Mean Serum Cortisol Concentrations Research Articles

Safety and effectiveness of a drug-loaded haemostatic sponge in chronic rhinosinusitis: a randomized, controlled, double-blind study

Some cases of chronic rhinosinusitis (CRS) require surgical treatment and postoperative nasal packing, but bleeding and adhesion are common complications after nasal surgery. Biodegradable drug-loaded implants hold great therapeutic options for the treatment of CRS, but little data are available regarding the safety and efficacy of a novel drug-loaded haemostatic sponge (DLHS) in the sinus. The aim of this study was to investigate the safety and efficacy of DLHS in the sinus. We conducted a prospective, randomized, controlled, double-blind clinical trial. In this clinical trial, 49 patients were enrolled and randomly divided into 2 groups: group A (n = 25) had the DLHS containing 1 mg budesonide and 0.67 mg sodium hyaluronate placed into the sinus, and group B (n = 24) had the Nasopore placed after ESS. Endoscopic follow-up was performed for 12 weeks, and the findings were classified using the discharge, inflammation, polyps/oedema (DIP) endoscopic appearance scores. All patients completed questionnaires to evaluate their sinonasal symptoms by using the sinonasal outcome test-22 (SNOT-22) Chinese version and visual analogue scale (VAS). Serum cortisol concentration in group A was measured prior to surgery and at days 1, 3, 7, and 14 after nasal surgery. Comparing group A and group B, at 2 weeks, no significant differences were observed in either objective or subjective parameters. The mean value of VAS for rhinorrhoea and DIP for oedema and the mean value of nasal adhesion were significantly lower in Group A than in Group B at 6 and 12 weeks, but a significant difference did not occur in SNOT-22 and VAS for dysosmia between the two groups at 6 and 12 weeks. The mean serum cortisol concentrations in group A at the follow-up were within normal limits without remarkable fluctuations. This study demonstrates the safety and efficacy of a novel biodegradable DLHS with the possibility of being used in CRS patients, and this sponge may reduce inflammation and minimize adhesions via controlled local drug delivery without measurable systemic exposure.

Short Rest Between Flights Is Associated With Increased Serum Stress Hormone Levels in Airline Pilots: A Cross-Sectional Study.

Work-related stress is a critical area of research in civil aviation, given the potential for severe consequences when airline pilots (APs) are overwhelmed or unable to perform optimally. While pilots are traditionally considered to be exposed to various stressors, the impact of specific occupational characteristics on stress in the aviation industry remains inadequately understood. Considering that biomarkers are increasingly being utilized as objective measures of stress in human research, this cross-sectional study investigated the association between occupational variables and serum levels of cortisol and dehydroepiandrosterone sulfate (DHEAS) as stress biomarkers in commercial APs. A total of 120 male APs completed a survey assessing the following work-related characteristics: position (captain vs. first officer), years of experience, total flight hours, flight hours in the preceding year, inter-flight rest duration, and flight route length. Serum cortisol and DHEAS concentrations were determined from venous blood samples obtained between 08:00 and 09:00 a.m., following a minimum eight-hour fasting period. The biomarker data were analyzed in relation to the aforementioned occupational characteristics. The mean serum cortisol and DHEAS concentrations in the entire cohort were 8.5±2.1 µg/dL and 214.6±96.4 µg/dL, respectively. There were no significant differences in the levels of the two stress hormones in relation to position, years of experience, total flight hours, flight hours in the preceding year, or flight route length. However, an inter-flight rest period of less than one hour was significantly associated with elevated serum cortisol (P<0.01) and reduced DHEAS levels (P<0.001) compared to longer rest durations. Notably, a stepwise decrease in DHEAS concentrations was observed for rest periods of <1 hour, 1-4 hours, 4-24 hours, and >24 hours. After adjustment for potential confounders in multivariable analyses, a rest period of <1 hour remained independently associated with both serum cortisol (odds ratio [OR]=1.09, 95% confidence interval [CI]=1.04-1.13, P<0.01) and DHEAS (OR=0.94, 95% CI=0.92-0.97, P<0.001). Serum stress hormones in APs are associated with short inter-flight rest periods. Optimization of rest durations may contribute to improved pilot well-being and performance. Further research is warranted to determine ideal rest period lengths and develop interventions to mitigate the potential adverse effects of abbreviated rest periods between flights.

