Differences In Plasma Cortisol Research Articles

Early life adversity in primates: Behavioral, endocrine, and neural effects

BackgroundEvidence suggests that early life adversity is associated with maladaptive behaviors and is commonly an antecedent of stress-related psychopathology. This is particularly relevant to rearing in primate species as infant primates depend on prolonged, nurturant rearing by caregivers for normal development. To further understand the consequences of early life rearing adversity, and the relation among alterations in behavior, physiology and brain function, we assessed young monkeys that had experienced maternal separation followed by peer rearing with behavioral, endocrine and multimodal neuroimaging measures. Methods50 young rhesus monkeys were studied, half of which were rejected by their mothers and peer reared, and the other half were reared by their mothers. Assessments were performed at approximately 1.8 years of age and included: threat related behavioral and cortisol responses, cerebrospinal fluid (CSF) measurements of oxytocin and corticotropin releasing hormone (CRH), and multimodal neuroimaging measures (anatomical scans, resting functional connectivity, diffusion tensor imaging, and threat-related regional glucose metabolism). ResultsThe results demonstrated alterations across behavioral, endocrine, and neuroimaging measures in young monkeys that were reared without their mothers. At a behavioral level in response to a potential threat, peer reared animals engaged in significantly less freezing behavior (p = 0.022) along with increased self-directed behaviors (p < 0.012). Levels of oxytocin in the CSF, but not plasma, were significantly reduced in the peer reared animals (p = 0.019). No differences in plasma cortisol or CSF CRH were observed. Diffusion tensor imaging revealed significantly decreased white matter density across the brain. Exploratory correlational and permutation analyses suggest that the impact of peer rearing on behavior, endocrine and brain structural alterations are mediated by separate parallel mechanisms. ConclusionsTaken together, these results demonstrate in NHPs the importance of maternal rearing on the development of brain, behavior and hormonal systems that are linked to social functioning and adaptive responses. The findings suggest that the effects of maternal deprivation are mediated via multiple independent pathways which may account for the heterogeneity in behavioral and biological alterations observed in individuals that have experienced this early life adversity.

Brief communication: Plasma cortisol concentration is affected by lactation, but not intra-nasal oxytocin treatment, in beef cows.

In mammals, including sheep and mice, lactation attenuates the hypothalamo-pituitary-adrenal axis and plasma cortisol concentration. Oxytocin, one neuropeptide present in the blood during lactation, may contribute to such stress attenuation. Providing oxytocin intra-nasally increases plasma oxytocin concentration in cattle and can be used in non-lactating cows to mirror plasma oxytocin concentration of lactating cows. Therefore, our hypothesis was that there would be no difference in plasma cortisol between non-lactating beef cows intra-nasally administered oxytocin and lactating beef cows intra-nasally treated with saline. Twenty Bos taurus cows were randomly allocated by lactational status to one of four treatments, in a 2×2 factorial arrangement: 1) Non-lactating, saline (NL-S; n = 5); 2) Non-lactating, oxytocin (NL-OXT; n = 5); 3) Lactating, saline (L-S; n = 5); and 4) Lactating, oxytocin (L-OXT; n = 5). Two hours pre-treatment, cows were catheterized, moved to their appropriate chute and baseline blood samples were collected at -60, -45, -30, and 0 minutes before treatments were administered. Directly following the 0-minute sample, cows were administered their intra-nasal treatment via a mucosal atomization device. Subsequently, blood was collected at 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 minutes. Non-lactating cows had greater (P = 0.02) plasma cortisol concentration compared with lactating cows. There was no lactation by treatment interactions for either plasma cortisol (P = 0.55) or oxytocin (P = 0.89) concentration. Although a treatment by time interaction was identified for oxytocin (P < 0.0001), there was no main effect of lactation on plasma oxytocin concentration (P = 0.34). Similar oxytocin and dissimilar cortisol concentration in lactating and non-lactating cows indicate that oxytocin alone cannot be responsible for reduced plasma cortisol in lactating ruminants. Further investigations are needed to elucidate alternative mechanisms that may be involved in the stress hypo-responsive condition of lactating mammals.

Pharmacodynamic studies of nasal tetracosactide with salivary glucocorticoids for a noninvasive Short Synacthen Test.

The Short Synacthen Test (SST) is the gold standard for diagnosing adrenal insufficiency. It requires invasive administration of Synacthen, venous sampling, and is resource-intensive. To develop a nasally administered SST, with salivary glucocorticoids measurement, to assess the adrenal response. We conducted 5 studies: 4 open-label, sequence-randomized, crossover, pharmacodynamic studies testing 6 doses/formulations and a repeatability study. Additionally, pharmacokinetic analysis was undertaken using our chosen formulation, 500 µg tetracosactide with mucoadhesive chitosan, Nasacthin003, in our pediatric study. Adult and children's clinical research facilities. A total of 36 healthy adult males and 24 healthy children. We administered all 6 nasal formulations using an European regulator endorsed atomization device. The IV comparators were 250 µg or 1 µg SST. We analyzed paired blood and saliva samples for plasma cortisol and salivary cortisol and cortisone. The addition of chitosan to tetracosactide and dose escalation increased peak cortisol response (P = 0.01 and 0.001, respectively). The bioavailability of Nasacthin003 was 14.3%. There was no significant difference in plasma cortisol at 60 minutes between 500 µg Nasacthin003 and 250 µg IV Synacthen (P = 0.17). The repeatability coefficient at 60 minutes was 105 nmol/L for IV Synacthen and salivary cortisol and cortisone was 10.3 and 21.1 nmol/L, respectively. The glucocorticoid response in children was indistinguishable from that of adults. Nasal administration of Nasacthin003 generates equivalent plasma cortisol values to the 250-µg IV SST and, with measurement at 60 minutes of salivary cortisol or cortisone, provides a noninvasive test for adrenal insufficiency.

