Concentrations of parabens in human breast tumours

Parabens are used as preservatives in many thousands of cosmetic, food and pharmaceutical products to which the human population is exposed. Although recent reports of the oestrogenic properties of parabens have challenged current concepts of their toxicity in these consumer products, the question remains as to whether any of the parabens can accumulate intact in the body from the long-term, low-dose levels to which humans are exposed. Initial studies reported here show that parabens can be extracted from human breast tissue and detected by thin-layer chromatography. More detailed studies enabled identification and measurement of mean concentrations of individual parabens in samples of 20 human breast tumours by high-pressure liquid chromatography followed by tandem mass spectrometry. The mean concentration of parabens in these 20 human breast tumours was found to be 20.6 +/- 4.2 ng g(-1) tissue. Comparison of individual parabens showed that methylparaben was present at the highest level (with a mean value of 12.8 +/- 2.2 ng g(-1) tissue) and represents 62% of the total paraben recovered in the extractions. These studies demonstrate that parabens can be found intact in the human breast and this should open the way technically for more detailed information to be obtained on body burdens of parabens and in particular whether body burdens are different in cancer from those in normal tissues. Copyright (C) 2004 John Wiley Sons, Ltd.

Consumption of soy isoflavones does not affect plasma total homocysteine or asymmetric dimethylarginine concentrations in healthy postmenopausal women

Postmenopausal women are at increased risk for cardiovascular disease because many risk factors are aggravated by menopause. Phytoestrogens may modulate risk factors favorably, involving mechanisms similar to estrogen. The effect of phytoestrogens on the atherogenic amino acids homocysteine and asymmetric dimethylarginine (ADMA) was investigated in a controlled intervention study in healthy postmenopausal women. A multicenter, double-blind, crossover intervention trial in 89 postmenopausal women from Denmark, Germany, and the UK was performed. Subjects consumed fruit cereal bars with or without soy isoflavones (50 mg/d) for 8 wk each with an 8-wk washout period in between. Urinary phytoestrogens increased significantly after isoflavone intervention (P < 0.001). lsoflavone supplementation did not affect plasma total homocysteine or ADMA. For homocysteine, changes from baseline were 0.32 mu mol/L (range: -0.31-0.92; 95% Cl 0.13-0.72), and 0.29 mu mol/L (range: 0.45-1.09;95% Cl 0.01-0.63, P = 0.286) for isoflavone treatment and placebo, respectively. For ADMA concentrations, changes from baseline were -0.02 mu mol/L (range: -0.08-0.03; 95% Cl -0.04-0.01, and 0.00 mu mol/L (range: 0,05-0.03: 95% Cl -0.03-0.01, P = 0.397) for isoflavone treatment and placebo, respectively, There was no association between plasma total homocysteine and ADMA. Changes from baseline in plasma ADMA and folate were negatively correlated (r= -0.18, P = 0.017). These results challenge the overall health effect of isoflavone supplementation in healthy postmenopausal women.

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.

Influence of environmental stress on distributions of times to first division in Escherichia coli populations, as determined by digital-image analysis of individual cells

The distributions of times to first cell division were determined for populations of Escherichia coli stationary-phase cells inoculated onto agar media. This was accomplished by using automated analysis of digital images of individual cells growing on agar and calculation of the "box area ratio." Using approximately 300 cells per experiment, the mean time to first division and standard deviation for cells grown in liquid medium at 37 degrees C and inoculated on agar and incubated at 20 degrees C were determined as 3.0 h and 0.7 h, respectively. Distributions were observed to tail toward the higher values, but no definitive model distribution was identified. Both preinoculation stress by heating cultures at 50 degrees C and postinoculation stress by growth in the presence of higher concentrations of NaCl increased mean times to first division. Both stresses also resulted in an increase in the spread of the distributions that was proportional to the mean division time, the coefficient of variation being constant at approximately 0.2 in all cases. The "relative division time," which is the time to first division for individual cells expressed in terms of the cell size doubling time, was used as measure of the "work to be done" to prepare for cell division. Relative division times were greater for heat-stressed cells than for those growing under osmotic stress.

Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations

Objective: To examine whether age-related increase in concentrations of circulating inflammatory mediators is due to concurrent increases in cardiovascular risk factors or is independent of these. Methods and results: Cytokines (IL-6, IL-18), chemokines (6Ckine, MCP-1, IP-10), soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin) and adipokines (adiponectin) were measured in the plasma of healthy male subjects aged 18-84 years (n = 162). These were related to known cardiovascular risk factors (age, BMI, systolic and diastolic blood pressure, plasma total cholesterol, LDL cholesterol, HDL cholesterol and triacylglycerol concentrations) in order to identify significant associations. Plasma concentrations of sVCAM-1, sE-selectin, IL-6, IL-18, MCP-1, 6Ckine, IP-10 and adiponectin, but not sICAM-1, were significantly positively correlated with age, as well as with several other cardiovascular risk factors. The correlations with other risk factors disappeared when age was controlled for. In contrast, the correlations with age remained significant for sVCAM-1, IL-6, MCP-1, 6Ckine and IP-10 when other cardiovascular risk factors were controlled for. Conclusions: Plasma concentrations of some inflammatory markers (sVCAM-1, IL-6, MCP-L 6Ckine, IP-10) are positively correlated with age, independent of other cardiovascular risk factors. This suggests that age-related inflammation may not be driven by recognised risk factors. (C) 2006 Elsevier Ireland Ltd. All rights reserved.

Moderate fish-oil supplementation reverses low-platelet, long-chain n-3 polyunsaturated fatty acid status and reduces plasma triacylglycerol concentrations in British Indo-Asians

Background: The mechanisms involved in the increased mortality from coronary artery disease in British Indo-Asians are not well understood. Objectives: This study aimed to investigate whether British Indo-Asian Sikhs have higher plasma triacylglycerol concentrations, lower platelet phospholipid levels, and lower dietary intakes of long-chain n-3 polyunsaturated fatty acids (PUFAs) than do age- and weight-matched Europeans and whether moderate dietary fish-oil intake can reverse these differences. Design: A randomized, double-blind, placebo-controlled, parallel, fish-oil intervention study was performed. After a 2-wk run-in period, 44 Europeans and 40 Indo-Asian Sikhs were randomly assigned to receive either 4.0 g fish oil [1.5 g eicosapentaenoic acid (EPA) and 1.0 g docosahexaenoic acid (DHA)] or 4.0 g olive oil (control) daily for 12 wk. Results: At baseline, the Indo-Asians had significantly higher plasma triacylglycerol, small dense LDL, apolipoprotein B, and dietary and platelet phospholipid n-6 PUFA values and significantly lower long-chain n-3 PUFAs (EPA and DHA) than did the Europeans. A significant decrease in plasma triacylglycerol, plasma apolipoprotein B-48, and platelet phospholipid arachidonic acid concentrations and a significant increase in plasma HDL concentrations and platelet phospholipid EPA and DHA levels were observed after fish-oil supplementation. No significant effect of ethnicity on the responses to fish-oil supplementation was observed. Conclusions: Moderate fish-oil supplementation contributes to a reversal of lipid abnormalities and low n-3 PUFA levels in Indo-Asians and should be considered as an important, yet simple, dietary manipulation to reduce CAD risk in Indo-Asians with an atherogenic lipoprotein phenotype.

