Quantitation of serum carotenoid concentrations in healthy inhabitants by high-performance liquid chromatography

Serum carotenoid concentrations in healthy subjects by age and sex were investigated, as determined by two high-performance liquid chromatography (HPLC) methods. Serum 'carotene' concentrations were 0.655 +/- 0.499 mumol/l 35.2 +/- 26.8 micrograms/dl) for 227 males, and 1,395 +/- 0.780 mumol/l (74.9 +/- 41.9 micrograms/dl) for 370 females. In addition, serum concentrations of alpha-carotene, beta-carotene, and lycopene were obtained from another sample included 356 males and 567 females living in the same area. alpha-Carotene for 356 males was 0.085 +/- 0.096 mumol/l (4.6 +/- 5.2 micrograms/dl), beta-carotene was 0.555 +/- 0.491 mumol/l (29.8 +/- 26.4 micrograms/dl), and lycopene was 0.372 +/- 0.273 mumol/l (20.0 +/- 14.7 micrograms/dl), respectively. Serum concentrations of alpha-carotene, beta-carotene as well as concentrations of lycopene in these inhabitants were significantly higher for females than for males (p less than 0.001).     

Plasma glutathione peroxidase in healthy young adults: influence of gender and physical activity

OBJECTIVES: Oxidative stress is implicated in the pathophysiology of many cardiovascular diseases. Plasma glutathione peroxidase (pl x GPx, GPx3) is an antioxidant enzyme found in the extracellular fluid. This study aimed to determine reference values for serum GPx3 concentration and GPx activity in young healthy males and females of similar aerobic fitness and to determine the impact of acute physical activity on serum GPx. DESIGN AND METHODS: 52 young, healthy but not physically trained subjects (24 male, 28 female; age = 20.4 +/- 0.7 yr, cycling VO(2 max) = 39.2 +/- 1.6 mL/kg/min; mean +/- SE) participated in this study. An independent group of 18 subjects participated in an acute, 90 min bout of 50% VO(2 max) cycling exercise. Serum GPx activity and GPx3 protein levels, as well as estradiol and 8-iso- prostaglandin F(2alpha) (8-iso-PGF(2alpha;) an index of lipid peroxidation) were determined. RESULTS: Females had significantly higher serum GPx3 concentration (29.1 +/- 1.6 vs. 24.2 +/- 1.3 mg/L, p < 0.01) and serum GPx activity (256.4 +/- 10.4 vs. 222.8 +/- 15.6 U/L, p < 0.05) than males; specific activity (U/mg) was not different between genders. There was no significant gender difference in 8-iso-PGF(2alpha). No significant correlation was found between either GPx activity or GPx3 concentration and serum estradiol or VO(2)(max). The acute, prolonged, mild intensity exercise did not affect serum GPx activity or 8-iso-PGF(2a) levels in males or females. CONCLUSIONS: The results of this study suggest that in a young, healthy but not physically well-trained population females are endowed with slightly higher serum GPx3 concentrations and GPx activities than males, but the functional significance of this has not been established. Furthermore, the results indicate that serum GPx levels are not associated with aerobic fitness level, or serum estradiol concentration and that acute, prolonged, mild exercise does not affect the activity of serum GPx in this population.     

Age-independent oxidative stress in elderly patients with non-insulin-dependent diabetes mellitus

