Effect of α-tocopherol megadoses on hematologic parameters and antioxidant capacity of rats in an ultraendurance probe.

This study was aimed to analyze the effect of two different megadoses of α-tocopherol (vit E) in the antioxidant activity and red and white blood series of Wistar rats after a 180-min ultraendurance probe. Three groups of 10 rats were analyzed; VEAG: acute administration of a megadoses of 5,000 IU/kg of vit E the day before the probe; VECG: chronic administration of 1,000 IU/kg/day of vit E for 6 days before the probe; CG: placebo administration. VEAG presented white cells, red blood cells, hematocrit, hemoglobin values significantly higher than CG and VECG (p < 0.05). The mean corpuscular hemoglobin and lymphocytes concentrations were significantly higher in the VECG than in the other two groups (p < 0.05). Similarly, VEAG presented a significantly higher vit E blood concentration than VECG and CG (p < 0.05), and VECG than CG (p < 0.05). Finally, we found a significantly positive correlation between trolox equivalent antioxidant capacity (TEAC) and red blood cells concentration (r = 0.374) and a significantly inverse correlation between TEAC and blood lactate concentration (r = -0.365). Our findings suggest that acute vit E megadoses could protect against transitory sport anemia symptoms and increase the white blood cell count in comparison with the chronic dose and control groups after an ultraendurance probe.

Renin-angiotensin system dual blockade using angiotensin receptor plus aliskiren decreases severe proteinuria in kidney transplant recipients.

BACKGROUND: Renin-angiotensin system (RAS) blockade has cardioprotective and renoprotective effects in the general population; however, whether dual blockade using angiotensin-receptor blockade (ARB) plus a renin inhibitor, aliskiren, can minimize severe proteinuria in kidney transplant recipients remains undetermined. OBJECTIVE: To analyze the efficacy and safety of dual blockade of the RAS with an ARB and aliskiren in kidney transplant recipients with severe proteinuria and creatinine concentration 2.5 mg/dL or less. PATIENTS AND METHODS: This prospective study included 16 patients (mean age 56 years; 10 men [62%] who had undergone cadaveric renal transplantation between 1992 and 2004. Immunosuppression therapy included a calcineurin inhibitor in 9 patients (56%) or mammalian target of rapamycin inhibitor in 7 (44%), and mycophenolate mofetil in 15 (94%). All received high-dose ARB II (1.0-3.5 g/24 h) because of marked proteinuria, with poor response. Accordingly, 11 patients also received aliskiren, and in 5 who were receiving an angiotensin-converting enzyme inhibitor, therapy was changed to aliskiren. Mean (range) follow-up was 11 (3-18) months. RESULTS: At 3 months, proteinuria decreased by 40%, and at 6 months by 60%. In addition, mean blood pressure was decreased significantly. Renal function remained stable, as did the serum potassium concentration. A slight but significant decrease in hemoglobin concentration was observed, with no clinical repercussions. CONCLUSIONS: Dual blockade of the RAS with ARB II plus aliskiren therapy demonstrated an additive effect to decrease severe proteinuria and blood pressure in kidney transplant recipients. Neither relevant adverse effects in renal function nor anemia or hyperkalemia were observed. These findings might contribute to prolonging long-term kidney graft survival.

A random comparison of fosinopril and nifedipine GITS in patients with primary renal disease.

