Effect of beta-carotene on immunological indexes in healthy male smokers.

To evaluate the immunomodulatory effects of beta-carotene we performed a randomized, double-blind trial in healthy male cigarette smokers. Lymphocyte subsets in peripheral blood were assessed by using double labeling with monoclonal antibodies before and after 14 wk beta-carotene (20 mg/d; n = 21) or placebo (n = 24) supplements. In addition we measured the ex vivo phytohemagglutinin and concanavalin A induced lymphocyte proliferation in a separate group (23 placebo, 24 beta-carotene). The beta-carotene and placebo groups were comparable on all initial characteristics. During the intervention plasma concentrations of beta-carotene increased 13-fold in the treatment group whereas retinol concentrations remained constant. Beta-carotene had no effect on lymphocyte subpopulations in peripheral blood. After treatment the beta-carotene group showed 12% higher PHA-induced lymphocyte proliferations than the placebo group (P = 0.02). For ConA induced proliferations no significant difference was observed. These results suggest that supplementary beta-carotene can moderately enhance certain aspects of immune response in healthy male cigarette smokers.

Bile acids, neutral steroids, and bacteria in feces as affected by a mixed, a lacto-ovovegetarian, and a vegan diet.

In a metabolic ward 12 healthy male subjects consumed mixed Western (M), lacto-ovovegetarian (L), and vegan (V) diets in a randomized order for 20 d each. The concentrations of deoxycholic acid, isolithocholic acid, and total bile acids in 4-d composites of feces on the L and V diets were significantly lower than on the M diet. The chenodeoxycholic-to-isolithocholic plus lithocholic acid ratio was significantly higher on the V diet. The concentrations of coprostanol and of coprostanol plus cholesterol were highest on M diet and lowest on V diet. The number of fecal lactobacilli and enterococci on the V diet was significantly lower than on the M or the L diets. This study showed a decrease in the concentration of fecal (secondary) bile acids by the L and the V diets and an alteration of the fecal flora composition by the V diet.

Dose-response relationships regarding vitamin B-6 in elderly people: a nationwide nutritional survey (Dutch Nutritional Surveillance System).

The dietary intake and biochemical status of vitamin B-6 in 476 apparently healthy Dutch elderly people (aged 65-79 y), who were not using drugs known to affect vitamin B-6 metabolism, were evaluated. Intake of vitamin B-6 per gram protein was related to biochemical data, namely plasma pyridoxal 5'-phosphate (PLP) and cofactor stimulation of aspartate aminotransferase in erythrocytes (AST-AC). Based on a cutoff point of 2.02 for AST-AC, approximately 9% of the elderly people not using vitamin B-6 supplements had a marginal vitamin B-6 status. About 7% were using vitamin B-6 supplements. Dietary intake of vitamin B-6 per gram protein was negatively related to AST-AC. Vitamin B-6 intakes per gram protein higher than 0.020 mg were necessary to ensure an AST-AC value less than 2.02. At high PLP values AST-AC hardly varied. The results seem to indicate a higher requirement of vitamin B-6 in elderly people than in younger adults.

Autoantibodies and immunoglobulin allotypes in healthy North American Blacks of different age groups.

A population of 291 healthy North American Black subjects of different ages was studied for immunoglobulin (Ig) allotypes and the prevalence of autoantibodies, to determine possible associations between Ig allotypes and age, autoantibodies and age, and Ig allotypes and autoantibodies. Indirect immunofluorescence was used to detect anti-gastric parietal cell, anti-smooth muscle, anti-thyroid microsomal, anti-nuclear, and anti-mitochondrial antibodies. The sera were typed for the Ig allotypes Gm(1, 2, 3, 5, 6, 13, 14, 17, and 21) and Km(1) with a hemagglutination-inhibition assay. A significant association between advanced age and an increased prevalence of anti-nuclear antibodies was observed in females. There was no significant association between Ig allotypes and the autoantibodies tested. The results suggest that Ig allotypes are not involved in the development of autoantibodies in healthy Blacks.

Complement activation associated with active cytomegalovirus infection in renal transplant patients, and its absence in transplant rejection episodes.

