Long-term, Dynamic Remodelling of the Corticotroph Transcriptome and Excitability After a Period of Chronic Stress.

Chronic stress results in long-term dynamic changes at multiple levels of the hypothalamic-pituitary-adrenal (HPA) axis resulting in stress axis dysregulation with long-term impacts on human and animal health. However, the underlying mechanisms and dynamics of altered of HPA axis function, in particular at the level of pituitary corticotrophs, during a period of chronic stress and in the weeks after its cessation (defined as "recovery") are very poorly understood. Here, we address the fundamental question of how a period of chronic stress results in altered anterior pituitary corticotroph function and whether this persists in recovery, as well as the transcriptomic changes underlying this.

Detection of gluten peptides in human duodenal fluids with immuno-liquid chromatography-mass spectrometry.

Gluten proteins are storage proteins in wheat that exhibit a certain resistance to gastrointestinal digestion. To explore solutions to cope with accidental ingestion of gluten in individuals suffering from gluten-related disorders, it is essential to monitor the fate of gluten peptides in biological samples, , gastrointestinal juices, blood plasma or urine. In this work, we aimed at developing a mass spectrometry (MS)-based method for measuring gluten peptides in human duodenal fluids.

Sex differences in pituitary corticotroph excitability.

Stress-related illness represents a major burden on health and society. Sex differences in stress-related disorders are well documented, with women having twice the lifetime rate of depression compared to men and most anxiety disorders. Anterior pituitary corticotrophs are central components of the hypothalamic-pituitary-adrenal (HPA) axis, receiving input from hypothalamic neuropeptides corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP), while regulating glucocorticoid output from the adrenal cortex.

Nutritional and lifestyle management of the aging journey: A narrative review.

With age, the physiological responses to occasional or regular stressors from a broad range of functions tend to change and adjust at a different pace and restoring these functions in the normal healthy range becomes increasingly challenging. Even if this natural decline is somehow unavoidable, opportunities exist to slow down and attenuate the impact of advancing age on major physiological processes which, when weakened, constitute the hallmarks of aging. This narrative review revisits the current knowledge related to the aging process and its impact on key metabolic functions including immune, digestive, nervous, musculoskeletal, and cardiovascular functions; and revisits insights into the important biological targets that could inspire effective strategies to promote healthy aging.

Corticotroph isolation from Pomc-eGFP mice reveals sustained transcriptional dysregulation characterising a mouse model of glucocorticoid-induced suppression of the hypothalamus-pituitary-adrenal axis.

Glucocorticoids (GC) are prescribed for periods > 3 months to 1%-3% of the UK population; 10%-50% of these patients develop hypothalamus-pituitary-adrenal (HPA) axis suppression, which may last over 6 months and is associated with morbidity and mortality. Recovery of the pituitary and hypothalamus is necessary for recovery of adrenal function. We developed a mouse model of dexamethasone (DEX)-induced HPA axis dysfunction aiming to further explore recovery in the pituitary.

Chronic stress facilitates bursting electrical activity in pituitary corticotrophs.

Coordination of an appropriate stress response is dependent upon anterior pituitary corticotroph excitability in response to hypothalamic secretagogues and glucocorticoid negative feedback. A key determinant of corticotroph excitability is large conductance calcium- and voltage-activated (BK) potassium channels that are critical for promoting corticotrophin-releasing hormone (CRH)-induced bursting that enhances adrenocorticotrophic hormone secretion. Previous studies revealed hypothalamic-pituitary-adrenal axis hyperexcitability following chronic stress (CS) is partly a function of increased corticotroph output.

Structure and Function of Bovine Whey Derived Oligosaccharides Showing Synbiotic Epithelial Barrier Protective Properties.

Commensal gut microbiota and probiotics have numerous effects on the host's metabolic and protective systems, which occur primarily through the intestinal epithelial cell interface. Prebiotics, like galacto-oligosaccharides (GOS) are widely used to modulate their function and abundance. However, important structure-function relations may exist, requiring a detailed structural characterization.

-Acylation controls functional coupling of BK channel pore-forming α-subunits and β1-subunits.

The properties and physiological function of pore-forming α-subunits of large conductance calcium- and voltage-activated potassium (BK) channels are potently modified by their functional coupling with regulatory subunits in many tissues. However, mechanisms that might control functional coupling are very poorly understood. Here we show that -acylation, a dynamic post-translational lipid modification of proteins, of the intracellular S0-S1 loop of the BK channel pore-forming α-subunit controls functional coupling to regulatory β1-subunits.

Randomised clinical trial: Bifidobacterium lactis NCC2818 probiotic vs placebo, and impact on gut transit time, symptoms, and gut microbiology in chronic constipation.

Background: Constipation is a prevalent gastrointestinal disorder. Patient dissatisfaction with prescribed medications is common, and there is need for alternative management strategies. Evidence shows that Bifidobacterium species may be beneficial in constipation.

Glucocorticoids Inhibit CRH/AVP-Evoked Bursting Activity of Male Murine Anterior Pituitary Corticotrophs.

Corticotroph cells from the anterior pituitary are an integral component of the hypothalamic-pituitary-adrenal (HPA) axis, which governs the neuroendocrine response to stress. Corticotrophs are electrically excitable and fire spontaneous single-spike action potentials and also display secretagogue-induced bursting behavior. The HPA axis function is dependent on effective negative feedback in which elevated plasma glucocorticoids result in inhibition at the level of both the pituitary and the hypothalamus.

