Methylxanthines are the psycho-pharmacologically active constituents of chocolate

Rationale: Liking, cravings and addiction for chocolate ("chocoholism") are often explained through the presence of pharmacologically active compounds. However, mere "presence" does not guarantee psycho-activity. Objectives: Two double-blind, placebo-controlled studies measured the effects on cognitive performance and mood of the amounts of cocoa powder and methylxanthines found in a 50 g bar of dark chocolate. Methods: In study 1, participants (n=20) completed a test battery once before and twice after treatment administration. Treatments included 11.6 g cocoa powder and a caffeine and theobromine combination (19 and 250 mg, respectively). Study 2 (n=22) comprised three post-treatment test batteries and investigated the effects of "milk" and "dark" chocolate levels of these methylxanthines. The test battery consisted of a long duration simple reaction time task, a rapid visual information processing task, and a mood questionnaire. Results: Identical improvements on the mood construct "energetic arousal" and cognitive function were found for cocoa powder and the caffeine+theobromine combination versus placebo. In chocolate, both "milk chocolate" and "dark chocolate" methylxanthine doses improved cognitive function compared with "white chocolate". The effects of white chocolate did not differ significantly from those of water. Conclusion: A normal portion of chocolate exhibits psychopharmacological activity. The identical profile of effects exerted by cocoa powder and its methylxanthine constituents shows this activity to be confined to the combination of caffeine and theobromine. Methylxanthines may contribute to the popularity of chocolate; however, other attributes are probably much more important in determining chocolate's special appeal and in explaining related self-reports of chocolate cravings and "chocoholism".

Endocannabinoid receptor antagonists: potential for obesity treatment

Obesity has been described as a global epidemic. Its increasing prevalence is matched by growing costs, not only to the health of the individual, but also to the medical services required to treat a range of obesity-related diseases. In most instances, obesity is a product of progressively less energetic lifestyles and the over-consumption of readily available, palatable, and highly caloric foods. Past decades have seen massive investment in the search for effective anti-obesity therapies, so far with limited success. An important part of the process of developing new pharmacologic treatments for obesity lies in improving our understanding of the psychologic and physiologic processes that govern appetite and bodyweight regulation. Recent discoveries concerning the endogenous cannabinoids are beginning to give greater insight into these processes. Current research indicates that endocannabinoids may be key to the appetitive and consummatory aspects of eating motivation, possibly mediating the craving for and enjoyment of the most desired, most fattening foods. Additionally, endocannabinoids appear to modulate central and peripheral processes associated with fat and glucose metabolism. Selective cannabinoid receptor antagonists have been shown to suppress the motivation to eat, and preferentially reduce the consumption of palatable, energy-dense foods. Additionally, these agents act to reduce adiposity through metabolic mechanisms that are independent of changes in food intake. Given the current state of evidence, we conclude that the endocannabinoids represent an exciting target for new anti-obesity therapies.

Resource availability and the persistence of seed-eating bird populations in agricultural landscapes – a mechanistic modelling approach

1. Reductions in resource availability, associated with land-use change and agricultural intensification in the UK and Europe, have been linked with the widespread decline of many farmland bird species over recent decades. However, the underlying ecological processes which link resource availability and population trends are poorly understood. 2. We construct a spatial depletion model to investigate the relationship between the population persistence of granivorous birds within the agricultural landscape and the temporal dynamics of stubble field availability, an important source of winter food for many of those species. 3. The model is capable of accurately predicting the distribution of a given number of finches and buntings amongst patches of different stubble types in an agricultural landscape over the course of a winter and assessing the relative value of different landscapes in terms of resource availability. 4. Sensitivity analyses showed that the model is relatively robust to estimates of energetic requirements, search efficiency and handling time but that daily seed survival estimates have a strong influence on model fit. Understanding resource dynamics in agricultural landscapes is highlighted as a key area for further research. 5. There was a positive relationship between the predicted number of bird days supported by a landscape over-winter and the breeding population trend for yellowhammer Emberiza citrinella, a species for which survival has been identified as the primary driver of population dynamics, but not for linnet Carduelis cannabina, a species for which productivity has been identified as the primary driver of population dynamics. 6. Synthesis and applications. We believe this model can be used to guide the effective delivery of over-winter food resources under agri-environment schemes and to assess the impacts on granivorous birds of changing resource availability associated with novel changes in land use. This could be very important in the future as farming adapts to an increasingly dynamic trading environment, in which demands for increased agricultural production must be reconciled with objectives for environmental protection, including biodiversity conservation.

A statistical mechanical approach for the computation of the climatic response to general forcings

The climate belongs to the class of non-equilibrium forced and dissipative systems, for which most results of quasi-equilibrium statistical mechanics, including the fluctuation-dissipation theorem, do not apply. In this paper we show for the first time how the Ruelle linear response theory, developed for studying rigorously the impact of perturbations on general observables of non-equilibrium statistical mechanical systems, can be applied with great success to analyze the climatic response to general forcings. The crucial value of the Ruelle theory lies in the fact that it allows to compute the response of the system in terms of expectation values of explicit and computable functions of the phase space averaged over the invariant measure of the unperturbed state. We choose as test bed a classical version of the Lorenz 96 model, which, in spite of its simplicity, has a well-recognized prototypical value as it is a spatially extended one-dimensional model and presents the basic ingredients, such as dissipation, advection and the presence of an external forcing, of the actual atmosphere. We recapitulate the main aspects of the general response theory and propose some new general results. We then analyze the frequency dependence of the response of both local and global observables to perturbations having localized as well as global spatial patterns. We derive analytically several properties of the corresponding susceptibilities, such as asymptotic behavior, validity of Kramers-Kronig relations, and sum rules, whose main ingredient is the causality principle. We show that all the coefficients of the leading asymptotic expansions as well as the integral constraints can be written as linear function of parameters that describe the unperturbed properties of the system, such as its average energy. Some newly obtained empirical closure equations for such parameters allow to define such properties as an explicit function of the unperturbed forcing parameter alone for a general class of chaotic Lorenz 96 models. We then verify the theoretical predictions from the outputs of the simulations up to a high degree of precision. The theory is used to explain differences in the response of local and global observables, to define the intensive properties of the system, which do not depend on the spatial resolution of the Lorenz 96 model, and to generalize the concept of climate sensitivity to all time scales. We also show how to reconstruct the linear Green function, which maps perturbations of general time patterns into changes in the expectation value of the considered observable for finite as well as infinite time. Finally, we propose a simple yet general methodology to study general Climate Change problems on virtually any time scale by resorting to only well selected simulations, and by taking full advantage of ensemble methods. The specific case of globally averaged surface temperature response to a general pattern of change of the CO2 concentration is discussed. We believe that the proposed approach may constitute a mathematically rigorous and practically very effective way to approach the problem of climate sensitivity, climate prediction, and climate change from a radically new perspective.

Marked influence of the bridging carbonyl ligands on the photo- and electrochemistry of the clusters [Ru-3(CO)(8)(mu-CO)(2)-(alpha-diimine)] (alpha-diimine = 2,2 '-bipyridine, 4,4 '-dimethyl-2,2 '-bipyridine and 2,2 '-bipyrimidine)

