The concise guide to pharmacology 2019/20: Ion channels

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14749. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

Women's sexual health and contraceptive needs after a severe obstetric complication ("near-miss"): a cohort study in Burkina Faso

BACKGROUND: Little is known about the reproductive health of women who survive obstetric complications in poor countries. Our aim was to determine how severe obstetric complications in Burkina Faso affect reproductive events in the first year postpartum. METHODS: Data were collected from a prospective cohort of women who either experienced life threatening (near-miss) pregnancy-related complications or an uncomplicated childbirth, followed from the end of pregnancy to one year postpartum or post-abortum. Documented outcomes include menses resumption, sexual activity resumption, dyspareunia, uptake of contraceptives, unmet needs for contraception and women's reproductive intentions.Participants were recruited in seven hospitals between December 2004 and March 2005 in six towns in Burkina Faso. RESULTS: Reproductive events were associated with pregnancy outcome. The frequency of contraceptive use was low in all groups and the method used varied according to the presence or not of a live baby. The proportion with unmet need for contraception was high and varied according to the time since end of pregnancy. Desire for another pregnancy was highest among near-miss women with perinatal death or natural abortion. Women in the near-miss group with induced abortion, perinatal death and natural abortion had significantly higher odds of subsequent pregnancy. Unintended pregnancies were observed mainly in women in the near-miss group with live birth and the uncomplicated delivery group. CONCLUSIONS: Considering the potential deleterious impact (on health and socio-economic life) of new pregnancies in near-miss women, it is important to ensure family planning coverage includes those who survive a severe complication

Gene expression in the rat brain: High similarity but unique differences between frontomedial-, temporal- and occipital cortex

<p>Abstract</p> <p>Background</p> <p>The six-layered neocortex of the mammalian brain may appear largely homologous, but is in reality a modular structure of anatomically and functionally distinct areas. However, global gene expression seems to be almost identical across the cerebral cortex and only a few genes have so far been reported to show regional enrichment in specific cortical areas.</p> <p>Results</p> <p>In the present study on adult rat brain, we have corroborated the strikingly similar gene expression among cortical areas. However, differential expression analysis has allowed for the identification of 30, 24 and 11 genes enriched in frontomedial -, temporal- or occipital cortex, respectively. A large proportion of these 65 genes appear to be involved in signal transduction, including the ion channel <it>Fxyd6</it>, the neuropeptide <it>Grp </it>and the nuclear receptor <it>Rorb</it>. We also find that the majority of these genes display increased expression levels around birth and show distinct preferences for certain cortical layers and cell types in rodents.</p> <p>Conclusions</p> <p>Since specific patterns of expression often are linked to equally specialised biological functions, we propose that these cortex sub-region enriched genes are important for proper functioning of the cortical regions in question.</p

The Ciliogenic Transcription Factor RFX3 Regulates Early Midline Distribution of Guidepost Neurons Required for Corpus Callosum Development

The corpus callosum (CC) is the major commissure that bridges the cerebral hemispheres. Agenesis of the CC is associated with human ciliopathies, but the origin of this default is unclear. Regulatory Factor X3 (RFX3) is a transcription factor involved in the control of ciliogenesis, and Rfx3–deficient mice show several hallmarks of ciliopathies including left–right asymmetry defects and hydrocephalus. Here we show that Rfx3–deficient mice suffer from CC agenesis associated with a marked disorganisation of guidepost neurons required for axon pathfinding across the midline. Using transplantation assays, we demonstrate that abnormalities of the mutant midline region are primarily responsible for the CC malformation. Conditional genetic inactivation shows that RFX3 is not required in guidepost cells for proper CC formation, but is required before E12.5 for proper patterning of the cortical septal boundary and hence accurate distribution of guidepost neurons at later stages. We observe focused but consistent ectopic expression of Fibroblast growth factor 8 (Fgf8) at the rostro commissural plate associated with a reduced ratio of GLIoma-associated oncogene family zinc finger 3 (GLI3) repressor to activator forms. We demonstrate on brain explant cultures that ectopic FGF8 reproduces the guidepost neuronal defects observed in Rfx3 mutants. This study unravels a crucial role of RFX3 during early brain development by indirectly regulating GLI3 activity, which leads to FGF8 upregulation and ultimately to disturbed distribution of guidepost neurons required for CC morphogenesis. Hence, the RFX3 mutant mouse model brings novel understandings of the mechanisms that underlie CC agenesis in ciliopathies

The impact of positive psychological interventions on well-being in healthy elderly people

This systematic review aims to evaluate the impact of Positive Psychological Interventions (PPIs) on well-being in healthy older adults. Systematic review of PPIs obtained from three electronic databases (PsycINFO, Scopus, and Web of Science) was undertaken. Inclusion criteria were: that they were positive psychology intervention, included measurement of well-being, participants were aged over 60 years, and the studies were in English. The Cochrane Collaboration Guidelines dimensions of quality control, randomization, comparability, follow-up rate, dropout, blinding assessors are used to rate the quality of studies by two reviewers independently. The RE-AIM (Reach, Efficacy, Adoption, Implementation, and Maintenance) for evaluation of PPIs effectiveness was also applied. The final review included eight articles, each describing a positive psychological intervention study. The reminiscence interventions were the most prevalent type of PPIs to promote and maintain well-being in later life. Only two studies were rated as high quality, four were of moderate-quality and two were of low-quality. Overall results indicated that efficacy criteria (89%), reach criteria (85%), adoption criteria (73%), implementation criteria (67%), and maintenance criteria (4%) across a variety of RE-AIM dimensions. Directions for future positive psychological research related to RE-AIM, and implications for decision-making, are described

