Vitamin E kinetics in smokers and nonsmokers.

Does cigarette smoking increase vitamin E utilization in vivo? A trial was carried out in 6 smokers and 5 nonsmokers of comparable ages and serum lipids. Subjects consumed 75 mg each d(3)-RRR and d(6)-all rac-alpha-tocopheryl acetates (natural and synthetic vitamin E, respectively) daily for 7 d with a standardized breakfast. Fasting blood samples were drawn on days -7, -6, -5, -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7, 9, 14, 21 (negative days indicate supplementation). In both groups, plasma d(3)-alpha-tocopherol concentrations were approximately double of d(6)-alpha-tocopherol. At day 0, the %d(3) alpha-tocopherols (d(3)-alpha-tocopherol/total-alpha-tocopherol x 100) were similar in both smokers and nonsmokers. Subsequently, there was a trend toward a faster exponential disappearance of the plasma %d(3) alpha-tocopherol in smokers compared with nonsmokers (0.30 +/- 0.04 compared with 0.24 +/- 0.05, p =.0565). The calculated %d(3) half-lives were 55.6 +/- 7.4 h in smokers and 72.1 +/- 17.3 h in nonsmokers (p =.0630). By day 21, the %d(3) in smokers had decreased to 1.4% +/- 0.3% while it was 2.2% +/- 0.7% (p =.0418) in the nonsmokers. These data suggest that smoking increases plasma vitamin E disappearance, but further studies are needed to confirm this finding and to assess its cause.

Ex vivo low-density lipoprotein oxidizability and in vivo lipid peroxidation in patients on CAPD.

BACKGROUND: Chronic renal failure is associated with accelerated atherosclerosis and a high incidence of cardiovascular disease. Oxidative modification of low-density lipoprotein (LDL) is considered a key event in atherogenesis. METHODS: We studied the ex vivo oxidizability of LDL exposed to Cu2+ ions (lag time, rate of propagation, maximum conjugated diene formation) and its relationship with LDL density, fatty acids, and antioxidants, along with plasma malondialdehyde (MDA) and autoantibodies against Cu2+-, MDA-, and hypochlorous acid-modified LDL and plasma antioxidants in 17 continuous ambulatory peritoneal dialysis (CAPD) patients and 21 healthy control subjects. RESULTS: LDL alpha- and gamma-tocopherol and total polyunsaturated fatty acid (PUFA) concentrations were significantly higher in the CAPD patients. LDL density was shifted to small, dense LDL. LDL oxidizability was comparable to that of healthy subjects. Lag time correlated positively with LDL alpha-tocopherol and inversely with both total PUFA concentrations and density; the rate of oxidation and LDL density correlated positively with total PUFA and total fatty acid concentrations, respectively. Ratios of autoantibody titers against oxidized to native LDL did not differ between the two groups. While plasma alpha- and gamma-tocopherol concentrations and tocopherol to cholesterol ratios were significantly higher, vitamin C concentrations were very low in the CAPD patients. MDA concentrations were 1.7 times higher than in healthy subjects. CONCLUSIONS: (1) Ex vivo LDL oxidizability is normal in CAPD patients as a result of efficient protection by LDL-associated lipophilic antioxidants, although the LDL composition is altered toward high oxidizability; and (2) the plasma antioxidant screen is insufficient due to impaired vitamin C status.

Leptin deficiency due to lipid apheresis: a possible reason for ravenous hunger and weight gain.

OBJECTIVE: To investigate how extracorporal cholesterol lowering therapy affects circulating leptin levels in patients with ravenous hunger after treatment and permanent weight gain. DESIGN: A case report. SUBJECT: 51 y old caucasian male patient with moderate chronic renal failure. MEASUREMENTS: Serum Leptin concentration (RIA, Linco Research Inc, St. Louis, MO, USA), total cholesterol, low density lipoprotein cholesterol, blood glucose levels, calorie intake by food records. RESULTS: During treatment total cholesterol was reduced by 50%. Serum Leptin levels showed a 42% reduction at the end of treatment, that by far exceeds the physiological diurnal variation. Calorie intake was significantly increased on days of treatment. CONCLUSION: We conclude that this artificial reduction in circulating leptin plays an important role in the pathogenesis of ravenous hunger and weight gain under extracorporal cholesterol lowering therapy in this case.

Lack of correlation between the alpha-tocopherol content of plasma and LDL, but high correlations for gamma-tocopherol and carotenoids.

