Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies.

Background Carotenoids, micronutrients in fruits and vegetables, may reduce breast cancer risk. Most, but not all, past studies of circulating carotenoids and breast cancer have found an inverse association with at least one carotenoid, although the specific carotenoid has varied across studies. Methods We conducted a pooled analysis of eight cohort studies comprising more than 80% of the world's published prospective data on plasma or serum carotenoids and breast cancer, including 3055 case subjects and 3956 matched control subjects. To account for laboratory differences and examine population differences across studies, we recalibrated participant carotenoid levels to a common standard by reassaying 20 plasma or serum samples from each cohort together at the same laboratory. Using conditional logistic regression, adjusting for several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs) using quintiles defined among the control subjects from all studies. All P values are two-sided. Results Statistically significant inverse associations with breast cancer were observed for α-carotene (top vs bottom quintile RR = 0.87, 95% CI = 0.71 to 1.05, Ptrend = .04), β-carotene (RR = 0.83, 95% CI = 0.70 to 0.98, Ptrend = .02), lutein+zeaxanthin (RR = 0.84, 95% CI = 0.70 to 1.01, Ptrend = .05), lycopene (RR = 0.78, 95% CI = 0.62 to 0.99, Ptrend = .02), and total carotenoids (RR = 0.81, 95% CI = 0.68 to 0.96, Ptrend = .01). β-Cryptoxanthin was not statistically significantly associated with risk. Tests for heterogeneity across studies were not statistically significant. For several carotenoids, associations appeared stronger for estrogen receptor negative (ER(-)) than for ER(+) tumors (eg, β-carotene: ER(-): top vs bottom quintile RR = 0.52, 95% CI = 0.36 to 0.77, Ptrend = .001; ER(+): RR = 0.83, 95% CI = 0.66 to 1.04, Ptrend = .06; Pheterogeneity = .01). Conclusions This comprehensive prospective analysis suggests women with higher circulating levels of α-carotene, β-carotene, lutein+zeaxanthin, lycopene, and total carotenoids may be at reduced risk of breast cancer.

Supplementation with fruit and vegetable soups and beverages increases plasma carotenoid concentrations but does not alter markers of oxidative stress or cardiovascular risk factors

This study was aimed at determining whether an increase of 5 portions of fruits and vegetables in the form of soups and beverages has a beneficial effect on markers of oxidative stress and cardiovascular disease risk factors. The study was a single blind, randomized, controlled, crossover dietary intervention study. After a 2-wk run-in period with fish oil supplementation, which continued throughout the dietary intervention to increase oxidative stress, the volunteers consumed carotenoid-rich or control vegetable soups and beverages for 4 wk. After a 10-wk wash-out period, the volunteers repeated the above protocol, consuming the other intervention foods. Both test and control interventions significantly increased the % energy from carbohydrates and decreased dietary protein and vitamin B-12 intakes. Compared with the control treatment, consumption of the carotenoid-rich soups and beverages increased dietary carotenoids, vitamin C, alpha-tocopherol, potassium, and folate, and the plasma concentrations of alpha-carotene (362%), beta-carotene (250%) and lycopene (31%) (P < 0.01) and decreased the plasma homocysteine concentration by 8.8% (P < 0.01). The reduction in plasma homocysteine correlated weakly with the increase in dietary folate during the test intervention (r = -0.35, P = 0.04). The plasma antioxidant status and markers of oxidative stress were not affected by treatment. Consumption of fruit and vegetable soups and beverages makes a useful contribution to meeting dietary recommendations for fruit and vegetable consumption.

Effects of chronic consumption of fruit and vegetable puree-based drinks on vasodilation, plasma oxidative stability and antioxidant status

