An analysis of the ‘legal high’ mephedrone

‘Legal highs’ are compounds, plant or fungal material which can be readily bought from the internet without legal restriction and the single chemicals may be structurally related to illegal drugs of abuse such as the amphetamines. Several recent deaths in the UK have been attributed to these legal highs and unfortunately there is little chemical or biological literature on these materials or certified standards. Here, we detail the analysis of the widely consumed synthetic N-methyl-cathinone analogue known as mephedrone ((1) 2-aminomethyl-1-tolyl-propan-1-one (4′-methylmethcathinone)) and report its spectral data and molecular properties. Material was purchased from an internet site and examined by extensive one- and two-dimensional NMR studies, high-resolution mass spectrometry, elemental analysis and optical rotation, which demonstrated the sample to be of high purity and racemic in nature.Additionally, we report the molecular modelling properties of methyl-cathinones and compare them to their corresponding methyl-amphetamine series. This indicated that the methyl-cathinones are considerably more hydrophilic than the methyl-amphetamines which may account for the higher doses that are needed to demonstrate similar effects. The presence of a ketone in the side chain introduces a far more planar quality to the methyl-cathinones which is absent in the methyl-amphetamine series, and this planarity may contribute to toxicity.     

Colleagues in conflict: An ‘in vivo’ analysis of the sociobiology controversy

Edward O. Wilson's forays into human sociobiology have been the target of persistent, vehement attack by his Harvard colleague in evolutionary biology, Richard C. Lewontin. Through examination of existing documents in the case, together with in-depth personal interviews of Wilson, Lewontin, and other biologists, the reasons for Wilson's stance and Lewontin's criticisms are uncovered. It is argued that the dispute is not primarily personally or politically motivated, but involves a conflict between long-term scientific-cum-moral agendas, with the reductionist program as a key issue. It is concluded that it is in the interest of both disputants to keep the controversy alive.     

SNA – a toolbox for the stoichiometric analysis of metabolic networks

Background  

Despite recent algorithmic and conceptual progress, the stoichiometric network analysis of large metabolic models remains a computationally challenging problem.     

Genes for the ‘H’ subunit of human ferritin are present on a number of human chromosomes

Summary DNa has been extracted from hamster-human and mouse-human hybrid cell lines, restricted with EcoRI, and hybridised to a probe for the H subunit of human ferritin, pDBR2. Sequences highly homologous to this probe have been found on at least eight human chromosomes: 1, 2, 3, 6p216cen, 11, 14, 20, and Xq23–25Xqter. Only the gene on chromosome 11 appears to be expressed in these hybrids Southern blotting of DNA from somatic cell hybrids containing different subsets of human chromosomes. The study shows that H subunit sequences are found on at least nine different chromosomes.     

An ecological network analysis of the structure,development and sustainability of China’s natural gas supply system security

Mitigating the impacts of climate change and ensuring energy supply security has compelled China’s policy makers to maximise the use of alternative and low carbon fuels. Use and production of natural gas (an energy source with low carbon emissions) has experienced remarkable growth in China during the last decade, making China the third largest consumer and importer in the world. This study applied a powerful system-oriented ecological network analysis (ENA) technique to study China’s natural gas policies as they pertain to guarantee supply security. Several indicators based on the ENA were measured to analyse the degree of connectivity, the contributions of different compartments, resource utilisation (aggradation), development (ascendancy) and sustainability of China’s natural gas supply system. It was found that China’s source and route diversification policy have caused the natural gas supply system to exhibit considerable network complexity, demonstrating the high level of development, flexibility and diversity of China’s natural gas supply system. However, the policy also has caused a decrease in the aggradation and sustainability from the perspective of an ecological system network. The most important compartments in terms of their contribution to China’s natural gas supply system were found to be domestic natural gas production and transit compartments.     

An automated method for the analysis of ‘particulate’ carbon and nitrogen in natural waters

A method is described for the measurement of the carbon and nitrogen content of particulate material in natural waters. Particulate material is separated by filtration through GF/C filters. The dried filter is encapsulated in silver foil using a purpose made press. Analysis is carried out using high temperature combustion with thermal conductivity detection of emission gasses. Analytical performance characteristics obtained with both standards and natural materials are given.     

Exhaled breath analysis: a review of ‘breath-taking’ methods for off-line analysis

Background

The potential of exhaled breath sampling and analysis has long attracted interest in the areas of medical diagnosis and disease monitoring. This interest is attributed to its non-invasive nature, access to an unlimited sample supply (i.e., breath), and the potential to facilitate a rapid at patient diagnosis. However, progress from laboratory setting to routine clinical practice has been slow. Different methodologies of breath sampling, and the consequent difficulty in comparing and combining data, are considered to be a major contributor to this. To fulfil the potential of breath analysis within clinical and pre-clinical medicine, standardisation of some approaches to breath sampling and analysis will be beneficial.