In 59 healthy human subjects (37 male and 22 female) the concentrations of the lipid-soluble antioxidants alpha- and gamma-tocopherol, alpha- and beta-carotene, lycopene, cryptoxanthin, canthaxanthin, and lutein + zeaxanthin were determined in plasma (mumol/L) and in isolated low density lipoproteins (LDL) (mumol/mmol cholesterol). Plasma alpha-tocopherol concentrations were significantly correlated with plasma total cholesterol concentrations (r2 = 0.51, P < 0.0001) yet not with the LDL alpha-tocopherol content (r2 = 0.05, ns). Plasma gamma-tocopherol concentrations were weakly correlated with plasma total cholesterol (r2 = 0.12, P < 0.003) and both absolute and cholesterol standardized plasma gamma-tocopherol concentrations correlated strongly with the LDL gamma-tocopherol content (r2 = 0.58 and r2 = 0.72, respectively). In contrast, carotenoid concentrations did not correlate with cholesterol concentrations, but their LDL content correlated significantly with the respective plasma concentrations (r2 = 0.67 to 0.92, all P < 0.0001). In a subgroup of study subjects (n = 13) the distribution of vitamin E and carotenoids among LDL was calculated. The proportion of plasma alpha- and gamma-tocopherol found in LDL was 48 +/- 7 (range, 36-61%) and 41 +/- 7%, respectively, suggesting that LDL was in most of these subjects not the main carrier for these antioxidants. The lipophilic carotenoids, however, were predominantly carried by LDL (e.g., beta-carotene: 87 +/- 10%), whereas the proportion of the more polar ones carried by LDL was much smaller (e.g., lutein + zeaxanthin: 36 +/- 6%). The results of this study show that plasma alpha-tocopherol concentrations are not predictive for the alpha-tocopherol content of LDL in nonsupplemented individuals. This finding could have implications in interpreting the cause of the inverse relationship between plasma alpha-tocopherol and risk of atherosclerosis.

Bone marrow changes following treatment of renal anemia with erythropoietin.

In 14 severely anemic patients with end-stage renal disease and chronic hemodialysis the effect of recombinant human erythropoietin (EPO) on hemopoiesis was investigated. Bone marrow biopsies were taken before and after four and 26 months of treatment with EPO to evaluate quantitative and qualitative changes of histomorphology. EPO induced normalization of maturation and an increase in cell mass of the erythropoietic line in all patients. The number of megakaryocyte also increased significantly with EPO treatment (P less than 0.01). At the time of the third bone marrow biopsy (26 months) erythropoiesis was normal. Megakaryopoiesis remained unchanged compared to the second biopsy (4 months). No cytomorphologic abnormalities or other evidence for malignant disorder could be detected in any of the patients. Hematocrit increased from a mean of 19 to 31 percent at the second evaluation (P less than 0.001). Platelet count had risen by a mean of 30,000 at four months (P less than 0.05) and slightly decreased at 26 months. These observations suggest great safety of long-term treatment with recombinant human erythropoietin, and demonstrate efficacy in correcting reduced and immature erythropoiesis in chronically hemodialyzed patients. EPO also stimulates human megakaryopoiesis.

[Clinical experiences with Wegener's granulomatosis from the nephrologic viewpoint]. / Klinische Erfahrungen mit der Wegenerschen Granulomatose aus nephrologischer Sicht.

Immunosuppressive treatment with cyclophosphamide and prednisolone has markedly improved the prognosis of Wegener's granulomatosis (WG). In patients with WG the detection of anti-neutrophil-cytoplasmic autoantibodies (ANCA or ACPA) has become an important parameter to confirm or even routinely establish the diagnosis of WG over the past few years. From 1985 to 1990 we observed and treated 12 patients (5 males and 7 females) aged 14-64 years (mean 41.1 years) with WG. In the same time span an analysis of 35 patients with rapidly progressive glomerulonephritis showed that the octiology was idiopathic in the majority of cases (54.3%), but nevertheless 8 cases (22.8%) were caused by WG. In 9 out of 10 cases the ANCA test was positive; whereas in 8 out of 10 cases we found a close correlation between the serum level of ANCA and disease activity. However, extraordinarily high serum levels (titres up to 1:2560) were recorded in one patient with WG without any clinical symptoms, whilst another patient with severe symptoms of WG showed a titre of only 1:5. 10 out of 12 patients were successfully brought to remission under cyclophosphamide-cortisone treatment. 4 out of 10 patients with renal insufficiency have been retained on the chronic haemodialysis regimen. 2 patients, aged 31 and 51 years, died within 2-5 months after the onset of clinical symptoms of WG.

[Continuous measurement of blood volume changes in hemodialysis using an ultrasound method]. / Kontinuierliche Messung von Blutvolumenänderungen während der Hämodialyse mit einer Ultraschallmethode.

Haemodialysis treatment comprises the removal of surplus body water, mainly by ultrafiltration. Frequent complications, such as hypotension, are believed to be related to an imbalance between blood volume reduction, based upon ultrafiltration, and vascular refilling. The control of fluid balance can be achieved by the measurement of blood volume changes. A new method of determining total blood protein concentration by ultrasonic means facilitates continuous monitoring of blood volume changes during haemodialysis. Blood volume monitoring was undertaken during 38 haemodialysis treatments (19 patients) in order to achieve a better adjustment of the patient's estimated dry weight. The relative change in blood volume was registered in 11 patients who were first ultrafiltrated to their estimated dry weight. In a following session the ultrafiltration was increased by 10%. The relative change in blood volume, normalized to the change in total body water, increased significantly from 1.16 +/- 1.11% (normal ultrafiltration) to 1.67 +/- 0.8% (normal ultrafiltration + 10%) (p less than 0.05). Thus, normalized blood volume reduction may serve as an approximation to adjust the patient's dry weight.