The physiology of saltwater acclimation in large juvenile Atlantic salmon Salmo salar.

The present study investigated the effects of transferring freshwater (FW) acclimated S. salar (678 g) that had been maintained under a constant photoperiod and thermal regime, into FW (salinity 0) and salt water (SW; salinity 35) on growth and physiological responses over a 28 day period. There were no mortalities observed throughout the study and no significant differences in mass or fork length between FW and SW groups after 28 days. Compared with fish transferred to FW, plasma osmolality and plasma chloride levels increased significantly in fish in SW by day 1. In the SW group, plasma chloride and osmolality had decreased significantly at day 14 when compared with day 1. Na+ -K+ -ATPase activity was significantly higher in SW compared with the FW group from day 7 and thereafter, but continued to increase until day 22. No differences in plasma cortisol and thyroxine were observed between FW and SW groups throughout the study. Plasma glucose significantly increased from day 1 to day 2 in SW but not in the FW group and levels were significantly reduced in SW compared with the FW group at day 28. Plasma cholesterol and triglyceride levels were significantly higher in FW at day 22 and day 14 to day 22, respectively, when compared with the SW group. In the SW group, plasma cholesterol and triglyceride levels did not change significantly throughout the study. The findings of this study suggest that large S. salar retained in FW maintain a high level of SW tolerance in the absence of photoperiod and thermal regimes necessary for smoltification, as demonstrated by 100% survival, unaffected growth performance, increased Na+ -K+ -ATPase activity and a capacity to regulate plasma chloride and osmolality for 28 days in the SW group.

Analysis of Stress Indicators for Evaluation of Animal Welfare and Meat Quality in Traditional and Jewish Slaughtering.

Simple SummaryCortisol and catecholamines (dopamine, norepinephrine and epinephrine) are released in response to stress and directly stimulate glycogen mobilization, thus influencing meat acidification. The aim of the study was to estimate and compare these stress indicators to evaluate the welfare of beef cattle, subjected to either traditional slaughtering (with stunning) or to slaughtering with religious Jewish rite (without stunning). Significant differences in plasma cortisol and catecholamine levels were observed during exsanguination by monitoring animals in the pre-slaughtering (before and after transportation) and slaughtering phases. Cortisol, dopamine and norepinephrine, but not epinephrine, were markedly higher in the animals slaughtered by the religious rite. Pursuing animal welfare in the religious slaughtering procedures could produce advantages in terms of hygiene, organoleptic quality and shelf life of meat.Sixty Charolais male beef cattle of eight months of age were divided into two groups according to the slaughtering method, i.e., traditional or Kosher (religious Jewish rite). The aim of the study was to detect and compare the plasma concentrations of cortisol and catecholamines (dopamine, norepinephrine and epinephrine), by Elisa and HPLC test. These four stress indicators were evaluated during three different stages of each animal productive life: on the farm (step 1), after transportation (step 2) and during bleeding (step 3). The patterns of the parameters measured were similar and, interestingly, revealed significant changes throughout the three steps considered. The greatest variation between the two methods of slaughtering was observed in step 3, where we found a statistically significant difference with all the parameters except epinephrine. In the animals slaughtered by the religious rite, cortisol, dopamine, norepinephrine and epinephrine were 68.70 ± 30.61 nmol/L; 868.43 ± 508.52 ng/L; 3776.20 ± 1918.44 ng/L; and 4352.20 ± 3730.15 ng/L, respectively, versus 45.08 ± 14.15 nmol/L; 513.87 ± 286.32 ng/L; 3425.57 ± 1777.39 ng/L; and 3279.97 ± 1954.53 ng/L, respectively, in the other animals. This suggests that the animals slaughtered by the Kosher rite are subjected to higher stress conditions at the exsanguination phase. The animals slaughtered by the religious Jewish rite showed lower cortisol and catecholamine levels on the farm (step 1) and after transportation to the slaughterhouse (step 2). This was likely because the animals selected at the end of step 1 by the Rabbis for the religious rite are usually the most docile and gentle.

