Serum beta-carotene and antioxidant micronutrients in children with cancer. The 'Cancer in Children and Antioxidant Micronutrients' French Study Group

Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc and selenium for 418 children with newly diagnosed malignancy were compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years old and recruited in 1986-1989. Age- and sex-adjusted serum concentrations of retinol, beta-carotene and alpha-tocopherol were significantly inversely associated with cancer. In similar models, the odds ratio (OR) comparing the highest with the lowest quintile was 2.06 (95% confidence interval [CI] 1.40-3.02) for retinol, 3.87 (95% CI: 2.54-5.90) for beta-carotene, 2.15 (95% CI: 1.48-3.10) for alpha-tocopherol, 1.29 (95% CI: 0.75-2.23) for selenium, and 1.94 (95% CI: 1.17-2.23) for zinc. The cancer sites that were associated with serum beta-carotene were, in general, leukaemia, lymphoma, central nervous system, bone and renal tumours. Moreover, leukaemia was associated with low mean serum levels of retinol, selenium and zinc. Subjects with lymphoma, bone and renal tumours also had lower mean retinol and alpha-tocopherol levels than controls. Brain tumour patients had low vitamin E levels. Low serum values of antioxidant vitamins were associated with childhood neoplasm occurrence. Some site-specific effect was reported. Low peripheral nutrient levels are not considered as cancer promoters but rather as an impairment of the body's defence mechanism occurring during the cancer-related metabolic and nutritional disturbances and inflammation processes.     

The influence of retinol, tocopherol and cimetidine on the ulcerogenic effect of Orthofen, indomethacin and naproxen

The influence of retinol, alpha-tocopherol, and cimetidine on ulceration induced by ortophen, indomethacin, naproxen was studied on rats. It was shown that alfa-tocopherol, retinol, and cimetidine reduce the damaging effect of these drugs on the gastroduodenal mucosa of rats thus normalizing the phospholipid content. The influence of alpha-tocopherol and retinol on the side-effects of ortophen was studied in children with rheumatoid arthritis. Ortophen was found to cause gastroduodenal side-effects in more than 30% of patients and decrease the levels of vitamin A and E in children. The use of retinol and alpha-tocopherol in cotherapy decreases the frequency and severity of side-effects and reduces the vitamin deficiency.     

Electrosyntheses of disaccharides from phenyl or ethyl 1-thioglycosides

Age- and sex-specific reference intervals of data derived from a healthy paediatric population are presented for retinol, beta-carotene, alpha-tocopherol, cholesterol and related proteins in serum. Age was an important covariate for the micronutrient concentration values. Retinol was highly correlated with alpha-tocopherol and cholesterol. Strong correlation was found with both beta-carotene and cholesterol. Serum levels were considered for their appropriateness as indicators of micronutrient status.     

A routine method for the simultaneous measurement of retinol, alpha-tocopherol and five carotenoids in human plasma by reverse phase HPLC

We describe a simple isocratic HPLC method for the accurate and precise measurement of retinol, alpha-tocopherol and the major carotenoids in plasma using UV detection. Reference ranges for retinol, alpha-tocopherol and five carotenoids are determined in a healthy population group. The most abundant carotenoids found in plasma were beta-carotene, lycopene, lutein and cryptoxanthin. Retinol, alpha-tocopherol and carotenoids were determined simultaneously using two internal standards, retinol acetate for retinol and tocopherol acetate for alpha-tocopherol and carotenoids. The use of echinenone as an internal standard for carotenoids was investigated. The protective effect of an antioxidant (ascorbic acid) on the stability of samples and extracted material is documented. The method is useful for the routine measurement of plasma retinol, alpha-tocopherol and carotenoids and could also be used in large scale epidemiological studies.     