Comparative clinical pharmacology of mometasone furoate, fluticasone propionate and fluticasone furoate

AimsTo investigate the pharmacokinetics and effects on the hypothalamic-pituitary-adrenal (HPA) axis of mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). MethodsStudy 1: Fourteen healthy participants received inhaled and intravenous MF (inhaled dose via Twisthaler) and FP (inhaled dose via Diskus), both given at 400 μg, using a randomised, single-dose, four-way crossover design. Study 2: Twenty-seven participants with mild to moderate asthma, who discontinued their corticosteroid medication for 5 days to obtain a baseline 24 h serum cortisol, received inhaled MF Twisthaler and FP Diskus, both given at 400 μg twice daily (BID), using a randomised, 14-day repeat dose, two-way crossover design. Study 3: Forty-four healthy participants were randomised to a double-blind, placebo-controlled, five-period crossover study where the following treatments were administered via the inhaled route for 7 days: FP Diskus (250, 500, 1000 μg BID), FF Diskus (100, 200, 400, 800, 1600 μg once daily [QD]) or placebo Diskus. In each study, 24-h serial blood samples were collected and assayed to assess concentrations of MF, 6β-hydroxy mometasone, mometasone, FP, FF and cortisol. Pharmacokinetic and serum cortisol parameters were estimated as geometric means and 95% confidence intervals (CI). ResultsStudy 1: For intravenous MF and FP, respectively: absolute bioavailability was 11.4% (95% CI: 7.5, 17.6) and 7.8% (6.3, 9.6); plasma clearance was 47 L/h (41, 52) and 60 L/h (52, 69); half-life was 7.4 h (6.9, 8.0) and 7.2 h (6.5, 8.0); and volume of distribution was 499 L (439, 567) and 623 L (557, 698). Inhalation of single dose MF or FP did not significantly affect serum cortisol (<10% reduction from baseline), whereas intravenous administration of MF or FP each changed serum cortisol by approximately −50% from baseline. Study 2: For MF and FP, respectively: area under the curve up to the last measurable concentration on Day 1 was 421 pg h/mL (270, 659) and 248 pg h/mL (154, 400), and on Day 14 was 1092 pg h/mL (939, 1269) and 591 pg h/mL (501, 696); absolute bioavailability was 12.8% (11.2, 14.2) and 8.9% (7.7, 10.2). On Day 14, 24-h serum cortisol change from baseline was −35% (−44%, −26%) and −18% (−28%, −5%) for MF and FP, respectively; the reduction was significantly greater for MF than FP (ratio for geometric adjusted mean serum cortisol concentration: 1.28 [1.04, 1.56]). Low plasma concentrations of 6β-hydroxy mometasone were detected after intravenous dosing (Study 1) and after multiple inhaled dosing (Study 2); mometasone was not detected in any samples. Study 3: Inhaled FP and FF had similar systemic bioavailability estimates (12.0% [11.0, 13.2] and 15.0% [12.0, 17.3], respectively), but a differential effect on the HPA axis which was in agreement with the known 1.7-fold higher glucocorticoid receptor-binding affinity of FF versus FP. However, for FP 250 μg BID and FF 100, 200 and 400 μg QD, reduction in serum cortisol was not significantly different from placebo. For higher doses, FP 500 and 1000 μg BID, and FF 800 and 1600 μg QD, changes in serum cortisol concentration relative to placebo were −30%, −70%, −41% and −90%, respectively. Repeat inhaled dosing of FP 1000 μg/day (within the therapeutic dose range) resulted in comparable cortisol suppression to MF in the therapeutic range (30% reduction); whereas for FF this occurred at more than 3-fold above the therapeutic dose range (644 μg/day). ConclusionsSingle inhaled and intravenous doses of MF and FP (400 μg) resulted in similar bioavailability and reductions in serum cortisol. Repeat dosing of inhaled MF and FP in the therapeutic range (800 μg/day) resulted in greater systemic exposure for MF, and a 35% reduction in serum cortisol that was 2-fold greater than for FP. The higher glucocorticoid receptor-binding affinity and bioavailability, lower clearance and the presence of active metabolites may contribute to the greater systemic exposure and effect on cortisol for MF. Repeat dosing of inhaled FP and FF resulted in similar systemic bioavailability but differed in terms of the dose required for comparable cortisol suppression to MF in the therapeutic range. Unlike FP and FF, MF has active metabolites that may contribute to its systemic effects, while device/formulation performance differences also exist between MF-containing products.