Physiological impacts and bioaccumulation of dietary Cu and Cd in a model teleost: The Amazonian tambaqui (Colossoma macropomum)

Increasing anthropogenic activities in the Amazon have led to elevated metals in the aquatic environment. Since fish are the main source of animal protein for the Amazonian population, understanding metal bioaccumulation patterns and physiological impacts is of critical importance. Juvenile tambaqui, a local model species, were exposed to chronic dietary Cu (essential, 500 μg Cu/g food) and Cd (non-essential, 500 μg Cd/g food). Fish were sampled at 10–14, 18–20 and 33–36 days of exposure and the following parameters were analyzed: growth, voluntary food consumption, conversion efficiency, tissue-specific metal bioaccumulation, ammonia and urea-N excretion, O2 consumption, Pcrit, hypoxia tolerance, nitrogen quotient, major blood plasma ions and metabolites, gill and gut enzyme activities, and in vitro gut fluid transport. The results indicate no ionoregulatory impacts of either of the metal-contaminated diets at gill, gut, or plasma levels, and no differences in plasma cortisol or lactate. The Cd diet appeared to have suppressed feeding, though overall tank growth was not affected. Bioaccumulation of both metals was observed. Distinct tissue-specific and time-specific patterns were seen. Metal burdens in the edible white muscle remained low. Overall, physiological impacts of the Cu diet were minimal. However dietary Cd increased hypoxia tolerance, as evidenced by decreased Pcrit, increased time to loss of equilibrium, a lack of plasma glucose elevation, decreased plasma ethanol, and decreased NQ during hypoxia. Blood O2 transport characteristics (P50, Bohr coefficient, hemoglobin, hematocrit) were unaffected, suggesting that tissue level changes in metabolism accounted for the greater hypoxia tolerance in tambaqui fed with a Cd-contaminated diet.

The impact of acute PAH exposure on the toadfish glucocorticoid stress response

The objective of the present study was to determine whether the polycyclic aromatic hydrocarbons (PAHs) associated with the Deepwater Horizon (DWH) oil spill impacted the stress response of teleost fish. The hypothesis was that intraperitoneal (IP) treatment with PAHs associated with the DWH oil spill or waterborne exposure to DWH oil high energy water-accommodated fraction (HEWAF) would result in the downregulation of the stress response of Gulf toadfish, Opsanus beta, a benthic marine teleost fish that resides in the Gulf of Mexico. In vivo plasma cortisol levels and adrenocorticotropic hormone (ACTH)-mediated cortisol secretion by in vitro isolated kidney tissue were measured. Toadfish at rest IP-treated with naphthalene had higher plasma cortisol compared to fluorene-treated and control fish; phenanthrene-treated fish tended to have higher plasma cortisol levels that fluorene-treated and controls. When subjected to an additional crowding stress, naphthalene and phenanthrene-treated fish were no longer able to mount a stress response compared to fluorene-treated and control fish, suggesting exhaustion of the stress response. Supporting this in vivo data, there tended to be less cortisol released by the kidney in vitro from naphthalene and phenanthrene-treated fish in response to ACTH compared to controls. In contrast, toadfish at rest exposed to 3% Slick A HEWAF did not have significantly different plasma cortisol levels compared to controls. But, exposed fish did have significantly less cortisol released by the kidney in vitro in response to ACTH. When toadfish were subjected to an additional stress, there were no significant differences in plasma cortisol or ACTH, suggesting the action of a secondary secretagogue to maintain plasma cortisol in vivo. Combined, these data suggest that in response to acute PAH exposure, there may be internalization or downregulation of the melanocortin 2 receptor (MC2R) that mediates the action of ACTH.

Surgical and not analgesic technique affects postoperative inflammation following colorectal cancer surgery: a prospective, randomized study.

Epidural analgesia reduces the surgical stress response. However, its effect on pro- and anti-inflammatory cytokines in the genesis of inflammation following major abdominal surgery remains unclear. Our main objective was to elucidate whether perioperative epidural analgesia prevents the inflammatory response following colorectal cancer surgery. Ninety-six patients scheduled for open or laparoscopic surgery were randomized to epidural analgesia (group E) or patient-controlled intravenous analgesia (group P). Surgery and anaesthesia were standardized in both groups. Plasma cortisol, insulin and serum cytokines [interleukin 1β (IL-1β), IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumour necrosis factor α, interferon γ, granulocyte-macrophage colony-stimulating factor, prostaglandin E2 and vascular endothelial growth factor] were measured preoperatively (T0), 1-6h postoperatively (T1) and 3-5days postoperatively (T2). Mixed model analysis was used, after logarithmic transformation when appropriate, for analyses of cytokines and stress markers. >There were no significant differences in any serum cytokine concentration between groups P and E at any time point except for IL-10 which was 87% higher in group P [median and range 4.1 (2.3-9.2) pg/ml] compared to group E [2.6 (1.3-4.7) pg/ml] (P=0.002) at T1. There was no difference in plasma cortisol and insulin between the groups at any time point after surgery. A significant difference in median serum cytokine concentration was found between open and laparoscopic surgery with higher levels of IL-6, IL-8 and IL-10 at T1 in patients undergoing open surgery compared to laparoscopic surgery. No difference in serum cytokine concentration was detected between the groups or between the surgical technique at T2. Open surgery, compared to laparoscopic surgery, has greater impact on these inflammatory mediators than epidural analgesia vs intravenous analgesia.