Surface charge control of electropermeabilization and glycophorin electroinsertion with 1,2-diacyl-sn-glycero-3-phosphocholine (lecithin) liposomes

beta-Carotene has been studied widely as a potential cancer-preventing agent. Recent studies found that subjects who took beta-carotene supplements orally had increases in their serum concentrations of alpha-carotene and lycopene that were large (> 150% increase) and significantly greater than such increases in subjects who received placebo and that similar supplementation was associated with a decrease of approximately 37% in plasma lutein concentrations. A biologic interaction between beta-carotene and other carotenoids was suggested. We measured concentrations of retinol, alpha-tocopherol, and five carotenoids in serum specimens from a random sample of subjects enrolled in a clinical trial of the use of antioxidant vitamins in preventing colonic adenomas. We used serum specimens obtained at enrollment and after the subjects took placebo (n = 54) or 25 mg beta-carotene/d (n = 54) orally for 4 y. In a multivariate analysis, baseline serum concentrations of the analytes, sex, body mass index, diet, smoking status, and age were associated with variable changes in some analytes over the 4-y period but supplementation with beta-carotene was related only to a mean increase in serum beta-carotene itself of 151%. We excluded with 95% confidence an increase in lycopene > 4.9%, an increase in alpha-carotene > 17.6%, and a decrease in lutein > 14.7% in subjects given beta-carotene. These results confirm previous findings that supplementation with beta-carotene given orally does not alter serum concentrations of retinol or alpha-tocopherol. The findings also indicate that beta-carotene supplementation, which results in a moderate increase in serum beta-carotene concentration, does not significantly change serum concentrations of other carotenoids.     

Oxidative modifications of blood serum in humans with coronary artery disease

Oxidative modifications of blood serum in humans with and without coronary artery disease were investigated. Four parameters were analyzed: the intensity of serum fluorescence, which is indicative of the content of lipofuscine-like lipid peroxidation products; the content of thiobarbituric acid-reactive substances; the lag-phase of serum oxidation by azo-compounds; and the content of lipophilic natural antioxidants--alpha-tocopherol, beta-carotene and ubiquinol-9(10). It was found that coronary artery disease resulted in a significant increase of serum fluorescence and the content of TBARS. The atherogenic disorders in humans with coronary artery disease drastically decreased the lag-phase of serum oxidation in the presence of 2,2'-azo-bis-(2-amidinopropane) dihydrochloride. The oxidative modifications of serum were in close correlation with the balance of natural lipophilic antioxidants in blood serum, i.e. alpha-tocopherol, ubiquinols and beta-carotene. The contents of all antioxidants tested in serum were significantly decreased in patients with coronary artery disease.     

Monitoring adenoviral p53 transduction efficiency by yeast functional assay

The pathogenesis of ossification of the posterior longitudinal ligament (OPLL) remains to be elucidated, though etiologic factors for OPLL have been identified. High levels of serum retinol and retinol binding protein (RBP) have been observed in patients with diffuse idiopathic skeletal hyperostosis (DISH). OPLL is often associated with DISH. In this study, the levels of serum retinol and RBP were determined in 70 patients with OPLL in the cervical spine, and compared with those in normal subjects. Bone metabolic markers of serum intact osteocalcin, urinary pyridinoline and deoxypyridinoline were examined as well. Among female patients, level of serum RBP was significantly higher in those in their 60's, and those with mixed type OPLL. Level of serum RBP was significantly higher in both sexes, and retinol was exhibited higher in female patients, if they were associated with DISH. Patients with OPLL exhibited no abnormal bone metabolic marker levels. These findings suggest that vitamin A may play a role in the development of OPLL.     