Impaired antioxidant defence is implicated in the development of cardiovascular complications in non-insulin-dependent diabetes (NIDDM). However, as many of these patients are elderly, observed changes in antioxidant status may be due to the patient's age rather than their disease. We sampled blood from 47 elderly NIDDM patients (21 male and 26 female; mean age +/- SD, 75.62 +/- 7.97 years), 66 young (30 male and 36 female; 24.52 +/- 4.72 years) and 58 healthy elderly volunteers (17 male and 41 female; 70.74 +/- 4.85 years), and measured the antioxidant glutathione, the marker for free-radical-damage lipid hydroperoxide products (LHP), vitamin E and total antioxidant capacity (TAC). There was a significant increase in LHP in the healthy elderly group compared with the young volunteers (3.14 +/- 1.5 vs. 2.14 +/- 1.38 mumol/l, p < 0.01). The values were much higher in NIDDM patients (7.02 +/- 2.29 mumol/l, p < 0.0001 vs. healthy elderly). There was a reduction in TAC in healthy elderly compared with the young (359.99 +/- 54.82 vs. 471.47 +/- 94.29 mumol/l trolox equivalents, p < 0.0001), but there was no further reduction in NIDDM patients. Similarly, glutathione was reduced to the same degree in healthy elderly and NIDDM patients (0.29 +/- 0.09, 0.30 +/- 0.11 vs. 0.54 +/- 0.19 mumol/l in young volunteers, p < 0.0001). Vitamin E concentrations were comparable in all groups (26.34 +/- 5.39 young volunteers, 31.50 +/- 8.23 healthy elderly and 30.98 +/- 9.03 mumol/l NIDDM patients), but after correction for serum cholesterol there was a significant reduction in the diabetic group compared with the young, but not with the elderly (5.54 +/- 1.55 vs. 6.67 +/- 1.86 vs. 6.31 +/- 1.85 (mumol/l)/(mmol/l), p < 0.01). We have demonstrated an age-dependent reduction in total antioxidant capacity and glutathione defence and an age-independent increase in LHP in elderly patients with NIDDM. Reduced concentrations of vitamin E were demonstrated in NIDDM patients compared with young, but not elderly, volunteers. Increased oxidative damage occurs independently of age in NIDDM patients despite comparable antioxidant defences in this age group.     

In vivo total antioxidant capacity: comparison of two different analytical methods.

Several methods to assess the total antioxidant capacity (TAC) are available. However, the final value of measured TAC in the sample depends on the procedure used in every specific assay. This makes crucial the comparison of different analytical methods. The aim of our study was to evaluate analytical characteristics and laboratory reliability of two different assays: the ferric-reducing ability (FRAP) assay and a new spectrophotometric test (OXY-adsorbent test, Diacron, Italy). Unselected outpatients referred to the Institute of Clinical Physiology were studied (n = 187, 58 females, 129 males, mean age: 65 +/- 13 years). All blood samples were maintained on ice, centrifuged within 15 minutes after blood collection and then stored at -80 degrees C until performance of assay procedures. OXY assay: The lower limit of sensitivity was 6 micromol HClO/ml. The assay was found to be linear up to 440 micromol HClO/ml (r = -0.99, p < 0.001). Absorbance was linear over a wide concentration range with solutions containing uric acid in purified form (0-1000 micromol/l, r = -0.996, p < 0.001), serum (r = -0.99, p < 0.01) or plasma serially diluted (r = -0.99, p < 0.01). Mean value in plasma samples accounted for 366.2 +/- 7.2 micromol HClO/ml. Mean OXY value in females (353.4 +/- 13.2 micromol HClO/ml) was not different from that detected in males (372 +/- 8.6 micromol HClO/ml). A significant difference was observed between subjects without and with hypertension in serum OXY levels (344.8 +/- 9.9 and 383.2 +/- 10 micromol HClO/ml, p < 0.01, respectively). FRAP assay: The lower limit of sensitivity was 15 micromol/l. Linearity was observed up to 1000 micromol/l (r = 0.998, p < 0.001). Absorbance was linear over a wide concentration range with solutions containing uric acid in purified form (0-1000 micromol/l, r = 0.997, p < 0.001), serum (r = 0.99, p < 0.01) or plasma serially diluted (r = 0.99, p < 0.01). FRAP mean value in plasma samples, evaluated in 102 patients, accounted for 514.1 +/- 19.1 micromol/l. Mean FRAP in females (469 +/- 22.5 micromol/l) was not different from that detected in males (535 +/- 25.6 micromol/l). FRAP vs. OXY: A significant direct relationship was observed when comparing FRAP with OXY levels in the whole population (r = 0.22, p < 0.05). Neither of the methods are expensive and they are speedy and simple to perform. Values are reproducible and linearly correlated to the concentration of antioxidants present in the samples. For this reason, these methods may be considered practicable indicators of total antioxidant capacity, for routinely potential use in every laboratory and useful in all the studies concerning the evaluation of oxidative stress.     