Response of the hypothalamic-pituitary-adrenal axis to stimulation tests before and after exercise training in old and young Standardbred mares1

This study tested the hypotheses that age-induced alteration in cortisol, ACTH, and glucose concentrations are due to differences in the response of the hypothalamic-pituitary-adrenal axis and that exercise training would attenuate these differences. Six old (22.0±0.7 yr; mean±SE) and 6 young (7.3±0.6 yr) unfit Standardbred mares ran 3 graded exercise tests (GXT): before (GXT1), after 8 wk of training (GXT2), and at study end at 15 wk (GXT3). Mares trained 3 d/wk at 60% maximum heart rate. Each mare underwent 5 endocrine stimulation tests pre- and posttraining: 1) control (CON), 2) adrenocorticotropin hormone (ACTHtest), 3) combined dexamethasone suppression/ACTH (DEX/ACTH), 4) dexamethasone suppression (DEX), and 5) combined DEX/corticotropin releasing factor (DEX/CRF). For CON, there was no difference in plasma cortisol between age groups pretraining (P=0.19), but young mares had a 102% higher mean (P=0.02) plasma cortisol concentration than old mares posttraining. The pretraining ACTHtest showed young mares had a 72% higher (P=0.05) overall plasma cortisol concentration compared to old. There was no overall age difference in cortisol in the posttraining ACTHtest, but old mares still had lower cortisol concentrations at 30 min during the test, suggesting decreased adrenal response to ACTH stimulation. There was no difference in cortisol response between old and young mares in DEX, DEX/ACTH, or DEX/CRF tests. Young mares had higher (P=0.02) overall plasma cortisol concentration posttraining in response to DEX/ACTH, but old mares showed no change. In CON and DEX/CRF, there were no age differences in plasma ACTH concentration, pre- or posttraining. Pretraining, there was no age difference in glucose response to DEX, but posttraining old mares had a 4% (P=0.04) lower overall plasma glucose concentration compared to young. Posttraining, old mares had lower mean plasma glucose concentrations during DEX compared to pretraining (P=0.02), but there was no change pre- vs. posttraining in young mares (P=0.19). Old and young mares had lower plasma glucose concentrations posttraining during DEX/ACTH (P<0.001 and P=0.05, respectively) and DEX/CRF (P<0.001 and P=0.003, respectively) compared to pretraining. Both the pituitary and adrenal glands experience a decline in function with age although the exact mechanisms behind such changes remain unknown. Exercise training facilitates the counteraction of these deficits.

Exposure to cadmium and plasma cortisol in workers exposed to urban stressor

The aim of this study is to estimate the exposure to Cd in a group of roadmen compared to a group of drivers by environmental monitoring and biological monitoring of blood and urinary Cd. It aims to evaluate whether exposure to Cd can affect plasma cortisol. The initial sample was composed by 130 employees of Municipal Police Force (roadmen and drivers). After administration of a clinical-anamnestic questionnaire were excluded 50 subjects who presented confounding factors and 30 subjects who weren't comparable. On a final sample of 25 drivers and 25 roadmen were conducted environmental monitoring of Cd, biological monitoring of urinary and blood Cd and assessment of cortisol. Personal exposure to Cd in air was significantly higher in roadmen compared to drivers (p = 0.015). Urinary and blood Cd were significantly increased in roadmen compared to drivers (p = 0.18 and p = 0.025). There weren't significant differences in plasma cortisol between drivers and roadmen (p> 0.05). The multiple linear regression analysis shows that urinary and blood Cd are dependent on the environment Cd levels and on the job (driver or roadmen) (p = 0.014 and p = 0.012) and plasma cortisol isn't dependent on blood and urinary Cd. The results show a higher concentration of Cd in roadmen both in air and urine and they don't indicate an influence of exposure to low doses of Cd on plasma cortisol.

Hematological Responses, Survival, and Respiratory Exchange in the Olive Flounder, Paralichthys olivaceus, during Starvation.

A 12-wk experiment was conducted to examine the hematological changes, survival, and respiratory exchange in the olive flounder, Paralichthys olivaceus, during starvation. The growth, survival and respiratory exchange rates of the starved group were lower than those of the fed group during the experiment. Blood analysis, including hematocrit, hemoglobin, red blood cells, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and mean corpuscular volume, did not differ significantly (p>0.05) between the fed and starved groups at the end of the experiment. There were no significant differences in plasma cortisol, glucose, Na+, Cl−, K+, or aspartate aminotransferase between the fed and starved groups (p>0.05). Alanine aminotransferase levels were higher in the starved group than in the fed group, whereas plasma osmolality was lower in the starved group than in the fed group. It was shown that starved fish had various problems after four weeks, which did not occur in the fed group. Long-term starvation is infrequent in aquaculture farms. However, starvation studies of this kind are very useful for a basic understanding of how physiological changes affect fish health, life expectancy, and growth.