Interaction of alpha-tocopherol with model human high-density lipoproteins

The effects of alpha-tocopherol on the properties of model high-density lipoproteins (HDLs), composed of human apolipoprotein A-I and dimyristoylphosphatidylcholine, were investigated by physicochemical methods. The intrinsic fluorescence of alpha-tocopherol and its effects on the polarization of fluorescence of 1,6-diphenyl-1,3,5-hexatriene, which probes the hydrocarbon region of the lipids, and 4-heptadecyl-7-hydroxycoumarin, which is a probe of lipid surfaces, suggest that alpha-tocopherol is located at the lipid-water interface. Relative to cholesterol, alpha-tocopherol in lipid surfaces is virtually inert physicochemically. Incorporation of alpha-tocopherol into HDLs induces only a modest increase in particle size, no change in the transition temperature, and little change in lipid polarity and lipid-lipid interactions. Moreover, alpha-tocopherol has only a negligible effect on the kinetic parameters of the lipophilic enzyme lecithin:cholesterol acyltransferase, which binds to phosphatidylcholine surfaces and forms cholesteryl esters. However, alpha-tocopherol has a dramatic inhibitory effect on the rate of association of apolipoprotein A-I with dimyristoylphosphatidylcholine, a process that occurs through the insertion of the protein into preformed defects in the lipid surface. It is proposed that alpha-tocopherol inhibits the rate of association of apolipoprotein A-I with dimyristoylphosphatidylcholine by inserting into defects within the lipid surface, thereby reducing the size and/or number of sites for insertion of apolipoprotein A-I.     

The effect of alpha-tocopherol and beta-carotene supplementation on COPD symptoms

The effects of alpha-tocopherol (50 mg/d) and beta-carotene (20 mg/d) supplementation on symptoms of chronic obstructive pulmonary disease were studied among the 29,133 participants of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study undertaken to investigate the effects of these two substances in the prevention of lung and other cancers. During the follow-up the supplementations did not affect the recurrence or incidence of chronic cough, phlegm, or dyspnea. The prevalence of chronic bronchitis and dyspnea at baseline was lower among those with high dietary intake of beta-carotene (OR = 0.78 and 0.67, respectively) or vitamin E (OR = 0.87 and 0.77) and high serum beta-carotene (OR = 0.59 and 0.62) and alpha-tocopherol (OR = 0.76 and 0.82). High intake and serum levels of retinol were associated with low prevalence of dyspnea (OR = 0.84 and 0.80, respectively) but not with chronic bronchitis. The results indicate no benefit from supplementation with alpha-tocopherol or beta-carotene on the symptoms of chronic obstructive pulmonary disorders but support the beneficial effect of dietary intake of fruits and vegetables rich in these compounds.     

Aspergillus airway colonization and invasive disease after lung transplantation

To assess the effect of hemolysis on serum retinol concentrations determined by direct fluorometry, we assayed 196 blood samples from children 6-72-mo of age with various grades of hemolysis for serum retinol by both fluorescence and HPLC. Mean serum retinol concentrations determined by HPLC did not differ significantly according to hemolysis grade; however, fluorometric values did. Additionally, serum retinol concentrations obtained from HPLC and those obtained from direct fluorometry were significantly different in samples with severe hemolysis. Multivariate-regression analysis showed that hemolysis grade was a significant predictor of the difference in mean serum retinol values determined by the two methods. Although severe hemolysis interfered with determinations of serum retinol by direct fluorometry, this method is still a viable choice for field studies of vitamin A status.     

Cerebrospinal fluid levels of alpha-tocopherol in amyotrophic lateral sclerosis

We compared CSF and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 30 patients with sporadic amyotrophic lateral sclerosis (SALS) and 78 matched controls. The mean CSF and serum vitamin E levels did not differ significantly between the 2 study groups. These values were not influenced by the clinical form (spinal versus bulbar) of SALS. CSF alpha-tocopherol levels did not correlate with age, age at onset, and duration of the disease. These results suggest that CSF and serum alpha-tocopherol concentrations are unrelated with the risk for ALS.     

