Aldo Keto Reductase 1B7 and Prostaglandin F2α Are Regulators of Adrenal Endocrine Functions

Prostaglandin F2α (PGF2α), represses ovarian steroidogenesis and initiates parturition in mammals but its impact on adrenal gland is unknown. Prostaglandins biosynthesis depends on the sequential action of upstream cyclooxygenases (COX) and terminal synthases but no PGF2α synthases (PGFS) were functionally identified in mammalian cells. In vitro, the most efficient mammalian PGFS belong to aldo-keto reductase 1B (AKR1B) family. The adrenal gland is a major site of AKR1B expression in both human (AKR1B1) and mouse (AKR1B3, AKR1B7). Thus, we examined the PGF2α biosynthetic pathway and its functional impact on both cortical and medullary zones. Both compartments produced PGF2α but expressed different biosynthetic isozymes. In chromaffin cells, PGF2α secretion appeared constitutive and correlated to continuous expression of COX1 and AKR1B3. In steroidogenic cells, PGF2α secretion was stimulated by adrenocorticotropic hormone (ACTH) and correlated to ACTH-responsiveness of both COX2 and AKR1B7/B1. The pivotal role of AKR1B7 in ACTH-induced PGF2α release and functional coupling with COX2 was demonstrated using over- and down-expression in cell lines. PGF2α receptor was only detected in chromaffin cells, making medulla the primary target of PGF2α action. By comparing PGF2α-responsiveness of isolated cells and whole adrenal cultures, we demonstrated that PGF2α repressed glucocorticoid secretion by an indirect mechanism involving a decrease in catecholamine release which in turn decreased adrenal steroidogenesis. PGF2α may be regarded as a negative autocrine/paracrine regulator within a novel intra-adrenal feedback loop. The coordinated cell-specific regulation of COX2 and AKR1B7 ensures the generation of this stress-induced corticostatic signal

Isolation of putative olfactory receptor sequences from pig nasal epithelium

International audienceBinding to olfactory receptors is the first step in odorant and pheromonal recognition and discrimination. These receptors constitute one of the most important, although poorly known, families of neuronal receptors. In this study we used degenerated oligonucleotides and a RT-PCR approach to selectively amplify olfactory receptors in the nasal epithelium of the domestic pig Sus scrofa. Several combinations of oligonucleotide were tested and allowed the isolation of eleven different partial sequences belonging to the seven transmembrane olfactory receptor family. These receptors formed a separate family within the seven transmembrane receptor superfamily in pigs. Using the criteria of Ben Arie et al. [Ben-Arie N., Lancet D., Taylor C., Khen M., Walker N., Ledbetter DH., Carrozzo R., Patel K., Sheer D., Lehrah H. and North M., Hum. Mol. Genet., 3 (1994) 229-235], the 11 receptors described here can be classified into three known families and seven subfamilies (one known and six new)

Preservation of parabens in water samples

Parabens are preservatives widely used in cosmetics, pharmaceutical and food products due to their antibacterial and antifungal activity. Their ubiquity in surface water and their potential adverse effects on human health and environment led to their inclusion into the French monitoring programme of aquatic environment. In order to help the laboratories improving their analytical skills regarding these chemicals, BIPEA organises since November 2016 proficiency testing schemes (PTS) according to ISO 17043 [1] for the quantification of butyl-, ethyl-, methyl- and propylparaben in freshwater. Parabens degradability in water by hydrolysis and photolysis raises the issue of their stability throughout the PT, especially for the samples with long delivery time or laboratories unable to perform their analyses at reception. In order to meet PT samples homogeneity and stability requirements, BIPEA conducted a comparative study on sample preservation by ascorbic acid and nitric acid. It included (i) an experimental PT for which parabens-spiked samples were proposed to the laboratories with each preservation agent separately, and (ii) a dedicated homogeneity and stability study performed by the French National Institute for Industrial Environment and Risks (INERIS). Overall preservation with nitric acid implied less dispersed results and closer to the spiking concentrations, especially for methylparaben, and a greater stability over time

Le moment RCB ou le rêve d’un gouvernement rationnel 1962-1978

Lancée en France en 1968, la rationalisation des choix budgétaires, dite RCB, constitue une séquence importante des politiques de réforme de l’État sous la Ve République. Elle est la première tentative d’une introduction généralisée du management dans la gestion des finances publiques. Croisant les approches d’historiens, de sociologues, de politistes et de juristes, cet ouvrage rassemble des enquêtes originales qui analysent les nombreuses dimensions de cette politique  : la genèse et le développement des savoirs et des techniques de rationalisation des choix budgétaires ; le processus de réforme, les coalitions et les luttes de pouvoir au sein de l’appareil d’État auxquelles il donne lieu ; enfin, son institutionnalisation dans l’administration française, ainsi que les appropriations variées dont la RCB a fait l’objet dans les différents ministères. Ce livre est le troisième volume d’une série d’ouvrages sur l’histoire de la gestion des finances publiques au xixe et au xxe siècle. Le premier volume (1815‑1914) étudiait le développement intriqué d’un droit public financier et des premiers instruments gestionnaires lui donnant corps dans l’administration. Le deuxième volume (1917‑1967) mettait en évidence la figure dominante du contrôle, sous toutes ses formes, appliqué à la dépense et à la gestion des services publics. En étudiant les dynamiques de réforme rangées sous le nom de rationalisation des choix budgétaires, le présent ouvrage montre comment la RCB se situe à la charnière de deux périodes et de deux conceptions du pilotage de l’État central : celle de la planification et des instruments de programmation de l’action publique ; celle du management public et du développement des méthodes modernes de gestion

Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy: Collaborative Analysis of Cohorts of HIV-1-Infected Patients

Background: The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods: We analyzed data on 20,379 treatment-naive HIV-1- infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results: Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count 350 cells/μL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions: Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART