Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects

The relations of cholesteryl ester transfer protein (CETP) activity to the distribution of low density lipoproteins (LDLs) and high density lipoproteins (HDLs) were investigated in fasting plasma samples from 27 normolipidemic subjects. LDL and HDL subfractions were separated by electrophoresis on 20-160 g/L and 40-300 g/L polyacrylamide gradient gels, respectively. Subjects were subdivided into two groups according to their LDL pattern. Monodisperse patterns were characterized by the presence of a single LDL band, whereas polydisperse patterns were characterized by the presence of several LDL bands of different sizes. To investigate the influence of lipid transfers on LDL patterns, total plasma was incubated at 37 degrees C in the absence of lecithin:cholesterol acyltransferase (LCAT) activity. The incubation induced a progressive transformation of polydisperse patterns into monodisperse patterns. Under the same conditions, initially monodisperse patterns remained unchanged. Measurements of the rate of radiolabeled cholesteryl esters transferred from HDL3s to very low density lipoproteins (VLDLs) and LDLs revealed that subjects with a monodisperse LDL pattern presented a significantly higher plasma CETP activity than subjects with a polydisperse LDL pattern (301 +/- 85%/hr per milliliter versus 216 +/- 47%/hr per milliliter, respectively; p < 0.02). In addition, when total plasma was incubated for 24 hours at 37 degrees C in the absence of LCAT activity, the relative mass of cholesteryl esters transferred from HDLs to apolipoprotein B-containing lipoproteins was greater in plasma with monodisperse LDL than in plasma with polydisperse LDL (0.23 +/- 0.06 versus 0.17 +/- 0.06, respectively; p < 0.02). These results indicated that in normolipidemic plasma, CETP could play an important role in determining the size distribution of LDL particles. The analysis of lipoprotein cholesterol distribution in the two groups of subjects sustained this hypothesis. Indeed, HDL cholesterol levels, the HDL:VLDL+LDL cholesterol ratio, and the esterified cholesterol:triglyceride ratio in HDL were significantly lower in plasma with the monodisperse LDL pattern than in plasma with the polydisperse LDL pattern (p < 0.01, p < 0.01, and p < 0.02, respectively). Plasma LCAT activity did not differ in the two groups. Plasma CETP activity correlated positively with the level of HDL3b (r = 0.542, p < 0.01) in the entire study population. Whereas plasma LCAT activity correlated negatively with the level of HDL2b (r = -0.455, p < 0.05) and positively with the levels of HDL2a (r = 0.475, p < 0.05) and HDL3a (r = 0.485, p < 0.05), no significant relation was observed with the level of HDL3b.(ABSTRACT TRUNCATED AT 400 WORDS)     

LDL isolated from Greek subjects on a typical diet or from American subjects on an oleate-supplemented diet induces less monocyte chemotaxis and adhesion when exposed to oxidative stress

