Corticosteroid Levels Research Articles

Healthcare resource use and cost associated with varying dosages of extended corticosteroid exposure in a US population

Aims: To quantify healthcare resource use (HCRU) and costs associated with varying levels of corticosteroid exposure.Materials and methods: Patients with a diagnosis of selected autoimmune and inflammatory diseases between 1 January 2006 and 30 September 2015 (“study period”) were selected from a de-identified, privately-insured claims database. Patients were stratified into four treatment cohorts based on the dosing and duration of continuous corticosteroid use following disease diagnosis: intermittent use with <60 days of corticosteroid use and ≥60 days of corticosteroid use with low (≤7.5 mg/day), medium (>7.5–≤15 mg/day), or high (>15 mg/day) dosage. Patients were followed from the date of their highest dose episode of corticosteroid use (“treatment index date”) until the earliest of the end of continuous corticosteroid use +30 days, disenrollment from health plan, or the end of the study period (“follow-up period”). HCRU and costs in the follow-up period were compared across treatment cohorts.Results: Of 78,704 patients who were identified for study inclusion, 29% had extended corticosteroid use lasting ≥60 days, and 71% had intermittent use. On average, patients in the high-dose cohort incurred twice the cost of intermittent users ($68,408 vs $32,690 in annualized total all-cause healthcare costs, USD). Adverse event-related medical costs accounted for ∼40% of medical costs, and were higher than disease-related medical costs for all cohorts with extended corticosteroid exposure. Comparing the high-dose and low-dose cohorts, the smaller savings in disease-related prescriptions ($1,680) occurred along with a much larger cost in adverse event-related spend ($13,464).Limitations: The impact of corticosteroids may be under-estimated because of conservative follow-up duration, and administrative data may contain inaccuracies in coding.Conclusions: Steroid use, especially at higher doses, is associated with higher HCRU and costs.

Quantitative characterization of the relationship between levels of extended corticosteroid use and related adverse events in a US population

Objective: This retrospective study assessed the incidence and timing of adverse events (AEs) among patients prescribed varying dose levels of corticosteroids in the US.Methods: Patients with selected autoimmune or inflammatory disease diagnoses between 2006 and 2015 were identified from a privately insured administrative database. Patients were stratified into treatment cohorts based on dosage and length of corticosteroid use: intermittent use with duration <60 days, and three extended use cohorts with duration ≥60 days at low (≤7.5 mg/day), medium (>7.5–≤15 mg/day) or high (>15 mg/day) prednisone-equivalent dosage. The incidence of and time to corticosteroid-related AEs were assessed by cohort.Results: A total of 78,704 patients met the selection criteria, of whom 9.5%, 11.0% and 8.6% were classified into the high-, medium-, and low-dose extended corticosteroid use cohorts, respectively. Corticosteroid exposure varied across study conditions, from 34% of dermatomyositis/polymyositis to 6% of psoriatic arthritis patients prescribed extended high dose. Hypertension, pneumonia and osteoporosis were the AEs with the highest incidence rates (41.9, 27.4 and 19.8 cases respectively per 1000 patient-months for the high-dose cohort). For most AEs, all levels of extended corticosteroid use exhibited significant risks of increased incidence compared to intermittent use. Some AEs had dose relationships, with higher dose correlated with higher incidence; other AEs had duration relationships with longer duration correlated with higher incidence regardless of dose. Average time to AE onset was relatively short, occurring at 2.3–6.7 months after corticosteroid initiation.Conclusions: Through a rigorous quantitative characterization, extended steroid exposure was associated with increased incidence and earlier onset of AEs among privately insured adults in the US.

