The use of asparaginase to reduce acrylamide levels in cooked food

Strategies proposed for reducing the formation of the suspected carcinogen acrylamide in cooked foods often rely on a reduction in the extent of the Maillard reaction, in which acrylamide is formed from the reaction between asparagine and reducing sugars. However, the Maillard reaction also provides desirable sensory attributes of cooked foods. Mitigation procedures that modify the Maillard reaction may negatively affect flavour and colour. The use of asparaginase to convert asparagine to aspartic acid may provide a means to reduce acrylamide formation, while maintaining sensory quality. This review collates research on the use of enzymes, asparaginase in particular, to mitigate acrylamide formation. Asparaginase is a powerful tool for the food industry and it is likely that its use will increase. However, the potential adverse effects of asparaginase treatment on sensory properties of cooked foods and the need to achieve sufficient enzyme–substrate contact remain areas for future research.

Scope and Limitations of The Co-Drug Approach to Topical Drug Delivery

Many currently available drugs show unfavourable physicochemical properties for delivery into or across the skin and temporary chemical modulation of the penetrant is one option to achieve improved delivery properties. Pro-drugs are chemical derivatives of an active drug which is covalently bonded to an inactive pro-moiety in order to overcome pharmaceutical and pharmacokinetic barriers. A pro-drug relies upon conversion within the body to release the parent active drug (and pro-moiety) to elicit its pharmacological effect. The main drawback of this approach is that the pro-moiety is essentially an unwanted ballast which, when released, can lead to adverse effects. The term ‘co-drug’ refers to two or more therapeutic compounds active against the same disease bonded via a covalent chemical linkage and it is this approach which is reviewed for the first time in the current article. For topically applied co-drugs, each moiety is liberated in situ, either chemically or enzymatically, once the stratum corneum barrier has been overcome by the co-drug. Advantages include synergistic modulation of the disease process, enhancement of drug delivery and pharmacokinetic properties and the potential to enhance stability by masking of labile functional groups. The amount of published work on co-drugs is limited but the available data suggest the co-drug concept could provide a significant therapeutic improvement in dermatological diseases. However, the applicability of the co-drug approach is subject to strict limitations pertaining mainly to the availability of compatible moieties and physicochemical properties of the overall molecule.

Tolerance of ruminant animals to high dose in-feed administration of a selenium-enriched yeast

The objective of the study was to determine if there were adverse effects on animal health and performance when a range of ruminant animals species were fed at least 10 times the maximum permitted European Union (EU) selenium (Se) dietary inclusion rate (0.568 mg Se/kg DM) in the form of selenium enriched yeast (SY) derived from a specific strain of Saccharomyces cerevisiae CNCM I-3060. In a series of studies, dairy cows, beef cattle, calves and lambs were offered either a control diet which contained no Se supplement or a treatment diet which contained the same basal feed ingredients plus a SY supplement which increased total dietary Se from 0.15 to 6.25, 0.20 to 6.74, 0.15 to 5.86 and 0.14 to 6.63 mg Se/kg DM, respectively. The inclusion of the SY supplement (P < 0.001) increased whole blood Se concentrations, reaching maximum mean values of 716, 1,505, 1,377, and 724 ng Se/mL for dairy cattle, beef cattle, calves and lambs, respectively. Selenomethionine accounted for 10% of total whole blood Se in control animals whereas the proportion in SY animals ranged between 40 and 75%. Glutathione peroxidase (EC 1.11.1.9) activity was higher (P < 0.05) in SY animals when compared with controls. A range of other biochemical and hematological parameters were assessed, but few differences of biological significance were established between treatments groups. There were no differences between treatment groups within each species with regard to animal physical performance or overall animal health. It was concluded that there were no adverse effects on animal health, performance and voluntary feed intake to the administration of at least ten times the EU maximum, or approximately twenty times the US FDA permitted concentration of dietary Se in the form of SY derived from a specific strain of Saccharomyces cerevisiae CNCM I-3060.