Essential fatty acids, plasma cholesterol, and fat-soluble vitamins in subjects with age-related maculopathy and matched control subjects

A matched-control study of plasma retinol, alpha-tocopherol, carotenoid, and cholesterol concentrations and the polyunsaturated fatty acid content of plasma and erythrocyte phospholipids was undertaken in 65 elderly patients with age-related maculopathy and 65 control subjects matched for age and sex. Despite the high statistical power of the study and large variations between subjects in the variables under consideration, no significant differences were noted between patients and control subjects. However, several statistically significant differences were noted between male and female subjects independent of their classification with maculopathy or as controls and age: plasma cholesterol, total phospholipids, alpha-tocopherol, and beta-cryptoxanthin concentrations were higher in females than in males. The mean plasma cholesterol concentration for the upper tertile of the whole sample was 7.6 mmol/L. Plasma concentrations of total carotenoids, alpha-carotene, and beta-carotene, but not alpha-tocopherol, were significantly lower in smokers than in non-smokers. The results of this study do not provide any evidence in favor of changing the dietary intake of polyunsaturated fatty acids or fat-soluble vitamins to protect against age-related maculopathy.     

Vitamin E serum levels in patients with leukemia, lymphoma and myeloma

The serum alpha-tocopherol levels were determined in a group of 182 patients with hematological neoplasms: 87 lymphoid or myeloid leukemias, 65 lymphomas and 30 myelomas. The levels did not differ from those of controls, when compared either globally or for diagnosis. Low alpha-tocopherol serum levels were observed in 6 patients (3.3%).     

Non-telomeric chromosome localization of (TTAGGG)n repeats in the genus Eulemur

Numerous dietary studies and several serum micronutrient studies have produced equivocal results on the relation of vitamins A and E to prostate cancer risk. To evaluate this association further, we conducted a nested case-control study in a cohort of 6860 Japanese-American men examined from 1971 to 1975. At the time of examination, a single blood specimen was obtained, and the serum was frozen. After a surveillance period of more than 20 years, 142 tissue-confirmed incident cases of prostate cancer were identified. Their stored sera and those of 142 matched controls were measured by high-performance liquid chromatography for the following: total carotenoids, lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, total retinoids, retinol, total tocopherols, alpha-tocopherol, delta-tocopherol, and gamma-tocopherol. Odds ratios for prostate cancer, based on quartiles of serum micronutrient levels, were determined using conditional logistic regression analysis. The odds ratio for the highest quartiles were 1.8 (95% confidence interval, 0.9-3.9) for beta-cryptoxanthin, 1.6 (0.8-3.5) for beta-carotene, 0.8 (0.4-1.5) for retinol, and 0.7 (0.3-1.5) for gamma-tocopherol, but none of the differences was statistically significant. For the other micronutrients, the results were also unremarkable. The findings of this study indicate that none of the micronutrients is strongly associated with prostate cancer risk.     

Serum concentrations of retinol, d-alpha-tocopherol and beta-carotene: effects of storage at -70 degrees C for five years

To investigate the effects of prolonged storage of serum samples at -70 degrees C on concentrations of micronutrients, we measured concentrations of retinol, d-alpha-tocopherol, and beta-carotene in serum samples drawn in 1986. We compared values we measured in 1991 to values we obtained in 1986, using the same analytical methods. The relative concentrations obtained in 1991 (mean +/- S.D.) were: retinol 99.7 +/- 12.6% (n = 23), d-alpha-tocopherol 100.7 +/- 6.4% (n = 19), and beta-carotene 103.4 +/- 13.7% (n = 28). Using these techniques of sample preparation and high-performance liquid chromatographic analysis, we found that the effects of storage of serum at -70 degrees C for five years appear insignificant in a small population of patients. However, we did identify clinically important changes in concentration (> 20% difference) in several individual subjects.     