Background: Fruit and vegetable-rich diets are associated with a reduced cardiovascular disease (CVD) risk. This protective effect may be a result of the phytochemicals present within fruits and vegetables (F&V). However, there can be considerable variation in the content of phytochemical composition of whole F&V depending on growing location, cultivar, season and agricultural practices, etc. Therefore, the present study investigated the effects of consuming fruits and vegetables as puree-based drinks (FVPD) daily on vasodilation, phytochemical bioavailability, antioxidant status and other CVD risk factors. FVPD was chosen to provide a standardised source of F&V material that could be delivered from the same batch to all subjects during each treatment arm of the study. Methods: Thirty-nine subjects completed the randomised, controlled, cross-over dietary intervention. Subjects were randomised to consume 200 mL of FVPD (or fruit-flavoured control), daily for 6 weeks with an 8-week washout period between treatments. Dietary intake was measured using two 5-day diet records during each cross-over arm of the study. Blood and urine samples were collected before and after each intervention and vasodilation assessed in 19 subjects using laser Doppler imaging with iontophoresis. Results: FVPD significantly increased dietary vitamin C and carotenoids (P < 0.001), and concomitantly increased plasma α- and β-carotene (P < 0.001) with a near-significant increase in endothelium-dependent vasodilation (P = 0.060). Conclusions: Overall, the findings obtained in the present study showed that FVPD were a useful vehicle to increase fruit and vegetable intake, significantly increasing dietary and plasma phytochemical concentrations with a trend towards increased endothelium-dependent vasodilation.

Further analyses on Micronesian banana, taro, breadfruit and other foods for provitamin A carotenoids and minerals

Few Micronesian foods have been analyzed for nutrient content. Information is needed on locally grown, culturally acceptable foods that could be promoted to alleviate, vitamin A deficiency in the Federated States of Micronesia. Using an ethnographic approach that included key informant interviews and observation, Micronesian cultivars with potential for high-carotenoid content according to their coloration were identified. These cultivars of banana, giant swamp taro, breadfruit and other foods were analyzed for alpha- and beta-carotene using high-performance liquid chromatography (HPLC) and for nine minerals using inductively coupled plasma (ICP). A wide range of provitamin A carotenoid levels was found in banana, taro, and breadfruit cultivars, some containing very high levels (beta-carotene content from 515 to 6360 mug/100 g in banana, 260 to 1651 mug/100 g in taro, and 295 to 868 mug/100 g in breadfruit, edible portion). Other cultivars contained moderate levels, but as they can be eaten in large quantities, they may contribute significantly to vitamin A status. The taro samples contained very high levels of zinc (mean 5.9 mg/100 g) and significant levels of other minerals (mean content of calcium was 120 mg/100 g). These staples with cultural acceptability and high availability potentially could play a role in vitamin A, micronutrient, and chronic disease programs in the Pacific. (C) 2003 Elsevier Science Ltd. All rights reserved.

Validation of a food-frequency questionnaire assessment of carotenoid and vitamin E intake using weighed food records and plasma biomarkers: The method of triads model

Background: Reliability or validity studies are important for the evaluation of measurement error in dietary assessment methods. An approach to validation known as the method of triads uses triangulation techniques to calculate the validity coefficient of a food-frequency questionnaire (FFQ). Objective: To assess the validity of an FFQ estimates of carotenoid and vitamin E intake against serum biomarker measurements and weighed food records (WFRs), by applying the method of triads. Design: The study population was a sub-sample of adult participants in a randomised controlled trial of beta-carotene and sunscreen in the prevention of skin cancer. Dietary intake was assessed by a self-administered FFQ and a WFR. Nonfasting blood samples were collected and plasma analysed for five carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene) and vitamin E. Correlation coefficients were calculated between each of the dietary methods and the validity coefficient was calculated using the method of triads. The 95% confidence intervals for the validity coefficients were estimated using bootstrap sampling. Results: The validity coefficients of the FFQ were highest for alpha-carotene (0.85) and lycopene (0.62), followed by beta- carotene (0.55) and total carotenoids (0.55), while the lowest validity coefficient was for lutein (0.19). The method of triads could not be used for b- cryptoxanthin and vitamin E, as one of the three underlying correlations was negative. Conclusions: Results were similar to other studies of validity using biomarkers and the method of triads. For many dietary factors, the upper limit of the validity coefficients was less than 0.5 and therefore only strong relationships between dietary exposure and disease will be detected.