Abnormal antioxidant vitamin and carotenoid status in chronic renal failure

Oxidative modification of plasma lipoproteins increases their atherogenicity. Nutritive antioxidants, including carotenoids, can prevent such lipoperoxidation and may protect against atherosclerosis. Plasma retinol, ascorbate, alpha-tocopherol and four carotenoids (lutein, lycopene, alpha-carotene and beta-carotene) were measured using HPLC in 45 patients with chronic renal failure (CRF) and in 21 controls. Plasma retinol was significantly increased in patients with CRF (conservative therapy mean of 3.7 mumol/l vs. 1.9 mumol/l; p < 0.001). Plasma lycopene was significantly lower in patients with CRF (healthy mean 0.44 mumol/l vs. conservative therapy mean 0.27 mumol/l and haemodialysis mean of 0.17 mumol/l; p < 0.001), a finding that persisted even after adjusting for plasma cholesterol. Low circulating antioxidant lycopene levels may contribute to an already impaired antioxidant defence system in patients with CRF. The process of haemodialysis further compromises antioxidant defences, principally by removing water-soluble ascorbate and urate, but does not appear to affect circulating carotenoid concentrations.      

Clinical usefulness of serum tartrate-resistant acid phosphatase activity determination to evaluate bone turnover.

The study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant acid phosphatase (TRAP) activity determined using an improved spectrophotometric assay. Enzyme activity was measured in 84 normal subjects and in 109 patients with common metabolic bone diseases. Mean values of serum TRAP activity in male subjects (n = 19; 10.4 +/- 2.15 U l-1) were not significantly different from those found in female subjects (n = 65; 10.8 +/- 1.8 U l-1). In the latter group mean values were significantly raised in post-menopausal subjects (10.5 +/- 2.0 U l-1; p less than 0.01) compared with mean values in pre-menopausal women (8.45 +/- 1.8 U l-1). We found a significant inverse correlation between serum TRAP activity values and bone mineral density (BMD) measured both at an ultradistal radial point (n = 33, r = -0.506; p less than 0.01), and at the lumbar spine (n = 57, r = -0.261; p less than 0.05). Mean serum TRAP activity values in patients with metabolic bone diseases were: primary hyperparathyroidism, n = 30: 14.2 +/- 4.89 U l-1, p less than 0.001 vs normal subjects; chronic maintenance haemodialysis, n = 19: 17.4 +/- 6.7, p less than 0.001; metastatic cancer, n = 13: 21.2 +/- 6.3, p less than 0.001; post-surgical hypoparathyroidism, n = 10: 9.9 +/- 1.8, NS; involutional osteoporosis, n = 20: 12.5 +/- 2.3 p less than 0.001; Paget's disease, n = 10: 16.8 +/- 3.5, p less than 0.001; osteomalacia, n = 7: 19.5 +/- 3.31, p less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum ferritin, iron status and plasma ascorbic acid in 40- to 49-year-old males in the Faroe Islands

Iron status (haemoglobin, S-ferritin, S-iron, S-transferrin, and transferrin saturation) was evaluated in an epidemiological survey comprising a representative sample of 118 (4%) of the 40- to 49-year-old Faroese male population. All had normal haemoglobin, (mean +/- SD 153 +/- 9 g/l; 9.5 +/- 0.6 mmol/l). Median S-ferritin was 151 micrograms/l, 5-95 percentile 46-588 micrograms/l, observed range 33-1166 micrograms/l. None had depleted iron stores (S-ferritin less than or equal to 20 micrograms/l), 2.5% had 'small' iron stores (S-ferritin 21-40 micrograms/l), 80.5% had 'normal' iron stores (S-ferritin 41-300 micrograms/l) and 17% had 'increased' iron stores (S-ferritin greater than 300 micrograms/l). Transferrin saturation values were greater than 16% in all males; high values greater than 50% were found in 9.3%, and the combination of high transferrin saturation and S-ferritin greater than 300 micrograms/l was found in 3.4% of the males. Median P-ascorbic acid was 26 mumol/l, 5-95 percentile 7-67 mumol/l; significantly higher in subjects taking vitamin supplements (n = 35, median 50 mumol/l) than in those not taking supplements (n = 81, median 23 mumol/l) (p less than 0.0001). There was no correlation between P-ascorbic acid and iron status markers. The results indicate a high frequency of ample iron reserves in the Faroese male population.     