The mechanisms underlying the cardiovascular benefits of Mediterranean-style diets are not fully understood. The high content of monounsaturated fatty acids in Mediterranean-style diets derived from oleate-rich olive oil may be beneficial in reducing low density lipoprotein (LDL) oxidation and its subsequent development of atherogenic properties. This study sought to assess the proinflammatory potential of LDL isolated from subjects consuming a diet naturally rich in olive oil. LDL was isolated from 18 Greek, 18 American, and 11 Greek-Americans subjects, all of whom were living in the United States. Fatty acid composition and vitamin E levels of LDL were determined, as was the extent of copper-mediated LDL oxidation. LDL was also mildly oxidized by exposure to fibroblasts overexpressing 15-lipoxygenase and tested in vitro for bioactivity by determining its ability to stimulate monocyte chemotaxis and adhesion to endothelial cells. To confirm that dietary fatty acids influence the proinflammatory properties of mildly oxidized LDL, LDL was also isolated from 13 healthy American subjects after consumption of an 8-week liquid diet supplemented with either oleic (n=6) or linoleic (n=7) acid and tested for bioactivity in a similar fashion. There were no differences in the baseline lipid profiles among the Greeks, Americans, or Greek-Americans. Oleic acid content in LDL was 20% higher in the Greek compared with the American or Greek-American subjects (P<0.001). The extent of in vitro LDL oxidation, measured by conjugated diene formation, was lower in the Greek subjects (P<0.02), but there was no difference in the lag time. Induction of monocyte chemotaxis and adhesion by mildly oxidized LDL was decreased by 42% in the Greek group compared with the American subjects (P<0.001). There was an inverse correlation between the oleic acid content of LDL and stimulation of monocyte chemotaxis (r=-0.64, P<0.001) and a positive correlation between the polyunsaturated fatty acid content of LDL (total linoleate and arachidonic acids levels in LDL) and stimulation of monocyte chemotaxis (r=0.51, P<0.01) in the entire cohort. There were no differences in LDL vitamin E content between the groups. In the liquid-diet groups, the oleic acid-supplemented group had a 113% higher oleic acid content in LDL and a 46% lower linoleic acid content in LDL than the linoleate-supplemented group (P<0.001), whereas the vitamin E content in LDL was equal in both groups. When exposed to oxidative stress, the LDL enriched in oleic acid promoted less monocyte chemotaxis (52% lower) and reduced monocyte adhesion by 77% in comparison with linoleate-enriched LDL (P<0.001). There was a strong, negative correlation between oleic acid LDL content and monocyte adhesion (r=-0.73, P<0.001) and a strong, positive correlation between polyunsaturated fatty acid LDL content and monocyte adhesion (r=0.87, P<0.001). This study demonstrates that dietary enrichment of LDL with oleic acid is realistic and readily achieved by using diets currently in use in Mediterranean countries. In addition, these data suggest that LDL enriched with oleic acid and reduced in polyunsaturated fatty acids may be less easily converted to a proinflammatory, minimally modified LDL.     

Characterisation of bovine transferrin receptor on normal activated and Theileria parva-transformed lymphocytes by a new monoclonal antibody

A murine IgM monoclonal antibody (mAb), IL-A77, has been generated that recognises the bovine transferrin receptor (TfR) and will be a useful tool to measure the activation state of bovine lymphocytes and macrophages. The antigen is detected on immature erythroid cells and proliferating lymphocytes. It is undetectable on resting lymphocytes, but appears within 24 h after stimulation with concanavalin A (ConA) or pokeweed mitogen (PWM). Immune precipitations of lysates of both labeled activated lymphocytes and bone marrow erythroid cells showed that, similar to human TfR, the bovine receptor is a disulfide-bonded dimer of two identical chains of M(r) 97,000. A similar 97,000 M(r) protein was eluted from a column containing immobilised bovine transferrin (Tf) using conditions known to elute the human TfR, and this protein was recognised by mAb IL-A77, proving that it detected bovine TfR. Although the mAb inhibited binding of transferrin to its receptor, it did not block proliferation of Theileria parva-transformed or ConA-stimulated lymphocytes. When cells were metabolically labeled with 35S-methionine, a second 90,000-M(r) TfR band was detected in Theileria parva-transformed cells, but not in stimulated lymphocytes. This form of the TfR was not expressed on the cell surface. It may be an.     

Troglitazone decreases the proportion of small, dense LDL and increases the resistance of LDL to oxidation in obese subjects