Diabetes mellitus and serum carotenoids: findings of a population-based study in Queensland, Australia

Background: Epidemiologic evidence suggests that serum carotenoids are potent antioxidants and may play a protective role in the development of chronic diseases including cancers, cardiovascular disease, and inflammatory diseases. The role of these antioxidants in the pathogenesis of diabetes mellitus remains unclear. Objective: This study examined data from a cross-sectional survey to investigate the association between serum carotenoids and type 2 diabetes. Design: Study participants were adults aged >= 25 y (n = 1597) from 6 randomly selected cities and towns in Queensland, Australia. Study examinations conducted between October and December 2000 included fasting plasma glucose, an oral-glucose-tolerance test, and measurement of the serum concentrations of 5 carotenoid compounds. Results: Mean 2-h postload plasma glucose and fasting insulin concentrations decreased significantly with increasing quintiles of the 5 serum carotenoids-alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, and lycopene. Geometric mean concentrations for all serum carotenoids decreased (all decreases were significant except that of lycopene) with declining glucose tolerance status. beta-Carotene had the greatest decrease, to geometric means of 0.59, 0.50, and 0.42 mu mol/L in persons with normal glucose tolerance, impaired glucose metabolism, and type 2 diabetes, respectively (P < 0.01 for linear trend), after control for potential confounders. Conclusions: Serum carotenoids are inversely associated with type 2 diabetes and impaired glucose metabolism. Randomized trials of diets high in carotenoid-rich vegetables and fruit are needed to confirm these results and those from other observational studies. Such evidence would have very important implications for the prevention of diabetes.

Dietary habits are major determinants of the plasma antioxidant status in healthy elderly subjects

Previous studies indicate that regular consumption of a diet rich in fruits and vegetables is associated with a lower risk for age-related diseases. The aim of the present study was to evaluate whether the often-reported age-related decrease of plasma antioxidants in man depends on differences in dietary intake or on other age- and gender-related factors. In this observational case-control study, thirty-nine community-dwelling healthy subjects aged 65 years and older consuming high intakes of fruits and vegetables daily (HI) and forty-eight healthy subjects aged 65 and older consuming low intakes of fruit and vegetables daily (LI) were enrolled. Plasma levels of retinol, tocopherols, carotenoids and malondialdehyde (MDA) as well as content of protein carbonyls in Ig G were measured. Plasma levels of retinol, tocopherols and carotenoids were significantly higher in group HI than in group LI subjects independent of age and gender. MDA levels were inversely correlated with vitamin A and α-carotene. Protein carbonyls were inversely correlated with γ-tocopherol. In the elderly, a higher daily intake of fruits and vegetables is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables. Modification of nutritional habits among other lifestyle changes should be encouraged to lower prevalence of disease risk factors in later life. © The Authors 2005.

Plasma antioxidant status, immunoglobulin G oxidation and lipid peroxidation in demented patients:Relevance to Alzheimer disease and vascular dementia

A large body of evidence supports a role of oxidative stress in Alzheimer disease (AD) and in cerebrovascular disease. A vascular component might be critical in the pathophysiology of AD, but there is a substantial lack of data regarding the simultaneous behavior of peripheral antioxidants and biomarkers of oxidative stress in AD and vascular dementia (VaD). Sixty-three AD patients, 23 VaD patients and 55 controls were included in the study. We measured plasma levels of water-soluble (vitamin C and uric acid) and lipophilic (vitamin E, vitamin A, carotenoids including lutein, zeaxanthin, β-cryptoxanthin, lycopene, α- and β-carotene) antioxidant micronutrients as well as levels of biomarkers of lipid peroxidation [malondialdehyde (MDA)] and of protein oxidation [immunoglobulin G (IgG) levels of protein carbonyls and dityrosine] in patients and controls. With the exception of β-carotene, all antioxidants were lower in demented patients as compared to controls. Furthermore, AD patients showed a significantly higher IgG dityrosine content as compared to controls. AD and VaD patients showed similar plasma levels of plasma antioxidants and MDA as well as a similar IgG content of protein carbonyls and dityrosine. We conclude that, independent of its nature - vascular or degenerative - dementia is associated with the depletion of a large spectrum of antioxidant micronutrients and with increased protein oxidative modification. This might be relevant to the pathophysiology of dementing disorders, particularly in light of the recently suggested importance of the vascular component in AD development. Copyright © 2004 S. Karger AG, Basel.

Testosterone Therapy Differently Regulates The Anti- And Pro-inflammatory Cytokines In The Plasma And Prostate Of Rats Submitted To Chronic Ethanol Consumption (uchb).

