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Care. --- Glucocorticoid receptors. --- Glucocorticoid. --- Hippocampal. --- Hypothalamic-pituitary-adrenal. --- Maternal care. --- Maternal-care. --- Maternal. --- Rat. --- Receptor. --- Receptors. --- Response. --- Responses. --- Stress.
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Endocrine and immune parameters, namely glucocorticoid receptors (GcR) and IFN-gamma production in peripheral blood mononuclear cells (PBMC), and corticosterone in plasma, were studied in groups of four male rabbits observed in seminatural conditions in relation to agonistic behaviour and to seasonal variations. These parameters were selected on the basis of the findings that the presence of GcR in PBMC gives an indication of the in vivo biological effects of glucocorticoids and that PBMC cytokine production and plasma corticosterone are related to social behaviour. The frequency of active and passive behaviours was used to rank the animals. Seasonal variations were present for agonistic behaviours (Attack, Follow, Chase) and For plasma corticosterone, which were significantly higher in winter. IFN-gamma production in PBMC was increased after social interactions in both seasons, while plasma corticosterone was increased only in winter: GcR capacity in PBMC was decreased after social interactions. The results indicate that social and physical environmental factors are correlated with immune-endocrine functions
Agonistic behaviour,seasonal variation,corticosterone,glucocorticoid receptors,ifn-gamma production,rabbit. --- Agonistic behaviour. --- Agonistic. --- Animal. --- Animals. --- Behavior. --- Behaviour. --- Blood mononuclear-cells. --- Blood. --- Corticosterone. --- Dominance. --- Endocrine. --- Frequency. --- Function. --- Glucocorticoid receptors. --- Glucocorticoid. --- Glucocorticoids. --- Group. --- Hippocampal electrical-activity. --- Immune. --- Interaction. --- Interactions. --- Invivo. --- Male. --- Parameters. --- Physical. --- Pituitary. --- Plasma corticosterone. --- Plasma-corticosterone. --- Plasma. --- Production. --- Rabbit. --- Rabbits. --- Rank. --- Receptor. --- Receptors. --- Release. --- Responses. --- Season. --- Seasonal variation. --- Social behaviour. --- Social interaction. --- Social interactions. --- Social-interaction. --- Social. --- Stress. --- Variation.
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This book covers the design and development of glucocorticoid receptor modulators (GRM) from cortisol to antibody-drug conjugate payloads over the last 70 years. The author starts with an introduction to the background of glucocorticoid receptor modulators as potential therapeutic modalities. This is followed by seven chapters in which he collates and discusses the medicinal chemistry journey of GRMs, reviewing topics such as cortisol-based glucocorticoids, the different approaches that have been pursued to enable chronic dosing of GRM compounds by inactivation in plasma and the liver, the application of prodrugs to GRMs, selective GRMs, targeted delivery of GRMs using polymers and nanoparticles, and rational drug design approaches applied in the development of GRMs. Particular attention is given to the development of glucocorticoid receptor modulators as immunology antibody-drug conjugate payloads. In the book’s final chapter, the author critiques the medicinal chemistry progress made since the discovery of cortisone and the promise of the latest antibody-drug conjugates that release a GRM payload. In this book, readers will also find an overview of the X-ray structures of glucocorticoid receptor antagonists and a list of all the earlier reviews that cover part of the medicinal chemistry story of GRM collated by keywords organized in a table. With several examples of crystal structures and molecular modeling, this book illustrates the huge effort by multiple companies and research groups to develop glucocorticoid receptor modulators. Professionals and scholars alike will find it a handy tool, and appreciate the latest research findings that it presents.
Medicinal chemistry. --- Pharmaceutical chemistry. --- Drugs—Design. --- Chemistry—Data processing. --- Chemistry—History. --- Medicinal Chemistry. --- Pharmaceutics. --- Structure-Based Drug Design. --- Computational Chemistry. --- History of Chemistry. --- Chemistry, Medical and pharmaceutical --- Chemistry, Pharmaceutical --- Drug chemistry --- Drugs --- Medical chemistry --- Medicinal chemistry --- Pharmacochemistry --- Chemistry --- Glucocorticoids --- Receptors. --- Glucocorticoid receptors --- Receptors, Glucocorticoid --- Design. --- Data processing. --- History. --- Drug design --- Pharmaceutical design --- Drug development
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Postnatal maternal separation increases hypothalamic corticotropin-releasing factor (CRF) gene expression and hypothalamic-pituitary-adrenal (HPA) and behavioral responses to stress. We report here that environmental enrichment during the peripubertal period completely reverses the effects of maternal separation on both HPA and behavioral responses to stress, with no effect on CRF mRNA expression. We conclude that environmental enrichment leads to a functional reversal of the effects of maternal separation through compensation for, rather than reversal of, the neural effects of early life adversity
Behavior. --- Behavioral-responses. --- Compensation. --- Corticotropin-releasing factor. --- Corticotropin-releasing-factor. --- Crf. --- Depression. --- Early experience,environmental enrichment,maternal separation,stress,corticotropin-releasing factor,glucocorticoid receptors. --- Early experience. --- Enrichment. --- Environmental enrichment. --- Expression. --- Gene-expression. --- Gene. --- Generations. --- Hippocampus. --- Hypothalamic-pituitary-adrenal. --- Increase. --- Increases. --- Life. --- Maternal separation. --- Maternal. --- Pituitary-adrenal responses. --- Prenatal stress. --- Rat. --- Reactivity. --- Receptor messenger-rna. --- Response. --- Responses. --- Separation. --- Stress reactivity. --- Stress. --- Transmission.