OBJECTIVE: Insulin resistance is associated with a predominance of small, atherogenic LDL particles that are more prone to oxidative modification. Treatment with the insulin-sensitizer troglitazone may improve LDL composition and resistance to oxidation. RESEARCH DESIGN AND METHODS: In a randomized double-blind crossover design, 15 obese subjects were treated with either 400 mg troglitazone daily or placebo for 8 weeks. Insulin sensitivity (clamp), (apo)lipoproteins, LDL subclass pattern, plasma TBARS, and ex vivo LDL oxidation were determined. RESULTS: Troglitazone treatment improved insulin sensitivity. LDL cholesterol increased from 2.58 +/- 0.18 to 2.77 +/- 0.20 mmol/l (P = 0.03) because of an increase in large (buoyant) LDL1 (from 0.45 +/- 0.04 to 0.62 +/- 0.09 mmol/l, P = 0.008). Because small (dense) LDL3 decreased, LDL1:LDL3 ratio increased (P = 0.02). Plasma TBARS concentration declined significantly, and the lag time of ex vivo LDL oxidation showed a small but significant increase. CONCLUSIONS: In obese subjects, treatment with troglitazone improves insulin sensitivity, increases the ratio of large buoyant to small dense LDL, and appears to enhance the resistance of the LDL particle to oxidation. These qualitative changes in lipoproteins may have a beneficial effect on cardiovascular risk profile and compensate for a small increase in LDL cholesterol.     

Hypocholesterolemic effect of lycopene and beta-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages

Beta-Carotene and lycopene are derived from plants, and they share similar initial synthetic pathway with cholesterol, which is synthesized in animal but not in plant cells. Thus, we sought to analyze the effect of carotenoids on macrophage cholesterol metabolism, in comparison to the effect of LDL cholesterol and of the cholesterol synthesis inhibitor, fluvastatin. In J-774 A. 1 macrophage cell line, the cellular cholesterol synthesis from [3H]-acetate, but not from [14C] mevalonate, was suppressed by 63% any by 73% following cell incubation with beta-carotene or lycopene (10 microM) respectively, in comparison to a 90% and 91% inhibition by LDL (100 micrograms of cholesterol), or by fluvastatin (10 micrograms/ml) respectively. However, unlike LDL derived cholesterol, which also suppresses macrophage LDL receptor activity, lycopene and beta-carotene augmented the activity of the macrophage LDL receptor, similarly to the effect of fluvasfatin. In agreement with these in vitro observations, dietary supplementation of tomato's lycopene (60 mg/day) to 6 males for a 3 months period resulted in a significant 14% reduction in their plasma LDL cholesterol concentrations. We thus conclude that dietary supplementation of carotenoids may act as moderate hypocholesterolemic agents, secondary to their inhibitory effect on macrophage 3-hydroxy-3-methyl glutaryl coenzyme A (HMGCoA) reductase, the rate limiting enzyme in cholesterol synthesis.     

Binding of apoB-containing lipoproteins from unfractionated human blood sera to immobilized LDL receptor

Binding of apoB-containing lipoproteins from unfractionated human blood sera to the immobilized bovine receptor of low density lipoproteins (LDL receptor) was studied. Peroxidase-labeled anti-human apoB antibodies were used to evaluate the lipoprotein binding. The equilibrium dissociation constant (Kd) of the interaction between apoB-containing lipoproteins from unfractionated human sera from healthy donors and the immobilized LDL receptor varied from 1 to 20 microg apoB/ml. To describe the binding of lipoproteins to the LDL receptor, a parameter of relative binding affinity (RBA) was used. RBA is inversely related to value of Kd and equal to unity for the standard serum. The RBA values for the binding of apoB-containing lipoproteins from unfractionated sera to the immobilized LDL receptor were found to correlate with the RBA values for the binding of isolated VLDL (r = 0.76, p < 0.001) and fail to correlate with the RBA values for the binding of isolated LDL. The RBA values for the binding of apoB-containing lipoproteins from unfractionated sera correlated with the RBA values for the binding of apoE-containing lipoproteins from unfractionated sera (r = 0.92, p < 0.001) and with values of triglyceride concentration in the sera (r = 0.93, p < 0.001). The RBA values for the binding of apoB-containing lipoproteins from sera of patients with FDB whose LDL were unable to bind to the LDL receptor did not significantly differ from the RBA values for the normal sera. However, the removal of VLDL from the normal sera significantly decreased the RBA values for the binding of apoB-containing lipoproteins from unfractionated sera. The results indicate that the different binding of apoB-containing lipoproteins to the immobilized LDL receptor mainly depended on the different binding of VLDL and not of LDL.     