Animal Behavior

Book Review| February 01 2018 Animal Behavior Animal Vigilance: Monitoring Predators and Competitors (1st Edition). By Guy Beauchamp. 2015. Academic Press. (ISBN 978-0-12-801983-2). 254 pp. E-Book. $49.95. Sara A. Fox Sara A. Fox 1Instructor of AP Biology, Scientific Research & Design Academy of Science and Technology (AST) The Woodlands College Park High School sfox@conroeisd.net Search for other works by this author on: This Site PubMed Google Scholar The American Biology Teacher (2018) 80 (2): 153. https://doi.org/10.1525/abt.2018.80.2.153 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Sara A. Fox; Animal Behavior. The American Biology Teacher 1 February 2018; 80 (2): 153. doi: https://doi.org/10.1525/abt.2018.80.2.153 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentThe American Biology Teacher Search Animal Vigilance is a comprehensive review of this aspect of the field of animal behavior. This text is designed for undergraduate and graduate students, as well as faculty with an interest in the topic. It begins by defining vigilance and the scope of this particular review, and provides a guide for students looking for research guidance. Beauchamp warns against some of the anthropomorphic terminology that still pervades in animal behavior, and provides a table that compares this language with the more suitable language of the field. I found this to be exceptionally helpful as I gained my footing with this subject, which I studied in college, but have not been involved in since. After providing an overview of the field, Beauchamp explains why animals engage in vigilance, both from a proximate and an ultimate perspective. These reasons range from levels of corticosteroids and the acuity of vision (proximate) to maintenance... You do not currently have access to this content.

Maternal hormonal milieu influence on fetal brain development

An adverse maternal hormonal environment during pregnancy can be associated with abnormal brain growth. Subtle changes in fetal brain development have been observed even for maternal hormone levels within the currently accepted physiologic ranges. In this review, we provide an update of the research data on maternal hormonal impact on fetal neurodevelopment, giving particular emphasis to thyroid hormones and glucocorticoids. Thyroid hormones are required for normal brain development. Despite serum TSH appearing to be the most accurate indicator of thyroid function in pregnancy, maternal serum free T4 levels in the first trimester of pregnancy are the major determinant of postnatal psychomotor development. Even a transient period of maternal hypothyroxinemia at the beginning of neurogenesis can confer a higher risk of expressive language and nonverbal cognitive delays in offspring. Nevertheless, most recent clinical guidelines advocate for targeted high‐risk case finding during first trimester of pregnancy despite universal thyroid function screening. Corticosteroids are determinant in suppressing cell proliferation and stimulating terminal differentiation, a fundamental switch for the maturation of fetal organs. Not surprisingly, intrauterine exposure to stress or high levels of glucocorticoids, endogenous or synthetic, has a molecular and structural impact on brain development and appears to impair cognition and increase anxiety and reactivity to stress. Limbic regions, such as hippocampus and amygdala, are particularly sensitive. Repeated doses of prenatal corticosteroids seem to have short‐term benefits of less respiratory distress and fewer serious health problems in offspring. Nevertheless, neurodevelopmental growth in later childhood and adulthood needs further clarification. Future studies should address the relevance of monitoring the level of thyroid hormones and corticosteroids during pregnancy in the risk stratification for impaired postnatal neurodevelopment.

Occlusal disharmony-induced stress causes osteopenia of the lumbar vertebrae and long bones in mice

Excessive exposure to glucocorticoids causes osteoporosis in children and adults. Occlusal disharmony is known to induce an increase in serum corticosteroid levels in murine models, but the influence of occlusal disharmony-induced stress on the bone mass during the growth period has not yet been clarified. The purpose of this study was to investigate whether occlusal disharmony-induced stress decreases bone mass. Five-week-old C57BL/6J male mice were used. A 0.5-mm increase in the vertical height of occlusion was used to induce occlusal disharmony for a period of 7 days. Serum corticosterone levels were significantly higher on post-induction day 7, with radiological evidence of osteopenia of the third lumbar vertebra and long bones of the hind limbs. Osteopenia was associated with a reduction of the mechanical properties of the tibia and femur, with significant suppression of bone formation parameters and an increase in bone resorption parameters, as evaluated by bone histomorphometric analysis of the tibial/femur metaphysis. Our findings at the level of bones were supported by our assessment of serum markers of systemic metabolism. Therefore, occlusal disharmony-induced stress may lead to osteopenia and reduce the mechanical strength of bone through an increase in serum glucocorticoid levels in mice.