Compliance with universal precautions among emergency department personnel caring for trauma patients

INTRODUCTION: Low intake of the fat-soluble antioxidants alpha-tocopherol and beta-carotene has been linked to greater risks of cardiovascular disease in epidemiologic studies. Obesity in adults is associated with lower levels of alpha-tocopherol and beta-carotene, which may contribute to the increased risk of cardiovascular disease associated with obesity. AIM: To examine serum concentrations of fat-soluble antioxidants in a large, nationally representative sample of obese and nonobese children. METHODS: Serum levels of alpha-tocopherol and beta-carotene were measured in 6139 children between the ages of 6 and 19 years enrolled in the National Health and Examination Survey, cycle III. Serum alpha-tocopherol levels were adjusted for fasting cholesterol and triglyceride levels. Nutritional intake was assessed by 24-hour dietary recall and food frequency questionnaires. RESULTS: Serum levels of beta-carotene were significantly lower in obese children compared with those found in normal weight children (0.22 0.14 micromol/L vs 0.29 0.17 micromol/L, P <.001). After adjustment was done for serum triglyceride and cholesterol levels, alpha-tocopherol levels were also significantly lower in obese children (2.68 0.59 vs 3.17 0.60, P <.001). Approximately one half of obese children had serum levels of beta-carotene and adjusted alpha-tocopherol in the lowest quartile compared with approximately one quarter of normal weight children (P <.001). No significant differences were seen in reported intake of beta-carotene, alpha-tocopherol, fruit, or vegetables between obese and nonobese children. CONCLUSION: Reduced serum levels of fat-soluble antioxidants are present in obese children.     

Effects of ondansetron on electrically evoked contraction in rat stomach fundus: possible involvement of 5-HT2B receptors

The effect of dietary RRR-gamma-tocopherol supplementation on serum and tissue alpha- and gamma-tocopherol concentrations was studied in vitamin-E-deficient rats fed diets containing adequate levels of RRR-alpha-tocopherol and graded levels of RRR-gamma-tocopherol over a 60 day period. Feeding rats with a RRR-alpha-tocopherol-supplemented diet induced in forebrain, sciatic endoneurium, skeletal muscle, heart and liver a marked increase in alpha-tocopherol concentration. In contrast, feeding rats with a diet containing the same level of RRR-gamma-tocopherol induced a small increase in gamma-tocopherol concentrations in brain, sciatic endoneurium, skeletal, muscle, heart and liver and a slight but significant decrease in alpha-tocopherol concentration in all tissues examined. In rats fed diets containing a constant level of RRR-alpha-tocopherol and graded levels of RRR-gamma-tocopherol, the concentrations of alpha-tocopherol in all tissues were much higher than those in rats fed a control diet containing RRR-alpha-tocopherol alone. The higher the gamma/alpha ratio, the more the alpha-tocopherol concentrations increased. Significant positive linear regressions were found between the gamma/alpha ratio and the alpha- and gamma-tocopherol concentrations in most of the tissues examined. These results indicate that when gamma-tocopherol was supplied continuously in the diet gamma-tocopherol accumulated significantly in the tissues but to a much smaller extent than when rats were fed with RRR-alpha-tocopherol. These experiments also indicate that gamma-tocopherol did not depress the serum and tissue alpha-tocopherol concentrations. On the contrary, gamma-tocopherol supplements induced a marked increase in alpha-tocopherol concentrations in the serum and tissues. These results suggest that there is a relationship between alpha- and gamma-tocopherol levels in vivo and that the biopotency of alpha-tocopherol should be reevaluated especially when high levels of gamma-tocopherol were present in the diet.     

Blood vitamins, mineral elements and inflammation markers as risk factors of vascular and non-vascular disease mortality in an elderly population