Association between plasma lipid, glucose, cortisol and adrenocorticotropic hormone levels and GR and ACTHR gene polymorphisms

To explore the association between plasma fat and glucose, cortisol and adrenocorticotropic hormone (ACTH) levels and genotypes of GR and ACTHR genes in healthy Chinese Han subjects. Two hundred healthy subjects were analyzed for GR and ACTHR gene polymorphisms using PCR-restriction fragment length polymorphism method. Plasma lipid, glucose, cortisol, ACTH levels were determined and correlated with the genotypes. No significant difference was found between plasma lipid and glucose levels and various GR and ACTHR genotypes. Subjects with AG genotype of GR 5556A/G polymorphism had lower plasma cortisol levels than AA genotype. Compared with subjects with GG genotype of GR 4534-4536GAG/AAA [GAGAGG (GluArg)>GAAAAG(GluLys)] polymorphism, those with AG genotype had significantly lower plasma cortisol levels. Subjects with CC and CG genotypes of GR 6294C/G polymorphism also had significantly lower plasma cortisol levels compared with those with GG genotype. With regard to plasma ACTH levels, those with TT genotype of ACTHR 2T/C polymorphism were significantly lower than CC and CT genotypes, and those with AG genotype for GR 5556 A/G polymorphism were also significantly lower than AA genotype. There was no difference in plasma cortisol and glucose levels between subjects with GR and ACTHR gene variants. GR gene variants (5556A/G, 4534-4536GAG/AAA and 6294C/G polymorphisms) may influence plasma cortisol level, and ACTHR 2T/C, GR 5556A/G polymorphisms may decrease plasma ACTH level.

Anti-Emetic Doses of Dexamethasone Suppress Cortisol Response in Laparoscopic Cholecystectomy

The efficacy of dexamethasone alone or in combination with a serotonergic antagonist to prevent nausea and vomiting in laparoscopic cholecystectomy is well established, but few data exist regarding its effects on perioperative cortisol and glucose levels. Fourteen non-diabetic subjects having elective laparoscopic choleycystectomy and standardised general anaesthesia were randomised to receive 8 mg of intravenous dexamethasone and tropisetron or tropisetron alone. Plasma cortisol and glucose were measured preinduction, at five and 24 hours postoperatively. There was no difference in plasma cortisol at five hours postoperatively in patients who received dexamethasone, but by 24 hours there was marked suppression compared to the control group (P < 0.005) to less than 5% of the preoperative value. There was a small but statistically significant elevation in blood glucose at 24 hours (P < 0.01) in the dexamethasone-treated group. In patients undergoing laparoscopic cholecystectomy, an anti-emetic dose of dexamethasone (8 mg) markedly suppresses plasma cortisol at 24 hours and causes a minor elevation in blood glucose.

Physiological stress response of Mountain Whitefish (Prosopium williamsoni) and White Sucker (Catostomus commersoni) sampled along a gradient of temperature and agrichemicals in the Oldman River, Alberta

Species differences in tolerance to environmental stressors can contribute to differences in species distribution and abundance along river gradients. Climate change and intensive agriculture are likely to have major effects on fish populations in temperate zones, yet understanding of the interactions between temperature and chemical stressors on fish physiology is limited. The objective of this study was to compare the stress responses of the Mountain Whitefish, (Prosopium williamsoni, a cold-water fish) and White Sucker (Catostomus commersoni, a cool-water fish), along a temperature and pesticide gradient in the Oldman River, Southern Alberta in spring and summer. Fish were seined, placed into an enclosure, and plasma cortisol, glucose, liver glycogen, and condition factor were measured. Plasma acetylcholinesterase (AChE) activity was used as an indicator of exposure to organophosphate and carbamates pesticides. Whitefish had lower plasma AChE activity and lower liver glycogen reserves compared to suckers at all sites and all sampling times but the differences in plasma cortisol were not species-specific and there were no differences in plasma glucose levels, except at one site. Plasma cortisol increased, and plasma glucose decreased along a downstream river gradient in whitefish in both spring and summer; in sucker only plasma cortisol fluctuated and only in the summer. Liver glycogen decreased along the river gradient in both species at both seasons. Our study detected important species-specific differences in AChE activities and responses of the physiological stress axis, suggesting that whitefish are more sensitive to temperature and pesticide stress than suckers.