Cortisol limits selected actions of synthetic glucocorticoids in the airway epithelium.

Cortisol, a physiologic glucocorticoid (GC), is essential for growth and differentiation of the airway epithelium. Epithelial function influences inflammation in chronic respiratory diseases. Synthetic GCs, including inhaled corticosteroids, exert anti-inflammatory effects in airway epithelium by transactivation of genes and by inhibition of proinflammatory cytokine release. We examined the effect of cortisol on the actions of synthetic GCs in the airway epithelium, demonstrating that cortisol acts like a partial agonist at the GC receptor (GR), limiting GC-induced GR-dependent transcription in the BEAS-2B human bronchial epithelial cell line. Cortisol also limited the inhibition of granulocyte macrophage colony-stimulating factor release by synthetic GCs in TNF-α-activated BEAS-2B cells. The relevance of these findings is supported by observations on tracheal epithelium obtained from mice treated for 5 d with systemic GC, showing limitations in selected GC effects, including inhibition of IL-6. Moreover, gene transactivation by synthetic GCs was compromised by standard air-liquid interface (ALI) growth medium cortisol concentration (1.4 μM) in the ALI-differentiated organotypic culture of primary human airway epithelial cells. These findings suggest that endogenous corticosteroids may limit certain actions of synthetic pharmacological GCs and contribute to GC insensitivity, particularly when corticosteroid levels are elevated by stress.-Prodanovic, D., Keenan, C. R., Langenbach, S., Li, M., Chen, Q., Lew, M. J., Stewart, A. G. Cortisol limits selected actions of synthetic glucocorticoids in the airway epithelium.

Importancia del glutamato en las funciones neuroendocrinológicas en la esclerosis múltiple relacionadas con la fatiga

Multiple sclerosis is an inflammatory disease, which still today affects the Northern-hemisphere population, generating a socioeconomically burden. One of the most unfavorable symptoms in this chronic disorder is fatigue. In this review, we favor and sustain a main alteration of the hypothalamus-pituitary-axis complex and its physiopathologic consequences, mostly related to glutamate and corticoid levels. We try to sustain our hypothesis in what is already reported, corroborating that the inflammatory cells release mainly glutamate, a neuro-toxic substance which leads to a demyelinating effect and as a main result fatigue as a symptom. When this hypothesis is demonstrated, we could trace therapeutic targets to stop the release of glutamate of these immunologic cells, in order to avoid fatigue in multiple sclerosis patients.

Plasmodium falciparum Treated with Artemisinin-based Combined Therapy Exhibits Enhanced Mutation, Heightened Cortisol and TNF-α Induction.

The artemisinin-based combined therapy (ACT) post-treatment illness in Plasmodium falciparum-endemic areas is characterized by vague malaria-like symptoms. The roles of treatment modality, persistence of parasites and host proinflammatory response in disease course are unknown. We investigated the hypothesis that ACT post-treatment syndrome is driven by parasite genetic polymorphisms and proinflammatory response to persisting mutant parasites. Patients were categorized as treated, untreated and malaria-negative. Malaria positive samples were analyzed for Pfcrt, Pfmdr1, K13 kelch gene polymorphisms, while all samples were evaluated for cytokines (TNF-α, IL-12p70, IL-10, TGF-β, IFN-γ) and corticosteroids (cortisol and dexamethasone) levels. The treated patients exhibited higher levels of parasitemia, TNF-α, and cortisol, increased incidence of parasite genetic mutations, and greater number of mutant alleles per patient. In addition, corticosteroid levels declined with increasing number of mutant alleles. TGF-β levels were negatively correlated with parasitemia, while IL-10 and TGF-β were negatively correlated with increasing number of mutant alleles. However, IL-12 displayed slight positive correlation and TNF-α exhibited moderate positive correlation with increasing number of mutant alleles. Since post-treatment management ultimately results in patient recovery, the high parasite gene polymorphism may act in concert with induced cortisol and TNF-α to account for ACT post-treatment syndrome.