Apolipoprotein B-48: comparison of fasting concentrations measured in normolipidaemic individuals using SDS-PAGE, immunoblotting and ELISA

Raised levels of chylomicrons and chylomicron remnants, which circulate following a meal, have been implicated in the development of atherosclerosis. Apolipoprotein (apo) B-48 is exclusively associated with chylomicron particles and provides a specific direct measurement of the number of intestinally derived lipoproteins in the circulation. The quantification of apo B-48 in biological samples is difficult due to the very low concentration in plasma, structural similarity to the N-terminal 48% of apo B-100 and lack of an appropriate standard for apo B-48. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), followed by coomassie blue staining, has been used for many years to measure apo B-48 levels in triacylglycerol (TAG)-rich lipoprotein samples. The raising of antiserum to apo B-48 has led to development of more sensitive and specific methods including immunoblotting and enzyme-linked immunosorbant assays (ELISAs). This has enabled direct measurement of apo B-48 in plasma without the need for separation into TAG-rich lipoproteins. A high degree of variability was observed in the apo B-48 concentrations reported in the literature both within and between the SDS-PAGE, immunoblotting and ELISA methods. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects

Background: Dietary a-linolenic acid (ALA) can be converted to long-chain n-3 polyunsaturated fatty acids (PUFAs) in humans and may reproduce some of the beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular disease risk factors. Objective: This study aimed to compare the effects of increased dietary intakes of ALA and EPA+DHA on a range of atherogenic risk factors. Design: This was a placebo-controlled, parallel study involving 150 moderately hyperlipidemic subjects randomly assigned to 1 of 5 interventions: 0.8 or 1.7 g EPA+DHA/d, 4.5 or 9.5 g ALA/d, or an n-6 PUFA control for 6 mo. Fatty acids were incorporated into 25 g of fat spread and 3 capsules to be consumed daily. Results: The change in fasting or postprandial lipid, glucose, or insulin concentrations or in blood pressure was not significantly different after any of the n-3 PUFA interventions compared with the n-6 PUFA control. The mean (+/-SEM) change in fasting triacylglycerols after the 1.7-g/d EPA+DHA intervention (-7.7 +/- 4.99%) was significantly (P < 0.05) different from the change after the 9.5-g/d ALA intervention (10.9 +/- 4.5%). The ex vivo susceptibility of LDL to oxidation was higher after the 1.7-g/d EPA+DHA intervention than after the control and ALA interventions (P < 0.05). There was no significant change in plasma a-tocopherol concentrations or in whole plasma antioxidant status in any of the groups. Conclusion: At estimated biologically equivalent intakes, dietary ALA and EPA+DHA have different physiologic effects.

Modelling and validation of Lactobacillus plantarum fermentations in cereal-based media with different sugar concentrations and buffering capacities

An unstructured mathematical model is proposed to describe the fermentation kinetics of growth, lactic acid production, pH and sugar consumption by Lactobacillus plantarum as a function of the buffering capacity and initial glucose concentration of the culture media. Initially the experimental data of L plantarum fermentations in synthetic media with different buffering capacity and glucose were fitted to a set of primary models. Later the parameters obtained from these models were used to establish mathematical relationships with the independent variables tested. The models were validated with 6 fermentations of L. plantarum in different cereal-based media. In most cases the proposed models adequately describe the biochemical changes taking place during fermentation and are a promising approach for the formulation of cereal-based probiotic foods. (C) 2008 Elsevier B.V. All rights reserved.

Mid-nineteenth century smoke concentrations near London

It has been proposed that Earth's climate could be affected by changes in cloudiness caused by variations in the intensity of galactic cosmic rays in the atmosphere. This proposal stems from an observed correlation between cosmic ray intensity and Earth's average cloud cover over the course of one solar cycle. Some scientists question the reliability of the observations, whereas others, who accept them as reliable, suggest that the correlation may be caused by other physical phenomena with decadal periods or by a response to volcanic activity or El Niño. Nevertheless, the observation has raised the intriguing possibility that a cosmic ray–cloud interaction may help explain how a relatively small change in solar output can produce much larger changes in Earth's climate. Physical mechanisms have been proposed to explain how cosmic rays could affect clouds, but they need to be investigated further if the observation is to become more than just another correlation among geophysical variables.

