On the organs of reproduction, and the development of the Myriapoda.

Mode of access: Internet.

Is cannabis a gateway drug? Testing hypotheses about the relationship between cannabis use and the use of other illicit drugs

We outline and evaluate competing explanations of three relationships that have consistently been found between cannabis use and the use of other illicit drugs, namely, ( 1) that cannabis use typically precedes the use of other illicit drugs; and that ( 2) the earlier cannabis is used, and ( 3) the more regularly it is used, the more likely a young person is to use other illicit drugs. We consider three major competing explanations of these patterns: ( 1) that the relationship is due to the fact that there is a shared illicit market for cannabis and other drugs which makes it more likely that other illicit drugs will be used if cannabis is used; ( 2) that they are explained by the characteristics of those who use cannabis; and ( 3) that they reflect a causal relationship in which the pharmacological effects of cannabis on brain function increase the likelihood of using other illicit drugs. These explanations are evaluated in the light of evidence from longitudinal epidemiological studies, simulation studies, discordant twin studies and animal studies. The available evidence indicates that the association reflects in part but is not wholly explained by: ( 1) the selective recruitment to heavy cannabis use of persons with pre-existing traits ( that may be in part genetic) that predispose to the use of a variety of different drugs; ( 2) the affiliation of cannabis users with drug using peers in settings that provide more opportunities to use other illicit drugs at an earlier age; ( 3) supported by socialisation into an illicit drug subculture with favourable attitudes towards the use of other illicit drugs. Animal studies have raised the possibility that regular cannabis use may have pharmacological effects on brain function that increase the likelihood of using other drugs. We conclude with suggestions for the type of research studies that will enable a decision to be made about the relative contributions that social context, individual characteristics, and drug effects make to the relationship between cannabis use and the use of other drugs.

Temperature influences the coercive mating and swimming performance of male eastern mosquitofish

Although the functional consequences of temperature variation have been examined for a wide range of whole-animal performance traits, the implications of thermal variation for reproductive behaviour or performance are poorly known. I examined the acute effects of temperature on the mating behaviour and swimming performance of male eastern mosquitofish, Gambusia holbrooki, which rely on a coercive strategy to obtain matings and are routinely exposed to wide daily temperature fluctuations. Males showed reproductive behaviours across the entire test temperature range of 14-38 degrees C, representing one of the widest reproductively active temperature ranges for any ectotherm. Both the time spent in pursuit of females and the total number of mating attempts increased with temperature to a plateau that started at approximately 22-26 degrees C. However, males maintained a constant level of copulations at 18-34 degrees C, the temperature range they routinely experience in southeast Queensland. In contrast, maximum swimming performance and approach speeds during copulations were highly thermally dependent across this temperature range. Thus, acute temperature variation has important fitness implications for male G. holbrooki, but mating performance was significantly limited only at extreme temperatures. (c) 2005 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

An investigation of the effects of antitumour and other drugs on cell morphology and the cytoskeleton of erythrocytes

Human arythrocytes were used as a model system for an investigation of the mechanism of action of the antiproliferative drug Adriamycin. Erythrocytes were induced to undergo a change in morphology by elevation of intracellular calcium. It was revealed that the widely used media employed for the study of morphological change were unsuitable; a new incubation medium was developed so that cells were metabolically replete. In this medium echinocytosis took place both in a calcium concentration- and time-dependent manner. Pretreatment of erythrocytes with Adriamycin (10 M for 10 mins) protected the erythrocytes against calcium-induced echinocytosis at calcium concentrations < 150M. SDS-PAGE analysis of the cytoskeletal proteins prepared from erythrocytes revealed the calcium-induced proteolysis of two main cytoskeletal proteins: band 2:1 and band 4:1. Only the rate of the proteolysis of band 2.1 correlated with the onset of echinocytosis. Adriamycin inhibited the breakdown of band 2.1 even when the cells formed echinocytes; this raises doubts concerning the importance of band 2.1 in the maintenance of discocyte morphology. Adriamycin only marginally inhibited the purified calcium-activated thio protease (calpain). Calcium-loading of human erythrocytes increased the phosphorylation of several major cytoskeletal proteins including pp120, band 3, band 4.1 and band 4.9. The pattern of increase resembled that induced by 12-0-tetradecanoyl-phorbol-13-acetate. Pre-treatment with Adriamycin prior to calcium loading caused a general lowering of basal phosphorylation. Adriamycin had no effect on the activity of the calcium-activated phospholipid-dependent protein kinase (protein kinase C). A hypothesis is put forward that the morphological transition of erythrocytes might be dependent upon the activity of a contractile system.

A predictive in vitro model of the impact of drugs with anticholinergic properties on human neuronal and astrocytic systems

The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary study we employed a co-culture of human-derived neurons and astrocytes (NT2.N/A) derived from the NT2 cell line. NT2.N/A cells possess much of the functionality of mature neurons and astrocytes, key cholinergic phenotypic markers and muscarinic acetylcholine receptors (mAChRs). The cholinergic response of NT2 astrocytes to the mAChR agonist oxotremorine was examined using the fluorescent dye fluo-4 to quantitate increases in intracellular calcium [Ca2+]i. Inhibition of this response by drugs classified as severe (dicycloverine, amitriptyline), moderate (cyclobenzaprine) and possible (cimetidine) on the Anticholinergic Cognitive Burden (ACB) scale, was examined after exposure to individual and pairs of compounds. Individually, dicycloverine had the most significant effect regarding inhibition of the astrocytic cholinergic response to oxotremorine, followed by amitriptyline then cyclobenzaprine and cimetidine, in agreement with the ACB scale. In combination, dicycloverine with cyclobenzaprine had the most significant effect, followed by dicycloverine with amitriptyline. The order of potency of the drugs in combination frequently disagreed with predicted ACB scores derived from summation of the individual drug scores, suggesting current scales may underestimate the effect of polypharmacy. Overall, this NT2.N/A model may be appropriate for further investigation of adverse anticholinergic effects of multiple medications, in order to inform clinical choices of suitable drug use in the elderly.

Diverse antiepileptic drugs increase the ratio of background synaptic inhibition to excitation and decrease neuronal excitability in neurones of the rat entorhinal cortex in vitro

Although most anti-epileptic drugs are considered to have a primary molecular target, it is clear that their actions are unlikely to be limited to effects on a single aspect of inhibitory synaptic transmission, excitatory transmission or voltage-gated ion channels. Systemically administered drugs can obviously simultaneously access all possible targets, so we have attempted to determine the overall effect of diverse agents on the balance between GABAergic inhibition, glutamatergic excitation and cellular excitability in neurones of the rat entorhinal cortex in vitro. We used an approach developed for estimating global background synaptic excitation and inhibition from fluctuations in membrane potential obtained by intracellular recordings. We have previously validated this approach in entorhinal cortical neurones [. Greenhill and Jones (2007a) Neuroscience 147:884-892]. Using this approach, we found that, despite their differing pharmacology, the drugs tested (phenytoin, lamotrigine, valproate, gabapentin, felbamate, tiagabine) were unified in their ability to increase the ratio of background GABAergic inhibition to glutamatergic excitation. This could occur as a result of decreased excitation concurrent with increased inhibition (phenytoin, lamotrigine, valproate), a decrease in excitation alone (gabapentin, felbamate), or even with a differential increase in both (tiagabine). Additionally, we found that the effects on global synaptic conductances agreed well with whole cell patch recordings of spontaneous glutamate and GABA release (our previous studies and further data presented here). The consistency with which the synaptic inhibition:excitation ratio was increased by the antiepileptic drugs tested was matched by an ability of all drugs to concurrently reduce intrinsic neuronal excitability. Thus, it seems possible that specific molecular targets among antiepileptic drugs are less important than the ability to increase the inhibition:excitation ratio and reduce overall neuronal and network excitability. © 2010 IBRO.

Systematic review and analysis of evidences on clinical efficacy and cost-effectiveness of biological drugs for the treatment of Ankylosing Spondylitis

Technology: Infliximab and comparator biological such as adalimumab, etanercept, golimumab. Conditions: Ankylosing spondylitis (AS) Issue: Infliximab is registered to be used in patients with AS. The aim of the Report is to evaluate the clinical efficacy and safety of infliximab and comparator biologicals for the treatment of adult AS. Methods: Systematic literature review and analysis as well as meta-analysis (direct and indirect comparison) of published randomised controlled clinical trials (RCT) were performed, all relevant health economics literature were identified ad analysed. Results: Clinical efficacy of biological therapies is based on good clinical evidences regarding to all clinical efficacy endpoints (ASAS20, ASAS40, ASAS 5/6, and BASDAI 50% response). Altogether, 22 trials are included in our meta-analysis, 12 infliximab, 3 adalimumab studies, 6 etanercept and 1 golimumab. Efficacy of biological treatments for the treatment of AS has been established by clinical scientific evidences, significant improvement at all outcomes considered was confirmed. According to the results of indirect comparison, there were no significant difference between biological treatments and placebo in terms of safety and tolerability endpoints. We found no significant difference between the clinical efficacy and safety of infliximab, adalimumab, etanercept and golimumab therapies. Cost-utility analysis of adalimumab and/or infliximab, etanercept and golimumab treatment for AS were performed in the UK, Canada, The Netherlands, Germany, Spain and France. There are no cost-utility studies from Eastern Central Europe. Implications for decision making: Efficacy of infliximab and comparator biologicals for the treatment of Ankylosing Spondylitis (AS) was proved by clinical evidence, significant improvement at all outcomes considered was confirmed. We found no significant differences in efficacy and safety of different biological treatments. Health economics results suggest that biological therapies are cost-effective alternatives for the treatment of AS in group of developed high income countries. There is a lack of health economics results in Central-Eastern European countries however these data are more and more required by governments and funders as part of the company economic dossiers.