Corticosteroid Treatment in Critically Ill Patients

Increased levels of tissue corticosteroids are associated with important protective responses of critically ill patients. Critical illness and its treatment interfere with the normal corticosteroid response to illness and induce tissue corticosteroid insufficiency. Therefore, corticosteroid is commonly used in critically ill patients. In intensive care units, the main reasons for using steroids are critical illness-related corticosteroid insufficiency (CIRCI), septic shock, acute respiratory distress syndrome (ARDS), airway edema, etc. CIRCI may be suspected due to symptoms or signs such as unconsciousness, hemodynamic instability, fever, or electrolyte imbalance. An adrenocorticotropic hormone stimulation test or measurement of a random plasma cortisol level is necessary to diagnose CIRCI. Corticosteroid administration can be helpful when CIRCI is confirmed. Similar to CIRCI, corticosteroid can be used in septic shock. However, corticosteroid administration is not recommended for patients with sepsis without shock. The use of corticosteroid in patients with ARDS is still controversial. Although steroids are commonly used for critically ill patients, there are controversies related to the use of steroids in the intensive care unit. In this article, we review the physiology of the corticosteroid response to critical illness and practical issues relating to the diagnosis and treatment of corticosteroid insufficiency in critically ill patients. Key Words: Adrenal insufficiency; Septic shock; Acute respiratory distress syndrome; Intensive care unit

Pharmacotherapeutic Effect of Stress Protectors in the Age Aspect

The data of the literature and the results of original experimental observations concerning the age aspects of stress reactions that accompany a person from birth to adulthood are given. Stress in children is emotional and is characterized by an increase in the thymus, as well as an increase in the level of corticosteroids in the blood, as a reflection of the innate immune-lymphoid defense of the child, which occurs in the process of the childbirth stress of mother. Other indicators of neurohormonal protection (adrenal glands, spleen, eosinopenia, hyperglycemia) are typical but less pronounced than in adults due to functional immaturity of systems and organs. The shift in the balance of the prooxidant-antioxidant system is not marked. In addition, child stress is manifested by deficiency of magnesium ( Mg 2+ ), a violation of the acid balance and immune deficiency. The above data serve as the basis for the proof of the need of involving in everyday complex therapy of any disease, depending on the indications, along with formulary preparations in children's doses of herbal sedatives (Valeriana officinalis, Cardamine pratensis), psycho-responsive tranquilizers and even neuroleptics, magnesium preparations, Echinacea in combination with Zinc and vitamin C. Also antioxidants, immunostimulants and stressors (piracetam, aminolon, taurine), plant adaptogenes (Panax, Eleutherococcus), which prevent a stress reaction, without violating the level of innate protection of the growing organism and the child's mental abilities at the level of its physical development, are recommended.

Clinical Endocrinology: A Review of Adrenal Gland Hormonal and Endocrine Metabolic Disorders.

The adrenal glands are controlled in part by the brain. The hypothalamus, a small area of the brain involved in hormonal regulation, produces corticotropin-releasing hormone (CRH) and vasopressin (also known as antidiuretic hormone). Vasopressin and CRH trigger the pituitary gland to secrete corticotropin (also known as adrenocorticotropic hormone or ACTH), which stimulates the adrenal glands to produce corticosteroids. The renin-angiotensin-aldosterone system, regulated mostly by the kidneys, causes the adrenal glands to produce more or less aldosterone. The body controls the levels of corticosteroids according to need. The levels tend to be much higher in the early morning than later in the day. When the body is stressed, due to illness or otherwise, the levels of corticosteroids increase dramatically.

Influence of parasite load on the diagnosis and occurrence of eosinophilia in alcoholic patients infected with Strongyloides stercoralis.

