Corticotropin-releasing hormone as the homeostatic rheostat of feto-maternal symbiosis and developmental programming In utero and neonatal life

A balanced interaction between the homeostatic mechanisms of mother and the devel- oping organism during pregnancy and in early neonatal life is essential in order to ensure optimal fetal development, ability to respond to various external and internal challenges, protection from adverse programming, and safeguard maternal care availability after parturition. In the majority of pregnancies, this relationship is highly effective resulting in successful outcomes. However, in a number of pathological settings, perturbations of the maternal homeostasis disrupt this symbiosis and initiate adaptive responses with unpre- dictable outcomes for the fetus or even the neonate. This may lead to development of pathological phenotypes arising from developmental reprogramming involving interaction of genetic, epigenetic, and environmental-driven pathways, sometimes with acute conse- quences (e.g., growth impairment) and sometimes delayed (e.g., enhanced susceptibility to disease) that last well into adulthood. Most of these adaptive mechanisms are activated and controlled by hormones of the hypothalamo-pituitary adrenal axis under the influ- ence of placental steroid and peptide hormones. In particular, the hypothalamic peptide corticotropin-releasing hormone (CRH) plays a key role in feto-maternal communication by orchestrating and integrating a series of neuroendocrine, immune, metabolic, and behavioral responses. CRH also regulates neural networks involved in maternal behavior and this determines efficiency of maternal care and neonate interactions. This review will summarize our current understanding of CRH actions during the perinatal period, focusing on the physiological roles for both mother and offspring and also how external challenges can alter CRH actions and potentially impact on fetus/neonate health

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual\u27s risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig\u27s potential to enhance clinical therapeutic innovation to improve human health. (Figure presented.)

Supplemental Material - Evaluation of the toxicity of WS-5 in a 90-days nose-only exposure in sprague-dawley rats

Supplemental Material for Evaluation of the toxicity of WS-5 in a 90-days nose-only exposure in sprague-dawley rats by Michael Jerome Oldham, Rahat Wadhwa Desai, James Randazzo, Guy Lalonde and Roxana Weil in Toxicology Research and Application.</p

Rising Prevalence of Opioid Use Disorder and Predictors for Opioid Use Disorder Among Hospitalized Patients With Chronic Pancreatitis

OBJECTIVES: We aimed to evaluate the prevalence, impact, and predictors of opioid use disorder (OUD) in hospitalized chronic pancreatitis (CP) patients. METHODS: A retrospective cohort study was performed using the National Inpatient Sample database from 2005 to 2014. Patients with a primary diagnosis of CP and OUD were included. The primary outcome was evaluating the prevalence and trend of OUD in patients hospitalized with CP. Secondary outcomes were to (1) assess the impact of OUD on health care resource utilization and (2) identify predictors of OUD in hospitalized CP patients. RESULTS: A total of 176,857 CP patients were included, and OUD was present in 3.8% of patients. The prevalence of OUD in CP doubled between 2005 and 2014. Patients with CP who had OUD were found to have higher mean length of stay (adjusted mean difference, 1.2 days; P \u3c 0.001) and hospitalization costs (adjusted mean difference, US $1936; P \u3c 0.001). Independent predictors of OUD in CP patients were obesity, presence of depression, and increased severity of illness. CONCLUSIONS: Opioid use disorder-related diagnoses are increasing among CP patients and are associated with increased health care resource utilization. Our study identifies patients at high-risk for OUD whose pain should be carefully managed