Walter Scott¹s Bannatyne Club, Elite Male Associational Culture, and the Making of Identities

Date of Acceptance: 10/01/2016

The Evolution of Male-Biased Dispersal under the Joint Selective Forces of Inbreeding Load and Demographic and Environmental Stochasticity

Peer reviewed

Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials

Objective: To assess the effects of selective cyclo-oxygenase-2 (COX 2) inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of vascular events. Design: Meta-analysis of published and unpublished tabular data from randomised trials, with indirect estimation of the effects of traditional NSAIDs. Data sources: Medline and Embase (January 1966 to April 2005); Food and Drug Administration records; and data on file from Novartis, Pfizer, and Merck. Review methods: Eligible studies were randomised trials that included a comparison of a selective COX 2 inhibitor versus placebo or a selective COX 2 inhibitor versus a traditional NSAID, of at least four weeks' duration, with information on serious vascular events (defined as myocardial infarction, stroke, or vascular death). Individual investigators and manufacturers provided information on the number of patients randomised, numbers of vascular events, and the person time of follow-up for each randomised group. Results: In placebo comparisons, allocation to a selective COX 2 inhibitor was associated with a 42% relative increase in the incidence of serious vascular events (1.2%/year v 0.9%/year; rate ratio 1.42, 95% confidence interval 1.13 to 1.78; P = 0.003), with no significant heterogeneity among the different selective COX 2 inhibitors. This was chiefly attributable to an increased risk of myocardial infarction (0.6%/year v 0.3%/year; 1.86, 1.33 to 2.59; P = 0.0003), with little apparent difference in other vascular outcomes. Among trials of at least one year's duration (mean 2.7 years), the rate ratio for vascular events was 1.45 (1.12 to 1.89; P = 0.005). Overall, the incidence of serious vascular events was similar between a selective COX 2 inhibitor and any traditional NSAID (1.0%/year v 0.9/%year; 1.16, 0.97 to 1.38; P = 0.1). However, statistical heterogeneity (P = 0.001) was found between trials of a selective COX 2 inhibitor versus naproxen (1.57, 1.21 to 2.03) and of a selective COX 2 inhibitor versus non-naproxen NSAIDs (0.88, 0.69 to 1.12). The summary rate ratio for vascular events, compared with placebo, was 0.92 (0.67 to 1.26) for naproxen, 1.51 (0.96 to 2.37) for ibuprofen, and 1.63 (1.12 to 2.37) for diclofenac. Conclusions: Selective COX 2 inhibitors are associated with a moderate increase in the risk of vascular events, as are high dose regimens of ibuprofen and diclofenac, but high dose naproxen is not associated with such an excess.

The Dynamics of Male and Female Street Prostitution in Manchester, England

This article examines male street prostitution in Manchester, England, and draws some comparisons to its female counterpart in this city. While the two sectors have some important similarities, we also find significant differences in the physical and social ecology of the places in which they work, in their behavior patterns, and in individuals’ demographics and work experiences. We find that ecological dif- ferences between the male and female markets have a major impact on partici- pants’ work practices, opportunities, and integration into the local community. The data also indicate that it is incorrect to speak of a monolithic male street market or sector in Manchester because sellers shift between settings (street, bar, and escorting), unlike the female street sector. We also find that the males demonstrate more diversity in their repertoires for earning money. The findings have implications for local government policy and for outreach workers who work with these populations.

Climate change and the evolution of loggerhead sex-ratio in Cabo Verde

[EN] Global warming can affect nesting success of sea turtles due to the rise of the sea level and the subsequent increased inundation or erosion of nesting beaches. Moreover, it can reduce male production to levels that can alter reproduction due to their temperature dependant sex determination (TSD). Now, mean nest temperatures all around the world predict a predominance of female hatchlings, and this trend may increase with global warming in the next decades.

Satellite tracking derived insights into migration and foraging strategies of male loggerhead turtles in the eastern Atlantic

[EN] In recent years, information about the movements and timing of migration by male sea turtles has begun to be unraveled. Here, we present the first satellite tracking of male loggerhead sea turtles (Caretta caretta) in the eastern Atlantic. Satellite linked transmitters were attached to five adult males, captured in the near shore waters off Boavista, Republic of Cape Verde. This archipelago hosts the single most important breeding site of loggerhead turtles in the eastern Atlantic.