Do all tannins have similar nutritional effects? A comparison of three Brazilian fodder legumes

Three tropical legumes, namely Leucaena leucocephala, Sesbania sesban and Cajanus cajan, were subjected to chemical analysis plus in vitro, in situ and in vivo evaluations. Three different assays were used to determine total tannins: adsorption to polyvinyl pyrrolidine (PVPP-tannins), radial diffusion (RD-tannins) and protein precipitation capacity (BSA-tannins). Total phenols, total tannins and condensed tannins were highest for Sesbania. RD-tannins were correlated with total phenols (r(2) = 0.93), PVPP-tannins (r(2) = 0.92) and condensed tannins (r(2) = 0.99). The protein precipitation capacity of Sesbania, Leucaena and Cajanus were 25.9, 6.13 and 4.05 mu g BSA/g DM, respectively. Gas production at 24h was negatively correlated with total phenols (r(2) = 0.99), PVPP-tannins (r(2) = 0.99) and condensed tannins (r(2) = 0.91). The RD-, PVPP-tannins and the response to polyethylene glycol (PEG) in the gas production assay appeared to be useful as a first screen for tannins. In situ degradability did not reflect any adverse effects of tannins. However, in vivo experiments showed that the apparent DM digestibility of Sesbania and Leucaena was lower than the basal diet. The apparent protein digestibility was lower for all legumes compared to the basal diet. Most treatments caused a negative nitrogen balance. The problems associated with browse feeding were not only related to tannin contents, other factors such as inherently poor digestibility and low energy intake may also have lead to the poor animal performance on these diets. We propose, given the limitations of current tannin assays, that it is not possible to predict beneficial or harmful nutritional effects from total tannin concentrations per se. (C) 2004 Elsevier B.V. All rights reserved.

Fracture incidence in relation to the pattern of use of hormone therapy in postmenopausal women

Context: Evidence is limited on the effects of different patterns of use of postmenopausal hormone therapy on fracture incidence and particularly on the effects of ceasing use. Objective: To investigate the effect of different patterns of hormone therapy use on fracture incidence. Design, Setting, and Participants: Prospective study of 138737 postmenopausal women aged 50 to 69 years recruited from the UK general population in 19961998 (the Million Women Study) and followed up for 1.9 to 3.9 years (average, 2.8 years) for fracture incidence. Main Outcome Measure: Adjusted relative risk (RR) for incident fracture (except fracture of the fingers, toes, and ribs) in hormone therapy users compared with never users at baseline. Results: A total of 5197 women (3.7%) reported 1 or more fractures, 79% resulting from falls. Current users of hormone therapy at baseline had a significantly reduced incidence of fracture (RR, 0.62; 95% confidence interval [CI], 0.58-0.66; P<.001). This protection was evident soon after hormone therapy began, and the RR decreased with increasing duration of use (P=.001). Among current users at baseline the RR of fracture did not vary significantly according to whether estrogen-only, estrogen-progestin, or other types of hormones were used (RR [95% CI], 0.64 [0.58-0.71], 0.58 [0.53-0.64], and 0.67 [0.56-0.80], respectively; P=19), nor did it vary significantly according to estrogen dose or estrogen or progestin constituents. The RR associated with current use of hormone therapy did not vary significantly according to 11 personal characteristics of study participants, including their age at menopause, body mass index, and physical activity. Past users of hormone therapy at baseline experienced no significant protection against fractures (RR, 1.07; 95% CI, 0.99-1.15); incidence rates returned to those of never-users within about a year of ceasing use. Conclusions: All types of hormone therapy studied confer substantial protection against fracture while they are used. This protection appears rapidly after use commences and wears off rapidly after use ceases. The older women are, the greater is their absolute reduction in fracture incidence while using hormone therapy.