Objectives

The aim of this review is to investigate the heterogeneity of breath sampling methods by performing an in depth bibliometric search to identify the current state of art in the area. In addition, the review will discuss and critique various breath sampling methods for off-line breath analysis.

Methods

Literature search was carried out in databases MEDLINE, BIOSIS, EMBASE, INSPEC, COMPENDEX, PQSCITECH, and SCISEARCH using the STN platform which delivers peer-reviewed articles. Keywords searched for include breath, sampling, collection, pre-concentration, volatile. Forward and reverse search was then performed on initially included articles. The breath collection methodologies of all included articles was subsequently reviewed.

Results

Sampling methods differs between research groups, for example regarding the portion of breath being targeted. Definition of late expiratory breath varies between studies.

Conclusions

Breath analysis is an interdisciplinary field of study using clinical, analytical chemistry, data processing, and metabolomics expertise. A move towards standardisation in breath sampling is currently being promoted within the breath research community with a view to harmonising analysis and thereby increasing robustness and inter-laboratory comparisons.

     

An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: Emerging ‘Novel Psychoactive Drugs’

Novel Psychoactive Drugs (NPD) can be sold without restriction and are often synthetic analogues of controlled drugs. The tryptamines are an important class of NPD as they bind to the various serotonin (5-HT) receptor subtypes and cause psychosis and hallucinations that can lead to injury or death through misadventure. Here we report on the structure elucidation and receptor binding profiles of two widely marketed tryptamine-derived NPDs, namely alpha-methyl-tryptamine and 5-methoxy-N,N-diallyl-tryptamine.     

Automated analysis of neuromuscular ‘jitter’

This paper describes an interactive program for real time analysis of the neuromuscular jitter. Two implementations, using different hardware for data acquisition, reflect the modular design and flexibility of the software. Details on the time windows are given as well as the available commands. The program features: (1) immediate feedback of acquired data; (2) optional manual editing of data; (3) simple, yet flexible commands; (4) several plot options of raw or analysed data; (5) database interface.     

Dynamics in the active site of β-secretase: a network analysis of atomistic simulations

The aspartic protease β-secretase (BACE) catalyzes the hydrolysis of the amyloid precursor protein (APP) which leads to amyloid-β aggregation and, ultimately, the perilous Alzheimer's disease. The conformational dynamics and free energy surfaces of BACE at three steps of the catalytic cycle are studied here by explicit solvent molecular dynamics simulations (multiple runs for a total of 2.2 μs). The overall plasticity of BACE is essentially identical for the three states of the substrate: the octapeptide reactant, gem-diol intermediate, and cleavage products. In contrast, the network of hydrogen bonds in the active site is more stable in the complex of BACE with the gem-diol intermediate than the other two states of the substrate. The spontaneous release of the C-terminal (P1'-P4') fragment of the product follows a single-exponential time dependence with a time constant of 50 ns and does not require the opening of the flap. The fast dissociation of the C-terminal fragment is consistent with the transmembrane location and orientation of APP and its further processing by γ-secretase. On the other hand, the N-terminal (P4-P1) fragment of the product does not exit the BACE active site within the simulation time scale of 80 ns. A unified network analysis of the complexes of BACE with the three states of the substrate provides an estimation of the activation free energy associated with the structural rearrangements that involve only noncovalent interactions. The estimated rearrangement barriers are not negligible (up to 3 kcal/mol) but are significantly smaller than the barrier of the peptide bond hydrolysis reaction.     

Cutting the first ‘teeth’: a new approach to functional analysis of conodont elements

The morphological disparity of conodont elements rivals the dentition of all other vertebrates, yet relatively little is known about their functional diversity. Nevertheless, conodonts are an invaluable resource for testing the generality of functional principles derived from vertebrate teeth, and for exploring convergence in a range of food-processing structures. In a few derived conodont taxa, occlusal patterns have been used to derive functional models. However, conodont elements commonly and primitively exhibit comparatively simple coniform morphologies, functional analysis of which has not progressed much beyond speculation based on analogy. We have generated high-resolution tomographic data for each morphotype of the coniform conodont Panderodus acostatus. Using virtual cross sections, it has been possible to characterize changes in physical properties associated with individual element morphology. Subtle changes in cross-sectional profile have profound implications for the functional performance of individual elements and the apparatus as a whole. This study has implications beyond the ecology of a single conodont taxon. It provides a basis for reinterpreting coniform conodont taxonomy (which is based heavily on cross-sectional profiles), in terms of functional performance and ecology, shedding new light on the conodont fossil record. This technique can also be applied to more derived conodont morphologies, as well as analogous dentitions in other vertebrates and invertebrates.     