Alcoholic patients are more susceptible to Strongyloides stercoralis infection. The chronic use of alcohol raises the levels of endogenous corticosteroids, which regulates the development of larvae and stimulates the differentiation of rhabditiform into infective filariform larvae, thus inducing internal autoinfection. Therefore, early diagnosis is important to prevent severe strongyloidiasis. The aim of this study was to evaluate the efficacy of parasitological methods, according to the parasite load and the number of stool samples, for diagnosis of S. stercoralis infection, as well the peripheral blood eosinophil count in alcoholic patients. A total of 330 patients were included in this study. The diagnosis was established using three parasitological methods: agar plate culture, Baermann-Moraes method and spontaneous sedimentation. Peripheral eosinophilia was considered when the level was &gt;600 eosinophils/mm3. The agar plate culture (APC) had the highest sensitivity (97.3%). However, the analysis of multiple samples increased the sensitivity of all parasitological methods. The sensitivities of the methods were influenced by the parasite load. When the larval number was above 10, the sensitivity of APC was 100%, while in spontaneous sedimentation the sensitivity reached 100% when the larval number was above 50. In the present study, 15.4% of alcoholic patients infected with S. stercoralis (12/78) had increased peripheral blood eosinophil count (above 600 eosinophils/mm3). For an efficient parasitological diagnosis of S. stercoralis infection in alcoholic patients, repeated examination by two parasitological methods must be recommended, including agar plate culture due to its higher sensitivity. Moreover, S. stercoralis infection was associated with eosinophilia, mostly in patients excreting up to 10 larvae/g faeces.

Protective effects of red grape (Vitis vinifera) juice through restoration of antioxidant defense, endocrine swing and Hsf1, Hsp72 levels in heat stress induced testicular dysregulation of Wister rat

Ability of red grape juice (RGJ), a known antioxidant, on testis of adult Wister rat to protect from oxidative stress induced damages by heat stress has been investigated in this study. Heat stress was induced maintaining body and testicular temperature at 43°C for 30min/day for 15 days using a hyperthermia induction chamber. Four groups of rats (n=6 per group) comprising of Group-I (control) –kept at 32°C, Group-II –exposed to heat stress alone, Group-III received RGJ (0.8ml/rat/day) alone and Group-IV –exposed to heat stress and received RGJ at same dose. Analysis of blood and testicular tissue exhibited significant reduction in serum testosterone, testicular superoxide dismutase, testicular catalase and testicular glutathione (all p < 0.001); whereas, significant rise in the level of serum corticosteroid, testicular lipid peroxidase and the apoptotic enzyme caspase-3 of testis (all p < 0.001) were observed along with substantial increase in testicular Hsp72 and Hsf-1, and decrease in 17β-HSD3 were noted in heat stressed rats compared to controls. In Group-IV rats, RGJ administration could restore these parameters to normal levels. The signs of retention were clear in Group-IV rats and found to be significantly different as compared to that of the Group-II rats. In testicular histology of rats exposed to heat stress alone revealed remarkable germ cell degeneration and tubular deformations which were prevented by RGJ treatment (Group-IV). The reduced number of sperm level in Group-II also restored in RGJ treatment (Group-IV). The above results indicate that consumption of RGJ may substantially protect testis from heat stress induce dysfunctions.

Acute development of Cushing syndrome in an HIV-infected child on atazanavir/ritonavir based antiretroviral therapy.

