Disorder

punk / post-punk Lire l’ouvrage en ligne sur OpenEdition Books. Présentation Les années 1970 et 1980 virent l’émergence de deux mouvements consécutifs, identifiés sous leur forme consacrée « punk » et « post-punk ». Ces courants artistiques sont apparus d’abord aux États-Unis et en Europe et ont engendré rapidement des sous-cultures dans le monde entier. Cet ouvrage présente des contributions qui couvrent quatre décennies et trois continents, avec des études de cas sur des zones bien connues ..

Se mobiliser contre le sida en Afrique : sous la santé globale, les luttes associatives

Dans les pays du Nord, les mobilisations associatives ont marqué très tôt l’histoire du sida. Qu’en est-il en Afrique, le continent le plus touché par l’épidémie ? Bien que des associations spécialisées y existent depuis de nombreuses années, peu d’attention leur a été accordée. Cet ouvrage, le premier d’une telle ampleur sur les dynamiques associatives liées au sida en Afrique, témoigne de l’évolution des formes collectives d’organisation et de résistance face à l’épidémie sur ce continent. Depuis le début des années 2000, le développement de l’accès aux traitements antirétroviraux et l’accroissement des financements internationaux ont transformé l’engagement et le travail associatifs. Ils ont aussi produit la diversification des catégories ciblées par les politiques de lutte contre le sida, incitant au recentrement des actions autour des « populations clés ». Dans ce contexte de santé globale, les échanges entre les associations locales et les organisations du Nord ou internationales conditionnent plus que jamais les formes de l’action associative contre le sida en Afrique

Se mobiliser contre le sida en Afrique : sous la santé globale, les luttes associatives

Dans les pays du Nord, les mobilisations associatives ont marqué très tôt l’histoire du sida. Qu’en est-il en Afrique, le continent le plus touché par l’épidémie ? Bien que des associations spécialisées y existent depuis de nombreuses années, peu d’attention leur a été accordée. Cet ouvrage, le premier d’une telle ampleur sur les dynamiques associatives liées au sida en Afrique, témoigne de l’évolution des formes collectives d’organisation et de résistance face à l’épidémie sur ce continent. Depuis le début des années 2000, le développement de l’accès aux traitements antirétroviraux et l’accroissement des financements internationaux ont transformé l’engagement et le travail associatifs. Ils ont aussi produit la diversification des catégories ciblées par les politiques de lutte contre le sida, incitant au recentrement des actions autour des « populations clés ». Dans ce contexte de santé globale, les échanges entre les associations locales et les organisations du Nord ou internationales conditionnent plus que jamais les formes de l’action associative contre le sida en Afrique

Pharmacological profile of a new, potent, and long-acting gonadotropin-releasing hormone antagonist: degarelix

We describe the pharmacological profile in rats and monkeys of degarelix (FE200486), a member of a new class of long-acting gonadotropin-releasing hormone (GnRH) antagonists. At single subcutaneous injections of 0.3 to 10 microg/kg in rats, degarelix produced a dose-dependent suppression of the pituitary-gonadal axis as revealed by the decrease in plasma luteinizing hormone (LH) and testosterone levels. Duration of LH suppression increased with the dose: in the rat, significant suppression of LH lasted 1, 2, and 7 days after a single subcutaneous injection of degarelix at 12.5, 50, or 200 microg/kg, respectively. Degarelix fully suppressed plasma LH and testosterone levels in the castrated and intact rats as well as in the ovariectomized rhesus monkey for more than 40 days after a single 2-mg/kg subcutaneous injection. In comparative experiments, degarelix showed a longer duration of action than the recently developed GnRH antagonists abarelix, ganirelix, cetrorelix, and azaline B. The in vivo mechanism of action of degarelix was consistent with competitive antagonism, and the prolonged action of degarelix was paralleled by continued presence of radioimmunoassayable degarelix in the general circulation. In contrast to cetrorelix and similarly to ganirelix and abarelix, degarelix had only weak histamine-releasing properties in vitro. These results demonstrate that the unique and favorable pharmacological properties of degarelix make it an ideal candidate for the management of sex steroid-dependent pathologies requiring long-term inhibition of the gonadotropic axis

Biodegradable PLGA microparticles for sustained release of a new GnRH antagonist: part II. In vivo performance

Poly (DL-lactide-co-glycolide) microparticles (MP) containing a highly potent peptidic gonadotropin releasing hormone antagonist (degarelix) of interest in the prostate cancer indication were screened for biological performance. Efficacy was tested in a castrated male rat model at 3 doses (0.4, 1.0 and 1.5 mg/kg) and assessed as inhibition of luteinizing hormone (LH) secretion. When increasing the dose, onset of inhibition was faster, inhibition was more intense, and duration of action was prolonged. The MP type was also highly influent. If spray-dried and microextrusion particles exhibited comparable potencies, double emulsion microspheres were significantly less potent, both for onset and duration of inhibition. Interestingly, for the latter type it was found that the degarelix fraction released upon reconstitution in the solution for injection was significantly lower (max 0.3%), in comparison to spray-dried MP (max 2%) or microextrusion (max 4%). With the three types of particles, increasing peptide content was detrimental for duration of action, but only little difference was noticed between particles based on different polymers. At 1.5 mg/kg, LH inhibition was achieved over 36 days with spray-dried MP based on 75/25 lactate/glycolate copolymer. This was superior by 1 week to the performance of unformulated degarelix given at the same dose

Chronic blockade of the melanocortin 4 receptor subtype leads to obesity independently of neuropeptide Y action, with no adverse effects on the gonadotropic and somatotropic axes

