The impact of the Psychoactive Substances Act 2016 on the online availability of MDMB-CHMICA.

BACKGROUND: In May 2016, the UK Government enacted the Psychoactive Substances Act which made it an offense to produce or supply many drugs including new psychoactive substances (NPS). AIM: We aimed to assess the impact of the Act on the availability of the synthetic cannabinoid receptor agonist methyl 2-[[1-(cyclohexylmethyl)indole-3-carbonyl]amino]-3,3-dimethylbutanoate (MDMB-CHMICA) from internet-based suppliers. DESIGN: Internet snapshot availability study. METHODS: We conducted two snapshot availability surveys looking at the number of websites offering to sell MDMB-CHMICA: the first in March prior to implementation of the Act and the second in June, 1 month post-implementation. RESULTS: In March and June 2016, we identified 47 and 38 websites, respectively, which offered to sell MDMB-CHMICA. There were no significant differences in the price of the drug nor the forms available for purchase. In the June survey there was a significant decrease in the number of websites which openly stated they were based in the UK (from 14 down to 2), three websites stated that they did not supply customers based in the UK and two websites stated they had ceased sales of MDMB-CHMICA due to the Act. CONCLUSIONS: This study showed a small but limited reduction in the availability of MDMB-CHMICA from internet-based suppliers following implementation of the Act.

Patch clamp recordings of hair cells isolated from zebrafish auditory and vestibular end organs.

The senses of hearing and balance in vertebrates are transduced by hair cells in the inner ear. Hair cells from a wide variety of organisms have been described electrophysiologically but this is the first report of the application of these techniques to the genetically tractable zebrafish model system. Auditory and vestibular hair cells isolated from zebrafish lagenae and utricles were patch clamped and both inward and outward currents under voltage clamp, and changes in membrane potential under current clamp were recorded. Cells displayed substantial diversity in their morphology, constellation of channel types, and level of excitability. While all cells showed evidence of the presence of fast-inactivating (A-type) K(+) channels, other K(+) channel types, including delayed rectifier, inward rectifier and large conductance Ca(2+)-activated K(+) (BK) channels were less common. Recorded Ca(2+) currents were identified pharmacologically as L-type. Non-linear regenerative voltage responses were evoked in more than half of the cells studied.

Toxic levels of glycosides in herbal medication: a potential cause of hyperkalaemia.

We report a previously healthy man presenting with life-threatening hyperkalaemia and heart failure. The only possible cause was thought to be the long list of herbal medications he was taking, several of which contained significant amounts of cardiac glycosides. Hyperkalaemia is known to be associated with digoxin toxicity and we present this as the likely cause in this case, and emphasize the importance of a thorough drug history in forming a differential diagnosis.

Body size evolution in Mesozoic birds.

The tendency for the mean body size of taxa within a clade to increase through evolution (Cope's Rule) has been demonstrated in a number of terrestrial vertebrate groups. However, because avian body size is strongly constrained by flight, any increase in size during the evolution of this lineage should be limited - there is a maximum size that can be attained by a bird for it to be able to get off the ground. Contrary to previous interpretations of early avian evolution, we demonstrate an overall increase in body size across Jurassic and Cretaceous flying birds: taxon body size increases from the earliest Jurassic through to the end of the Cretaceous, across a time span of 70 Myr. Although evidence is limited that this change is directional, it is certainly nonrandom. Relative size increase occurred presumably as the result of an increase in variance as the avian clade diversified after the origin of flight: a progression towards larger body size is seen clearly within the clades Pygostylia and Ornithothoraces. In contrast, a decrease in body size characterizes the most crownward lineage Ornithuromorpha, the clade that includes all extant taxa, and potentially may explain the survival of these birds across the Cretaceous-Palaeogene boundary. As in all other dinosaurs, counter selection for small size is seen in some clades, whereas body size is increasing overall.

Lipoprotein fractionation in deuterium oxide gradients: a procedure for evaluation of antioxidant binding and susceptibility to oxidation.

Oxidative modifications of lipoproteins appear to contribute to their atherogenicity. Very low and low density lipoproteins (VLDL and LDL) are protected against these modifications by antioxidants that can be incorporated in vivo or in vitro into the particles. We describe here ultracentrifugal procedures for isolation of VLDL and LDL that do not require subsequent dialysis or buffer equilibration. Lipoproteins were isolated in buffers with physiological ionic composition prepared in D2O (deuterium oxide). This allowed measurements of the content of antioxidants and of the susceptibility to oxidation of the isolated LDL without further manipulations. Conventional ultracentrifugal methods use high salt concentrations and require additional steps to eliminate them. This introduces uncertainties in the evaluation of antioxidant binding and on measurements of their effect on VLDL and LDL oxidation. With the method described, the composition of the isolated VLDL and LDL was indistinguishable from that of fractions isolated with KBr gradients. Also, the content of alpha-tocopherol was similar. LDL isolated with KBr solutions appeared to bind 20-45% more of the probucol present in serum than LDL isolated in isotonic solutions prepared with D2O. This was the case with probucol incorporated into plasma or serum in vivo or in vitro. Five out of seven LDL isolated with the D2O procedure from different human sera appeared more resistant to Cu(2+)-catalyzed oxidation than those obtained with KBr gradients from the same serum. In addition to the gradient procedure, we also describe a preparative version of the method that can be used with multiple samples.

Congenital intraspinal neuroblastoma with intraspinal calcification in the neonatal period: report of a case with a 32-year follow-up.

Punctate and amorphous intraspinal calcification associated with interpediculate widening in a neonate with lower extremity paresis is probably pathognomonic for congenital calcified intraspinal neuroblastoma.