BACKGROUND: The need for protecting agents against degenerative processes of the body has been proposed to be especially high in elderly people. In order to evaluate the prognostic value of various biochemical factors in ageing the associations of blood concentrations of several vitamins, mineral elements and some other suggested risk factors with vascular and non-vascular mortality were studied in an elderly population. METHODS: A large health survey with complete clinical evaluation was carried out in the City of Turku in 1982-1983. A random sample of 344 community-living elderly individuals aged 65 years or older, stratified into four age groups, was studied. During the 13 years follow-up 225 subjects had died. Calcium, magnesium, copper, ceruloplasmin, zinc, selenium, iron, ferritin, transferrin, alpha-tocopherol, retinol, folate, vitamin B12, malondialdehyde, orosomucoid and insulin levels were analysed from the blood specimens. The relations between the compounds measured and relative mortality risks during the 13-year follow-up were analysed by Cox proportional hazards model adjusting for other known risk factors. RESULTS AND CONCLUSIONS: High concentrations of serum copper, orosomucoid and insulin were associated with increased risk of vascular mortality. The relative risks within the subjects of the highest tertile of serum concentrations were 2.2 for copper, 1.8 for orosomucoid, and 1.8 for insulin when adjusted for many confounding risk factors. Low serum vitamin B12 concentrations appeared to be significantly (P = 0.01) associated with increased vascular mortality. The associations were essentially not more significant when adjusted only for age. Contrary to earlier observations concentrations of serum magnesium, selenium, alpha-tocopherol, iron and its binding proteins or plasma and erythrocyte folate were not associated with increased mortality risk when adjusted for confounding risk factors. The authors suggest that in elderly subjects these elements and compounds are at the most weak, and probably non-independent risk factors for vascular mortality.     

Delaying colostrum intake by one day impairs plasma lipid, essential fatty acid, carotene, retinol and alpha-tocopherol status in neonatal calves

To study whether a delayed start of colostrum feeding in calves affects plasma lipids, fatty acids and fat-soluble vitamins, one group was fed colostrum (milkings 1-4) on d 1 and 2, then mature milk up to d 7, whereas two other groups were fed glucose or water on d 1, colostrum (milkings 1-4) on d 2 and 3 and then mature milk up to d 7. In calves fed colostrum on d 1, starting 5-7 h after birth, plasma concentrations of triglycerides, phospholipids, total cholesterol and of essential and nonessential fatty acids in triglyceride, phospholipid and cholesterol ester fractions as well as of carotene, retinol and alpha-tocopherol up to d 7 were significantly higher than in calves in which colostrum feeding started after >24 h of life. On the other hand, plasma concentrations of vitamin B-6, vitamin B-12 and folic acid were not influenced. Results indicated reduced efficiency of absorption of colostral fatty acids and of fat-soluble vitamins, but not of (selected) water-soluble vitamins, if colostrum is not fed on d 1 of life. In conclusion, colostrum intake within the first 24 h of life is required for an adequate plasma lipid, essential fatty acid, carotene, retinol and alpha-tocopherol status in the first week of life of calves.     

Antibiotic pharmacodynamics in cerebrospinal fluid

The CSF half-lives of lipophilic agents, such as quinolones, are similar to those in serum and peak concentrations in CSF are achieved relatively quickly. In contrast, the pharmacokinetics of hydrophilic agents (beta-lactams and vancomycin) in CSF often differ from those in serum. In particular, the half-lives of these agents in CSF tend to be extended, and the time to achieve peak concentrations in CSF is delayed. Hydrophilic antibiotics, such as beta-lactams, penetrate poorly through the BBB, but CSF penetration is significantly increased in the presence of inflammation. In contrast, lipophilic antibiotics, such as quinolones, enter the CSF more efficiently and their penetration is not inflammation dependent. The pharmacodynamic properties of antibiotics in CSF are generally similar to those in other body sites; beta-lactam agents and vancomycin are time-dependent, whereas the quinolones and aminoglycosides are concentration-dependent. However, a notable difference from infections in other sites is that quinolones have a short PAE in CSF and need to continually exceed the MBC for maximal effectiveness. Thus, in CSF, quinolones demonstrate features of both concentration-dependency and time-dependency, evidence that the AUC/MBC is an important predictor of effectiveness. With the exception of quinolones, many antibiotics appear to have prolonged sub-MIC effects and longer half-lives in CSF than in serum, suggesting that dosing intervals longer than those used traditionally would be effective in meningitis. However, this requires clinical verification.