Changes in the adrenal gland and cortisol secretions in experimental acute Trypanosoma brucei brucei infection in Sahel bucks

The effects of experimental acute Trypanosoma brucei brucei infection on the function and structure of the adrenal gland of Sahel bucks were studied for forty days. Eight Sahel bucks aged between 8 and 15 months were used. They were divided into two groups of five (infected) and three (uninfected) bucks. Group I were inoculated with 1ml containing about 1×10⁶ trypanosomes (Trypanosoma brucei brucei, Federe strain) via the jugular vein. Group II was uninfected control. Parasitaemia in the infected bucks appeared 3-4 days post-infection. The mean serum cortisol concentrations of the uninfected control and the infected groups at day 0 were 3.33 ± 0.44 μg/dl and 2.4 ± 0.29μg/dl, respectively. By day 4 post-infection, the mean serum cortisol concentration of the infected group increased to its peak value of 21.8 ± 6.25μg/dl compared to 3.0 ± 0.86 μg/dl of the uninfected control on the day all infected bucks became parasitaemic. Grossly, the adrenal glands of the infected group were enlarged. Histopathologically, there was adrenal cortical hypertrophy in the infected group. The results indicate that acute trypanosomosis due to experimental T. brucei brucei infection in Sahel buck caused hypertrophy of the adrenal gland and a significant increase in the circulatory cortisol concentration of the infected bucks at the onset of parasitaemia followed by a decrease to pre-infection cortisol concentration till the end of the 40 days duration of the experiment. Further study on the long-term effect of experimental Trypanosoma brucei brucei infection on the adrenal gland of Sahel bucks is recommended.

Strategic administration of an appeasing substance to improve performance and physiological responses of Bos indicus feedlot cattle.

This study was designed to evaluate the timing of administration of the bovine appeasing substance (BAS) on performance and physiological responses of Bos indicus feedlot cattle. Nellore bulls (n = 100) were ranked by initial body weight (BW; 341 ± 18.5 kg) and assigned to receive BAS (n = 50) or placebo (CON; n = 50) on day -2 of the experiment. Treatments (5 mL) were applied topically to the nuchal skin area of each bull. Bulls were loaded into commercial livestock trailers immediately after treatment administration, transported for 880 km, and unloaded on day -1 at a commercial feedyard. On day 0, bulls within each treatment were again assigned to receive, in a 2 × 2 factorial arrangement, BAS or CON as described previously (25 bulls/treatment combination). Upon treatment administration on day 0, bulls were housed in 12 feedlot pens (3 pens/treatment) for a 108-d feeding period, which was divided into an adaptation (days 0-19), growing (days 20-60), and finishing (days 61-108) phases. Dry matter intake (DMI) was measured daily from days 0 to 108, whereas blood samples and hair from the tail switch were collected on days -2, 0, 19, 60, and 108. Administration of BAS prior to loading (day -2) improved ADG, FE, and DMI during adaptation and across the 108-d feeding period (P ≤ 0.08), resulting in greater (P = 0.03) hot carcass weight and dressing percentage upon slaughter on day 109. A treatment × day interaction was detected for serum glucose concentrations (P = 0.05), which was greater (P = 0.03) on day 60 of the feeding period in bulls receiving CON prior to loading. Administration of BAS at feedlot entry (day 0) improved DMI, ADG, and FE during adaptation (P ≤ 0.05), but it did not impact (P ≥ 0.18) performance and carcass traits during the 108-d feeding period. Bulls administered BAS prior to loading and at feedlot entry had less (P ≤ 0.05) mean serum cortisol concentrations across the 108-d feeding period (loading × feedlot entry interaction; P = 0.10) and greater (P ≤ 0.05) serum insulin concentration on day 60 (loading × feedlot entry × day interaction; P = 0.05). In summary, BAS administration prior to loading increased the overall feedlot performance of Nellore bulls. These outcomes were noted in bulls that received or not a second BAS administration at feedlot entry, suggesting that the benefits of BAS are exploited when this substance is administered before transport to the feedlot.