An ultrastructural study of mitosis and cytokinesis in normal ‘resting’ human breast

Summary The parenchyma of the normal resting human breast was examined by electron microscopy to characterize the cells undergoing mitosis and the mechanism by which the normal tissue architecture is maintained during this process. In this study of 112 mitotic cells, it was found that the mitotic cells were luminally positioned, polarised epithelial cells with no evidence of myoepithelial cell division. Ultrastructurally, the nuclear and cytoplasmic changes were consistent with previous reports of mitosis in other tissues. However, unlike all previous reports, two specific orientations of the nuclear spindle and thus the planes of cytokinesis were observed. In a few cases the spindle formed parallel to the lumen and division resulted in two luminally positioned daughter cells. However, in the majority of mitotic cells the spindle was approximately at right angles to the lumen and this orientation resulted in a luminally and a basally positioned daughter cell. It is proposed that the abnormally positioned basal daughter cell could develop into a myoepithelial cell or undergo deletion (apoptosis). Thus the two orientations of mitosis may explain the mechanism by which the epithelial and myoepithelial cell populations were maintained by a single progenitor cell without disrupting the integrity of the tissue architecture.     

‘An island of socialism in a capitalist country’: Postsocialist Russian science and the culture of the state

Through a comparison of privatization programs in two physics institutes, this article explores the ways in which scientists in the Siberian science city of Akademgorodok adapted to the low levels of state funding available to them in the 1990s. Scientists transformed structures that were available under socialism into hybrid state-private ventures. Rather than ‘freeing’ Russian science from its former dependence on the state, however, these changes have reconfigured, and in some cases even strengthened, the relationship between state power and the production of knowledge. Seeing ‘the state’ as it is constituted in Russian scientists' discourse challenges Western models of the autonomy of science.     

Morphology of haemoglobin-containing human erythrocyte ‘ghosts’

Resealed erythrocyte ‘ghosts’ have been proposed as in vivo carriers for enzymes in the therapy of inherited metabolic diseases. A long life-span of this carrier is required when the erythrocyte ‘ghost’ is intended to be the site of substrate degradation in the circulation. Erythrocyte ‘ghosts’ have been prepared that show cell content and membrane transport characteristics that are closely similar to those of normal erythrocytes. Since the morphology of these ‘ghosts’ could probably also affect the in vivo life-span, haemoglobin-containing human erythrocyte ‘ghosts’ have been studied using scanning electron-microscopy.Preparation of the erythrocyte ‘ghosts’ involved a method of hypo-osmotic dialysis and consecutive iso-osmotic dialysis. Samples for scanning electron microscopy were prepared by fixation in glutaraldehyde, with post-fixation in osmium tetroxide. Dehydration was obtained by increasing concentrations of ethanol and critical-point-drying. Control experiments with normal erythrocytes showed no major artefacts by the methods used. Erythrocyte ‘ghosts’ showed polymorphic shapes. Two thirds were stomatocytes, but echinocytes and cells with deep invaginations or inter-twisted infoldings were also observed. Distribution of the different cell types could be affected by the preparation techniques used. Washing of the erythrocyte ‘ghosts’ at very low centrifugation speeds resulted in 60% of the cells appearing as biconcave discoids and one third as stomatocytes.The results demonstrate that the preparation disturbed the balance of the biconcave shape of resealed erythrocyte ‘ghosts’. Minor alterations of the methods allowed the preparation of erythrocyte ‘ghosts’, the majority of which showed morphology closely similar to that of normal erythrocytes. Attention must be given to all preparation factors to avoid irreversible damage and therefore prior to use of these cells in patients or when methods are altered, the morphology of these cellular carriers must be closely controlled.     

Amelioration of human osteoarthritis symptoms with topical ‘biotherapeutics’: a phase I human trial

Osteoarthritis (OA) treatments presently rely on analgesics, which manage pain but fail to restore imbalances between catabolic and anabolic processes that underlie OA pathogenesis. Recently, biologic (biotherapeutic) drugs, which alter the activity of catabolic agents such as nitric oxide and inflammatory cytokines in ways, allowing tissue regeneration, were evaluated for efficacy in OA treatment. These studies failed to demonstrate dramatic abatement of OA symptoms by these drugs, but suggested strategies by which biologic agents might be used to treat OA. The present review summarizes current understanding of OA pathogenesis and evolving treatments. Preliminary evaluations of a novel biotherapeutic strategy are presented here. Twenty OA patients receiving sour topical cherry seed extract (SCE), an inducer of heme oxygenase-1 (HO-1), a major physiological protectant against oxidative stress exhibited significantly decreased joint pain and activation of CD4+ T cells expressing inflammatory cytokines (p < 0.05), significantly decreased peripheral blood C-reactive protein (CRP), and increased leukocyte HO-1 (p < 0.05) in comparison with ten placebo-treated patients. SCE inhibits joint-damaging inflammatory mediator production. This agent therefore meets the main criterion for classification as a “biotherapeutic,” or “biologic” agent. The negligible toxicity and low cost of such materials make them promising contributors to OA treatment, sustainable within resource limitations of a wide range of patients.