Impact of physical fitness and glycemic control on in vivo insulin action in adolescents with IDDM

The relationship of in vivo insulin-mediated glucose utilization to the state of physical fitness and the degree of glycemic control was examined in 27 adolescents with insulin-dependent diabetes mellitus (IDDM) compared with 10 nondiabetic adolescent control subjects. In vivo total-body insulin-mediated glucose metabolism was evaluated by the hyperinsulinemic-euglycemic clamp. Physical fitness was assessed by maximal oxygen consumption (VO2 max) during cycle ergometry. Patients and control subjects had similar levels of VO2 max (34.9 +/- 8.6 vs. 38.6 +/- 9.9 ml.kg-1.min-1, P = 0.3). Patients had lower total-body insulin-mediated glucose metabolism compared with control subjects (33.9 +/- 14.3 vs. 63.8 +/- 17.2 mumol.kg-1.min-1, P = 0.0002). Among the patients, females had lower total-body insulin-mediated glucose metabolism compared with males (24.2 +/- 2.8 vs. 40.7 +/- 3.4 mumol.kg-1.min-1, P less than 0.001); however, this difference disappeared after correcting for sex differences in fitness levels. Insulin-mediated glucose metabolism correlated with VO2 max in patients and control subjects (r = 0.83, r = 0.81, P less than 0.05). The regression of total-body insulin-mediated glucose metabolism on VO2 max for patients was -2.84 +/- 0.255 VO2 max and for control subjects was 7.12 +/- 0.143 VO2 max, indicating that for similar degrees of physical fitness patients have lower total body insulin-mediated glucose metabolism levels than control subjects. In patients, total-body insulin-mediated glucose metabolism correlated with the degree of glycemic control as assessed by the level of glycosylated hemoglobin (r = -0.63, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation of hypoalbuminemia with a low level of dehydroepiandrosteron sulphate in blood serum of patients during chronic hemodialysis

AIM: To study dehydroepiandrosterone sulphate (DEA-S) in patients on chronic hemodialysis (HD) and its correlation with body mass and serum albumin. MATERIAL AND METHODS: DEA-S and cortisol in the serum were measured at enzyme immunoassay (EIA) in 124 patients (56 males, 68 females, mean age 47+/-12 years) on chronic HD. HD was made for 4 hours, on the average, 3 times a week using bicarbonate solution for dialysis. DEA-S and cortisol in blood serum were measured with EIA. RESULTS: A DEA-S level was higher in males than in females (7.6+/-5.3 and 3.4 +/-2.7 mcmol/l, respectively, p < 0.001). A negative correlation was found between the age and content of DEA-S (r = -0.36; p < 0.001). No correlation was established between DEA-S and cortisol content in blood serum (r-0.06; p = 0.6). Serum albumin was less in patients with low DEA-S. The multifactorial regression analysis showed an independent direct relationship between the levels of DEA-S and albumin in blood serum. CONCLUSION: DEA-S levels in HD patients depend on gender and age. The hormone concentrations are higher in males. Hypoalbuminemia in HD patients is associated with low DEA-S in blood serum.     

Oral cyclophosphamide versus chlorambucil in the treatment of patients with membranous nephropathy and renal insufficiency

We treated patients with idiopathic membranous nephropathy (iMGN) and renal insufficiency, using: (i) (n = 15) monthly cycles of steroids (1 g methyl-prednisolone i.v. on three consecutive days, followed by oral prednisone 0.5 mg/kg/day months 1, 3 and 5) and chlorambucil (0.15 mg/kg/day months 2, 4 and 6); or (ii) (n = 17) oral cyclophosphamide (1.5-2.0 mg/kg/day for 1 year) and steroids in a comparable dose. The groups were comparable in age, renal function and levels of proteinuria. During the 6 months preceding treatment, serum creatinine levels increased from 148 +/- 50 to 219 +/- 73 mumol/l in the chlorambucil group and from 164 +/- 86 to 274 +/- 126 mumol/l in the cyclophosphamide group. Median (range) follow-ups were: chlorambucil 38 months (8-71); cyclophosphamide 26 months (5-68) (NS). Renal function improved in both groups, but the improvement was short-lived in the chlorambucil group; 12 months after starting treatment, mean serum creatinine was 6.3 mumol/l lower in the chlorambucil group and 121 mumol/l lower in the cyclophosphamide group (p < 0.01). Four chlorambucil-treated patients developed ESRD, and five needed a second course of therapy, whereas only one cyclophosphamide-treated patient developed ESRD (p < 0.05). Remissions of proteinuria occurred more frequently after cyclophosphamide treatment (15/17 vs. 5/15; p < 0.01). Side-effects necessitated interruption of treatment in six patients on cyclophosphamide and in 11 on chlorambucil (p < 0.05). In our patients, oral cyclophosphamide was better tolerated than oral chlorambucil. The suggested greater efficacy of the oral cyclophosphamide regimen needs to be ascertained by longer follow-up.      