OBJECTIVE: To investigate in a random comparison the capacity of an angiotensin converting enzyme inhibitor (fosinopril), and that of a long-acting dihydropiridine (nifedipine GITS) to modify the decay in renal function in patients with primary renal disease, exhibiting a progressive increase in serum creatinine during the previous 2 years. METHODS: A randomized, open-label, multicenter study with a minimum follow-up of 3 years. A total of 241 patients were included in the study. All of them were hypertensive and had a 25% or at least 0.5 mg/dl increase in the value of serum creatinine during the 24 months prior to entering the study. Initial doses of fosinopril and nifedipine GITS were 10 and 30 mg respectively, and titration to 30 and 60 mg was performed if needed to obtain the expected blood pressure goal (< 140/90 mmHg). Furosemide, atenolol, and doxazosin were added as second, third, and fourth drugs if necessary, for blood pressure control. The primary end-point of the study was the appearance of double the serum creatinine values and/or the need to enter a dialysis programme. Secondary end-points were cardiovascular events, death, changes in 24 h proteinuria, and the evolution of serum creatinine. Data reflect the analysis performed by intention to treat. RESULTS: Mean age of the group was 54 +/- 14, and 59% were males. Primary glomerulonephritis (31%), nephrosclerosis (26%) and polycystic kidney disease (19%) were the three most frequent diagnostic findings. After 3 years of follow-up, 21% (27/127) of patients treated with fosinopril, and 36% (40/112) of those receiving nifedipine GITS presented a primary end-point, (OR 0.47, 95% confidence intervals 0.26-0.84, P = 0.01). Renal survival was significantly better when fosinopril constituted the first step therapy (P = 0.002). These results did not seem to be influenced by the type of primary renal disease. Proteinuria decreased at the end of the study by a mean of 57% in the fosinopril group and increased by 7% in the group receiving dihydropiridine. Blood pressure control did not differ among groups for diastolic values. During follow-up, however, the patients receiving ACEi showed systolic blood pressure values 4-6 mmHg lower. CONCLUSION: In patients with chronic renal failure and hypertension due to primary renal disease, fosinopril significantly differed from nifedipine GITS by its capacity to slow the progressive decay in renal function. The drugs also differed by their capacity to lower blood pressure. The better control, in particular of systolic blood pressure, in the fosinopril arm could have contributed in a relevant manner to the attainment of a better outcome when the ACEi was employed.

Effect of magnesium deficiency on enterocyte Ca, Fe, Cu, Zn, Mn and Se content.

In previous studies based on indirect procedures, we reported that Mg deficit increased the bioavailability of a number of elements such as calcium, zinc, iron, copper, manganese and decreased selenium absorption. The present study was designed to verify these findings by direct methods. We investigated the effect of dietary magnesium deficiency on enterocyte Ca, Fe, Zn, Cu, Mn and Se concentrations. Male Wistar rats were fed a Mg-deficient diet (129 mg Mg/kg food) for 70 days. Whole enterocytes from the upper jejunum were isolated and Ca, Fe, Zn, Cu, Mn and Se were determined. The results were compared with findings in a control group that was pair-fed with an identical diet except that it covered this species's nutritional requirements for Mg (480 mg Mg/kg food). The Mg-deficient diet significantly increased enterocyte content of Ca, Fe, Zn, Cu and Mn; however, we found no significant changes in the Se content of these cells. These data support the results obtained by indirect methods.

The role of phytic acid in legumes: antinutrient or beneficial function?

This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.

Changes in bioavailability and tissue distribution of selenium caused by magnesium deficiency in rats.

OBJECTIVE: We investigated the effect of dietary magnesium (Mg) deficiency on the bioavailability and tissue distribution of selenium (Se). METHODS: Wistar rats were fed an Mg-deficient diet for 70 days (D). Selenium content in plasma, whole blood, skeletal muscle, heart, kidney and femoral bone was determined after 7, 35, 49 and 70 days on a Mg-deficient diet. RESULTS: The Mg-deficient diet significantly decreased Se absorption from week 7 until the end of the experimental period; this effect was accompanied by a significant decrease in Se balance. We found a direct linear correlation between Se absorption and retention (balance) (pair-fed controls r = 0.842, p < 0.001; Mg-deficient rats r = 0.959, p < 0.001), and between Se absorbed and plasma Se concentration (controls r = 0.527, p < 0.02; Mg-deficient rats r = 0.704, p < 0.001). In general there were no significant correlations between urinary Se and any other parameter. Tissue analyses showed that after 7 days, Mg deficiency reduced erythrocyte Se and significantly increased plasma and kidney Se. Heart Se was significantly increased only at the end of the study. We found no significant changes in skeletal muscle or bone Se at any time during the experimental period. CONCLUSION: Chronic Mg deficiency decreases Se absorption and retention and erythrocyte concentrations of this mineral, and increases Se in plasma, kidney and heart. Under our experimental conditions, absorption appears to play an important role in the regulation of the tissue distribution of Se.