The contraceptive efficacy of a self-assembling intra-uterine device in domestic mares.

The primary aim of this study was to investigate the contraceptive efficacy of a self-assembling uterine device (iUPOD™) in the mare. In addition, the effects of iUPODs on oestrous cyclicity, uterine health and circulating concentrations of cortisol were evaluated. Domestic mares underwent oestrous monitoring and artificial insemination. After subsequent ovulation, mares underwent either placement (n = 7) or sham placement (n = 7; controls) of an iUPOD device. Devices were left in place for at least 3 months. Pregnancy diagnoses were carried out 14 days post-ovulation, with any pregnancies terminated at 28 days post-ovulation. All mares underwent weekly blood sampling with or without reproductive examinations throughout the study. Towards the end of the study, multiple serum samples collected over three consecutive days were analysed for concentrations of cortisol. Endometrial biopsies were collected before artificial insemination and during the subsequent breeding season. Endometrial cytology and bacterial cultures were performed before device removal (iUPOD mares) or at the end of the study (control mares). Pregnancies were diagnosed in 0 of 7 iUPOD mares versus 7 of 7 control mares. Placement of iUPODs was associated with extended luteal phases and variable accumulations of intra-uterine fluid. Bacterial culture results suggested that the mild endometritis associated with iUPODs was sterile in six of seven mares. Short-term placement of iUPODs had no detrimental effects on endometrial architecture. Mean serum cortisol concentrations were significantly lower in iUPOD mares than control mares. iUPODs represent a promising means of fertility control in the mare.

The impact of racing on serum concentrations of acute-phase proteins in racing dromedary camels

This study was designed to evaluate the impact of racing on serum concentrations of haptoglobin (Hp) and serum amyloid A (SAA) acute-phase proteins (APPs) in racing camels (Camelus dromedarius). Blood samples were collected 24 h prior to a 5-km race (T0) and within 2 h of completion of the race (T1). The white blood cell counts (WBCCs) were determined in EDTA blood samples. In the serum samples, the concentrations of cortisol, lactate, Hp, and SAA were determined within 2 weeks of sampling. Compared to pre-race values, the post-race WBCCs did not differ significantly. The mean serum cortisol concentrations increased significantly post-race; however, the mean serum lactate concentrations decreased significantly following the race. The serum concentrations of Hp and SAA APPs increased significantly post-race. The elevations of Hp and SAA suggest that an acute-phase reaction occurred in the camels after the race, thus shedding light on the impact of racing on the release of APPs.

Haematology and serum biochemistry of adult free-ranging mountain brushtail possums (Trichosurus cunninghami), including correlations with season, sex, age, habitat type and disease status