Evaluating the ability of a numerical weather prediction model to forecast tracer concentrations during ETEX 2

In this paper the meteorological processes responsible for transporting tracer during the second ETEX (European Tracer EXperiment) release are determined using the UK Met Office Unified Model (UM). The UM predicted distribution of tracer is also compared with observations from the ETEX campaign. The dominant meteorological process is a warm conveyor belt which transports large amounts of tracer away from the surface up to a height of 4 km over a 36 h period. Convection is also an important process, transporting tracer to heights of up to 8 km. Potential sources of error when using an operational numerical weather prediction model to forecast air quality are also investigated. These potential sources of error include model dynamics, model resolution and model physics. In the UM a semi-Lagrangian monotonic advection scheme is used with cubic polynomial interpolation. This can predict unrealistic negative values of tracer which are subsequently set to zero, and hence results in an overprediction of tracer concentrations. In order to conserve mass in the UM tracer simulations it was necessary to include a flux corrected transport method. Model resolution can also affect the accuracy of predicted tracer distributions. Low resolution simulations (50 km grid length) were unable to resolve a change in wind direction observed during ETEX 2, this led to an error in the transport direction and hence an error in tracer distribution. High resolution simulations (12 km grid length) captured the change in wind direction and hence produced a tracer distribution that compared better with the observations. The representation of convective mixing was found to have a large effect on the vertical transport of tracer. Turning off the convective mixing parameterisation in the UM significantly reduced the vertical transport of tracer. Finally, air quality forecasts were found to be sensitive to the timing of synoptic scale features. Errors in the position of the cold front relative to the tracer release location of only 1 h resulted in changes in the predicted tracer concentrations that were of the same order of magnitude as the absolute tracer concentrations.

Effect of feed restriction and supplemental dietary fat on gut peptide and hypothalamic neuropeptide mRNA concentrations in growing wethers

The objectives of the present study were 1) to evaluate the effects of supplemental fat and ME intake on plasma concentrations of glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide, ghrelin, and oxyntomodulin; and 2) to determine the association of these peptides with DMI and the hypothalamic concentration of mRNA for the following neuropeptides: neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC). In a completely randomized block design with a 2 x 2 factorial arrangement of treatments, 32 pens with 2 wethers each were restricted-fed (2.45 Mcal/lamb per day) or offered diets ad libitum (n = 16) with or without 6% supplemental fat (n = 16) for a period of 30 d. Dry matter intake was measured daily. On d 8, 15, 22, and 29, BW was measured before feeding, and 6 h after feeding, blood samples were collected for plasma measurement of insulin, GLP-1, CCK, ghrelin, glucose-dependent insulinotropic polypeptide, oxyntomodulin, glucose, and NEFA concentrations. On d 29, blood was collected 30 min before feeding for the same hormone and metabolite analyses. At the end of the experiment, wethers were slaughtered and the hypothalami were collected to measure concentrations of NPY, AgRP, and POMC mRNA. Offering feed ad libitum (resulting in greater ME intake) increased plasma insulin and NEFA concentrations (P = 0.02 and 0.02, respectively) and decreased hypothalamic mRNA expression of NPY and AgRP (P = 0.07 and 0.02, respectively) compared with the restricted-fed wethers. There was a trend for the addition of dietary fat to decrease DMI (P = 0.12). Addition of dietary fat decreased insulin and glucose concentrations (P < 0.05 and 0.01, respectively) and tended to increase hypothalamic mRNA concentrations for NPY and AgRP (P = 0.07 and 0.11, respectively). Plasma GLP-1 and CCK concentrations increased in wethers offered feed ad libitum compared with restricted-fed wethers, but the response was greater when wethers were offered feed ad libitum and had supplemental fat in the diet (fat x intake interaction, P = 0.04). The prefeeding plasma ghrelin concentration was greater in restricted-fed wethers compared with those offered feed ad libitum, but the concentrations were similar 6 h after feeding (intake x time interaction, P < 0.01). Supplemental dietary fat did not affect (P = 0.22) plasma ghrelin concentration. We conclude that insulin, ghrelin, CCK, and GLP-1 may regulate DMI in sheep by regulating the hypothalamic gene expression of NPY, AgRP, and POMC.

