Mineralocorticoid receptor antagonists eplerenone and spironolactone modify adrenal cortex morphology and physiology

Mineralocorticoid receptor antagonists (MRAs) are a class of anti-hypertensive drugs that act by blocking aldosterone action. The aim of this study was to evaluate whether the MRAs spironolactone and eplerenone influence adrenal cortical physiology and morphology. Spontaneous hypertensive rats (SHR, n = 18) and normotensive rats (WKY, n = 18) were randomly exposed to a daily dose of spironolactone (n = 6), eplerenone (n = 6), or no drug (n = 6) over 28 days. After that, aldosterone, corticosterone, and 11-deoxycorticosterone plasma concentrations were quantified. Adrenal glands were subjected to morphological analysis to assess lipid droplets content, capsular width, cell proliferation, and steroidogenic proteins expression. The adrenal cortex in untreated SHR showed higher lipid droplet content as than in WKY. In SHR, MRA treatment was associated with higher circulating aldosterone levels and Ki-67 expression in aldosterone-secreting cells. In WKY, the only difference observed after MRA spironolactone treatment was a narrower capsule. There was no difference in abundance of steroidogenic enzyme between groups. In conclusion, MRAs modify adrenal gland function and morphology in SHR. The effects observed within the adrenal glomerulosa with aldosterone-secreting cell proliferation and higher circulating aldosterone levels suggests that MRA treatment provokes activation of the renin angiotensin system. The prognostic value of hyperaldosteronism secondary to MRAs blockade requires further investigation.Funding: This research was funded by the Associação dos Amigos do Serviço de Endocrinologia do Hospital de São João (2020–2021). Unit for Multidisciplinary Research in Biomedicine (UMIB) is funded by the Foundation for Science and Technology (FCT)-Portugal (UIDB/00215/2020 and UIDP/00215/2020—approval date: 2019)

Electrophysiological Heterogeneity of Fast-Spiking Interneurons: Chandelier versus Basket Cells

In the prefrontal cortex, parvalbumin-positive inhibitory neurons play a prominent role in the neural circuitry that subserves working memory, and alterations in these neurons contribute to the pathophysiology of schizophrenia. Two morphologically distinct classes of parvalbumin neurons that target the perisomatic region of pyramidal neurons, chandelier cells (ChCs) and basket cells (BCs), are generally thought to have the same "fast-spiking" phenotype, which is characterized by a short action potential and high frequency firing without adaptation. However, findings from studies in different species suggest that certain electrophysiological membrane properties might differ between these two cell classes. In this study, we assessed the physiological heterogeneity of fast-spiking interneurons as a function of two factors: species (macaque monkey vs. rat) and morphology (chandelier vs. basket). We showed previously that electrophysiological membrane properties of BCs differ between these two species. Here, for the first time, we report differences in ChCs membrane properties between monkey and rat. We also found that a number of membrane properties differentiate ChCs from BCs. Some of these differences were species-independent (e.g., fast and medium afterhyperpolarization, firing frequency, and depolarizing sag), whereas the differences in the first spike latency between ChCs and BCs were species-specific. Our findings indicate that different combinations of electrophysiological membrane properties distinguish ChCs from BCs in rodents and primates. Such electrophysiological differences between ChCs and BCs likely contribute to their distinctive roles in cortical circuitry in each species. © 2013 Povysheva et al

The novel mu-opioid antagonist, GSK1521498, reduces ethanol consumption in C57BL/6J mice.

RATIONALE Using the drinking-in-the-dark (DID) model, we compared the effects of a novel mu-opioid receptor antagonist, GSK1521498, with naltrexone, a licensed treatment of alcohol dependence, on ethanol consumption in mice. OBJECTIVE We test the ability of GSK1521498 to reduce alcohol consumption and compare its intrinsic efficacy to that of naltrexone by comparing the two drugs at doses matched for equivalent receptor occupancy. METHODS Thirty-six C57BL/6J mice were tested in a DID procedure. In 2-day cycles, animals experienced one baseline, injection-free session, and one test session when they received two injections, one of test drug and one placebo. All animals received GSK1521498 (0, 0.1, 1 and 3 mg/kg, i.p., 30 min pre-treatment) and naltrexone (0, 0.1, 1 and 3 mg/kg, s.c. 10 min pre-treatment) in a cross-over design. Receptor occupancies following the same doses were determined ex vivo in separate groups by autoradiography, using [3H]DAMGO. Binding in the region of interest was measured integrally by computer-assisted microdensitometry and corrected for non-specific binding. RESULTS Both GSK1521498 and naltrexone dose-dependently decreased ethanol consumption. When drug doses were matched for 70-75 % receptor occupancy, GSK1521498 3 mg/kg, i.p., caused a 2.5-fold greater reduction in alcohol consumption than naltrexone 0.1 mg/kg, s.c. Both GSK1521498 and naltrexone significantly reduced sucrose consumption at a dose of 1 mg/kg but not 0.1 mg/kg. In a test of conditioned taste aversion, GSK1521498 (3 mg/kg) reduced sucrose consumption 24 h following exposure to a conditioning injection. CONCLUSIONS Both opioid receptor antagonists reduced alcohol consumption but GK1521498 has higher intrinsic efficacy than naltrexone

Determination of Region of Influence Obtained by Aircraft Vertical Profiles Using the Density of Trajectories from the HYSPLIT Model