For many wildlife species only limited data are available on haematology and blood biochemistry for free-ranging populations because these are often difficult to obtain. We collected blood samples from wild adult mountain brushtail possums (Trichosurus cunninghami) in the Strathbogie Ranges, Victoria (Australia), over two years, to provide reference values for haematological and some serum biochemical parameters (serum protein, sodium, chloride, potassium, urea, creatinine, creatine kinase and cortisol) for free-ranging animals. We also investigated patterns associated with sex, season, age, habitat type and disease status, including a form of skin disease (rumpwear – one of the major diseases of brushtail possums) and parasite loads. Values for several blood parameters correlated with sex, and most also changed significantly with season. Eosinophil counts increased significantly with the number of strongyle eggs in faeces, and packed cell volume decreased significantly with increasing numbers of ticks. Surprisingly, there was a significant negative relationship between mean population serum cortisol concentrations and the prevalence of rumpwear. Serum sodium and chloride concentrations were significantly lower in possums with moderate to severe rumpwear; however, the biological significance of this is unclear. While there is a growing body of data on the blood parameters of marsupials, these are mainly derived from captive animals, or single sample sets from wild populations, thus are unlikely to accurately reflect the changing status of wild animals/populations across seasons and under varying environmental conditions and parasite loads. More comprehensive, longer-term data from free-ranging marsupial populations, such as those presented here, provide extremely important reference data to aid in determining the health status of wild populations and interpreting data collected from individuals.

Comparison of VIDAS and Radioimmunoassay Methods for Measurement of Cortisol Concentration in Bovine Serum

Radioimmunoassay (RIA) is the “gold standard” method for evaluation of serum cortisol concentration. The VIDAS cortisol test is an enzyme-linked fluorescent assay designed for the MiniVidas system. The aim of this study was to compare the VIDAS method with RIA for measurement of bovine serum cortisol concentration. Cortisol concentrations were evaluated in 40 cows using both VIDAS and RIA methods, the latter as the reference method. A paired Student's t-test, Pearson's correlation analysis, Bland-Altman plot, and Deming regression analysis were used to compare the two methods. There was no statistically significant difference between mean serum cortisol concentrations measured by VIDAS or RIA methods (P = 0.6570). Both methods were able to detect significant differences in mean low and high cortisol concentrations (P < 0.00014 RIA and P < 0.0016 VIDAS). The correlation coefficient was low, but a Bland-Altman plot and Deming regression analysis show neither constant nor proportional error. The VIDAS method produced slightly higher values than RIA, but the difference was small and in no case did the mean value move the normal range. Results suggest that VIDAS method is suitable for the determination of bovine serum cortisol concentration in studies of large numbers of animals.

Endocrine Changes in Harbor Seal (Phoca vitulina) Pups Undergoing Rehabilitation

Rehabilitating pinniped pups are often admitted to care centers as neonates and generally lack maternal investment and are in poor body condition. Upon admittance to a rehabilitation facility, pups are typically fed a milk replacement formula via gavage, which is switched to frozen fish upon weaning. While rehabilitation has been successful in terms of recovery and release, preweaning growth rates in captivity are consistently lower than in the wild. Indicators of stress (cortisol and total thyroxine; TT4), and standard morphometrics, of harbor seal pups in rehabilitation (n = 20) were determined for both preweaned and weaned pups. Hormone concentrations and standard morphometrics from pups in care were compared with free-ranging harbor seal pups (n = 59). Pups in rehabilitation gained mass on both milk and fish diets. Preweaned pups had greater mean serum cortisol and similar TT4 concentrations than weaned pups. Free-ranging harbor seal pups were heavier and longer than preweaned and weaned pups in rehabilitation. The free-ranging pups had the lowest cortisol and highest TT4 concentrations of any of the pups. These results suggest that weaned pups that have undergone rehabilitation are not physiologically equivalent to free-ranging weaned pups. Additional research is needed regarding physiological changes in endocrine values during early development under captive care conditions. This information should be useful to marine mammal rehabilitation centers in their development of care protocols and release criteria for rehabilitating harbor seal pups.

Influence of dominance status on adrenal activity and ovarian cyclicity status in captive African elephants