Changes in tissue calcium and phosphorus content and plasma concentrations of parathyroid hormone and calcitonin after long-term magnesium deficiency in rats.

OBJECTIVE: The present study was undertaken to investigate the effect of dietary magnesium (Mg) deficiency on plasma levels of parathyroid hormone (PTH) and calcitonin (CT), and the changes in tissue calcium (Ca) and phosphorus (P) content. METHODS: Wistar rats were fed an Mg-deficient diet. Plasma levels of PTH and CT, and Ca and P content in plasma, whole blood, skeletal muscle, heart, kidney, femoral bone and brain, were determined after 7, 35, 42, 49, 56, 63 and 70 days. RESULTS: Mg deficiency significantly increased plasma levels of ionic Ca after 1 week of deficiency, and significantly increased total Ca in plasma and whole blood after 5 weeks. Whole blood and plasma levels of P decreased significantly after 8 and 5 weeks, respectively, in comparison with values obtained in pair-fed control rats. Plasma levels of CT were not modified by hypercalcemia and hypomagnesemia. Plasma PTH decreased significantly during the first 3 weeks, then recovered gradually, reaching control values in week 7 and remaining stable thereafter, despite elevated levels of ionic Ca. The Mg-deficient diet led to calcification in skeletal muscle, heart, kidney and femur, detectable as early as week 5. However, P content increased only in kidney after 1 week, decreased in heart and femur after 5 weeks, and did not change in muscle. The Mg-deficient diet did not significantly modify Ca or P content in brain. CONCLUSION: Mg deficiency led to tissue calcification and decreased P levels in blood, heart, and femur. These changes did not affect CT secretion. PTH appeared to be more closely related with hypomagnesemia than with hypercalcemia.

Nitrendipine in the therapeutic management of elderly hypertensive patients: results of a multicenter trial. Andalousian Hypertension Group.

Two hundred forty-seven [142 women (57.49%)] elderly patients with essential hypertension (diastolic blood pressure between 95 and 114 mm Hg) and an average age of 67.4 +/- 6 years were included in an open multicenter ambulatory trial. One hundred thirty-seven had some kind of associated disease. After a 15-day washout period, the patients began nitrendipine therapy (10 mg o.d.). After 1 month, the dose was increased to 20 mg o.d. in patients with diastolic blood pressure (DPB) greater than or equal to 95 mm Hg, and thereafter 5 and 10 mg o.d. of bisoprolol was added to the maximal dose of nitrendipine (20 mg o.d.) in the case of patients with DBP greater than or equal to 95 mm Hg at the end of the second and third months, respectively. At the end of the 6-month follow-up period, the systolic and diastolic pressures had dropped -35 and -21 mm Hg, respectively, without any change in heart rate or Quetelet index. In 210 patients (84.9%), blood pressure control was achieved: 26 (10.5%) with 10 mg of nitrendipine, 149 (60.3%) with 20 mg of nitrendipine, and 35 (14.1%) by adding bisoprolol. The lipid profile, glucose, potassium, uric acid, or creatinine did not change negatively. Sixty-six (26.72%) patients reported clinical side effects, although these were mild; only 15 (6.07%) patients were excluded because of side effects. Nitrendipine has been shown to have a high therapeutic efficacy and biochemical tolerance for first-line treatment of elderly patients with mild-to-moderate essential hypertension with or without associated diseases.

Insulin in bovine colostrum and milk: evolution throughout lactation and binding to caseins.