An 11-year-old male with perinatally acquired human immune deficiency virus (HIV) infection on antiretroviral regimen, which included abacavir plus lamivudine (Epzicom), didanosine, ritonavir and atazanavir presented with bilateral axillary striae, increased appetite, fatigue, facial swelling and acute weight gain. Two months prior to presentation, the patient had received a diagnostic and therapeutic intra-articular triamcinolone injection in the knee for pain relief and subsequently became progressively swollen in the face, developed striae bilaterally at the axillae, experienced increased appetite, fatigue and an 8 pound weight gain. During the endocrine workup, suspicion for adrenal insufficiency prompted 24-h urine collection for free cortisol, which was found to be undetectable (below LLQ of 1.0 µg/L). This prompted further evaluation of the hypothalamic–pituitary axis (HPA) by standard dose adrenocorticotropic hormone (ACTH) stimulation test. A 250 µg cosyntropin stimulation test was performed and confirmed HPA axis suppression. Baseline cortisol level was <1 µg/dL and stimulated cortisol level at 30 min was 3.8 µg/dL. The patient was diagnosed with iatrogenic Cushing syndrome and suppression of HPA axis secondary to the drug interaction between ritonavir (RTV) and intra-articular triamcinolone injection. Following endocrine evaluation and workup, the patient was admitted for planned orthopaedic procedure including elective left hamstring lengthening, distal femoral osteotomy and patellar tendon advancement. Taking into consideration the diagnosis of iatrogenic Cushing syndrome, at the start of the surgical procedure, 100 mg IV stress dose of hydrocortisone followed by 50 mg hydrocortisone every 8 h for 24 h was administered. Stress dosing was discontinued 24 h after the procedure. Throughout the hospitalization and upon discharge, the patient continued his ART. From initial presentation, patient has remained clinically stable throughout surgery and postoperative period.Learning points:Drug–drug interaction between ritonavir and triamcinolone can cause Cushing syndrome.Although triamcinolone has a half-life of 3 h, an intra-articular injection may be systematically absorbed for 3 weeks after injection, and adrenal suppression may last as long as 30 days.Co-administration of ritonavir and corticosteroids may result in an increase of plasma levels of corticosteroids levels, as they are both eliminated by CYP3A metabolism, and this interaction has the potential to prolong the half-life of triamcinolone several fold.No specific guidelines are available for the management of iatrogenic Cushing syndrome secondary to ritonavir and corticosteroids.One treatment option includes replacing ritonavir with a non-protease inhibitor-based regimen.Initiating hydrocortisone replacement therapy to prevent an adrenal crisis is also an alternate option.

Corticosteroids and the brain

The brain is continuously exposed to varying levels of adrenal corticosteroid hormones such as corticosterone in rodents and cortisol in humans. Natural fluctuations occur due to ultradian and circadian variations or are caused by exposure to stressful situations. Brain cells express two types of corticosteroid receptors, i.e. mineralocorticoid and glucocorticoid receptors, which differ in distribution and affinity. These receptors can mediate both rapid non-genomic and slow gene-mediated neuronal actions. As a consequence of these factors, natural (e.g. stress-induced) shifts in corticosteroid level are associated with a complex mosaic of time- and region-dependent changes in neuronal activity. A series of experiments in humans and rodents have revealed that these time- and region-dependent cellular characteristics are also reflected in distinct cognitive patterns after stress. Thus, directly after a peak of corticosteroids, attention and vigilance are increased, and areas involved in emotional responses and simple behavioral strategies show enhanced activity. In the aftermath of stress, areas involved in higher cognitive functions become activated allowing individuals to link stressful events to the specific context and to store information for future use. Both phases of the brain's response to stress are important to face a continuously changing environment, promoting adaptation at the short as well as long term. We argue that a balanced response during the two phases is essential for resilience. This balance may become compromised after repeated stress exposure, particularly in genetically vulnerable individuals and aggravate disease manifestation. This not only applies to psychiatric disorders but also to neurological diseases such as epilepsy.

Impact of Adrenal Steroids on Regulation of Adipose Tissue.

Corticosteroids are secreted by the adrenal glands and control the functions of adipose tissue via the activation of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). In turn, adipocytes release a large variety of adipokines into the bloodstream, regulating the function of several organs and tissues, including the adrenal glands, hereby controlling corticosteroid production. In adipose tissue, the activation of the MR by glucocorticoids (GC) and aldosterone affects important processes such as adipocyte differentiation, oxidative stress, autophagic flux, adipokine expression as well as local production of GC through upregulation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Notably, the proinflammatory responses induced by the MR are counteracted by activation of the GR, whose activity inhibits the expression of inflammatory adipokines. Both GR and MR are deeply involved in adipogenesis and adipose expansion; hence pharmacological blockade of these two receptors has proven effective against adipose tissue dysfunction in experimental models of obesity and metabolic syndrome (MetS), suggesting a potential use for MR and GR antagonists in these clinical settings. Importantly, obesity and Cushing's syndrome (CS) share metabolic similarities and are characterized by high levels of circulating corticosteroids, which in turn are able to deeply affect adipose tissue. In addition, pharmacological approaches aimed at reducing aldosterone and GC levels, by means of the inhibition of CYP11B2 (aldosterone synthase) or 11β-HSD1, represent alternative strategies to counter the detrimental effects of excessive levels of corticosteroids, which are often observed in obesity and, more general, in MetS. © 2017 American Physiological Society. Compr Physiol 7:1425-1447, 2017.