Influence of cadmium on resistance to antibiotics in salmonellae isolated from pigs

Repeated cultivations (4 passages) of salmonellae (18 strains) resistant to cadmium, streptomycin and beta-lactam antibiotics in Müller-Hinton Broth (MHB) and Mac-Conkey Broth (MCB) without and with CdSO4 (2, 20 and 100 mg/L) showed a higher toxic effect of cadmium in MCB. The strains survived at CdSO4 100 mg/L in MHB for four transfers, in MCB only a single transfer. In dependence on the medium used and amount of metal added, the increase of resistance to antibiotics was different. In MHB, the same levels of resistance to carbenicillin and streptomycin were induced by CdSO4 (20 and 100 mg/L), in MCB it was by 2 and 20 mg/L. Simultaneous stop of the growth of a control culture S. typhimurium with chromosomal resistance to streptomycin, isolates with and without plasmid in MCB which contained CdSO4 100 mg/L, and the results of conjugal transfer of resistance suggest that changes of resistance to antibiotics were not mediated by determinants of resistance to antibiotics. The binding of cadmium to outer membrane protein can cause a decreased permeability to these antibiotics as a resistance mechanism.     

Differences in the in vitro response of lymphocytes from leukotic and normal cattle to concanavalin A

The response of cultured peripheral blood lymphocytes from cattle affected with bovine leukosis and from animals free of detectable leukosis to the nonspecific mitogen Concanavalin A ws determined by the measurement of 3H-thymidine incorporation. The stimulatory effect of the mitogen was significantly decreased in leukotic lymphocytes in comparison with normal lymphocytes. This depression was dependent on the severity of the disease. Leukotic lymphocytes showed high basal levels of spontaneous thymidine uptake possibly due to their low maturity. It is suggested that leukotic lymphocytes are not stimulated by Concanavalin A because of their B cell characteristics. A residual cell population of normal reacting lymphocytes--enriched by nylon wool column fractionation--is probably responsible for the remaining but weak in vitro reaction of leukotic lymphocytes.     

Influence of insulin on cholesterol removal from macrophages and cholesterol ester uptake by HepG2 cells

The fact that an increased blood insulin level is observed in patients with coronary artery disease (CAD) confirms the hypothesis that insulin promotes the development of atherosclerosis. The low high-density lipoprotein (HDL) concentration observed in such patients may contribute to alteration in reverse cholesterol transport and promote the accumulation of sterols in vascular tissue. We examined the effect of insulin (20-1000 microU mL-1) on cholesterol efflux into HDL3 particles from human blood monocyte/macrophages and rat peritoneal macrophages preloaded with labelled cholesterol esters, and the influence of insulin on the accumulation of sterols by rat liver cells and HepG2 cell line in vitro models. Insulin at concentrations up to 250 microU mL-1 inhibited the efflux of cholesterol from rat macrophages and promoted high uptake of sterols by both types of hepatic cells. Pharmacological concentrations higher than 250 microU mL-1 exerted the opposite effect. In the case of human macrophages, an insulin concentration of 20 microU mL-1 increased cholesterol removal, whereas 100-200 microU mL-1 insulin inhibited cholesterol removal from cells, and very high concentrations (> 350 microU mL-1) again increased cholesterol removal. We have shown that insulin excess counteracts the beneficial effects of HDL in removing cellular cholesterol and, therefore, may promote development of atherogenesis.     

