The primary headaches: genetics, epigenetics and a behavioural genetic model

The primary headaches, migraine with (MA) and without aura (MO) and cluster headache, all carry a substantial genetic liability. Familial hemiplegic migraine (FHM), an autosomal dominant mendelian disorder classified as a subtype of MA, is due to mutations in genes encoding neural channel subunits. MA/MO are considered multifactorial genetic disorders, and FHM has been proposed as a model for migraine aetiology. However, a review of the genetic studies suggests that the FHM genes are not involved in the typical migraines and that FHM should be considered as a syndromic migraine rather than a subtype of MA. Adopting the concept of syndromic migraine could be useful in understanding migraine pathogenesis. We hypothesise that epigenetic mechanisms play an important role in headache pathogenesis. A behavioural model is proposed, whereby the primary headaches are construed as behaviours, not symptoms, evolutionarily conserved for their adaptive value and engendered out of a genetic repertoire by a network of pattern generators present in the brain and signalling homeostatic imbalance. This behavioural model could be incorporated into migraine genetic research

Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

Docteur, puis-je boire de l'alcool avec mes antibiotiques ?

Qui n'a pas été confronté, lors de la prescription d'antibiotiques, à la question : «Docteur, est-ce que je peux continuer à boire mon verre de vin ?». Cet article passe en revue les antibiotiques incriminés et les mécanismes connus ou suspectés de leur interaction avec l'éthanol. «L'effet antabuse» n'est pas l'exclusivité du métronidazole : certaines céphalosporines (céfamandole, céfazoline, etc.) et certains antifongiques (kétoconazole, griséofulvine) sont impliques. L'érythromycine, par son activité prokinétique, accélère l'absorption de l'éthanol et diminuerait son métabolisme de premier passage. L'alcool pourrait renforcer les effets des fluoroquinolones et des antimalariques sur le système nerveux central. Faut-il par principe déconseiller la prise d'alcool lors de traitement antibiotique ou faut-il prescrire des molécules ne présentant pas de risque d'interaction ? A chacun sa réponse

Regrouping rabbit does in a familiar or novel pen: Effects on agonistic behaviour, injuries and core body temperature

Regrouping female rabbits in group-housing systems is common management practice in rabbit breeding, which may, however, induce agonistic interactions resulting in social stress and severe injuries. Here we compared two methods of regrouping female rabbits with respect to their effects on behaviour, stress and injuries. Thus, we introduced two unfamiliar rabbits into a group of rabbits either in the group's familiar pen (HOME) or in a novel disinfected pen (NOVEL), and assessed the effects of these treatments on general activity, number and duration of agonistic interactions, number and severity of injuries and body temperature as a measure of stress. General activities were not affected by the method of regrouping. Also, treatment had no effect on the number and duration of agonistic interactions. However, the numbers of injuries (P=0.030) as well as body temperature on the first clay after regrouping (p=0.0036) were increased in rabbits regrouped in a novel clean pen. These findings question the recommendation to introduce unfamiliar does into established groups in a neutral environment and indicate that regrouping in the group's home pen may decrease the risk of severe injuries and social stress. (C) 2011 Elsevier B.V. All rights reserved

Pharmacokinetics and pharmacodynamics of IFN-beta 1a in healthy volunteers

The pharmacokinetics of recombinant human interferon-beta1a (IFN-beta1a) (Rebif, Ares-Serono, Geneva, Switzerland) were investigated in healthy volunteers following intravenous (i.v.) administration of increasing single doses of the drug (22 microg/6 million international units [MIU], 44 microg/12 MIU, and 66 microg/18 MIU); i.v., intramuscular (i.m.), and subcutaneous (s.c.) administration of a 66-microg dose; and repeated s.c. administration of four 66-microg doses at 48-h intervals. The disposition of IFN-beta1a followed triexponential decay after i.v. administration (half-lives 3 min, 42 min, and 22 h, respectively). After s.c. and i. m. administration, absorption was the rate-limiting factor in the terminal phase. The median absolute bioavailabilities were 30% and 27%, respectively. The accumulation ratio after repeated s.c. injections was 2.4, and a terminal half-life of 66 h was observed. Intracellular 2-5A synthetase activity and serum neopterin and beta2-microglobulin concentrations increased after all IFN-beta1a injections and remained elevated following every-other-day administration. The local tolerance was good, and the systemic tolerance was satisfactory

Design of nest access grids and perches in front of the nests: Influence on the behavior of laying hens.

In aviary systems for laying hens, it is important to provide suitable nest access platforms in front of the nests, allowing hens to reach and explore each of the nests easily. This access platform is needed to achieve good nest acceptance by the hens and thereby prevent mislaid eggs. In the present experiment, the behavior of hens using 2 different nest access platforms, a plastic grid and 2 wooden perches, was examined. Furthermore, the nests were placed on both sides of the aviary rack (corridor side and outdoor side), either integrated into the aviary rack itself (integrated nest; IN) or placed on the walls of the pens (wall nest; WN), resulting in a 2 × 2 factorial design Four thousand five hundred white laying hens were housed in 20 test pens. The eggs in the nests and mislaid eggs were collected daily, and the behavior of hens on the nest accesses was filmed during wk 25 and 26, using focal observation and scan sampling methods. More balancing, body contact, and agonistic interactions were expected for nests with perches, whereas more walking and nest inspections were expected for nests with grids. There were more mislaid eggs and balancing found in pens equipped with nests with wooden perches. More agonistic interactions and balancing, less standing, and a longer duration of nest inspection were found with the WN compared with the IN. Interactions between platform design and position of the nests were found for duration of nest visits, body contact, and walking, with the highest amount for WN equipped with plastic grids. Nests on the corridor side were favored by the hens. Nest-related behaviors, such as nest inspection, standing, and walking, decreased over time as did the number of hens on the nest accesses, whereas sitting increased. These results indicate that the hens had more difficulties in gripping the perches as designed. The lower number of hens on the nest access platforms in front of IN may be due to a better distribution around nests and tier changes within the aviary rack. Based on these results, grids rather than perches provide for improved nesting behavior