Climatic Variation: Effects on Stress Levels, Feed Intake, and Bodyweight of Broilers

ABSTRACT Chickens tolerate a very narrow range of climatic variation, and therefore, it is essential to determine the most suitable climatic area and weather for broiler production in open-house systems. In this study, 3060 broilers were used as experimental birds to investigate the effects of seasonal differences and climatic variations on the growth performance of broilers reared in an open-house system. Birds were kept under various treatment models that differ in climate Tropic zone, sub tropic zone and temperate zones. Data were recorded during July-August as summer months and January-February as winter months. Collected data was analyzed using the least square procedure given by Harvey-1990. Significantly higher (p<0.05) level of corticosteroids and H/L ratio of between the experimental birds was observed and consequent effect on feed intake was determined. The body weight and FCR at 42 day was significantly (p≤0.05) higher during winter season in subtropical zone. Subtropical climatic zone was found significantly better than other climatic zone. Efficient management of broiler farming that corresponds for effective feed intake during heat/cold stress to maximize bird’s efficiency can significantly increase production efficiency and acquiesce highest profit to broiler farming.

NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents.

Neuropeptide FF (NPFF) belongs to the RFamide family and is known as a morphine-modulating peptide. NPFF regulates various hypothalamic functions through two receptors, NPFFR1 and NPFFR2. The hypothalamic-pituitary-adrenal (HPA) axis participates in physiological stress response by increasing circulating glucocorticoid levels and modulating emotional responses. Other RFamide peptides, including neuropeptide AF, neuropeptide SF and RFamide related peptide also target NPFFR1 or NPFFR2, and have been reported to activate the HPA axis and induce anxiety- or depression-like behaviors. However, little is known about the action of NPFF on HPA axis activity and anxiety-like behaviors, and the role of the individual receptors remains unclear. In this study, NPFFR2 agonists were used to examine the role of NPFFR2 in activating the HPA axis in rodents. Administration of NPFFR2 agonists, dNPA (intracerebroventricular, ICV) and AC-263093 (intraperitoneal, IP), time-dependently (in rats) and dose-dependently (in mice) increased serum corticosteroid levels and the effects were counteracted by the NPFF receptor antagonist, RF9 (ICV), as well as corticotropin-releasing factor (CRF) antagonist, α-helical CRF(9-41) (intravenous, IV). Treatment with NPFFR2 agonist (AC-263093, IP) increased c-Fos protein expression in the hypothalamic paraventricular nucleus and induced an anxiogenic effect, which was evaluated in mice using an elevated plus maze. These findings reveal, for the first time, that the direct action of hypothalamic NPFFR2 stimulates the HPA axis and triggers anxiety-like behaviors.

Long Term Physiologic and Behavioural Effects of Housing Density and Environmental Resource Provision for Adult Male and Female Sprague Dawley Rats.