Neuropeptide Y (NPY) is a powerful orexigenic factor, and alphaMSH is a melanocortin (MC) peptide that induces satiety by activating the MC4 receptor subtype. Genetic models with disruption of MC4 receptor signaling are associated with obesity. In the present study, a 7-day intracerebroventricular infusion to male rats of either the MC receptor antagonist SHU9119 or porcine NPY (10 nmol/day) was shown to strongly stimulate food and water intake and to markedly increase fat pad mass. Very high plasma leptin levels were found in NPY-treated rats (27.1 +/- 1.8 ng/ml compared with 9.9 +/- 0.9 ng/ml in SHU9119-treated animals and 2.1 +/- 0.2 ng/ml in controls). As expected, NPY infusion induced hypogonadism, characterized by an impressive decrease in seminal vesicle and prostate weights. No such effects were seen with the SHU9119 infusion. Similarly, whereas the somatotropic axis of NPY-treated rats was fully inhibited, this axis was normally activated in the obese SHU9119-treated rats. Chronic infusion of SHU9119 strikingly reduced hypothalamic gene expression for NPY (65.2 +/- 3.6% of controls), whereas gene expression for POMC was increased (170 +/- 19%). NPY infusion decreased hypothalamic gene expression for both POMC and NPY (70 +/- 9% and 75.4 +/- 9.5%, respectively). In summary, blockade of the MC4 receptor subtype by SHU9119 was able to generate an obesity syndrome with no apparent side-effects on the reproductive and somatotropic axes. In this situation, it is unlikely that hyperphagia was driven by increased NPY release, because hypothalamic NPY gene expression was markedly reduced, suggesting that hyperphagia mainly resulted from loss of the satiety signal driven by MC peptides. NPY infusion produced hypogonadism and hyposomatotropism in the face of markedly elevated plasma leptin levels and an important reduction in hypothalamic POMC synthesis. In this situation NPY probably acted both by exacerbating food intake through Y receptors and by reducing the satiety signal driven by MC peptides

Chronic administration of neuropeptide Y into the lateral ventricle of C57BL/6J male mice produces an obesity syndrome including hyperphagia, hyperleptinemia, insulin resistance, and hypogonadism

Neuropeptide Y (NPY) is involved in the central regulation of appetite, sexual behavior, and reproductive function. We have previously shown that chronic infusion of NPY into the lateral ventricle of normal rats produced an obesity syndrome characterized by hyperphagia, hyperinsulinism and collapse of reproductive function. We further demonstrated that acute inhibition of LH secretion in castrated rats was preferentially mediated by the NPY receptor subtype 5 (Y(5)). In the present study, the effects of chronic, central infusion of NPY, or the mixed Y2-Y5 agonist PYY(3-36), were evaluated both in normal male C57BL/6J mice and Sprague-Dawley rats. After a 7-day infusion to male mice, both NPY and PYY(3-36) at 5 nmol per day, induced marked hyperphagia leading to significant increases in body and fat pad weights. Furthermore, both compounds markedly reduced several markers of the reproductive axis. In the rat study, PYY(3-36) was more active than NPY to inhibit the pituitary-testicular axis, confirming the importance of the Y5 subtype for such effects. In the mouse, chronic NPY infusion induced a sustained increase in corticosterone and insulin secretion. Plasma leptin levels were also markedly increased possibly explaining the observed reduction in gene expression for hypothalamic NPY. Gene expression for hypothalamic POMC was reduced in the NPY- or PYY(3-36)-infused mice, suggesting that NPY exacerbated food intake by both acting through its own receptor(s), and reducing the satiety signal driven by the POMC-derived alpha-MSH. The present study in the mouse suggests in analogy with available rat data, that constant exposure to elevated NPY in the hypothalamic area unabatedly enhances food intake leading to an obesity syndrome including increased adiposity, insulin resistance, hypercorticism, and hypogonadism, reminiscent of the phenotype of the ob/ob mouse, that displays elevated hypothalamic NPY secondary to lack of leptin negative feedback action

Stimulation of the gonadotropic axis by the neuropeptide Y receptor Y1 antagonist/Y4 agonist 1229U91 in the male rat

Neuropeptide Y (NPY) is a highly potent orexigenic substance that is also known to modulate gonadotropin secretion. Five receptor subtypes for NPY have been identified, and a potent antagonist for the receptor subtype 1 (Y1), 1229U91, also known as GW1229 or GR231118, has been described. Subsequently, 1229U91 was also shown to represent a highly potent agonist for the Y4 receptor subtype. Very unexpectedly, intracerebroventricular administration of 1229U91 elicited an intense, dose-dependent surge of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in intact male rats that lasted for 6 h. Such stimulation was absent when a potent gonadotropin-releasing hormone antagonist was administered systemically, suggesting that 1229U91 acts centrally to stimulate gonadotropin-releasing hormone release. 1229U91 administration had no effect on growth hormone, thyroid-stimulating hormone, and corticosterone secretions. In addition to 1229U91, four other parent dimer molecules described earlier produced a marked and sustained stimulation of LH when injected intracerebroventricularly that was proportional to their binding affinity for the Y4 receptor. Central administration of the specific Y1 antagonist BIBO3304 (20 microgram) had no effect on LH secretion, making it unlikely for 1229U91 to stimulate LH secretion by an antagonistic action on the Y1 receptor subtype, thus suggesting a Y4 receptor mediation. In conclusion, the 1229U91 molecule displays an interesting conformational epitope that is able to generate large LH surges, possibly by activating Y4 or Y4-like receptor subtypes or by acting on a NPY receptor unrelated target