Sex differences in the hepatic uptake of sulphobromophthalein in the rat

Sex difference in the hepatic uptake of sulphobromophthalein (BSP) was investigated in male and female rats in three different experimental models. In the intact animal the BSP plasma disappearance rate was significantly higher (P less than 0.01) in females than in males when 0.15 or 1.5 mumol/kg body wt. was injected. Comparable values were found at the highest BSP dose (15 mumol/kg body wt.) used. In the perfused liver, the first-pass hepatic extraction and the uptake velocity were significantly higher (P less than 0.001) in female rats at low BSP doses (0.3-750 mumol/g of liver) whereas identical values were found at higher concentrations. In hepatocytes isolated by collagenase perfusion, the BSP uptake occurs via two different uptake sites in both sexes. The Km of the high affinity sites was lower in females than in males (3.67 +/- 0.58 vs 7.24 +/- 0.68 mumol/l, P less than 0.001) whereas Vmax. showed comparable values (2.70 +/- 0.36 vs 2.47 +/- 0.45 nmol of BSP/mg of protein, NS). In contrast, no difference was found in the kinetic parameters of the low affinity sites (Km 50.6 +/- 31.1 vs 61.0 +/- 17.5 mumol/l; Vmax. 21.9 +/- 13.2 vs 25.0 +/- 3.6 nmol of BSP/mg of protein, mean +/- SD, NS, females and males respectively). Taken together these data show that low doses of BSP are taken up by the liver more efficiently in female than in male rats and are consistent with a sex-related difference in the affinity but not in the number of the BSP high affinity uptake sites.     

Serum ferritin and iron status in a population of 'healthy' 85-year-old individuals

Iron status, including S-ferritin, S-iron, S-total iron binding capacity (TIBC), TIBC saturation, haemoglobin (Hb) and dietary iron intake, was assessed in a population study comprising 92 healthy 85-year-old subjects (32 males, 60 females). S-iron, S-TIBC, TIBC saturation and S-ferritin values were not significantly different in the two sexes. Males had a geometric mean S-ferritin of 130 micrograms/l, females of 98 micrograms/l. Ferritin levels less than 15 micrograms/l (i.e. depleted iron stores) were found in one female (1.6%); and in one male (3.1%), who in addition had iron deficiency anaemia. None of the females displayed latent iron deficiency (i.e. S-ferritin less than 15 micrograms/l and S-TIBC saturation less than 15%) or iron deficiency anaemia. Arithmetic mean Hb was 145 +/- 13 (SD) g/l (9.0 +/- 0.8 mmol/l) in males and 139 +/- 11 g/l (8.6 +/- 0.7 mmol/l) in females (p less than 0.02). Median nutritional iron intake was 10 mg/day (range 3-17), higher in males (median 12) than in females (median 9) (p less than 0.0001). Iron intake showed significant correlations to S-iron, S-TIBC and TIBC saturation, but not to S-ferritin.     

Renal insufficiency and treatment of persistent cardiac insufficiency with converting enzyme inhibitor