Comparative effects of fatty acids on endothelial inflammatory gene expression

Background: Endothelial dysfunction may be related to adverse effects of some dietary fatty acids (FAs). Although in vitro studies have failed to show consistent findings, this may reflect the diverse experimental protocols employed and the limited range of FAs and end points studied. Aims: To investigate the effect of dietary FA type (saturated, monounsaturated, n-6 and n-3 polyunsaturated fatty acids), concentration, incubation time and cell stimulation state, on a broad spectrum of endothelial inflammatory gene expression. Methods: Using human umbilical vein endothelial cells, with and without stimulation (+/- 10 ng/ml TNF alpha), the effects of arachidonic (AA), docosahexaenoic (DHA), eicosapentaenoic (EPA), linoleic (LA), oleic (OA) and palmitic acids (PA) (10, 25 and 100 mu M), on the expression of genes encoding a number of inflammatory proteins and transcription factors were assessed by quantitative real time RT-PCR. Results: Individual FAs differentially affect endothelial inflammatory gene expression in a gene-specific manner. EPA, LA and OA significantly up-regulated MCP-1 gene expression compared to AA (p = 0.001, 0.013, 0.008, respectively) and DHA (p < 0.0005, = 0.004, 0.002, respectively). Furthermore, cell stimulation state and FA incubation time significantly influenced reported FA effects on gene expression. Conclusions: The comparative effects of saturated, monounsaturated, n-6 and n-3 polyunsaturated FAs on endothelial gene expression depend on the specific FA investigated, its length of incubation, cell stimulation state and the gene investigated. These findings may explain existing disparity in the literature. This work was funded by the EC, Framework Programme 6 via the LIPGENE project (FOOD-CT-2003-505944).

Acute effects of meal fatty acids on postprandial NEFA, glucose and apo E response: implications for insulin sensitivity and lipoprotein regulation?

Our aim was to determine whether meal fatty acids influence insulin and glucose responses to mixed meals and whether these effects can be explained by variations in postprandial NEFA and Apo, which regulate the metabolism of triacylglycerol-rich lipoproteins (Apo C and E). A single-blind crossover study examined the effects of single meals enriched in saturated fatty acids SFA), n-6 PUFA and MUFA on plasma metabolite and insulin responses. The triacylglycerol response following the PUFA meal showed a lower net incremental area under the curve than following the SFA and MUFA meals (P < 0.007). Compared with the SFA meal, the PUFA meal showed a lower net incremental area under the curve for the NEFA response from initial suppression to the end of the postprandial period (180-480 min; P < 0.02), and both PUFA and MUFA showed a lower net incremental glucose response (P < 0.02), although insulin concentrations were similar between meals. The pattern of the Apo E response was also different following the SFA meal (P < 0.02). There was a significant association between the net incremental NEFA (180-480 min) and glucose response (r(s)=0.409, P=0.025), and in multiple regression analysis the NEFA response accounted for 24 % of the variation in glucose response. Meal SFA have adverse effects on the postprandial glucose response that may be due to greater elevations in NEFA arising from differences in the metabolism of SFA- v. PUFA- and MUFA-rich lipoproteins. Elevated Apo E responses to high-SFA meals may have important implications for the hepatic metabolism of triacylglycerol-rich lipoproteins.

The effects of maternal postnatal depression and child sex on academic performance at age 16 years: a developmental approach

Background: Postnatal depression (PND) is associated with poor cognitive functioning in infancy and the early school years; long-term effects on academic outcome are not known. Method: Children of postnatally depressed (N = 50) and non-depressed mothers (N = 39), studied from infancy, were followed up at 16 years. We examined the effects on General Certificate of Secondary Education (GCSE) exam performance of maternal depression (postnatal and subsequent) and IQ, child sex and earlier cognitive development, and mother–child interactions, using structural equation modelling (SEM). Results: Boys, but not girls, of PND mothers had poorer GCSE results than control children. This was principally accounted for by effects on early child cognitive functioning, which showed strong continuity from infancy. PND had continuing negative effects on maternal interactions through childhood, and these also contributed to poorer GCSE performance. Neither chronic, nor recent, exposure to maternal depression had significant effects. Conclusions: The adverse effects of PND on male infants’ cognitive functioning may persist through development. Continuing difficulties in mother–child interactions are also important, suggesting that both early intervention and continuing monitoring of mothers with PND may be warranted.

Storm surge frequency reduction in Venice under climate change

Increased tidal levels and storm surges related to climate change are projected to result in extremely adverse effects on coastal regions. Predictions of such extreme and small-scale events, however, are exceedingly challenging, even for relatively short time horizons. Here we use data from observations, ERA-40 reanalysis, climate scenario simulations, and a simple feature model to find that the frequency of extreme storm surge events affecting Venice is projected to decrease by about 30% by the end of the twenty-first century. In addition, through a trend assessment based on tidal observations we found a reduction in extreme tidal levels. Extrapolating the current +17 cm/century sea level trend, our results suggest that the frequency of extreme tides in Venice might largely remain unaltered under the projected twenty-first century climate simulations.