Changes in overbite and face height from 5 to 45 years of age in normal subjects

Periodate-oxidized ADP (oADP)2 and periodate-oxidized ATP (oATP) stimulate the permeability transition in energized rat liver mitochondria measured as the Ca2+-efflux induced by Ca2+ and Pi. In the presence of Mg2+ and Pi, mitochondria lose intramitochondrial adenine nucleotides at a slow rate. oATP induces a strong decrease of the matrix adenine nucleotides which is inhibited by carboxyatractyloside. Under these conditions, Mg2+ prevents the opening of the permeability transition pore. EGTA prevents the Pi-induced slow efflux of adenine nucleotides, but is without effect on the oATP-induced strong decrease of adenine nucleotides. This oATP-induced strong adenine nucleotide efflux is inhibited by ADP. oATP reduces the increase of matrix adenine nucleotides occurring when the mitochondria are incubated with Mg2+ and ATP. This effect of oATP is also prevented by carboxyatractyloside. oATP is not taken up by the mitochondria. It is suggested that oATP induces a strong efflux of matrix adenine nucleotides by the interaction with the ADP/ATP carrier from the cytosolic side. The induction of the mitochondrial permeability transition by oADP and oATP is attributed to two mechanisms-a strong decrease in the intramitochondrial adenine nucleotide content, especially that of ADP, and a stabilization of the c-conformation of the ADP/ATP carrier.     

In vitro effects of the pyrethroid S-bioallethrin on lymphocytes and basophils from atopic and nonatopic subjects

Synthetic pyrethroids are increasingly used as insecticides and marketed as having relatively low human toxicity. The aim of this study was to examine the in vitro effects of the synthetic pyrethroid S-bioallethrin on human blood lymphocytes and basophils in atopic individuals and nonatopic control subjects. S-bioallethrin caused inhibition of lymphocyte proliferation after a 72-h culture period in a concentration-dependent manner. The inhibition of the lymphocyte proliferation by S-bioallethrin at the concentration 6.5 microM correlated well with the total serum IgE values (r = -0.89, P < 0.001). Samples from atopic subjects were more sensitive to this inhibition than those from nonatopic volunteers. The regulatory interleukin-4/interferon-gamma (JL-4/IFN-gamma) balance showed a significant difference between atopic and nonatopic subjects after a short-term culture period (24 h) in the presence of the same concentration range of S-bioallethrin (P < 0.001). Additionally, IFN-gamma secretion was consistently lower in cells from the atopic donors. Furthermore, S-bioallethrin induced histamine release from human basophils in a concentration-dependent manner. Although the effect was small compared to histamine liberators such as N-formyl-Met-Leu-Phe and anti-IgE, the response to S-bioallethrin was significantly different in atopic donors from nonatopic (P = 0.0431). These findings are the first demonstration of the immunotoxicologic properties of the synthetic pyrethroid S-bioallethrin by this combined in vitro approach with human lymphocytes and basophils. Further studies will investigate the responses of lymphocytes from patients who are sensitive to these agents.     

Fenofibrate reduces plasma cholesteryl ester transfer from HDL to VLDL and normalizes the atherogenic, dense LDL profile in combined hyperlipidemia

The effect of fenofibrate on plasma cholesteryl ester transfer protein (CETP) activity in relation to the quantitative and qualitative features of apoB- and apoA-I-containing lipoprotein subspecies was investigated in nine patients presenting with combined hyperlipidemia. Fenofibrate (200 mg/d for 8 weeks) induced significant reductions in plasma cholesterol (-16%; P < .01), triglyceride (-44%; P < .007), VLDL cholesterol (-52%; P = .01), LDL cholesterol (-14%; P < .001), and apoB (-15%; P < .009) levels and increased HDL cholesterol (19%; P = .0001) and apoA-I (12%; P = .003) levels. An exogenous cholesteryl ester transfer (CET) assay revealed a marked decrease (-26%; P < .002) in total plasma CETP-dependent CET activity after fenofibrate treatment. Concomitant with the pronounced reduction in VLDL levels (37%; P < .005), the rate of CET from HDL to VLDL was significantly reduced by 38% (P = .0001), whereas no modification in the rate of cholesteryl ester exchange between HDL and LDL occurred after fenofibrate therapy. Combined hyperlipidemia is characterized by an asymmetrical LDL profile in which small, dense LDL subspecies (LDL-4 and LDL-5, d = 1.039 to 1.063 g/mL) predominate. Fenofibrate quantitatively normalized the atherogenic LDL profile by reducing levels of dense LDL subspecies (-21%) and by inducing an elevation (26%; P < .05) in LDL subspecies of intermediate density (LDL-3, d = 1.029 to 1.039 g/mL), which possess optimal binding affinity for the cellular LDL receptor. However, no marked qualitative modifications in the chemical composition or size of LDL particles were observed after drug treatment. Interestingly, the HDL cholesterol concentration was increased by fenofibrate therapy, whereas no significant change was detected in total plasma HDL mass. In contrast, the HDL subspecies pattern was modified as the result of an increase in the total mass (11.7%) of HDL2a, HDL3a, and HDL3b (d = 1.091 to 1.156 g/mL) at the expense of reductions in the total mass (-23%) of HDL2b (d = 1.063 to 1.091 g/mL) and HDL3c (d = 1.156 to 1.179 g/mL). Such changes are consistent with a drug-induced reduction in CETP activity. In conclusion, the overall mechanism involved in the fenofibrate-induced modulation of the atherogenic dense LDL profile in combined hyperlipidemia primarily involves reduction in CET from HDL to VLDL together with normalization of the intravascular transformation of VLDL precursors to receptor-active LDLs of intermediate density.     