In 20 patients with a cadaveric renal allograft, serial measurements were made of the serum complement factors C3, C4, factor B (FB), and C3d, the stable conversion product of C3. Measurements were started immediately before transplantation and continued thereafter once a week to investigate whether these assays help to differentiate between acute allograft rejection (R) and an active cytomegalovirus (CMV) infection. Fifteen patients had one or more R episodes, and 9 patients suffered from an active CMV infection. Six patients had an R episode and subsequently a CMV infection 13-64 days after R. No significant changes were found in the levels of C3, C4, and FB during R or CMV infection. C3d levels remained unchanged or decreased slightly during R. However, there was a 43-500% increase in the C3d level during CMV infection. This difference in the behavior of levels of C3d during R and CMV infection is significant (P less than 0.01), and suggests that serial measurements of C3d may be useful in differentiating CMV infection from R after renal transplantation.

Effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator and plasminogen activator inhibitor.

Short-term effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were studied in two age groups of volunteers (20-30 and 45-55 years), each consisting of eight healthy males. The alcohol (30 g in red port and wine) was consumed during a standard dinner. Two blood samples were drawn: one in the postprandial phase, and one the next morning after fasting overnight. Alcohol consumption tended to increase platelet aggregation and production of hydroxy fatty acids, reduced plasma t-PA activity and increased PAI activity in the postprandial phase. After the overnight fast the effects on t-PA and PAI had disappeared whereas at that time alcohol consumption tended to decrease platelet function. The effects of alcohol on t-PA and PAI activity appeared mainly in the older age group, whereas the t-PA activity in this group was already much lower, irrespective of alcohol consumption.

Dietary fat and the risk of breast cancer.

Age-adjusted dietary fat intake of 133 incident Dutch breast cancer cases was significantly (p less than 0.01) higher than in 289 apparently healthy controls (mean and standard deviation: 102 +/- 36 g and 92 +/- 30 g, respectively). The age-adjusted relative odds of breast cancer showed a positive trend (p less than 0.05) with increasing fat intake. The multivariate adjusted relative odds was 3.5 (95% Cl = 1.6-7.6) for subjects in the highest quintile of fat intake (above 113 g) compared to those in the lowest quintile (below 65 g); this corresponds to a 30% increased risk per 10% of energy derived from fat. The association could not be attributed to energy intake, nor to the degree of saturation of the fat nor to any specific dietary source of fat.

Effects of moderate alcohol consumption on platelet aggregation, fibrinolysis, and blood lipids.

To investigate the effect of moderate alcohol consumption on blood constituents related to cardiovascular disease, 12 male volunteers consumed (instead of their usual alcoholic drinks) four different standardized amounts of red wine in addition to their habitual diet. Each dose was given to the subjects during a period of 5 weeks in a randomized order, all subjects receiving the four doses. They consisted of 0, 2, and 4 glasses/d, providing 0, 23, and 46 g alcohol/d as well as in "binge drinking" (14 glasses in the weekend, comparable to an average of 2 glasses/d). The results showed a clear dose-related response to the drinking for several blood constituents. Most marked was a decrease in the tissue-type plasminogen activator activity and to a lesser degree an increase in plasminogen levels. Collagen-induced platelet aggregation was reduced, affecting all parameters measured. Levels of HDL3-cholesterol, gammaglutamyltransferase, and urate showed a small but significant increase. No change was noted in the levels of alkaline phosphatase, alanine-aminotransferase, aspartate-aminotransferase, bile acids, folate, fibrinogen, the ADP-induced platelet aggregation, platelet secretion, or in hematologic values. The results are only partially in accordance with the presumed protective action of moderate drinking on the cardiovascular system and show a stronger response to the consumption of alcohol in coagulation and fibrinolysis factors than in blood lipids.

The effect of beta-carotene on sputum cytology in smokers: a preliminary study.