Effects of psychotherapy for anxiety in children and adolescents: a meta-analytic review

This paper provides a comprehensive quantitative review of high quality randomized controlled trials of psychological therapies for anxiety disorders in children and young people. Using a systematic search for randomized controlled trials which included a control condition and reported data suitable for meta-analysis, 55 studies were included. Eligible studies were rated for methodological quality and outcome data were extracted and analyzed using standard methods. Trial quality was variable, many studies were underpowered and adverse effects were rarely assessed; however, quality ratings were higher for more recently published studies. Most trials evaluated cognitive behavior therapy or behavior therapy and most recruited both children and adolescents. Psychological therapy for anxiety in children and young people was moderately effective overall, but effect sizes were small to medium when psychological therapy was compared to an active control condition. The effect size for non-CBT interventions was not significant. Parental involvement in therapy was not associated with differential effectiveness. Treatment targeted at specific anxiety disorders, individual psychotherapy, and psychotherapy with older children and adolescents had effect sizes which were larger than effect sizes for treatments targeting a range of anxiety disorders, group psychotherapy, and psychotherapy with younger children. Few studies included an effective follow-up. Future studies should follow CONSORT reporting standards, be adequately powered, and assess follow-up. Research trials are unlikely to address all important clinical questions around treatment delivery. Thus, careful assessment and formulation will remain an essential part of successful psychological treatment for anxiety in children and young people.

Pungent general anesthetics activate transient receptor potential-A1 to produce hyperalgesia and neurogenic bronchoconstriction

BACKGROUND: Volatile anesthetics such as isoflurane and halothane have been in clinical use for many years and represent the group of drugs most commonly used to maintain general anesthesia. However, despite their widespread use, the molecular mechanisms by which these drugs exert their effects are not completely understood. Recently, a seemingly paradoxical effect of general anesthetics has been identified: the activation of peripheral nociceptors by irritant anesthetics. This mechanism may explain the hyperalgesic actions of inhaled anesthetics and their adverse effects in the airways. METHODS: To test the hypothesis that irritant inhaled anesthetics activate the excitatory ion-channel transient receptor potential (TRP)-A1 and thereby contribute to hyperalgesia and irritant airway effects, we used the measurement of intracellular calcium concentration in isolated cells in culture. For our functional experiments, we used models of isolated guinea pig bronchi to measure bronchoconstriction and withdrawal threshold to mechanical stimulation with von Frey filaments in mice. RESULTS: Irritant inhaled anesthetics activate TRPA1 expressed in human embryonic kidney cells and in nociceptive neurons. Isoflurane induces mechanical hyperalgesia in mice by a TRPA1-dependent mechanism. Isoflurane also induces TRPA1-dependent constriction of isolated bronchi. Nonirritant anesthetics do not activate TRPA1 and fail to produce hyperalgesia and bronchial constriction. CONCLUSIONS: General anesthetics induce a reversible loss of consciousness and render the patient unresponsive to painful stimuli. However, they also produce excitatory effects such as airway irritation and they contribute to postoperative pain. Activation of TRPA1 may contribute to these adverse effects, a hypothesis that remains to be tested in the clinical setting.

Increasing doxorubicin activity against breast cancer cells using PPARγ-ligands and by exploiting circadian rhythms

Doxorubicin is effective against breast cancer, but its major side effect is cardiotoxicity. The aim of this study was to determine whether the efficacy of doxorubicin on cancer cells could be increased in combination with PPARγ agonists or chrono-optimization by exploiting the diurnal cycle. We determined cell toxicity using MCF-7 cancer cells, neonatal rat cardiac myocytes and fibroblasts in this study. Doxorubicin damages the contractile filaments of cardiac myocytes and affects cardiac fibroblasts by significantly inhibiting collagen production and proliferation at the level of the cell cycle. Cyclin D1 protein levels decreased significantly following doxorubicin treatment indicative of a G1 /S arrest. PPARγ agonists with doxorubicin increased the toxicity to MCF-7 cancer cells without affecting cardiac cells. Rosiglitazone and ciglitazone both enhanced anti-cancer activity when combined with doxorubicin (e.g. 50% cell death for doxorubicin at 0.1 μM compared to 80% cell death when combined with rosiglitazone). Thus, the therapeutic dose of doxorubicin could be reduced by 20-fold through combination with the PPARγ agonists, thereby reducing adverse effects on the heart. The presence of melatonin also significantly increased doxorubicin toxicity, in cardiac fibroblasts (1 μM melatonin) but not in MCF-7 cells. Our data show, for the first time, that circadian rhythms play an important role in doxorubicin toxicity in the myocardium; doxorubicin should be administered mid-morning, when circulating levels of melatonin are low, and in combination with rosiglitazone to increase therapeutic efficacy in cancer cells while reducing the toxic effects on the heart.