The purpose of this retrospective study was to consider impaired renal function in patients with severe congestive heart failure after converting enzyme inhibition and to emphasize the characteristics of this population. The study concerned 26 patients (pts), 72.5 +/- 8.1 years old, with a severe congestive heart failure (NYHA Class IV). Before treatment serum creatinine was slightly increased and the introduction of angiotensin converting enzyme inhibitor (ACEI) - Captopril 58.9 +/- 17.3 mg/j or enalapril 9.2 +/- 4.4 mg - impaired renal function from 132.0 +/- 50.7 mumol/l to 183.5 +/- 139.3 mumol/l (n = 26; p less than 0.05). Patients were separated in 3 groups: in group I; 15 pts, serum creatinine remained unchanged under ACEI in despite of the significant decrease of blood pressure (BP); from 140.7 +/- 24.0/82.5 +/- 13.4 to 120.3 +/- 12.8/71.8 +/- 8.7 mmHg (p less than 0.01). The cause of heart failure was an ischemic heart disease (IHD) in 15 patients (chi 2 test, p less than 0.05), a dilated cardiomyopathy in 4 pts and an aortic or mitral valvular regurgitation in 2 pts. In contrast renal function was significantly impaired in group II; serum creatinine increased from 120.8 +/- 25.2 to 189.0 +/- 80.7 mumol/l under ACEI. BP remained unchanged 136.9 +/- 29.0/78.1 +/- 4.9 and 118.7 +/- 13.6/75.6 +/- 7.6 mmHg respectively before and after treatment. There was 4 pts with dilated cardiomyopathy, 4 pts with mitral or aortic valvular regurgitation and only one with IHD. The introduction of an ACEI in two pts--group III--with severe tricuspid regurgitation induced an acute and reversal renal failure (serum creatinine at 600 mumol/l).     

Serum thiocyanate and smoking: interpretation of serum thiocyanate levels observed in a large health study

In a Norwegian health study involving 25,300 persons the mean serum thiocyanate level in non-smokers was 33.9 mumol/l for males and 33.5 mumol/l for females. In moderate smokers (five to nine cigarettes per day) the mean level was 59.6 mumol/l for males and 70.9 mumol/l for females. In heavy smokers (greater than 25 cigarettes per day) the mean level was 87.3 mumol/l in males and 99.7 mumol/l in females. The difference between the thiocyanate levels in females and males smoking the same number of cigarettes can be explained by the sex difference in distribution volume for thiocyanate. Among non-smokers the mean level of serum thiocyanate was the same whether the persons had been indirectly exposed to tobacco smoke or not. The mean serum thiocyanate levels were up to 10 mumol/l higher in the last half part of the year than in the first part. This can be explained by seasonal variations in the content of thiocyanate in the diet. The range of the individual thiocyanate level was great both in non-smokers and in smokers, resulting in a large overlap. Serum thiocyanate can therefore not distinguish all non-smokers from all smokers. However, by choosing suitable 'cut-off levels' it is possible to extract from the total population groups consisting of a large majority of smokers and only a few non-smokers and vice versa.     

Prevalence of low HDL cholesterol,and relationship between serum HDL and cardiovascular disease in elderly Spanish population: the PREV‐ICTUS study

Objective: To assess the prevalence of low serum high‐density lipoprotein cholesterol (HDL‐C) concentration and the relationship between HDL‐C and established cardiovascular disease (CVD) in an elderly Mediterranean population. Methods: Analysis of Prevención del Riesgo de Ictus, a population‐based study on Spanish subjects aged ≥ 60 years. Low HDL‐C was defined following the European guidelines for cardiovascular prevention [men: < 40 mg/dl (< 1.0 mmol/l); women: < 46 mg/dl (< 1.2 mmol/l)]. The relationship between low HDL‐C or HDL‐C concentration (in quintiles) and CVD was assessed through multivariate models that included cardiovascular risk factors, statins and subclinical organ damage. Results: On 6010 subjects (71.7 years, 53.5% women), low HDL‐C was present in 17.5% [95% confidence interval (CI): 16.5–18.5] and was more frequent in women [20.4% (19.0–21.8) vs. 14.1% (12.8–15.4) in men p < 0.001] and in patients with diabetes, CVD or statin therapy. Low HDL‐C was independently associated with CVD [adjusted odds ratio (OR): 1.46, 95% CI: 1.22–1.74, p < 0.001]. The prevalence of CVD was higher as HDL‐C concentration was lower (chi‐square trend < 0.001). Compared with the highest quintile [> 65 mg/dl (> 1.67 mmol/l)], adjusted OR for CVD were 1.39 (1.10–1.76), 1.41 (1.11–1.80), 1.49 (1.18–1.89) and 1.91 (1.52–2.39), respectively for those in the fourth [57–65 mg/dl (1.46–1.67 mmol/l)], third [51–56 mg/dl (1.31–1.45 mmol/l)], second [46–50 mg/dl (1.18–1.30 mmol/l)] and first [< 46 mg/dl (< 1.18 mmol/l)] quintiles of HDL‐C. This association was seen in males and females. Conclusions: A total of 17.5% of this Spanish population aged ≥ 60 years had low HDL‐C. We found a strong, independent and inverse association between HDL‐C concentrations and established CVD, even at ranges of HDL‐C considered as normal.     