Bonding, photochemical and electrochemical properties of the clusters [Ru-3(CO)(8)(mu-CO)(2)(alpha-diimine)] (alpha-diimine=2,2'-bipyridine (1), 4,4'-dimethyl-2,2'-bipyridine (2) and 2,2'-bipyrimidine (3)) are strongly influenced by the presence of bridging carbonyl ligands. Irradiation at 471 nm initially results in the population of a sigma(Ru-3)pi*(alpha-diimine) excited state. From this state, fast decay takes place to the optically hardly directly accessible pi(Ru/mu-CO) pi*(alpha-diimine) lowest excited state. These assignments agree with theoretical (TD-DFT) results, resonance Raman and picosecond time-resolved infrared spectra. The involvement of the bridging carbonyl ligands in the electron transfer increases the energetic barrier for the formation of open-structure photoproducts such as biradicals and zwitterions. Zwitterions were therefore only obtained in strongly coordinating media such as pyridine at 250 K. The bridging carbonyl ligands also stabilize the radical anions produced upon one-electron reduction of the clusters [Ru-3(CO)(8)(mu-CO)(2)(alpha-diimine)] and observed with cyclic voltammetry, EPR and IR spectroelectrochemistry (for alpha-diimine=2,2'-bipyrimidine). In contrast, open-triangle intermediates formed along the reduction path to [Ru(CO)(2)(alpha-diimine)](n) and [Ru-2(CO)(8)](2-) are more reactive than their triosmium analogues.

In vitro fermentation of rice bran combined with Lactobacillus acidophilus 14 150B or Bifidobacterium longum 05 by the canine faecal microbiota

The fermentability of rice bran (RB), alone or in combination with one of two probiotics, by canine faecal microbiota was evaluated in stirred, pH-controlled, anaerobic batch cultures. RB enhanced the levels of bacteria detected by probes Bif164 (bifidobacteria) and Lab158 (lactic acid bacteria); however, addition of the probiotics did not have a significant effect on the predominant microbial counts compared with RB alone. RB sustained levels of Bifidobacterium longum 05 throughout the fermentation; in contrast, Lactobacillus acidophilus 14 150B levels decreased significantly after 5-h fermentation. RB fermentation induced changes in the short-chain fatty acid (SCFA) profile. However, RB combined with probiotics did not alter the SCFA levels compared with RB alone. Denaturing gradient gel electrophoresis analysis of samples obtained at 24 h showed a treatment effect with RB, which was not observed in the RB plus probiotic systems. Overall, the negative controls displayed lower species richness than the treatment systems and their banding profiles were distinct. This study illustrates the ability of a common ingredient found in pet food to modulate the canine faecal microbiota and highlights that RB may be an economical alternative to prebiotics for use in dog food.

A human volunteer study to assess the impact of confectionery sweeteners on the gut microbiota composition.

Sweeteners are being sourced to lower the energetic value of confectionery including chocolates. Some, especially non-digestible carbohydrates, may possess other benefits for human health upon their fermentation by the colonic microbiota. The present study assessed non-digestible carbohydrate sweeteners, selected for use in low-energy chocolates, for their ability to beneficially modulate faecal bacterial profiles in human volunteers. Forty volunteers consumed a test chocolate (low-energy or experimental chocolate) containing 22·8 g of maltitol (MTL), MTL and polydextrose (PDX), or MTL and resistant starch for fourteen consecutive days. The dose of the test chocolates was doubled every 2 weeks over a 6-week period. Numbers of faecal bifidobacteria significantly increased with all the three test treatments. Chocolate containing the PDX blend also significantly increased faecal lactobacilli (P = 0·00 001) after the 6 weeks. The PDX blend also showed significant increases in faecal propionate and butyrate (P = 0·002 and 0·006, respectively). All the test chocolates were well tolerated with no significant change in bowel habit or intestinal symptoms even at a daily dose of 45·6 g of non-digestible carbohydrate sweetener. This is of importance not only for giving manufacturers a sugar replacement that can reduce energetic content, but also for providing a well-tolerated means of delivering high levels of non-digestible carbohydrates into the colon, bringing about improvements in the biomarkers of gut health.

Dietary prebiotics: current status and new definition

In November 2008, a group of scientists met at the 6th Meeting of the International Scientific Association of Probiotics and Prebiotics (ISAPP) in London, Ontario, Canada, to discuss the functionality of prebiotics. As a result of this, it was concluded that the prebiotic field is currently dominated by gastrointestinal events. However, in the future, it may be the case that other mixed microbial ecosystems may be modulated by a prebiotic approach, such as the oral cavity, skin and the urogenital tract. Therefore, a decision was taken to build upon the current prebiotic status and define a niche for ‘dietary prebiotics’. This review is co-authored by the working group of ISAPP scientists and sets the background for defining a dietary prebiotic as ‘‘a selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health’’.