The use of biomarkers is a promising approach to the study of human cancer risk. Bronchial metaplasia in sputum cytology may be a marker for potential premalignancy that can be used for population studies. We recently performed a randomized, controlled trial in smokers on the effect of 14 weeks beta-carotene (20mg/day) on markers for DNA damage. We now have evaluated the application of sputum cytology in this study and performed a preliminary evaluation of the effect of beta-carotene. Of the 150 potential participants in this trial 75 were not eligible because they failed to produce sputum samples (n = 29), or because samples were unsatisfactory (n = 46). The eligible group was older (41 vs 37 years) and had smoked longer (23 vs 19 years), but had similar cigarette consumption (mean 21/day) and plasma cotinine levels. Metaplasia was graded in seven categories. Only 11 subjects (15%) showed minor or mild atypia on study entry. Agreement within and between observers was 95% within the same or an adjacent category. We observed no significant correlation between before and after treatment final metaplasia scores in either the beta-carotene (Spearman R = 0.18, P = 0.3) or placebo group (Spearman R = 0.17, P = 0.3). Initial metaplasia scores were somewhat higher in the beta-carotene group (n = 33) than in the placebo group (n = 42) (P = 0.06). Final metaplasia scores were similar in both groups (P = 0.69), and there was no decrease in metaplasia scores in the beta-carotene group (P = 0.75). This study indicates that sputum cytology may not yet be a readily applicable marker in studies of a healthy asymptomatic population, because many smokers do not spontaneously produce sputum, more severe lesions are rare, and variation over time in the minor lesions in large. Therefore, the preliminary evidence that beta-carotene has no influence should be interpreted with care.

Association of Gm allotypes with the occurrence of ankylosing spondylitis in HLA-B27-positive anterior uveitis.

We studied immunoglobulin Gm and Km allotypes in 54 patients with HLA-B27-positive anterior uveitis and in 204 healthy controls. No differences were noted between the two groups. Dividing the patients with anterior uveitis into those with ankylosing spondylitis (No. = 22) and those without it (No. = 32), produced interesting results. The Gm 1, 3, 17; 23; 5, 13, 21 phenotype was significantly (P = .007) increased in those within the ankylosing spondylitis and anterior uveitis group. Of these 22 patients, ten (45.5%) carried the Gm 1, 3, 17; 23; 5, 13, 21 phenotype compared to two of 32 (6.3%) in those with anterior uveitis alone and 33 of 204 (16.2%) normal controls. There were no significant differences between patients and controls in the frequencies of the other phenotypes tested.

Clustering of dietary variables and other lifestyle factors (Dutch Nutritional Surveillance System).

STUDY OBJECTIVE: The aim was to investigate whether dietary factors cluster in a favourable or unfavourable way and to characterise the groups identified by lifestyle and sociodemographic variables. DESIGN AND SETTING: This cross sectional study was based on data of the 1987-1988 Dutch national food consumption survey (DNFCS), obtained from a panel by a stratified probability sample of the non-institutionalised Dutch population. PARTICIPANTS: 3781 adults (1802 males and 1979 females) of the DNFCS, aged 19 to 85 years, were studied. MEASUREMENTS AND MAIN RESULTS: To estimate dietary intake two day food records were used. Lifestyle factors were collected by structured questionnaire and sociodemographic variables were available from panel information. Cluster analysis was used to classify subjects into groups based on similarities in dietary variables. Subsequently, these groups were characterised by sociodemographic and lifestyle factors as well as by the consumption of food groups. Eight clusters were found. In comparison with the guidelines, the dietary quality in four clusters was poor. The cluster with the poorest dietary intake (high intake of fat, cholesterol, and alcohol; low intake of dietary fibre) showed on average a high consumption of animal products (except milk), fats and oils, snacks, and alcoholic beverages, and a low consumption of fruit, potatoes, vegetables, and sugar rich products. Smoking, body mass index, dietary regimen on own initiative, hours of sleep, gender, age, socioeconomic status, and day of the week were found to discriminate among the clusters. CONCLUSIONS: Cluster analysis resulted in substantial differences in mean nutrient intake and seems useful for dietary risk group identification. Undesirable lifestyle habits were interrelated in some clusters, but an exclusive lifestyle for health risk has not been found.

Supplementation with selenium-rich bread does not influence platelet aggregation in healthy volunteers.

In order to establish the effect of an increased dietary selenium supply on platelet glutathione peroxidase (EC 1.11.1.9.; GSH-Px) and platelet aggregation, six healthy subjects were supplemented with 200 micrograms Se as Se-rich bread for 6 weeks. Another six subjects received low-Se bread and served as controls. Platelet GSH-Px activity increased significantly in the supplementation group, whereas no effect could be observed on platelet aggregation. The results of this study do not support the hypothesis that an increased dietary Se intake has a favourable influence on platelet aggregation.