Plasma ghrelin and oxytomodulin concentrations in lactating dairy cows receiving abomasal soybean oil, corn starch, and casein infusions

The effects of increased postruminal supply of casein, corn starch, and soybean oil on plasma concentrations of the gastrointestinal hormones ghrelin and oxyntomodulin (OXM) were investigated. Four mid-lactation Holstein cows were used in a 4×4 Latin square. Treatments were continuous abomasal infusions (23h/d) for 7 d of water, soybean oil (500g/d), corn starch (1100g/d), or casein (800g/d). Jugular vein plasma was obtained every 30min for 7h on days 1 and 7. Soybean oil and casein infusion decreased preprandial plasma ghrelin concentration by approximately 20% on both d (time-by-treatment P<0.10); however, dry matter intake (DMI) was depressed only after 7 d of oil infusion. Infusion of soybean oil, corn starch, or casein did not change the plasma OXM concentration (P>0.20). The present data indicate that plasma ghrelin concentration is depressed immediately before feeding by the postruminal infusion of soybean oil and casein, but it is not affected during the postprandial period. Plasma ghrelin concentration was not altered (P>0.20), pre- or postfeeding, by increased postruminal supply of corn starch. In addition, plasma OXM concentration did not respond (P>0.20) to postruminal nutrient infusion. In conclusion, a decrease in DMI when fat is infused could be partially explained by the decrease in prefeeding plasma ghrelin concentration, but a decrease in prefeeding plasma ghrelin concentration is not always associated with a decrease in DMI, as observed for the infusion of casein. Plasma OXM concentration was not affected by postruminal infusion of macronutrients.

Effect of abomasal glucose infusion on plasma concentrations of gut peptides in periparturient dairy cows

Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic plasma concentrations of gut peptides. The experimental design was a randomized block design with repeated measurements. Cows were assigned to one of 2 treatments: control or infusion of 1,500 g of glucose/d into the abomasum from the day of parturition to 29 d in milk. Cows were sampled 12 ± 6 d prepartum and at 4, 15, and 29 d in milk. Concentrations of glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1(7–36) amide, and oxyntomodulin were measured in pooled samples within cow and sampling day, whereas active ghrelin was measured in samples obtained 30 min before and after feeding at 0800 h. Postpartum, dry matter intake increased at a lower rate with infusion compared with the control. Arterial, portal venous, and hepatic venous plasma concentrations of the measured gut peptides were unaffected by abomasal glucose infusion. The arterial, portal venous, and hepatic venous plasma concentrations of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1(7–36) amide increased linearly from 12 d prepartum to 29 d postpartum. Plasma concentrations of oxyntomodulin were unaffected by day relative to parturition. Arterial and portal venous plasma concentrations of ghrelin were lower postfeeding compared with prefeeding concentrations. Arterial plasma concentrations of ghrelin were greatest prepartum and lowest at 4 d postpartum, giving a quadratic pattern of change over the transition period. Positive portal venous-arterial and hepatic venous–arterial concentration differences were observed for glucagon-like peptide 1(7–36) amide. A negative portal venous–arterial concentration difference was observed for ghrelin pre-feeding. The remaining portal venous–arterial and hepatic venous–arterial concentration differences of gut peptides did not differ from zero. In conclusion, increased postruminal glucose supply to postpartum transition dairy cows reduced feed intake relative to control cows, but did not affect arterial, portal venous, or hepatic venous plasma concentrations of gut peptide hormones. Instead, gut peptide plasma concentrations increased as lactation progressed. Thus, the lower feed intake of postpartum dairy cows receiving abomasal glucose infusion was not attributable to changes in gut peptide concentrations.