Ethanol consumption damages the prostate, and testosterone is known by anti-inflammatory role. The cytokines were investigated in the plasma and ventral prostate of UChB rats submitted or not to testosterone therapy by ELISA and Western blot, respectively. Additionally, inflammatory foci and mast cells were identified in the ventral prostate slides stained by hematoxylin and eosin and toluidine blue, respectively. Inflammatory foci were found in the ethanol-treated animals and absent after testosterone therapy. Plasma levels of IL-6 and IL-10 were not changed while TNFα and TFG-β1 were increased in the animals submitted testosterone therapy. Regarding to ventral prostate, IL-6 did not alter, while IL-10, TNFα, and TFG-β1 were increased after testosterone therapy. Ethanol increases NFR2 in addition to high number of intact and degranulated mast cell which were reduced after testosterone therapy. So, ethanol and testosterone differentially modulates the cytokines in the plasma and prostate.

Propylthiouracil Quantification In Human Plasma By High-performance Liquid Chromatography Coupled With Electrospray Tandem Mass Spectrometry: Application In A Bioequivalence Study.

A rapid, sensitive and specific method for quantifying propylthiouracil in human plasma using methylthiouracil as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by liquid-liquid extraction using an organic solvent (ethyl acetate). The extracts were analyzed by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS) in negative mode (ES-). Chromatography was performed using a Phenomenex Gemini C18 5μm analytical column (4.6mm×150mm i.d.) and a mobile phase consisting of methanol/water/acetonitrile (40/40/20, v/v/v)+0.1% of formic acid. For propylthiouracil and I.S., the optimized parameters of the declustering potential, collision energy and collision exit potential were -60 (V), -26 (eV) and -5 (V), respectively. The method had a chromatographic run time of 2.5min and a linear calibration curve over the range 20-5000ng/mL. The limit of quantification was 20ng/mL. The stability tests indicated no significant degradation. This HPLC-MS/MS procedure was used to assess the bioequivalence of two propylthiouracil 100mg tablet formulations in healthy volunteers of both sexes in fasted and fed state. The geometric mean and 90% confidence interval CI of Test/Reference percent ratios were, without and with food, respectively: 109.28% (103.63-115.25%) and 115.60% (109.03-122.58%) for Cmax, 103.31% (100.74-105.96%) and 103.40% (101.03-105.84) for AUClast. This method offers advantages over those previously reported, in terms of both a simple liquid-liquid extraction without clean-up procedures, as well as a faster run time (2.5min). The LOQ of 20ng/mL is well suited for pharmacokinetic studies. The assay performance results indicate that the method is precise and accurate enough for the routine determination of the propylthiouracil in human plasma. The test formulation with and without food was bioequivalent to reference formulation. Food administration increased the Tmax and decreased the bioavailability (Cmax and AUC).

Reduced Plasma Angiotensin Ii Levels Are Reversed By Hydroxyurea Treatment In Mice With Sickle Cell Disease.

Sickle cell disease (SCD) pathogenesis leads to recurrent vaso-occlusive and hemolytic processes, causing numerous clinical complications including renal damage. As vasoconstrictive mechanisms may be enhanced in SCD, due to endothelial dysfunction and vasoactive protein production, we aimed to determine whether the expression of proteins of the renin-angiotensin system (RAS) may be altered in an animal model of SCD. Plasma angiotensin II (Ang II) was measured in C57BL/6 (WT) mice and mice with SCD by ELISA, while quantitative PCR was used to compare the expressions of the genes encoding the angiotensin-II-receptors 1 and 2 (AT1R and AT2R) and the angiotensin-converting enzymes (ACE1 and ACE2) in the kidneys, hearts, livers and brains of mice. The effects of hydroxyurea (HU; 50-75mg/kg/day, 4weeks) treatment on these parameters were also determined. Plasma Ang II was significantly diminished in SCD mice, compared with WT mice, in association with decreased AT1R and ACE1 expressions in SCD mice kidneys. Treatment of SCD mice with HU reduced leukocyte and platelet counts and increased plasma Ang II to levels similar to those of WT mice. HU also increased AT1R and ACE2 gene expression in the kidney and heart. Results indicate an imbalanced RAS in an SCD mouse model; HU therapy may be able to restore some RAS parameters in these mice. Further investigations regarding Ang II production and the RAS in human SCD may be warranted, as such changes may reflect or contribute to renal damage and alterations in blood pressure.

Intrahippocampal Infusion Of Crotamine Isolated From Crotalus Durissus Terrificus Alters Plasma And Brain Biochemical Parameters.

Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus durissus terrificus. Here we sought to investigate the inflammatory and toxicological effects induced by the intrahippocampal administration of crotamine isolated from Crotalus whole venom. Adult rats received an intrahippocampal infusion of crotamine or vehicle and were euthanized 24 h or 21 days after infusion. Plasma and brain tissue were collected for biochemical analysis. Complete blood count, creatinine, urea, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine-kinase (CK), creatine kinase-muscle B (CK-MB) and oxidative parameters (assessed by DNA damage and micronucleus frequency in leukocytes, lipid peroxidation and protein carbonyls in plasma and brain) were quantified. Unpaired and paired t-tests were used for comparisons between saline and crotamine groups, and within groups (24 h vs. 21 days), respectively. After 24 h crotamine infusion promoted an increase of urea, GOT, GPT, CK, and platelets values (p ≤ 0.01), while red blood cells, hematocrit and leukocytes values decreased (p ≤ 0.01). Additionally, 21 days after infusion crotamine group showed increased creatinine, leukocytes, TBARS (plasma and brain), carbonyl (plasma and brain) and micronucleus compared to the saline-group (p ≤ 0.01). Our findings show that crotamine infusion alter hematological parameters and cardiac markers, as well as oxidative parameters, not only in the brain, but also in the blood, indicating a systemic pro-inflammatory and toxicological activity. A further scientific attempt in terms of preserving the beneficial activity over toxicity is required.

Human Herpesvirus Infections Of The Central Nervous System: Laboratory Diagnosis Based On Dna Detection By Nested Pcr In Plasma And Cerebrospinal Fluid Samples.

Infections of the central nervous systems (CNS) present a diagnostic problem for which an accurate laboratory diagnosis is essential. Invasive practices, such as cerebral biopsy, have been replaced by obtaining a polymerase chain reaction (PCR) diagnosis using cerebral spinal fluid (CSF) as a reference method. Tests on DNA extracted from plasma are noninvasive, thus avoiding all of the collateral effects and patient risks associated with CSF collection. This study aimed to determine whether plasma can replace CSF in nested PCR analysis for the detection of CNS human herpesvirus (HHV) diseases by analysing the proportion of patients whose CSF nested PCR results were positive for CNS HHV who also had the same organism identified by plasma nested PCR. In this study, CSF DNA was used as the gold standard, and nested PCR was performed on both types of samples. Fifty-two patients with symptoms of nervous system infection were submitted to CSF and blood collection. For the eight HHV, one positive DNA result-in plasma and/or CSF nested PCR-was considered an active HHV infection, whereas the occurrence of two or more HHVs in the same sample was considered a coinfection. HHV infections were positively detected in 27/52 (51.9%) of the CSF and in 32/52 (61.5%) of the plasma, difference not significant, thus nested PCR can be performed on plasma instead of CSF. In conclusion, this findings suggest that plasma as a useful material for the diagnosis of cases where there is any difficulty to perform a CSF puncture.

PARAFAC: uma ferramenta quimiométrica para tratamento de dados multidimensionais. Aplicações na determinação direta de fármacos em plasma humano por espectrofluorimetria

Since the last decade, the combined use of chemometrics and molecular spectroscopic techniques has become a new alternative for direct drug determination, without the need of physical separation. Among the new methodologies developed, the application of PARAFAC in the decomposition of spectrofluorimetric data should be highlighted. The first objective of this article is to describe the theoretical basis of PARAFAC. For this purpose, a discussion about the order of chemometric methods used in multivariate calibration and the development of multi-dimensional methods is presented first. The other objective of this article is to divulge for the Brazilian chemical community the potential of the combination PARAFAC/spectrofluorimetry for the determination of drugs in complex biological matrices. For this purpose, two applications aiming at determining, respectively, doxorrubicine and salicylate in human plasma are presented.

Determinação rápida de fármacos básicos em plasma por cromatografia a gás com detector de nitrogênio e fósforo

A simple and fast method for determination of 40 basic drugs in human plasma employing gas-chromatography with nitrogen-phosphorus detection was developed and validated. Drugs were extracted from 800 µL of plasma with 250 µL of butyl acetate at basic pH. Aliquots of the organic extract were directly injected on a column with methylsilicone stationary phase. Total chromatographic run time was 25 min. All compounds were detected in concentrations ranging from therapeutic to toxic levels, with intermediate precision CV% below 11.2 and accuracy in the range of 92-114%.