"Health for All" in England and Brazil?

This article discusses the achievements and challenges that England and Brazil face in relation to their capacity to address inequalities in health through health promotion and public health policies. Using secondary data (policy texts and related documents), this article contextualizes, explains, and critically appraises health promotion and public health efforts for the reduction of inequalities in health in the 2 countries. A historic documentary analysis was undertaken, with hermeneutics as the methodological framework.

Large conductance Ca²⁺-activated K⁺ (BK) channels promote secretagogue-induced transition from spiking to bursting in murine anterior pituitary corticotrophs.

Anterior pituitary corticotroph cells are a central component of the hypothalamic-pituitary-adrenal (HPA) axis essential for the neuroendocrine response to stress. Corticotrophs are excitable cells that receive input from two hypothalamic secretagogues, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) to control the release of adrenocorticotrophic hormone (ACTH). Although corticotrophs are spontaneously active and increase in excitability in response to CRH and AVP the patterns of electrical excitability and underlying ionic conductances are poorly understood.

Large conductance Ca -activated K channels (BK) promote secretagogue-induced transition from spiking to bursting in murine anterior pituitary corticotrophs.

Anterior pituitary corticotroph cells are a central component of the hypothalamic-pituitary-adrenal (HPA) axis essential for the neuroendocrine response to stress. Corticotrophs are excitable cells that receive input from two hypothalamic secretagogues, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) to control the release of adrenocorticotrophin hormone (ACTH). Although corticotrophs are spontaneously active and increase in excitability in response to CRH and AVP the patterns of electrical excitability and underlying ionic conductances are poorly understood.

Teaching seven principles for public health ethics: towards a curriculum for a short course on ethics in public health programmes.

Background: Teaching ethics in public health programmes is not routine everywhere - at least not in most schools of public health in the European region. Yet empirical evidence shows that schools of public health are more and more interested in the integration of ethics in their curricula, since public health professionals often have to face difficult ethical decisions.

Discussion: The authors have developed and practiced an approach to how ethics can be taught even in crowded curricula, requiring five to eight hours of teaching and learning contact time.

Failing to professionalise, struggling to specialise: the rise and fall of health promotion as a putative specialism in England, 1980-2000.

Significant attention has been paid to the history of public health in England during the final part of the twentieth century. Within this, however, the field that came to be known as specialist health promotion (SHP) has been relatively neglected. Between 1980 and 2000 those working in this field, generally known as health promotion specialists (HPSs), enjoyed a relative rise in policy and practice prominence before SHP was effectively abandoned by government and others charged with developing and sustaining public-health structures.

Participant responsibility, researcher vulnerability and empirical ethics: a reply to Loughlin.

In a recent issue of this journal, Michael Loughlin offers a critique of work we undertook that we described and discussed in the same issue, and which might be seen as forming part of the so-called empirical turn in ethics. Here we respond to Loughlin's criticisms of our work. While he declares that generally, there is potential value in empirically informed ethics, we understand him to be concerned about our particular project on two counts.

Sialic acid utilization.

Early postnatal development encounters milk as a key environmental variable and yet the sole nutrient source. One evolutionary conserved constituent of milk is sialic acid, which is generally displayed on glycoconjugates and free glycans. During early postnatal development, high sialic acid need was proposed to be unmet by the endogenous sialic acid synthetic capacity.

Thermodynamic stability of the cubatic phase of hard cut spheres evaluated by expanded ensemble simulations.

The system of hard cut spheres (disk-shaped particles formed by symmetrically truncating the end caps of a sphere) exhibits an intriguing "cubatic" phase with cubic orientational symmetry. However, it is unclear whether this phase is metastable with respect to the columnar phase. We attempt to provide an answer to this question by carrying out free energy calculations by the expanded ensemble Monte Carlo method.

Dealing with systems and understanding contexts: what it might mean to be a 'good health care practitioner'.

The increasing complexity of contemporary health care policy and practice leads us to ask questions about what might constitute 'the good health care practitioner'. Yet, attempts through empirical work to address such questions are sparse. This paper reports on a small-scale qualitative study, which sought to explore questions with a number of health care professionals and academics about the nature of 'the good practitioner'.

Health, health care and the problem of intrinsic value.

Philosophical conceptual attempts to clarify the nature of health frequently alight on the idea that its value is intrinsic. It is asserted that health is a value in itself and as such can be abstracted from thoughts of preference or utility (subjective or instrumental value). In contrast, I argue here that it is highly problematic to conceive of the value of health in terms other than the instrumental.

Sialic acid utilisation and synthesis in the neonatal rat revisited.

Background: Milk is the sole source of nutrients for neonatal mammals and is generally considered to have co-evolved with the developmental needs of the suckling newborn. One evolutionary conserved constituent of milk and present on many glycoconjugates is sialic acid. The brain and colon are major sites of sialic acid display and together with the liver also of synthesis.

Yeast, beef and pork extracts counteract Clostridium difficile toxin A enterotoxicity.

Clostridium difficile is responsible for a large proportion of nosocomial cases of antibiotic-associated diarrhoea and pseudomembranous colitis. The present study provides evidence that yeast, beef and pork extracts, ingredients commonly used to grow bacteria, can counteract C. difficile toxin A enterotoxicity in vitro and in vivo.