Alcohol consumption in relation to food intake and smoking habits in the Dutch National Food Consumption Survey.

The interrelationships between alcohol consumption, energy and food intake and smoking habits were studied in 1145 men and 1171 women, aged 22-49 years, in the Dutch National Food Consumption Survey, in which a 48-h dietary record method was used. The aim of the study was to investigate the effects of alcohol consumption on dietary habits and smoking. A strong relationship between alcohol consumption and energy intake was found. The energy derived from alcohol was not compensated for by lower intake of other nutrients. There was no increase in Quetelet's index with increasing alcohol consumption, except for non-smoking men who were heavy drinking on midweek days. Possible explanations for this apparent lack of an overall effect of alcohol calories are discussed. Alcohol consumption was much higher on weekend days than on midweek days. No differences in nutrient intake were found between non-drinkers, moderate drinkers and heavy drinkers on midweek days. On weekend days, however, there was a slightly higher total fat and saturated fat intake in moderately drinking men. For women cholesterol intake was found to be higher in moderate and heavy drinkers. Finally, a strong positive relationship between alcohol consumption and smoking was observed. It is concluded that the observations with respect to energy and nutrient intake and smoking habits are not indicative of a healthier lifestyle in moderate alcohol users between 22 and 49 years of age. Consequently, the more favourable prognosis of moderate drinkers cannot be ascribed to a more healthy lifestyle.

Subentities within adult primary IgA-nephropathy.

Since its definition is purely descriptive, IgA-nephropathy (IGAN) may comprise more disease entities which share the (epi)phenomenon of mesangial IgA-depositions. IGAN patients with macroscopical hematuria (macro-H) differ from the other IGAN patients in 9 aspects: history, HLA-DR, Gm-allotypes, actuarial kidney survival, initial creatinine clearance, initial proteinuria, initial microhematuria, age at presentation and light microscopy of the renal biopsy. The difference in the last five parameters may either be explained by the existence of subentities or by earlier detection of patients with macro-H. The dissimilarity in the first four parameters can only be due to the former theory. Therefore, we conclude that IGAN probably comprises at least two disease entities.

The reproducibility of the conversion of nitrate to nitrite in human saliva after a nitrate load.

We investigated the reproducibility of the inter- and intra-individual variations in the conversion of nitrate to nitrite in saliva. Saliva samples were collected from 20 volunteers just before and at regular intervals after a nitrate load on four non-consecutive days within a period of 2 months. On three occasions beetroot juice was the nitrate source and on one occasion a nitrate solution was given. Despite large day-to-day variations it was possible to discriminate between subjects with a consistently high or low nitrate conversion after a nitrate load. Neither saliva sampling before a nitrate load nor single saliva samples are sufficient to obtain clear information about individual capacities for nitrate-nitrite conversion.

Effects of Caramel Colour III on the number of blood lymphocytes: a human study on Caramel Colour III immunotoxicity and a comparison of the results with data from rat studies.

Administration of the colour additive Ammonia Caramel Colour (Caramel Colour III) to rats has been associated with decreased lymphocyte counts, specifically in rats fed a diet low in vitamin B6. This effect is rapidly reversible and is caused by an imidazole derivative (THI) in Caramel Colour III. In the present paper, the conduct of a human study with Caramel Colour III is outlined and the results of blood lymphocyte counts are presented. No decrease in the number of blood lymphocytes occurred in marginally vitamin B6-deficient humans who consumed Caramel Colour III at the acceptable daily intake level (200 mg/kg body weight/day) for 7 days. These data are discussed in relation to the effects of Caramel Colour III and THI on blood lymphocyte numbers in rats.

Effects of the colour additive caramel colour III on the immune system: a study with human volunteers.