Quantitative ultrasound in monitoring of skeletal status in adults with end-stage renal disease

The aim of the longitudinal study was to assess skeletal status in 29 subjects (18 males and 11 females) with end-stage renal disease (ESRD) being on regular hemodialysis. Control group consisted of 494 healthy subjects (305 males and 189 females). Skeletal status was evaluated by quantitative ultrasound measurements at the hand phalanges using DBM Sonic 1200 (IGEA, Carpi, Italy), which measures amplitude-dependent speed of sound (Ad-SoS, in m/s), performed three times: at the baseline, six and 12 months later. A precision expressed in root mean square-CV% was 0.72% in males and 0.43% in females. The values of Ad-SoS, T-score and Z-score at the baseline were significantly lower than in controls (p < 0.05). The mean values of Ad-SoS decreased over a period of observation; in the whole group from 1979 +/- 106 m/s to 1928 +/- 105 m/s, p < 0.0001, in males from 2003 +/- 93 m/s to 1949 +/- 111 m/s, p < 0.001 and in females from 1940 +/- 121 m/s to 1894 +/- 108 m/s, p < 0.05. Ad-SoS Z-scores dropped significantly over a period of the study in whole group (-1.14 +/- 1.64 to -2.08 +/- 2.26, p < 0.01), in males (-0.63 +/- 1.44 to -1.74 +/- 2.29, p < 0.0001) and in females nonsignificant decrease was observed. Using the least significant change (LSC) values for skeletal measurement, a decrease in Ad-SoS was noted in 15 subjects (52%). The values of PTH were over a normal limit. In the whole group main factors negatively influencing current Ad-SoS values were duration of dialysis, age and PTH. The skeletal status in subjects with ESRD on hemodialysis was seriously affected, and longitudinal measurements showed its aggravation over a time of the study.     

Clinico-pathological correlations and long-term follow-up of 253 United Kingdom patients with IgA nephropathy. A report from the MRC Glomerulonephritis Registry.

The Medical Research Council's Glomerulonephritis Registry was used to study clinicopathological correlations and renal survival in patients with IgA nephropathy reported between 1978 and 1985. IgA nephropathy was the histological diagnosis in 9.3 per cent of all renal biopsies reported to the registry during this period, and in 18.1 per cent of those with a primary glomerulonephritis. The 10-year cumulative renal survival rate accounting for censored data (Kaplan-Meier) was 83.3 per cent. Univariate analysis of survival curves (log-rank test) found the following parameters to be significantly correlated with poor renal survival: serum creatinine > 120 mumol/l (p < 0.001), hypertension (p < 0.001), serum albumin < 40 g/l (p < 0.005), proteinuria > 1 g (p < 0.025), age > 30 years (p < 0.025), and focal mesangial proliferation (p < 0.05). There was no significant difference in renal survival between males and females. Multivariate analysis (Cox's proportional hazards model) revealed that only a serum creatinine of > 120 mumol/l and a serum albumin of < 40 g/l were independently predictive of outcome. These findings indicate marked similarities between the UK experience of IgA nephropathy and the published European experience. IgA nephropathy is not a benign condition in the UK and patients with impaired renal function and/or those with a reduced serum albumin are significantly more likely to progress to end-stage renal failure within 10 years.     

Normal serum pepsinogen I levels in adults: a population-based study with special reference to Helicobacter pylori infection and parietal cell antibodies