The North American African (Loxodonta africana) elephant population is not self-sustaining, in part because of a high rate of abnormal ovarian activity. About 12% of adult females exhibit irregular cycles and 31% do not cycle at all. Our earlier work revealed a relationship between dominance status and ovarian acyclicity, with dominant females being more likely to not cycle normally. One theory is that dominant females may be expending more energy to maintaining peace within the captive herd than for supporting reproduction. The goal of this study was to determine if there was a relationship among dominance status, serum cortisol concentrations, and ovarian acyclicity. We hypothesized that adrenal glucocorticoid activity would be increased in dominant, noncycling elephants as compared with subdominant individuals. Blood samples were collected weekly over a 2-year period in 81 females of known dominance and cyclicity status, and analyzed for cortisol. Based on a path analysis model (Reticular Action Model Or Near Approximation [RAMONA]), noncycling, dominant African elephant females did not have higher mean serum cortisol concentrations, or exhibit more variability (i.e., coefficient of variation, standard deviation) in cortisol secretion. This study suggests that alterations in adrenal activity are not related to dominance status nor contribute directly to acyclicity in captive African elephants.

Effect of progestins on serum hormones, semen production, and agonistic behavior in the gerenuk (Litocranius walleri walleri)

The use of progestins to suppress endogenous testosterone production to reduce agonistic behavior and prevent semen production was studied in gerenuk. Five male gerenuk (20 months to 3 years of age), housed as a bachelor group, were treated with 3 monthly injections of medroxyprogesterone acetate (MPA; 2.5-20 mg/kg), followed by a melengestrol acetate implant (MGA; 0.3 g/kg) for 2 months. Blood samples collected monthly were assayed for serum testosterone and cortisol using enzyme-linked immunoassays. Quantitative behavioral data were collected for 30 min 3/week starting 1 month before treatment. Body weight, testes volume, and semen traits were measured before treatment, after MPA treatment, and after MGA treatment. Results showed lower (P<0.05) mean serum testosterone concentrations after MPA (4.34 pg/ml) and MGA (5.02 pg/ml) treatment compared to pre-treatment values (65.9 pg/ml) in four of five gerenuk. The remaining sub-adult gerenuk had low testosterone initially (4.9 pg/ml) that did not decrease further with treatment (1.4 and 7.8 pg/ml for MPA and MGA, respectively). Mean serum cortisol concentrations decreased markedly after treatment with MPA (6.0+/-3.7 ng/ml) and MGA (0.8+/-0.3 ng/ml). Cortisol concentrations were regained rapidly post-treatment (42.8+/-4.8 ng/ml) and were not significantly different from the pre-treatment value (60.6+/-12.6 ng/ml; P>0.05). The mean incidence of combined aggressive/dominant behaviors (horning, sparring, supplanting, threat) was not different before and after treatment. Body weight, total numbers of spermatozoa produced per ejaculate, percent motility, and percent normal spermatozoa declined maximally 8 months after treatment. Mean testes volume decreased (P<0.05) after MGA treatment (10.53 cm(3)vs. 11.96 cm(3) pre-treatment). Elevated hepatic enzymes and bile acids were seen in three of five animals after progestin treatment and anorexia was noted in two males after MGA implant removal, however two of three males had elevated liver enzymes before progestin treatment began. Results show that reducing serum testosterone concentration does not seem to modify agonistic behavior in bachelor gerenuk groups. Zoo Biol 26:245-257, 2007. (c) 2007 Wiley-Liss, Inc.

Effect of low doses of cosyntropin on serum cortisol concentrations in clinically normal dogs

To determine the lowest of 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, or 0.01 microg/kg) administered IV that stimulates maximal cortisol secretion in clinically normal dogs. 10 clinically normal dogs. 5 dose-response experiments were performed in each of the dogs. Each dog received 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, and 0.01 microg/kg) IV in random order (2-week interval between each dose). Serum samples for determination of cortisol concentrations were obtained before (baseline) and at 10, 20, 30, 40, 50, 60, 120, and 240 minutes after cosyntropin administration. Compared with baseline values, mean serum cortisol concentration in the study dogs increased significantly after administration of each of the 5 cosyntropin doses. Mean peak serum cortisol concentration was significantly lower after administration of 0.01, 0.05, and 0.1 microg of cosyntropin/kg, compared with findings after administration of 0.5 and 1.0 microg of cosyntropin/kg. After administration of 0.5 and 1.0 microg of cosyntropin/kg, mean peak serum cortisol concentration did not differ significantly; higher doses of cosyntropin resulted in more sustained increases in serum cortisol concentration, and peak response developed after a longer interval. Administration of cosyntropin IV at a dose of 0.5 microg/kg induced maximal cortisol secretion in healthy dogs. Serum cortisol concentration was reliably increased in all dogs after the administration of each of the 5 doses of cosyntropin. These data should be useful in subsequent studies to evaluate the hypothalamic-pituitary-adrenal axis in healthy and critically ill dogs.