Mechanisms of whole-body glycogen deposition after oral glucose in normal subjects. Influence of the nutritional status

It is known that prior fasting enhances whole-body glycogen retention after glucose ingestion. To identify the involved mechanisms, 33 normal volunteers underwent a total fast, varying between 14 h and 4 days, and ingested thereafter 75 g glucose labeled with [14C]glucose. Measurements of oral glucose oxidation (expired 14CO2, corrected for incomplete recovery) and total carbohydrate (CHO) oxidation (indirect calorimetry) were performed over the following 5 h. These data allowed us to calculate oral glucose storage (uptake oxidation), glycogen oxidation (CHO oxidation - oral glucose oxidation), and net CHO balance (oral glucose uptake - CHO oxidation). As compared with an overnight fast, prolonged fasting (4 days) inhibited the uptake (64.8 vs. 70.3 g/5 h; P < 0.01) and the oxidation (10.9 vs. 20.0 g/5 h; P < 0.001) of oral glucose and stimulated slightly its conversion to glycogen (53.9 vs. 50.3 g/5 h; P < 0.05). The latter effect played only a minor role in the marked increase in net CHO balance (52.3 vs. 25.2 g/5 h; P < 0.001), which was almost entirely related to a decrease in glycogen oxidation (1.6 vs. 25.1 g/5 h; P < 0.001). Considering the whole series of data, including intermediate durations of fast, it was observed that the modifications in postprandial CHO metabolism, induced by fasting, correlated strongly with basal CHO oxidation, suggesting that the degree of initial glycogen depletion is a major determinant of glycogen oxidation and net CHO storage. Thus, prior fasting stimulates postprandial glycogen retention, mainly through an inhibition of the glycogen turnover that exists in overnight-fasted subjects, during the absorptive period.     

Autoantibodies to the insulin receptor. Effect on the insulin-receptor interaction in IM-9 lymphocytes

The serum of some patients with insulin-resistant "diabetes" contains antibodies that bind to and block the cell membrane receptors for insulin. In this report, we have characterized the effects of the antireceptor antibodies on the interaction of (125)I-insulin with its receptor on the human lymphoblastoid cell line IM-9. Up to 95% of specific insulin binding can be inhibited by pretreatment of the cells with these immunoglobulins. The onset of the inhibitory effect is time- and temperature-dependent, and the effect is reversed extremely slowly if the cells are suspended in a large excess of antibody-free buffer. These features of antibody binding can be easily distinguished from those for insulin binding to its receptor. The inhibitory effect of the antibodies can be reversed by exposure of the cells to conditions known to elute surface immunoglobulins. The three antireceptor sera studied appear to alter the insulin-receptor interaction in different ways. Two antisera markedly reduce receptor affinity through combined effects on the insulin association and dissociation rates, and, additionally, have smaller effects on available receptor number. A third antiserum primarily affects available receptor number and has little effect on receptor affinity. All three antisera inhibit the capacity of insulin to promote negatively cooperative site-site interactions among insulin receptors. The data suggest that these autoantibodies to the insulin receptor bind to different determinants on the receptor and may therefore be useful as unique probes of insulin receptor structure and function.     