Aircraft atmospheric profiling is a valuable technique for determining greenhouse gas fluxes at regional scales (104–106 km2). Here, we describe a new, simple method for estimating the surface influence of air samples that uses backward trajectories based on the Lagrangian model Hybrid Single-Particle Lagrangian Integrated Trajectory Model (HYSPLIT). We determined “regions of influence” on a quarterly basis between 2010 and 2018 for four aircraft vertical profile sites: SAN and ALF in the eastern Amazon, and RBA and TAB or TEF in the western Amazon. We evaluated regions of influence in terms of their relative sensitivity to areas inside and outside the Amazon and their total area inside the Amazon. Regions of influence varied by quarter and less so by year. In the first and fourth quarters, the contribution of the region of influence inside the Amazon was 83–93% for all sites, while in the second and third quarters, it was 57–75%. The interquarter differences are more evident in the eastern than in the western Amazon. Our analysis indicates that atmospheric profiles from the western sites are sensitive to 42–52.2% of the Amazon. In contrast, eastern Amazon sites are sensitive to only 10.9–25.3%. These results may help to spatially resolve the response of greenhouse gas emissions to climate variability over Amazon

A Unified Picture of Disk Galaxies where Bars, Spirals and Warps Result from the Same Fundamental Causes

Bars and spiral arms have played an important role as constraints on the dynamics and on the distribution of dark matter in the optical parts of disk galaxies. Dynamics linked to the dissipative nature of gas, and its transformation into stars provide clues that spiral galaxies are driven by dissipation close to a state of \textit{marginal stability} with respect to the dynamics in the galaxy plane. Here we present numerical evidences that warps play a similar role but in the transverse direction. N-body simulations show that typical galactic disks are also marginally stable with respect to a bending instability leading to typical observed warps. The frequent occurrence of warps and asymmetries in the outer galactic disks give therefore, like bars in the inner disks, new constraints on the dark matter, but this time in the outer disks. If disks are marginally stable with respect to bending instabilities, our models suggest that the mass within the HI disks must be a multiple of the detected HI and stars, i.e., disks must be heavier than seen. But the models do not rule out a traditional thick halo with a mass within the HI disk radius similar to the total disk mass.Comment: 10 pages, 2 postscript figures, to appear in the proceedings of the conference "Penetrating Bars through Masks of Cosmic Dust: The Hubble Tuning Fork strikes a New Note", South Africa, June 200

Improving the quality of publications in and advancing the paradigms of clinical and social pharmacy practice research: The Granada statements

Pharmacy and pharmaceutical sciences embrace a series of different disciplines. Pharmacy practice has been defined as the scientific discipline that studies the different aspects of the practice of pharmacy and its impact on health care systems, medicine use, and patient care. Thus, pharmacy practice studies embrace both clinical pharmacy and social pharmacy elements. Like any other scientific discipline, clinical and social pharmacy practice disseminates research findings using scientific journals. Clinical pharmacy and social pharmacy journal editors have a role in promoting the discipline by enhancing the quality of the articles published. As has occurred in other health care areas (i.e., medicine and nursing), a group of clinical and social pharmacy practice journal editors gathered in Granada, Spain to discuss how journals could contribute to strengthening pharmacy practice as a discipline. The result of that meeting was compiled in these Granada Statements, which comprise 18 recommendations gathered into six topics: the appropriate use of terminology, impactful abstracts, the required peer reviews, journal scattering, more effective and wiser use of journal and article performance metrics, and authors selection of the most appropriate pharmacy practice journal to submit their work. (c) 2023 FIP

Improving the Quality of Publications in and Advancing the Paradigms of Clinical and Social Pharmacy Practice Research: The Granada Statements

Pharmacy and pharmaceutical sciences embrace a series of different disciplines. Pharmacy practice has been defined as the scientific discipline that studies the different aspects of the practice of pharmacy and its impact on health care systems, medicine use, and patient care. Thus, pharmacy practice studies embrace both clinical pharmacy and social pharmacy elements. Like any other scientific discipline, clinical and social pharmacy practice disseminates research findings using scientific journals. Clinical pharmacy and social pharmacy journal editors have a role in promoting the discipline by enhancing the quality of the articles published. As has occurred in other health care areas (i.e., medicine and nursing), a group of clinical and social pharmacy practice journal editors gathered in Granada, Spain to discuss how journals could contribute to strengthening pharmacy practice as a discipline. The result of that meeting was compiled in these Granada Statements, which comprise 18 recommendations gathered into six topics: the appropriate use of terminology, impactful abstracts, the required peer reviews, journal scattering, more effective and wiser use of journal and article performance metrics, and authors selection of the most appropriate pharmacy practice journal to submit their work.</jats:p

Improving the quality of publications in and advancing the entire paradigms of clinical and social pharmacy practice research: the Granada statements; [Améliorer la qualité des publications et faire progresser l'ensemble des paradigmes de la recherche sur la pratique clinique et sociale de la pharmacie: les déclarations de Grenade]

Pharmacy and pharmaceutical sciences embrace a series of different disciplines. Pharmacy practice has been defined as the scientific discipline that studies the different aspects of the practice of pharmacy and its impact on health care systems, medicine use, and patient care. Thus, pharmacy practice studies embrace both clinical pharmacy and social pharmacy elements. Like any other scientific discipline, clinical and social pharmacy practice disseminates research findings using scientific journals. Clinical pharmacy and social pharmacy journal editors have a role in promoting the discipline by enhancing the quality of the articles published. As has occurred in other health care areas (i.e., medicine and nursing), a group of clinical and social pharmacy practice journal editors gathered in Granada, Spain to discuss how journals could contribute to strengthening pharmacy practice as a discipline. The result of that meeting was compiled in these Granada Statements, which comprise 18 recommendations gathered into six topics: the appropriate use of terminology, impactful abstracts, the required peer reviews, journal scattering, more effective and wiser use of journal and article performance metrics, and authors selection of the most appropriate pharmacy practice journal to submit their work. Copyright (c) 2023 John Libbey Eurotext