Prolonged exercise does not cause lymphocyte DNA damage or increased apoptosis in well-trained endurance athletes

Recent research has demonstrated that lymphocyte apoptosis sensitivity appears to be related to training status and exercise intensity. This work investigated the effect of prolonged, submaximal treadmill running on percentage (%) apoptosis, % necrosis and DNA strand breaks in lymphocytes and related these to changes in total lymphocyte and blood cortisol concentrations in well-trained runners. Venous blood samples (n = 14) were taken immediately before (PRE), immediately after (IPE) and 3 h after (3PE) 2.5 h of treadmill running at 75% of VO2 max from eight well-trained male endurance athletes (age 34.2 +/- 2.44 years) and analysed for cellular content and serum cortisol concentrations. Lymphocytes were isolated from whole blood and % apoptotic and necrotic cell were detected by flow cytometry using Annexin V-FITC and propidium iodide uptake. DNA strand breaks were measured by single-cell gel electrophoresis. Despite a significant (P < 0.001) exercise-induced increase in mean serum cortisol concentrations and reduction in lymphocyte counts, the mean % Annexin-V positive cells (13.3 +/- 6.78 in PRE, 11.3 +/- 5.51 in IPE and 12.8 +/- 6.75 in 3PE samples) were not significantly different at the three time-points (P > 0.05). Mean DNA strand breaks in the lymphocytes also did not change significantly (P > 0.05) rising from 25.7 +/- 2.16 to 26.9 +/- 1.89 and 27.1 +/- 1.38 microm in IPE and 3PE samples, respectively. The exercise-induced changes in total blood lymphocyte counts and cortisol concentrations did not result in a significant change in % apoptotic lymphocytes or DNA strand breaks in the endurance-trained athletes during this prolonged, submaximal exercise.

Stereotypic swaying and serum Cortisol concentrations in three captive African elephants (Loxodonta africana)

AbstractThe behaviour and serum Cortisol concentrations of three captive female African elephants(Loxodonta africana)were studied to determine whether their stereotypic swaying was more prevalent before regularly scheduled events in the elephants’ routine, and whether the elephants that exhibited more stereotyped swaying had lower mean serum cortisol concentrations. Behavioural data were collected during hour-long observations balanced across three periods, and during 15-min observations prior to the elephants being moved to different portions of their enclosure. Observational data were collected using instantaneous focal sampling of behaviours every 30s. Serum cortisol measures were obtained through weekly blood withdrawal from the elephants’ ears. Of the three elephants, two exhibited stereotyped swaying, which accounted for a mean of 0.4% of the scans during the hour-long observations and a mean of 18% of the scans prior to the elephants being moved between different parts of the enclosure. Swaying was highly variable among the individual elephants during both categories of observations. Additionally, both elephants swayed more prior to moving in the afternoon than prior to moving in the morning. Analyses of serum cortisol concentrations indicated that each elephant had a different mean cortisol level, which did not clearly correspond with the expression of swaying. The findings indicate that a rigidly scheduled management event may elicit stereotyped swaying in the studied elephants. Future research should document the behavioural and physiological effects of an altered management routine to improve captive elephant welfare.

Prolonged suppression of the innate immune system in the horse following an 80 km endurance race.

