as a consequence of impaired H+ urinary excretion by the decreased kidney NH3 synthesis. Two key enzymes participate: a) Phosphate-dependent glutaminase under the genomic control of metabolic acidosis and b) Phosphate independent glutaminase localized on proximal tubule microvili under the nongenomic control. Two types of kidney disease metabolic acidoses are dominant: a) Hyperchloremic metabolic acidosis usually on the basis of hereditary or toxic alterations, isolated or as a part of Fanconi syndrome. b) Hyperphosphatemic metabolic acidosis of renal insufficiency. Metabolic acidosis shares serious consequences: metabolic acidosis increases protein catabolism of amino acids, inhibits proteosynthesis (albumin!), accelerates renal osteodystrophy development, modulates calcidiol and parathormone plasma levels and evokes insulin resistance. The present therapy requires full correction of metabolic acidosis!

Free radical disease prevention and nutrition.

An improved antioxidant status (overthreshold plasma values of essential antioxidants) minimizes the oxidative damage. The levels of antioxidant vitamins C and E, ,,antioxidant" trace elements selenium, zinc, copper and iron were measured in two groups of adults with different nutritional habits--alternative (vegetarians; n=110) and traditional (mixed diet, control, n=101). The prevalence of iron and zinc deficiencies was found in the alternative group (20% vs 11%--iron, 13% vs 9%--zinc) as a consequence of higher intake of plant trace element absorption inhibitors. As opposed to the latter, the control group had higher findings of iron and copper levels over the optimal range (18% vs 8%--iron, 11% vs 2%--copper). The subjects on mixed diet was showed a significant negative linear correlation between serum zinc and iron levels. This favourable relationship means a decrease in Fenton reaction by indirect zinc effect. Average plasma values of vitamin C, vitamin C/vitamin E, vitamin E/ cholesterol (LDL protection), vitamin E/triacylglycerols (polyunsaturated fatty acid protection) in vegetarians are over the threshold with high number of individual overthreshold values (94% vs 17%--vitamin C, 100% vs 58%--vitamin C/vitamin E, 89% vs 68%--vitamin E/cholesterol, 100% vs 64%--vitamin E/triacylglycerols). Homocysteine levels in vegetarians (36% atherogenic levels) correlate significantly inversely to vitamin C levels, the fact of which means a positive vitamin C effect in free radical remove also in hyperhomocysteinemia. Plant food is a rich source of antioxidants. A correct vegetarian nutrition or optimized mixed diets with regular and frequent consumption of protective food commodities may be an effective contribution to the age-related chronic degenerative disease prevention. (Tab. 2, Fig. 2, Ref. 31.).

Effects of ramipril in nondiabetic nephropathy: improved parameters of oxidatives stress and potential modulation of advanced glycation end products.

Enhanced oxidative stress is involved in the progression of renal disease. Since angiotensin converting enzyme inhibitors (ACEI) have been shown to improve the antioxidative defence, we investigated, in patients with nondiabetic nephropathy, the short-term effect of the ACEI ramipril on parameters of oxidative stress, such as advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), homocysteine (Hcy), and lipid peroxidation products. Ramipril (2.5-5.0 mg/day) was administered to 12 newly diagnosed patients for 2 months and data compared with a patient group under conventional therapy (diuretic/beta-blockers) and with age- and sex-matched healthy subjects (CTRL). Patients had mild to moderate renal insufficiency and showed, in the plasma, higher fluorescent AGE and carboxymethyllysine (CML) levels, as well as elevated concentrations of AOPPs, lipofuscin and Hcy when compared with CTRL. Basal data of the patients on conventional therapy did not differ significantly from the ramipril group, except for higher Hcy levels in the latter. Administration of ramipril resulted in a drop in blood pressure and proteinuria, while creatinine clearance remained the same. The fluorescent AGEs exhibited a mild but significant decline, yet CML concentration was unchanged. The AOPP and malondialdehyde concentrations decreased, while a small rise in neopterin levels was evident after treatment. The mentioned parameters were not affected significantly in the conventionally treated patients. Evidence that ramipril administration results in a mild decline of fluorescent AGEs is herein presented for the first time. The underlying mechanism may be decreased oxidative stress, as indicated by a decline in AOPPs and malondialdehyde.

Kidney function and age related mineral imbalance in postmenopausal women with osteopenia/osteoporosis.

BACKGROUND: Negative mineral balance in postmenopausal women appears to be an important risk factor for osteoporosis and subsequent bone fractures. Its pathogenesis has not been elucidated. OBJECTIVES: To elucidate the participation of the kidney and ageing on mineral balance in postmenopausal women. METHODS: 36 postmenopausal women with osteopenia or osteoporosis, aged 46-75 years were evaluated by determination of mineral balance, kidney functions, 25(OH)-cholecalciferol [25(OH)D], 1,25(OH)2-cholecalciferol [1,25(OH)2D] and intact parathormone plasma levels. RESULTS: Plasma calcium (Ca) concentrations were low and they did not decrease further with ageing. Urinary Ca excretion decreased (r = -0.425, p < 0.01) with age without changes in the fractional excretion of Ca. A similar decrease of urinary excretion was found in the urinary excretion of phosphorus (Pi) (r = -0.335; p < 0.03) and magnesium (Mg) (r = -0.355; p < 0.03). All patients' kidney functions were in the age-related reference range. Plasma 25(OH)D concentrations were in the range of moderate to severe deficiency, related inversely to age (r = -0.357; p < 0.03) and Ca urinary excretion (r = 0.343; p < 0.04) and to plasma creatinine concentration (r = 0.381; p < 0.02). Plasma 1,25(OH)2D concentrations were also low, they did not change with age and were highly correlated with Ca urinary excretion (r = 0.458; p < 0.005). The intact parathormone (iPTH) plasma concentrations were in the reference range, without any changes during aging. CONCLUSIONS: Pi, Mg and dominantly Ca imbalance in postmenopausal women with osteopenia or osteoporosis accentuates with age and besides their insufficient intake the vitamin D deficiency takes part. These data support the need for increased supplementation of Ca and vitamin D with increasing age. (Tab. 3, Fig. 4, Ref. 18.).