Comparison of strain of mental workers by characteristics

To compare of strain of mental workers by characteristics. 851 participants were sampled with stratified cluster random methods from various kinds of occupations, including teachers in primary and middle schools, doctors, bankers and environmental protection officers. The psychological strain was measured with SCL-90 and General Well-being Schedule (GWB). The physiological strain were assessed by Plasma sugar, TG, HDL, VLDL, LDL, CHOL, cortisol and ACTH level, neurobehavioral reaction function. The subjects at age of 40-years exhibited the highest scores of SCL-90 significantly among three groups. Likewise, 20-years service group were higher than 10- and under 10 years groups. However females' GWB scores were higher than males'. It tended to be higher in postgraduate and undergraduate teachers than others groups, indicating the greater psychological strain increased, the higher age and service were. Plasma sugar, LDL, TG and CHOL level were compared; Subjects 40- years group were higher than 30- and 20 age groups, as well as senior versus minor. Female teachers were lower than males. Meanwhile single subjects were lower than married. As HDL level, 30-age group were lower decreased than 40-years group; 10-service group were responsible for lower HDL level than 20-years group; Divorced and spouse-lost teachers were higher concentration than single and married. VLDL level in under 10 years service were lower than 10-years group; The senior was the highest level of VLDL among three groups and the minor was the lowest. The tendency was equal to increased professional title; Married and spouse-lost groups were higher than single groups. It had no individual difference in plasma cortisol and ACTH. But reaction sensitivity in 40- and 30-age groups were lower than 20-age group. Likewise, 20- years service teachers had lower reaction and action sensitivity than 10- and under 10 years groups; Senior group was lowest among three groups; However 40- years old group were lower than 20- years group, postgraduate and undergraduate teachers were higher than others groups in muscle endurance. It indicated that reaction and action sensitivity had descent tendency with increased age and service length. Psychological strain is higher with increased age, length of service and education career. The trend is the same as plasma sugar, TG, CHOL, HDL, LDL and VLDL, but neurobehavioral reaction function is decreased. In addition general well-being feeling of females is lower than males.

The physiological stress response and oxidative stress biomarkers in rainbow trout and brook trout from selenium‐impacted streams in a coal mining region

Selenium (Se) is an essential element that can be toxic at concentrations slightly greater than those required for homeostasis. The main chronic toxic effects of Se in fish are teratogenic deformities, but Se can also activate the physiological stress response and redox cycle with reduced glutathione causing oxidative damage. Rainbow trout, Oncorhynchus mykiss, appear to be more sensitive to Se than brook trout, Salvelinus fontinalis. The objective of this study was to compare the physiological stress response (plasma cortisol, glucose, triiodothyronine, thyroxine, gill Na+/K+ ATPase, cortisol secretory capacity, K and liver somatic index) and oxidative stress biomarkers (liver GSH, GPx, lipid peroxidation, vitamin A and vitamin E) in rainbow trout (RNTR) and brook trout (BKTR) collected from reference and Se-exposed streams. The physiological stress response was not impaired (cortisol secretory capacity unchanged); although there were species differences in plasma cortisol and plasma glucose levels. Liver GSH, GPx and vitamin levels were higher in RNTR than BKTR, but lipid peroxidation levels were not different. The elevated GSH reserves may make RNTR more sensitive to Se-induced lipid peroxidation, but this may be offset by the RNTR's higher antioxidant (GPx and vitamin) levels. Species-specific biochemical differences may mediate differences in Se sensitivity and be used in aquatic Se risk assessments.

Running in a running wheel substitutes for stereotypies in mink (Mustela vison) but does it improve their welfare?

This experiment investigated whether access to a running wheel affects the development of stereotypies during restricted feeding and whether selection for high or low levels of stereotypy affects the use of the running wheel. Sixty-two female mink kept in standard cages and selected for high or low levels of stereotypy were used. Thirty of these females had access to a running wheel whereas thirty-two female mink had no access to running wheels. The number of turns of the running wheel, behaviour, feed consumption, body weight and the concentration of plasma cortisol were measured during the winter period. Mink with access to a running wheel did not perform stereotypic behaviour and mink selected for a high level of stereotypies had more turns in the running wheel than mink selected for low levels of stereotypies. Mink with access to a running wheel used the running wheel for the same amount of time as mink without access to a running wheel performed stereotypies, and the daily rhythms of the two types of activity were identical with a peak around feeding time. No other behavioural differences between stereotyping and non-stereotyping mink were found and neither was there any difference in plasma cortisol. Due to the similarities between stereotypies and wheel running it is not possible unambiguously to conclude that access to a running wheel improve the welfare of the mink.

Pharmacokinetic, pharmacodynamic, efficacy, and safety data from two randomized, double-blind studies in patients with asthma and an in vitro study comparing two dry-powder inhalers delivering a combination of salmeterol 50 μg and fluticasone propionate 250 μg: Implications for establishing bioequivalence of inhaled products