The changes in insulin concentration in bovine milk in the first period of lactation and its association with other milk proteins were studied. Highest concentration was found in the first milking (327 ng/ml). This concentration fell within the first 24 h postpartum to about 50% of its initial value. By d 3, the level was about 25%, and, on d 7, a stable concentration was reached at approximately 46 ng/ml (about 14% of its initial value). This concentration is about 100 times higher than that in serum, which suggests a specific mechanism of transfer from blood to milk. Colostral whey obtained by ultrafiltration or ultracentrifugation contains much less insulin than colostrum. When colostrum or milk was incubated with [125I]insulin and whey and casein fractions were separated by precipitation, it was observed that most insulin remained with the casein. However, when colostrum was incubated with [125I]insulin and subjected to gel filtration, most of the radioactivity corresponded to free insulin, indicating that insulin is associated with the precipitated casein but not with the casein micelles in solution.

Synthesis and evolution of concentration of beta-lactoglobulin and alpha-lactalbumin from cow and sheep colostrum and milk throughout early lactation.

Synthesis of beta-lactoglobulin and alpha-lactalbumin by explants of ovine mammary gland and evolution of concentration of these proteins in cow and sheep colostrum and milk throughout early lactation have been studied. The evolution of both proteins was similar in cow and sheep species. The highest concentration was found in the first milking (19 and 2 mg/ml for beta-lactoglobulin and alpha-lactalbumin, respectively). Then, levels of beta-lactoglobulin decreased sharply and those of alpha-lactalbumin slowly during the first days of lactation, reaching stable values during the second week postpartum (4 and 1.5 mg/ml). The concentration ratio beta-lactoglobulin/alpha-lactalbumin was four times greater in colostrum than in mature milk. On the other hand, synthesis of these proteins represented about 25-30% of the synthesized total soluble proteins. The synthesis ratio beta-lactoglobulin/alpha-lactalbumin in explants obtained at 12 and 30 hours postpartum was found to be 3.5 and 1.7. These results indicate that the synthesis and secretion of beta-lactoglobulin are comparatively greater than those of alpha-lactalbumin during colostral period, suggesting that beta-lactoglobulin could have some specific function during this period.

Recovery study in Mg-deficient rats given an organic source of Mg.

Recovery from Mg deficiency was studied in rats given an organic source of Mg derived from yeast (Saccharomyces cerevisiae) cultured in an Mg gluconate-enriched medium, as the only source of Mg. Magnesium was given either at a rate above the RDA or as a supplement to the regular laboratory diet at the rate of 70 mg Mg/100 g food, of which 40 mg Mg was in the form of MgCO3 and the remaining 30 mg Mg was in the form of the organic product under study. The results showed a good degree of digestive and metabolic utilization of the organic compound, which led to the recovery of normal Mg levels in blood and bone by the end of the 1st week of treatment, and in muscle by the 3rd week of treatment. Muscle Mg content appears to be a good indicator of deficiency. Supplementation above the RDA failed to improve recovery rates in deficient animals.

Nutritional availability of magnesium and calcium in magnesium-supplemented diets.

The nutritive utilization of magnesium and calcium was studied using two different formulations of Mg: MgCO3 and an organic dietary Mg preparation. The influence of supplementation with the latter was also studied. The dietary organic magnesium did not modify food intake, which remained adequate in all animals used in the present experiments. Magnesium in both inorganic compound and organic preparation form was well absorbed; furthermore, absorption levels of the latter remained quite stable throughout the different experimental periods. Mg balance in both muscle and femur was similar in all groups studied. Digestive utilization of Ca and Ca content in the longissimus dorsi were higher in animals fed the organic Mg preparation while Ca levels in blood and femur were not affected.

[Comparative prospective randomized multicenter study of 2 dosage protocols of nitrendipine in patients with mild to moderate hypertension]. / Estudio multicéntrico prospectivo randomizado comparativo de dos esquemas posológicos de nitrendipina en pacientes hipertensos leves-moderados.