Simple SummaryThe effect of housing on rodent well-being has received increasing scrutiny in recent years in North America in an attempt to define adequate standards of animal care. Typically, the adequacy of cage size is determined by species and body weight, with little consideration being given to the cage complexity and impact on animal welfare. Further, most studies evaluate different caging methods over relatively short periods of time, which may not be realistic for typical colony settings. Inappropriate housing may lead to boredom, aggression, and the development of abnormal behaviour and function, which in turn may affect animal responses during research protocols. In this study, we evaluated the impact of group housing rats by sex in double wide cages with the addition of polyvinyl chloride (PVC) tubes for shelter, a nylon chew toy, and a piece of food enrichment given three times weekly over the course of five months. These groups were compared to rats that were single or pair-housed by sex in standard cages provided only with a nylon chew toy. We found that group-housed rats were more active and continued to engaged in positive social behaviours, such as grooming, for the duration of the study, with minimal impact on other aspects of animal function.There is considerable interest in refining laboratory rodent environments to promote animal well-being, as well as research reproducibility. Few studies have evaluated the long term impact of enhancing rodent environments with resources and additional cagemates. To that end, male and female Sprague Dawley (SD) rats were housed singly (n = 8/sex), in pairs (n = 16/sex), or in groups of four (n = 16/sex) for five months. Single and paired rats were housed in standard cages with a nylon chew toy, while group-housed rats were kept in double-wide cages with two PVC shelters and a nylon chew toy and were provided with food enrichment three times weekly. Animal behaviour, tests of anxiety (open field, elevated plus maze, and thermal nociception), and aspects of animal physiology (fecal corticoid levels, body weight, weekly food consumption, organ weights, and cerebral stress signaling peptide and receptor mRNA levels) were measured. Significant differences were noted, primarily in behavioural data, with sustained positive social interactions and engagement with environmental resources noted throughout the study. These results suggest that modest enhancements in the environment of both male and female SD rats may be beneficial to their well-being, while introducing minimal variation in other aspects of behavioural or physiologic responses.

A phase II trial of abiraterone acetate (AA) without prednisone in castration resistant prostate cancer (CRPC).

5040 Background: AA blocks CYP17 and suppresses adrenal androgens and glucocorticoids. Given the risk of mineralocorticoid excess (ME), AA is administered with corticosteroids. In this phase II multicenter, single-arm study, we assess the safety of AA without steroids in CRPC. The primary objective is to determine the proportion of men requiring prednisone to manage ME. Methods: Eligible patients had CRPC with controlled blood pressure (BP) ( &lt; 140/90 on ≤3 agents) and a normal or ≥3.5 mmol/L potassium. Patients initially received AA (1000 mg daily) alone. Patients who developed a BP ≥ 140/90 were treated with anti-hypertensives (HTN) and/or a mineralocorticoid antagonist (MA) prior to steroids. Hypokalemia was treated with supplementation or a MA. Patients with persistent or severe ME were initiated on prednisone (5 mg twice daily). To assess response to steroids, prednisone was added to AA at PSA progression. Therapy was continued until radiographic progression, toxicity, or withdrawal. Results: 60 patients were enrolled of whom 51 (83%) had metastases 16 (27%) received prior chemotherapy, 6 (10%) enzalutamide, and 4 (7%) ketoconazole. Grade (G) 3-4 adverse events (AEs) of interest included HTN (G3 n = 8, 13%; G4 n = 1, 2%), hypokalemia (G3 n = 4, 7%; G4 n = 0), fatigue (G3 n = 1, 2%; G4 n = 0). There was no G ≥3 edema. 9 patients (15%) initiated prednisone for toxicity: HTN (n = 3, 5%), hypokalemia (n = 4, 7%), fatigue (n = 2, 3%). Baseline PSA was 15.4 ng/mL. Time to nadir PSA was 2.5 months (IQR 1.4, 6.3) and median nadir PSA was 2.1 ng/mL. 67% of patients (n = 40) experienced a ≥50% PSA decline and 35% (n = 21) experienced a ≥90% decline. 19 patients (32%) initiated prednisone for PSA progression. Median time to prednisone initiation in patients with PSA progression was 6.1 months (IQR 4.9, 11.7); 5 patients (8.3%) had a PSA decline and 1 achieved a ≥50% decline. Levels of corticosteroids will be reported. Conclusions: In CRPC, AA without steroids is feasible, however clinically significant AEs, particularly HTN, can occur in a minority of patients. HTN and hypokalemia can be treated with anti-HTN agents or potassium without steroids in the majority. Use of AA without prednisone needs to be balanced with the potential risk of toxicity. Clinical trial information: NCT02025010.