Self-assembled molecular complexes and coordination polymers of CdII, hexamine, and monocarboxylates: structural analysis and theoretical studies of supramolecular interactions

Four new cadmium(II) complexes [Cd-2(bz)(4)(H2O)(4)(mu 2-hmt)]center dot Hbz center dot H2O (1), [Cd-3(bz)(6)(H2O)(6)(mu 2-hmt)(2)]center dot 6H(2)O (2), [Cd(pa)(2)(H2O)(mu(2)-hmt)](n) (3), and {[Cd-3(ac)(6)(H2O)(3)(mu(3)-hmt)(2)]center dot 6H(2)O}(n) (4) with hexamine (hmt) and monocarboxylate ions, benzoate (bz), phenylacetate (pa), or acetate (ac) have been synthesized and characterized structurally. Structure determinations reveal that 1 is dinuclear, 2 is trinuclear, 3 is a one-dimensional (1D) infinite chain, and 4 is a two-dimensional (2D) polymer with fused hexagonal rings consisting of Cd-II and hmt. All the Cd-II atoms in the four complexes (except one CdII in 2) possess seven-coordinate pentagonal bipyramidal geometry with the various chelating bidentate carboxylate groups in equatorial sites. One of the CdII ions in 2, a complex that contains two monodentate carboxylates is in a distorted octahedral environment. The bridging mode of hmt is mu 2- in complexes 1-3 but is mu 3- in complex 4. In all complexes, there are significant numbers of H-bonds, C-H/pi, and pi-pi interactions which play crucial roles in forming the supramolecular networks. The importance of the noncovalent interactions in terms of energies and geometries has been analyzed using high level ab initio calculations. The effect of the cadmium coordinated to hmt on the energetic features of the C-H/pi interaction is analyzed. Finally, the interplay between C-H/pi and pi-pi interactions observed in the crystal structure of 3 is also studied.

Renewable energy in the UK countryside: policy and practice

Of the technologies currently available for producing energy from renewable sources in the British climate all except one depend on a single ingredient, namely land. Therefore other than offshore wind generation, which has been slow and expensive to establish, renewables have had to be derived almost entirely from the land, whether as sites for turbines or areas on which to grow feedstocks for biomass and biofuels. Of these, only wind turbines have been developed in any number while economic conditions have until now been unfavourable for biomass and biofuel. The UK is unlikely to meet its present targets under the Kyoto agreement, due to a mixture of limited funding and problems of policy. Peter Prag examines the present position and the potential outlook.

Predicting space climate change

The recent decline in the open magnetic flux of the Sun heralds the end of the Grand Solar Maximum (GSM) that has persisted throughout the space age, during which the largest‐fluence Solar Energetic Particle (SEP) events have been rare and Galactic Cosmic Ray (GCR) fluxes have been relatively low. In the absence of a predictive model of the solar dynamo, we here make analogue forecasts by studying past variations of solar activity in order to evaluate how long‐term change in space climate may influence the hazardous energetic particle environment of the Earth in the future. We predict the probable future variations in GCR flux, near‐Earth interplanetary magnetic field (IMF), sunspot number, and the probability of large SEP events, all deduced from cosmogenic isotope abundance changes following 24 GSMs in a 9300‐year record.

Probiotics and prebiotics

The human large intestine is an intensively colonised area containing bacteria that are health promoting, as well as pathogenic - This has led to functional food developments that fortify the former at the expense of the latter - Probiotics have a long history of use in humans as live microbial feed additions - In contrast, a prebiotic is a non digestible food ingredient that beneficially affects the host by targeting indigenous components thought to be positive - Dietary carbohydrates, such as fibres are candidate prebiotics but most promise has been realised with oligosaccharides - As prebiotics exploit non-viable food ingredients, their applicability in diets is wide ranging - As gastrointestinal disorders are prevalent in terms of human health, both probiotics and prebiotics serve an important role in the prophylactic management of various acute and chronic gut derived conditions - Examples include protection from gastroenteritis and some inflammatory conditions.