OBJECTIVE: Low serum pepsinogen I (PG I) values are common in subjects with advanced corpus atrophy with or without parietal cell antibodies (PCA). Elevated values are usual during Helicobacter pylori infection. MATERIAL AND METHODS: PG I levels were determined in two randomly selected cross-sectional adult population samples using the Gastroset PGI test kits. The sera (408 in 1973 and 504 in 1994), tested earlier for H. pylori infection and now for PCA, represented subjects living in Vammala, Finland. RESULTS: In the PCA-negative population, the mean (+/-SD) PG I level was significantly higher in men than in women among both H. pylori-negative (88.13+/-34.16 microg/l versus 72.43+/-29.31 microg/l; p<0.0001) and H. pylori-positive (110.50+/-50.59 microg/l, versus 97.74+/-44.82 microg/l, p<0.0001) subjects; the difference between all H. pylori-positive and -negative subjects was also significant (p<0.001). In the 10-year age groups, age had no impact on the mean PG I levels in H. pylori-negative subjects (p=0.860). In the PCA-positive population, the 10 H. pylori-positive subjects had higher mean PG I levels (112.96+/-53.62 microg/l) than the 13 H. pylori-negative subjects (32.57+/-27.59 microg/l; p=0.002); the latter mean was also significantly lower than that of the PCA- and H. pylori-negative subjects (80.08+/-32.69 microg/l; p<0.0001). CONCLUSIONS: Men had higher normal PG I values than women, but there was no significant variation by age. H. pylori infection was associated with elevated PG I levels and a small decrease with increasing age. Non-infected PCA-positive subjects showed the lowest mean PG I level.     

Gender-dependent effect of ageing on peripheral insulin action

The aim of the present study was to investigate the effect of both gender and age on insulin secretion, peripheral insulin effectiveness and insulin-receptor binding. Eighty healthy volunteers, 40 females of mean age 38.47 +/- 11.37 years and mean BMI 21.99 +/- 2.06 kg/m(2) and 40 males of mean age 34.87 +/- 11.22 years and mean BMI 22.65 +/- 2.31 kg/m(2), with normal glucose tolerance participated in the study. Peripheral insulin effectiveness was measured by the artificial endocrine pancreas, using the euglycaemic hyperinsulinaemic clamp technique and insulin-receptor binding on circulating mononuclear blood cells. Peripheral insulin sensitivity was significantly higher in females as compared to males (p < 0.001), while males demonstrated higher total number of insulin receptors (p < 0.0001) and number of high-affinity receptors (p < 0.01). Peripheral insulin sensitivity decreased with ageing in both males and females, the reduction in females being more pronounced (p < 0.05). In the group under 40 years, the females demonstrated significantly higher insulin sensitivity as compared to males (p < 0.001) and lower insulin-receptor binding. Over 40 years, females presented higher peripheral insulin sensitivity and higher insulin-receptor binding. The percentage of specifically bound insulin increased significantly with ageing in females and decreased in males. We consider that probably the higher androgen level in males affects the post-receptor processes in insulin action and despite the higher insulin-receptor binding, males have lower insulin sensitivity. The androgen levels in females increase with ageing, which could probably affect peripheral insulin sensitivity at the post-receptor level. In conclusion, our results demonstrate that when analysing peripheral insulin effectiveness and insulin-receptor binding, one should always consider both gender and age.     

Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid

Elevated plasma homocysteine, an independent risk factor for cardiovascular disease (CVD) can be lowered by administration of pharmacological doses of folic acid. The effect of lower doses in apparently normal subjects is currently unknown but is highly relevant to the question of food fortification. Healthy male volunteers (n = 30) participated in a chronic intervention study (26 weeks). Folic acid supplements were administered daily at doses increasing from 100 micrograms (6 weeks), to 200 micrograms (6 weeks), to 400 micrograms (14 weeks). Fasting blood samples collected before, during and 10 weeks post intervention were analysed for plasma homocysteine, serum and red- cell folate levels. Results, expressed as tertiles of baseline plasma homocysteine concentration, showed significant (p < or = 0.001) homocysteine lowering in the top (10.90 +/- 0.83 mumol/l) and middle (9.11 +/- 0.49 mumol/l) tertiles only. In the low tertile, where the mean baseline homocysteine level was 7.07 +/- 0.84 mumol/l, no significant response was observed. Of the three folic acid doses, 200 micrograms appeared to be as effective as 400 micrograms, while 100 micrograms was clearly not optimal. There is thus a minimal level of plasma homocysteine below which folic acid has no further lowering effect, probably because an optimal folate status has been reached. A dose as low as 200 micrograms/day of folic acid is effective in lowering plasma homocysteine concentrations in apparently normal subjects. Any public health programme for lowering homocysteine levels, with the goal of diminishing CVD risk, should not be based on unnecessarily high doses of folic acid.