MODIS-based vegetation index has sufficient sensitivity to indicate stand-level intra-seasonal climatic stress in oak and beech forests

Context: Variation in photosynthetic activity of trees induced by climatic stress can be effectively evaluated using remote sensing data. Although adverse effects of climate on temperate forests have been subjected to increased scrutiny, the suitability of remote sensing imagery for identification of drought stress in such forests has not been explored fully. Aim: To evaluate the sensitivity of MODIS-based vegetation index to heat and drought stress in temperate forests, and explore the differences in stress response of oaks and beech. Methods: We identified 8 oak and 13 beech pure and mature stands, each covering between 4 and 13 MODIS pixels. For each pixel, we extracted a time series of MODIS NDVI from 2000 to 2010. We identified all sequences of continuous unseasonal NDVI decline to be used as the response variable indicative of environmental stress. Neural Networks-based regression modelling was then applied to identify the climatic variables that best explain observed NDVI declines. Results: Tested variables explained 84–97% of the variation in NDVI, whilst air temperature-related climate extremes were found to be the most influential. Beech showed a linear response to the most influential climatic predictors, while oak responded in a unimodal pattern suggesting a better coping mechanism. Conclusions: MODIS NDVI has proved sufficiently sensitive as a stand-level indicator of climatic stress acting upon temperate broadleaf forests, leading to its potential use in predicting drought stress from meteorological observations and improving parameterisation of forest stress indices.

Density of insect-pollinated grassland plants decreases with increasing surrounding land-use intensity

Pollinator declines have raised concerns about the persistence of plant species that depend on insect pollination, in particular by bees, for their reproduction. The impact of pollinator declines remains unknown for species-rich plant communities found in temperate seminatural grasslands. We investigated effects of land-use intensity in the surrounding landscape on the distribution of plant traits related to insect pollination in 239 European seminatural grasslands. Increasing arable land use in the surrounding landscape consistently reduced the density of plants depending on bee and insect pollination. Similarly, the relative abundance of bee-pollination-dependent plants increased with higher proportions of non-arable agricultural land (e.g. permanent grassland). This was paralleled by an overall increase in bee abundance and diversity. By isolating the impact of the surrounding landscape from effects of local habitat quality, we show for the first time that grassland plants dependent on insect pollination are particularly susceptible to increasing land-use intensity in the landscape.

Single-carrier frequency domain equalisation for hammerstein communication systems using complex-valued neural networks

Single-carrier (SC) block transmission with frequency-domain equalisation (FDE) offers a viable transmission technology for combating the adverse effects of long dispersive channels encountered in high-rate broadband wireless communication systems. However, for high bandwidthefficiency and high power-efficiency systems, the channel can generally be modelled by the Hammerstein system that includes the nonlinear distortion effects of the high power amplifier (HPA) at transmitter. For such nonlinear Hammerstein channels, the standard SC-FDE scheme no longer works. This paper advocates a complex-valued (CV) B-spline neural network based nonlinear SC-FDE scheme for Hammerstein channels. Specifically, We model the nonlinear HPA, which represents the CV static nonlinearity of the Hammerstein channel, by a CV B-spline neural network, and we develop two efficient alternating least squares schemes for estimating the parameters of the Hammerstein channel, including both the channel impulse response coefficients and the parameters of the CV B-spline model. We also use another CV B-spline neural network to model the inversion of the nonlinear HPA, and the parameters of this inverting B-spline model can easily be estimated using the standard least squares algorithm based on the pseudo training data obtained as a natural byproduct of the Hammerstein channel identification. Equalisation of the SC Hammerstein channel can then be accomplished by the usual one-tap linear equalisation in frequency domain as well as the inverse B-spline neural network model obtained in time domain. Extensive simulation results are included to demonstrate the effectiveness of our nonlinear SC-FDE scheme for Hammerstein channels.