Administration of the colour additive Caramel Colour III to rats has been associated with decreased numbers of lymphocytes and several other changes in the immune system, as well as in immune function parameters, specifically in animals fed a diet with a relatively low vitamin B6 content. The effects are caused by the imidazole derivative 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI). Caramel Colour III is commonly used in food products such as bakery products, soya-bean sauces, brown sauces, gravies, soup aromas, brown (dehydrated) soups, brown malt caramel blend for various applications, vinegars and beers, and effects in humans on dietary intake cannot be excluded. Elderly male volunteers with a marginal deficit in vitamin B6 were considered a relevant and potentially sensitive group to study possible effects of Caramel Colour III on blood lymphocyte numbers (total and within subsets) or on proliferative responses of lymphocytes to mitogenic stimulation. In addition, several other haematological parameters, as well as serum immunoglobulin levels and immunoglobulin production in vitro by pokeweed mitogen-stimulated mononuclear blood cells were studied. The results of this double-blind intervention study demonstrated that in a selected test group of apparently healthy elderly male volunteers with a biochemically marginally deficient vitamin B6 status, Caramel Colour III containing 23 (commercial sample) or 143 (research sample) ppm THI and administered at the level of the current acceptable daily intake of 200 mg/kg body weight/day for 7 days did not affect any of the factors investigated.

The safety assessment of novel foods. Guidelines prepared by ILSI Europe Novel Food Task Force.

The diversity of novel foods and novel ingredients covered by the scope of the EU regulation is such that a check list approach to safety evaluation is inappropriate. Rather, a case-by-case approach is required taking into account the composition of the novel food, its intake, its role in the diet and the intended target group. The SAFEST approach provides a means of targeting the safety evaluation on those aspects, nutritional or toxicological, of a novel food which are of particular concern. Using this approach, novel foods are assigned to one of three classes on the basis of certain background information. For those novel foods which can be shown to be in SAFEST class 1, namely those which are substantially equivalent to a traditional counterpart, no further information is required to demonstrate their safety. For those novel foods in SAFEST class 2, i.e. those sufficiently similar to a traditional counterpart or differing from it only in particular, well defined, characteristics, the evaluation will focus on those differences. Only in the case of novel foods which are not in class 1 or class 2 is extensive testing of the whole food likely to be required. Even in these cases, the testing should follow a scientifically-based hierarchical approach involving: literature reviews; chemical analysis; appropriate in vitro and in vivo tests; and, if necessary, confirmation of safety and nutritional value in humans. Examination of the causes of any adverse effects reported by consumers after the novel food or ingredient has been approved and is introduced into the market may provide additional reassurance of safety.

Detection of plasmacytoma of the nasal cavity by immunoelectrophoresis of nasal washing fluid.

A patient with a solitary IgG-lambda plasmacytoma of the nasal cavity is described. Immunoelectrophoresis of the nasal washing fluid showed the presence of the same paraprotein. After radiotherapy the tumour and the paraprotein disappeared. Recurrence of the tumour after 6 months was again associated with the presence of the paraprotein in the nasal washing fluid. Immunoelectrophoresis of nasal washings may offer an easy method in detection and follow-up of localized plasmacytomas of the upper respiratory tract.

Body composition, health status and urinary magnesium excretion among elderly people (Dutch Nutrition Surveillance System).

Magnesium (Mg) requirements depend on body weight. Recommended dietary allowances (RDA) are mostly given in absolute amounts and are mostly similar for adults, despite differences in body composition in the adult age range. We therefore studied the interrelations of 24 h urinary Mg excretion with body build and body composition indicators, as well as with factors potentially affecting the metabolism of Mg, among 520 elderly men and women seen in a nationwide survey. Mg intake data were also obtained in the Dutch Food Composition Survey amount 5898 subjects. The results showed lower mean Mg intake among elderly people (especially men) and positive associations of body weight and body height with urinary Mg excretion, but not when expressed per mmol of creatinine excreted. Mg excretion per mmol of creatinine was not associated with body weight, body height, body mass index or body fatness (women), suggesting that the amount of fat mass did not affect Mg excretion. Mg excretion was positively correlated with Mg intake, creatinine clearance, excretion of sodium, potassium and calcium, and coffee consumption, indicating interactions at the kidney level that may increase Mg losses. Elderly people using diuretics and/or anticholinergics and male diabetics had a higher mean Mg excretion per mmol of creatinine. The results show that, besides the Mg intake, several factors affect the urinary Mg excretion among elderly people. These factors were body build and body composition, dietary intake, drug use, kidney function, and diabetes. A quantification of the effects cannot be made yet, and controlled studies on those factors potentially affecting the requirement of Mg are needed.