Seasonal variations in the composition of urine from normal subjects: a longitudinal study

The volume, pH and composition of 24-h urine samples, collected by 13 healthy male adults, were followed over a period of one year. Significant and systematic variations in urine pH, calcium, phosphate, oxalate, uric acid, potassium and magnesium were observed. A significant but non-sinusoidal variation in sodium excretion was found but there were no significant changes in urinary volume, creatinine or hydroxyproline. Many of the observed changes could be attributed to variations in the pattern of food consumption throughout the year but calcium, phosphate and oxalate were exceptions in that seasonal variations in these parameters appeared to be due to the effects of sunlight (or vitamin D) rather than to the diet.     

Effect of indomethacin on the renal response to angiotensin II receptor blockade in healthy subjects

BACKGROUND: Non-steroidal anti-inflammatory drugs are known to promote sodium retention and to blunt the blood pressure lowering effects of several classes of antihypertensive agents including beta-blockers, diuretics and angiotensin converting enzyme (ACE) inhibitors. The purpose of the present study was to investigate the acute and sustained effects of indomethacin on the renal response to the angiotensin II receptor antagonist valsartan and to the ACE inhibitor enalapril. METHODS: Twenty normotensive subjects maintained on fixed sodium intake (100 mmol sodium/day) were randomized to receive for one week: valsartan 80 mg o.d., enalapril 20 mg o.d., valsartan 80 mg o.d. + indomethacin 50 mg bid and enalapril 20 mg o.d. + indomethacin 50 mg bid. This single-blind study was designed as a parallel (valsartan vs. enalapril) and cross-over trial (valsartan or enalapril vs. valsartan + indomethacin or enalapril + indomethacin). Renal hemodynamics and urinary electrolyte excretion were measured for six hours after the first and seventh administration of each treatment regimen. RESULTS: The results show that valsartan and enalapril have comparable renal effects characterized by no change in glomerular filtration rate and significant increases in renal plasma flow and sodium excretion. The valsartan- and enalapril-induced renal vasodilation is not significantly blunted by indomethacin. However, indomethacin similarly abolishes the natriuresis induced by the angiotensin II antagonist and the ACE inhibitor. CONCLUSIONS: This observation suggests that although angiotensin receptor antagonists do not affect prostaglandin metabolism, the administration of a non-steroidal anti-inflammatory drug blunts the natriuretic response to angiotensin receptor blockade.     

Effect of aging on the body composition of dialyzed subjects. Comparison with normal subjects

A bioimpedance analyzer (BIA-CHIP; Akern RJL System) was applied to 366 normal subjects (171 men and 195 women). Each gender group was divided into eight groups, according to age: 20-29 years; 30-39 years; 40-49 years; 50-59 years; 60-69 years; 70-79 years; 80-89 years; and 90-95 years. The same was done with 44 hemodialysis patients (22 men, 22 women), each being evaluated 15 times over a period of 5 years: these were divided into seven groups (seven, because no patient was older than 89) using the same criteria. For each subject, 23 parameters were determined: 5 directly measured (height, weight, resistance, reactance, phase angle) and the others (fat and lean mass, body water, body cell mass, extra and intracellular water, etc.) from appropriate equations. Twenty-four thousand data points were collected and served to form a data bank. Men and women on hemodialysis showed different effects of aging: women normalized their BC at an age > 70 years, whereas men continued to have a muscle mass lower than that of normal subjects until the age of 80. A computerized program (Nutritio) permits fast and reliable evaluation of the nutritional status of hemodialysis patients, each subject being compared with both the similarly aged population (dialyzed or not) or with his or her own data, obtained over time.