Background: The use of dry-powder inhalers (DPIs) to administer respiratory medicines is increasing, and new DPIs are likely to be developed because of expiring patents. However, there is considerable debate concerning the extent to which DPIs are interchangeable without altering disease control or the safety profile of the treatment. Objective: This study was designed to compare the pharmacokinetic (PK), pharmacodynamic (PD), efficacy, and safety data for 2 DPIs delivering a combination of salmeterol 50 μg plus fluticasone propionate (FP) 250 μg (SFC 50/250) to investigate assumptions of bioequivalence. Methods: Three studies compared SFC 50/250 delivery using a reservoir powder inhalation device (RPID) and a Diskus® multiple-dose inhaler: an in vitro assessment of fine-particle-mass (FPM) profiles of the emitted doses; a PK/PD study of SFC 50/250 administered in two 14-day crossover treatment periods to 22 adults with moderate, persistent asthma to determine the equivalence of the RPID and Diskus inhaler in terms of drug delivery and systemic exposure; and a 12-week clinical efficacy and safety study of SFC 50/250 in 270 patients ≥12 years of age with moderate, persistent asthma to assess the equivalence of the RPID and Diskus inhaler based on peak expiratory flow (PEF) rates. FPM was summed from the quantity of active pharmaceutical ingredient deposited on stages 1 to 5 of a cascade impactor, representing an aerodynamic particle size range of 0.8 to 6.2 μm. Systemic exposure to SFC 50/250 was declared no greater with RPID than with the Diskus inhaler if the upper limit of the 90% CI for the ratio of FP AUC for the 2 devices was below the upper limit of the equivalence range (ie, <1.25). Adverse events, clinical laboratory test results, and vital signs were recorded throughout the 2 clinical studies. Results: In vitro, mean FPM values for the RPID and Diskus inhaler, respectively, were 13.1 and 12.8 μg/dose for salmeterol ( P = NS) and 66.8 and 66.2 μg/dose for FP ( P = NS). The only notable differences were mean FP for particle sizes 2.3 to 3.2 μm (21.4 μg/dose for RPID, 25.6 μg/dose for Diskus) and for sizes 4.0 to 6.2 μm (17.3 μg/dose for RPID, 11.7 μg/dose for Diskus). In the PK/PD study, there were 22 patients (16 men and 6 women), most (86%) of whom were white. Mean (SD) age was 26.0 (5.0) years (range, 19-35 years), and mean (SD) weight was 67.3 (8.9) kg. The 2 inhalers did not meet the criteria for declaring bioequivalence: estimated ratios (RPID:Diskus) were 2.00 (90% CI, 1.56 to 2.55) for FP AUC up to the time point of next dosing and 1.92 (90% CI, 1.64 to 2.25) for salmeterol maximum observed plasma concentration at the end of the dosing interval (at steady state). Urine cortisol (0–24 hours) was significantly lower for the RPID than for the Diskus inhaler (ratio, 0.74 [95% CI, 0.57 to 0.96]; P = 0.026); no significant difference in plasma cortisol was noted between the 2 inhalers (ratio, 0.85 [95% CI, 0.7 to 1.04]). A small but statistically significant increase in maximum heart rate (5 beats/min) was noted in the RPID group (ratio, 1.05 [95% CI, 1.01 to 1.10]; P = 0.029). No notable differences in other PD end points were observed. Drug-related adverse events occurred in both groups (2 [dysphagia and tremor] in the RPID group and 3 [2 cases of dysphonia, 1 case of mucous-membrane irritation] in the Diskus group). There were 270 patients (136 females, 134 males) in the clinical efficacy and safety study, most (94%) of whom were white; mean (SD) age was 37.2 (17.0) years (range, 11–77 years) in the RPID group and 35.4 (17.2) years (range, 12–77 years) in the Diskus group. The RPID and the Diskus inhaler met the predefined equivalence criteria (±15 L/min) in terms of mean change in morning PEF from baseline: 3.9 L/min (95% CI, -3.1 to 11.0). The 2 SFC 50/250 inhalers were well tolerated; the most frequently reported adverse event was bronchitis, reported by 12% of the patients in the RPID group and 9% of those in the Diskus group. The only serious adverse event, which occurred in the RPID group and was related to bronchial infection, was considered unrelated to treatment. Conclusions: In vitro particle size distribution data were potentially superimposable for the RPID and the Diskus inhaler. The 2 devices were considered to be clinically equivalent in terms of mean morning PEF but were not considered equivalent in terms of PK systemic exposure. The 2 SFC 50/250 inhalers were well tolerated and had comparable safety profiles; no serious adverse events were attributed to the study product.