134 patients with mild to moderate hypertension received nitrendipine during 6 months in an increasing fashion. Therapeutic goal was achieved in 92% of the patients (DBP less than 95 mmHg) in which BP decreased from 168.4 +/- 13.7/105.0 +/- 1.1 to 140.9 +/- 12.7/84.4 +/- 6.6 (p less than 0.001). In patients whose BP was not controlled with a single initial doses of 20 mg/day, the degree of control was similar with 40 mg single dose and 20 mg twice a day. The most frequently encountered undesirable effects were those caused by the vasodilator action of the drug. No changes in blood glucose and plasma lipid levels were found.

Time-course levels of alpha 2-macroglobulin and albumin in cow colostrum and milk and alpha 2-macroglobulin levels in mastitic cow milk.

Time-course levels of alpha 2-macroglobulin and albumin in cow's colostrum and milk during lactation were investigated in order to obtain data that could help to elucidate the biological role of alpha 2-macroglobulin in mammary secretions. Levels of these proteins were also studied in mastitic cow milk and were related to the degree of mastitis, which could allow its use as a mastitis marker. The highest concentration of alpha 2-macroglobulin was found in the first milking (386.7 micrograms/ml). This value decreased very rapidly during the colostral period, attaining its definitive value during the 2nd wk postpartum (4.5 micrograms/ml). The albumin/alpha 2-macroglobulin ratio increased by 6.8 in the first milking to 44.4 at 2 wk postpartum, indicating that the increase of alpha 2-macroglobulin was greater than that of albumin. In mastitic cow's milk, the concentration of alpha 2-macroglobulin (48.1, 71.4, and 89.0 microgram/ml) was also higher than that in normal milk. This increase was found to be related to the degree of mastitis as determined by the California Test.

Concentration of lactoferrin and transferrin throughout lactation in cow's colostrum and milk.

The evolution of the concentration of lactoferrin and transferrin was studied in cow's colostrum and milk throughout lactation. The highest concentrations of both proteins were found in the first milking (0.83 mg/ml for lactoferrin and 1.07 mg/ml for transferrin), decreasing sharply during the first days of lactation (colostral period). Thereafter, the concentrations of these proteins decreased slowly, reaching their definitive values during the third week post-partum (0.09 mg/ml for lactoferrin and 0.02 mg/ml for transferrin). The ratio transferrin/albumin in colostrum (first milking), mature milk, milk from mastitic cows and serum was determined, and found to be four times greater in colostrum than in mature or mastitic milk, suggesting a specific transport of transferrin from blood to milk.

Influence of hydrocortison acetate on the evolution of the nutritive utilization of calcium and phosphorus and their contents on the longissimus dorsi muscle during gestation in the rat.

The evolution of the nutritive utilization and plasma and muscular content of calcium and phosphorus in rats is studied, as well as the influence that hydrocortisone acetate has (4 mg/100 g weight and day), on them. In pregnant rats injected with saline solution, the retention of calcium is higher on the days 15-18 as a consequence of the increase on the net absorption of the cation. The balance of phosphorus reaches its maximum hight on days 18-21 of gestation, due to the decrease of the urinary excretion during these days. The administration of hydrocortisone acetate to pregnant rats originate a decrease of the net absorption and an increase of the urinary excretion of calcium and phosphorus, which leads to significantly lower balances than those of animals injected with saline solution. The hormone maintains the animals in a negative balance of phosphorus until day 18 of gestation. Besides, it impedes the high retention of calcium which is found with the control pregnant rats on days 15-18. In general, the content in calcium and phosphorus by gram of dry matter of Longissimus dorsi muscle is not modified during gestation. From day 9 of the treatment with hydrocortisone acetate a significant decrease of calcium and phosphorus of the muscle is observed, that in calcium is the more marked the more the treatment is prolonged. This effect seems to be due to the catabolic action of the hormone.