Gap junctions in olfactory neurons modulate olfactory sensitivity

<p>Abstract</p> <p>Background</p> <p>One of the fundamental questions in olfaction is whether olfactory receptor neurons (ORNs) behave as independent entities within the olfactory epithelium. On the basis that mature ORNs express multiple connexins, I postulated that gap junctional communication modulates olfactory responses in the periphery and that disruption of gap junctions in ORNs reduces olfactory sensitivity. The data collected from characterizing connexin 43 (Cx43) dominant negative transgenic mice OlfDNCX, and from calcium imaging of wild type mice (WT) support my hypothesis.</p> <p>Results</p> <p>I generated OlfDNCX mice that express a dominant negative Cx43 protein, Cx43/β-gal, in mature ORNs to inactivate gap junctions and hemichannels composed of Cx43 or other structurally related connexins. Characterization of OlfDNCX revealed that Cx43/β-gal was exclusively expressed in areas where mature ORNs resided. Real time quantitative PCR indicated that cellular machineries of OlfDNCX were normal in comparison to WT. Electroolfactogram recordings showed decreased olfactory responses to octaldehyde, heptaldehyde and acetyl acetate in OlfDNCX compared to WT. Octaldehyde-elicited glomerular activity in the olfactory bulb, measured according to odor-elicited <it>c-fos </it>mRNA upregulation in juxtaglomerular cells, was confined to smaller areas of the glomerular layer in OlfDNCX compared to WT. In WT mice, octaldehyde sensitive neurons exhibited reduced response magnitudes after application of gap junction uncoupling reagents and the effects were specific to subsets of neurons.</p> <p>Conclusions</p> <p>My study has demonstrated that altered assembly of Cx43 or structurally related connexins in ORNs modulates olfactory responses and changes olfactory activation maps in the olfactory bulb. Furthermore, pharmacologically uncoupling of gap junctions reduces olfactory activity in subsets of ORNs. These data suggest that gap junctional communication or hemichannel activity plays a critical role in maintaining olfactory sensitivity and odor perception.</p

Study of pallial neurogenesis in shark embryos and the evolutionary origin of the subventricular zone

The dorsal part of the developing telencephalon is one of the brain areas that has suffered most drastic changes throughout vertebrate evolution. Its evolutionary increase in complexity was thought to be partly achieved by the appearance of a new neurogenic niche in the embryonic subventricular zone (SVZ). Here, a new kind of amplifying progenitors (basal progenitors) expressing Tbr2, undergo a second round of divisions, which is believed to have contributed to the expansion of the neocortex. Accordingly, the existence of a pallial SVZ has been classically considered exclusive of mammals. However, the lack of studies in ancient vertebrates precludes any clear conclusion about the evolutionary origin of the SVZ and the neurogenic mechanisms that rule pallial development. In this work, we explore pallial neurogenesis in a basal vertebrate, the shark Scyliorhinus canicula, through the study of the expression patterns of several neurogenic markers. We found that apical progenitors and radial migration are present in sharks, and therefore, their presence must be highly conserved throughout evolution. Surprisingly, we detected a subventricular band of ScTbr2-expressing cells, some of which also expressed mitotic markers, indicating that the existence of basal progenitors should be considered an ancestral condition rather than a novelty of mammals or amniotes. Finally, we report that the transcriptional program for the specification of glutamatergic pallial cells (Pax6, Tbr2, NeuroD, Tbr1) is also present in sharks. However, the segregation of these markers into different cell types is not clear yet, which may be linked to the lack of layering in anamniotesThis work was supported by the Spanish Ministerio de Economía y Competitividad-FEDER (BFU2014-5863-1P)S

Gender differences and access to a sports dietitian influence dietary habits of collegiate athletes

BACKGROUND: Limited research exists on the effect of a sports dietitian (SD) on athletes’ dietary habits and nutrient periodization, which is the deliberate manipulation of macronutrient intake to match training goals. Further, the difference in dietary habits between men and women collegiate athletes has been understudied. A survey questionnaire examining dietary habits and practices was administered to athletes at two universities that employed a full time SD. Not all athletes used the SD as their primary source for nutritional guidance. The purposes were to examine the effect of a SD as a primary source of nutrition information, and the effect of gender on dietary habits in collegiate athletes. METHODS: Three hundred eighty-three women (n = 240) and men (n = 143) student-athletes (mean ± SD: age = 19.7 ± 1.4 years) from 10 collegiate sports took a 15-min survey consisting of questions on dietary habits and practices. Topics queried included eating habits, breakfast habits, hydration habits, nutritional supplementation use, pre-workout nutrition, post-workout nutrition, nutrition during team trips, and nutrient timing. Data were sorted by the athlete’s source of nutritional information (i.e., sport dietitian, other). Data analysis consisted of descriptive statistics and 2-way Pearson X(2) analyses (p ≤ 0.10). RESULTS: When a SD was indicated as the primary nutrition information source, athletes appeared to have a greater understanding of nutrient periodization (47.12 % vs. 32.85 %), were more likely to have school-provided boxed meals while on team trips (21.29 % vs. 6.77 %), and also less likely to consume fast food while on team trips (9.90 % vs. 19.55 %). Men athletes consumed fast food or restaurant meals more frequently, had higher weekly and more frequent alcohol intake during the competitive season. Women athletes were more likely to prepare meals, eat breakfast 7 days a week, and have school-provided boxed meals. CONCLUSIONS: Positive effects on dietary habits were observed when a SD was the primary nutrition information source. Practitioners should be aware of the gender differences in alcohol intake, fast food consumption, and knowledge of nutrient periodization. Collegiate athletes and athletic staff members could benefit from SD access to safeguard against dietary habits detrimental to performance