Combined transcriptomic-(1)H NMR metabonomic study reveals yhat monoethylhexyl phthalate stimulates adipogenesis and glyceroneogenesis in human adipocytes

Adipose tissue is a major storage site for lipophilic environmental contaminants. The environmental metabolic disruptor hypothesis postulates that some pollutants can promote obesity or metabolic disorders by activating nuclear receptors involved in the control of energetic homeostasis. In this context, monoethylhexyl phthalate (MEHP) is of particular concern since it was shown to activate the peroxisome proliferator-activated receptor γ (PPARγ) in 3T3-L1 murine preadipocytes. In the present work, we used an untargeted, combined transcriptomic-(1)H NMR-based metabonomic approach to describe the overall effect of MEHP on primary cultures of human subcutaneous adipocytes differentiated in vitro. MEHP stimulated rapidly and selectively the expression of genes involved in glyceroneogenesis, enhanced the expression of the cytosolic phosphoenolpyruvate carboxykinase, and reduced fatty acid release. These results demonstrate that MEHP increased glyceroneogenesis and fatty acid reesterification in human adipocytes. A longer treatment with MEHP induced the expression of genes involved in triglycerides uptake, synthesis, and storage; decreased intracellular lactate, glutamine, and other amino acids; increased aspartate and NAD, and resulted in a global increase in triglycerides. Altogether, these results indicate that MEHP promoted the differentiation of human preadipocytes to adipocytes. These mechanisms might contribute to the suspected obesogenic effect of MEHP.

In vitro fermentation of lactulose-derived oligosaccharides by mixed fecal microbiota

Fermentation properties of oligosaccharides derived from lactulose (OsLu) and lactose (GOS) have been assessed in pH-controlled anaerobic batch cultures using lactulose and Vivinal-GOS as reference carbohydrates. Changes in gut bacterial populations and their metabolic activities were monitored over 24 h by fluorescent in situ hybridization (FISH) and by measurement of short-chain fatty acid (SCFA) production. Lactulose-derived oligosaccharides were selectively fermented by Bifidobacterium and lactic acid bacterial populations producing higher SCFA concentrations compared to GOS. The highest total SCFA production was from Vivinal-GOS > lactulose > OsLu > GOS. Longer incubation periods produced a selective fermentation of OsLu when they were used as a carbon source reaching the highest selective index scores. The new oligosaccharides may constitute a good alternative to lactulose, and they could belong to a new generation of prebiotics to be used as a functional ingredient for improving the composition of gut microflora.

Evaluation of drug physical form during granulation, tabletting and storage

An active pharmaceutical ingredient (API) was found to dissociate from the highly crystalline hydrochloride form to the amorphous free base form, with consequent alterations to tablet properties. Here, a wet granulation manufacturing process has been investigated using in situ Fourier transform (FT)-Raman spectroscopic analyses of granules and tablets prepared with different granulating fluids and under different manufacturing conditions. Dosage form stability under a range of storage stresses was also investigated. Despite the spectral similarities between the two drug forms, low levels of API dissociation could be quantified in the tablets; the technique allowed discrimination of around 4% of the API content as the amorphous free base (i.e. less than 1% of the tablet compression weight). API dissociation was shown to be promoted by extended exposure to moisture. Aqueous granulating fluids and manufacturing delays between granulation and drying stages and storage of the tablets in open conditions at 40◦C/75% relative humidity (RH) led to dissociation. In contrast, non-aqueous granulating fluids, with no delay in processing and storage of the tablets in either sealed containers or at lower temperature/humidity prevented detectable dissociation. It is concluded that appropriate manufacturing process and storage conditions for the finished product involved minimising exposure to moisture of the API. Analysis of the drug using FT-Raman spectroscopy allowed rapid optimisation of the process whilst offering quantitative molecular information concerning the dissociation of the drug salt to the amorphous free base form.