Study on the Greek demographic chart of psychic disorders

Background: The use of dry-powder inhalers (DPIs) to administer respiratory medicines is increasing, and new DPIs are likely to be developed because of expiring patents. However, there is considerable debate concerning the extent to which DPIs are interchangeable without altering disease control or the safety profile of the treatment.Objective: This study was designed to compare the pharmacokinetic (PK), pharmacodynamic (PD), efficacy, and safety data for 2 DPIs delivering a combination of salmeterol 50 μg plus fluticasone propionate (FP) 250 μg (SFC 50/250) to investigate assumptions of bioequivalence.Methods: Three studies compared SFC 50/250 delivery using a reservoir powder inhalation device (RPID) and a Diskus® multiple-dose inhaler: an in vitro assessment of fine-particle-mass (FPM) profiles of the emitted doses; a PK/PD study of SFC 50/250 administered in two 14-day crossover treatment periods to 22 adults with moderate, persistent asthma to determine the equivalence of the RPID and Diskus inhaler in terms of drug delivery and systemic exposure; and a 12-week clinical efficacy and safety study of SFC 50/250 in 270 patients ≥12 years of age with moderate, persistent asthma to assess the equivalence of the RPID and Diskus inhaler based on peak expiratory flow (PEF) rates. FPM was summed from the quantity of active pharmaceutical ingredient deposited on stages 1 to 5 of a cascade impactor, representing an aerodynamic particle size range of 0.8 to 6.2 μm. Systemic exposure to SFC 50/250 was declared no greater with RPID than with the Diskus inhaler if the upper limit of the 90% CI for the ratio of FP AUC for the 2 devices was below the upper limit of the equivalence range (ie, <1.25). Adverse events, clinical laboratory test results, and vital signs were recorded throughout the 2 clinical studies.Results: In vitro, mean FPM values for the RPID and Diskus inhaler, respectively, were 13.1 and 12.8 μg/dose for salmeterol (P = NS) and 66.8 and 66.2 μg/dose for FP (P = NS). The only notable differences were mean FP for particle sizes 2.3 to 3.2 μm (21.4 μg/dose for RPID, 25.6 μg/dose for Diskus) and for sizes 4.0 to 6.2 μm (17.3 μg/dose for RPID, 11.7 μg/dose for Diskus). In the PK/PD study, there were 22 patients (16 men and 6 women), most (86%) of whom were white. Mean (SD) age was 26.0 (5.0) years (range, 19-35 years), and mean (SD) weight was 67.3 (8.9) kg. The 2 inhalers did not meet the criteria for declaring bioequivalence: estimated ratios (RPID:Diskus) were 2.00 (90% CI, 1.56 to 2.55) for FP AUC up to the time point of next dosing and 1.92 (90% CI, 1.64 to 2.25) for salmeterol maximum observed plasma concentration at the end of the dosing interval (at steady state). Urine cortisol (0–24 hours) was significantly lower for the RPID than for the Diskus inhaler (ratio, 0.74 [95% CI, 0.57 to 0.96]; P = 0.026); no significant difference in plasma cortisol was noted between the 2 inhalers (ratio, 0.85 [95% CI, 0.7 to 1.04]). A small but statistically significant increase in maximum heart rate (5 beats/min) was noted in the RPID group (ratio, 1.05 [95% CI, 1.01 to 1.10]; P = 0.029). No notable differences in other PD end points were observed. Drug-related adverse events occurred in both groups (2 [dysphagia and tremor] in the RPID group and 3 [2 cases of dysphonia, 1 case of mucous-membrane irritation] in the Diskus group). There were 270 patients (136 females, 134 males) in the clinical efficacy and safety study, most (94%) of whom were white; mean (SD) age was 37.2 (17.0) years (range, 11–77 years) in the RPID group and 35.4 (17.2) years (range, 12–77 years) in the Diskus group. The RPID and the Diskus inhaler met the predefined equivalence criteria (±15 L/min) in terms of mean change in morning PEF from baseline: 3.9 L/min (95% CI, -3.1 to 11.0). The 2 SFC 50/250 inhalers were well tolerated; the most frequently reported adverse event was bronchitis, reported by 12% of the patients in the RPID group and 9% of those in the Diskus group. The only serious adverse event, which occurred in the RPID group and was related to bronchial infection, was considered unrelated to treatment.Conclusions: In vitro particle size distribution data were potentially superimposable for the RPID and the Diskus inhaler. The 2 devices were considered to be clinically equivalent in terms of mean morning PEF but were not considered equivalent in terms of PK systemic exposure. The 2 SFC 50/250 inhalers were well tolerated and had comparable safety profiles; no serious adverse events were attributed to the study product.

Evaluation of plasma cortisol levels and behavior in dogs wearing bark control collars

On wk −1, 24 healthy mixed breed kennel dogs were screened by physical examination, complete blood count, serum biochemistry, and plasma cortisol measurement. Dogs were tested to ensure they barked at an unfamiliar dog. Dogs were randomly assigned to control, electronic bark collar or lemon spray bark collar groups ( n = 8 per group). On wk 0 (acclimation baseline), dogs wore inactivated collars 30 min/day for 3 consecutive days. On wks 1 and 2, dogs wore an activated collar 30 min/day for 3 consecutive days. Controls wore an inactivated collar. The bark stimulus was an unfamiliar dog walked in front of the run, three times, 30 s per presentation. Plasma cortisol was measured wk −1, wk 0 d 3, wk 1 d 1, wk 1 d 3 and wk 2 d 3. ACTH was measured wk 0 d 3 and wk 1 d 1. Barking and activity were measured each session. Results Dogs wearing electronic or lemon spray collars barked less than controls ( P < 0.05) by the 2nd day wearing an activated collar, with no significant difference in barking between collars. Mean numbers of collar corrections per dog on the 1st day wearing an activated collar were 4.0 (electronic) and 2.0 (lemon spray); the values decreased to 0 for both collars on the 3rd day. ACTH levels did not differ among groups ( P > 0.05). Mean plasma cortisol levels were within the reference range for all groups throughout the study. Overall, there was a significant time effect ( P < 0.05) but no significant difference in plasma cortisol between the control, lemon spray and electronic collar groups ( P > 0.05). Activity did not change significantly over time ( P > 0.05). Conclusion Electronic and lemon spray bark collars significantly reduced barking, with no significant difference between collar types. Dogs with either type of bark collar had an increase in plasma cortisol the 1st day wearing the activated collar, but this was not statistically significant ( P > 0.05). There was no statistically significant difference in plasma cortisol levels between dogs wearing control, lemon spray or electronic collars.