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Studies of the brain inform us about the cognitive abilities of animals and hence affect the extent to which animals of that species are respected However, they can also tell us how an individual is likely to be perceiving, attending to, evaluating, coping with, enjoying, or disturbed by its environment, and so can give direct information about welfare. In studies of welfare, we are especially interested in how an individual feels. Since this depends upon high-level brain processing, we have to investigate brain function. Brain correlates of preferred social, sexual and parental situations include elevated oxytocin in the para-ventricular nucleus of the hypothalamus. Abnormal behaviour may have brain correlates, for example, high frequencies of stereotypy are associated with down-regulated P and kappa receptors and dopamine depletion in the frontal cortex. Such results help in evaluating the effects of treatment on welfare. Some brain changes, such as increased glucocorticoid receptors in the frontal lobes or increased activity in the amygdala, may be a sensitive indicator of perceived emergency. Active immunological defences lead to cytokine production in the brain, vagal nerve activity and sickness effects. Some aspects of brain function can be temporarily suppressed, for example, by opioids when there is severe pain, or permanently impaired, for example, in severely impoverished environments or during depression. Coping attempts or environmental impact can lead to injury to the brain, damage to hippocampal neurons, remodelling of dendrites in the hippocampus, or to other brain disorganisation. Brain measures can explain the nature and magnitude of many effects on welfare
Ability. --- Abnormal behaviour,adrenal,animal welfare,brain measures,coping,opioids. --- Abnormal behaviour. --- Activity. --- Amygdala. --- Animal welfare. --- Animal-welfare. --- Animal. --- Animals. --- Behavior. --- Behaviour. --- Brain. --- Cognitive-ability. --- Coping. --- Cortex. --- Damage. --- Depression. --- Dopamine. --- Emergency. --- Environment. --- Environments. --- Frequency. --- Frontal cortex. --- Frontal lobes. --- Frontal-cortex. --- Frontal. --- Function. --- Glucocorticoid receptors. --- Glucocorticoid. --- Hippocampal-neurons. --- Hippocampal. --- Hippocampus. --- Hypothalamus. --- Impoverished. --- Injuries. --- Injury. --- Neurons. --- Nucleus. --- Opioid. --- Opioids. --- Oxytocin. --- Pain. --- Paraventricular nucleus. --- Production. --- Receptor. --- Receptors. --- Responses. --- Sexual. --- Sheep. --- Situations. --- Social. --- Sows. --- Stereotypies. --- Stereotypy. --- Stress. --- Systems. --- Treatment. --- Us. --- Welfare.
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The present study investigated the effects of post-weaning social isolation (SI) on behavioural and neuroendocrine reactivity to stress of male and female rats. Innate aspects of fear and anxiety were assessed in the open field and elevated plus maze tests. Spontaneous startle reflex and conditioned fear response were further investigated. The neuroendocrine response of isolates was examined by measuring basal and stress release of ACTH and corticosterone and by evaluating the mRNA expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors using in situ hybridization. Locomotor activity in the open field was not modified by chronic SI. In males, but not females, SI produced an anxiogenic profile in the elevated plus maze. Male isolates showed a trend towards increased startle reflex amplitude relative to socially-reared controls. Moreover, SI in males produced alterations of the HPA axis functioning as reflected by higher basal levels of ACTH, and enhanced release of ACTH and corticosterone following stress. In contrast, startle response or HPA axis functioning were not altered in female isolates. Social isolates from both genders showed reduced contextual fear-conditioning. Finally, the mRNA expression of MR and GR was not modified by SI. The results of the present study suggest that chronic SI increases emotional reactivity to stress and produces a hyperfunction of the HPA axis in adult rats, particularly in males. (C) 2003 Elsevier B.V. All rights reserved
Acoustic startle response. --- Acth. --- Activity. --- Adult rats. --- Adult-rat. --- Adult-rats. --- Adult. --- Anxiety. --- Conditioned fear. --- Control. --- Corticosterone. --- Differentially reared rats. --- Elevated plus maze. --- Elevated plus-maze. --- Emotional reactivity. --- Expression. --- Fear. --- Female rats. --- Female. --- Females. --- Field. --- Gender. --- Glucocorticoid receptors. --- Glucocorticoid. --- Hpa axis. --- Hybridization. --- Increase. --- Increases. --- Innate. --- Isolation. --- Latent inhibition. --- Level. --- Locomotor activity. --- Locomotor-activity. --- Male lewis. --- Male. --- Males. --- Maternal separation. --- Mineralocorticoid receptors. --- Neuroendocrine. --- Open field. --- Open-field. --- Post weaning. --- Prepulse inhibition. --- Rat. --- Rats. --- Reactivity. --- Receptor. --- Receptors. --- Reflex. --- Release. --- Response. --- Social isolation. --- Social-isolation. --- Social. --- Sprague-dawley. --- Startle. --- Strain differences. --- Stress. --- Switzerland. --- Test. --- Tests. --- Time.
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