An increased susceptibility to bacterial and viral infections of the respiratory tract, which results in a loss of performance, has been reported in racehorses. Much research has focused on the influence of high-intensity exercise of a short duration on immune system function in horses, but scant attention has been given to prolonged endurance exercise as an immune modulator. The objective of this study was to evaluate the effect of an 80 km endurance race on the monocyte and neutrophil oxidative burst, serum cortisol, glutamine and plasma glucose concentrations in 8 endurance-trained horses (mean +/- s.d. age 9.4 +/- 2.2 years). Blood samples were drawn from the horses prior to and following an 80 km ride. Mean time for completion of the 80 km race was 306 +/- 40 mins. Immediately post race mean serum cortisol concentration, blood monocyte and neutrophil counts were higher and blood lymphocyte counts and plasma glucose concentration were lower compared with prerace values (P < 0.05). Neutrophil and monocyte oxidative burst activity decreased following the race and had not regained prerace values after 3 days of rest (P < 0.05). The present study indicates that long duration exercise in horses has a negative impact on the function of the innate immune system that lasts several days post race. Precise mechanisms instigating the fall in innate immune system function are unclear and multifactorial, but may be attributed, at least in part, to a high serum cortisol response during very prolonged exercise. A prolonged bout of exercise results in a long-term suppression of the innate immune system function in horses which may, in part, account for the observed increase of infectious episodes in horses during training.

Effect of High Starting Dose of Budesonide Inhalation Suspension on Serum Cortisol Concentration in Young Children with Recurrent Wheezing Episodes

Introduction. There are no available data on the safety of recommended schedules for the initiation of treatment with budesonide inhalation suspension in children with recurrent wheezing episodes. We compared the safety of high and low starting dose of budesonide by measuring their effect on plasma cortisol concentration. Methods. A randomized double-blind, placebo-controlled design was used. Twenty-nine children ages 6 months to 3 years were divided into three groups: (1) high starting dose: 1 mg budesonide inhalation suspension twice daily followed by a stepwise decrease of 25% every second day for 8 days (n = 11); (2) low starting dose: 0.25 mg twice daily for 8 days (n = 11); (3) placebo (n = 7). The 8 AM (fasting) and 1-hour post-ACTH stimulation plasma cortisol concentrations were measured before and 10 days after initiation of budesonide treatment. Results. Before treatment and after 8–10 days of treatment, there was no significant difference in mean serum cortisol concentration in the high starting dose, low-dose and placebo groups, either at 8 AM or at 1 hour after ACTH stimulation. Conclusion. The administration of nebulized suspension of budesonide at a high starting dose (2 mg/day for 2 days) followed by a rapid stepwise decrease over 8 days was safe, causing similar changes in serum cortisol levels to low-dose budesonide suspension or placebo.

Increased adrenocortical and adrenomedullary hormonal activity in 12-year-old children born small for gestational age

Objectives: To determine whether adrenal hormonal activity is altered in children born small for gestational age (SGA), and whether concentrations of adrenal hormones relate to those of serum lipids or to anthropometric measures. Study design: We studied 55 SGA children and 55 appropriate for gestational age (AGA) children at the age of 12 years in a case-control setting. The concentrations of fasting serum cortisol, dehydroepiandrosterone sulfate (DHEAS), plasma epinephrine (E), and norepinephrine (NE) were analyzed. Results: The SGA children had significantly higher mean concentrations of serum DHEAS (3.53 vs 2.89 μmol/L, P =.009) and plasma E (0.33 vs 0.25 nmol/L, P =.005) than their age- and sex-matched control subjects. The mean serum cortisol and plasma NE concentrations did not differ significantly between the groups. However, the SGA children in the highest quartile for serum cortisol had significantly higher concentrations of plasma E (0.50 vs 0.28 nmol/L, P <.001), serum LDL (3.21 vs 2.73 mmol/L, P =.025) and total cholesterol (5.06 vs 4.42 mmol/L, P =.021) than the SGA children in the lower cortisol quartiles. The factors associating with high levels of plasma E in the SGA children were high level of serum cortisol [odds ratio (OR) = 3.8, 95% confidence interval (95% CI) = 1.5-10], LDL cholesterol (OR = 3.9, 95% CI = 1.3-12), male sex (OR = 8.3, 95% CI = 1.0-68) and low birth weight (OR = 1.4, 95% CI = 1.0-1.8) in multiple logistic regression analysis. Conclusions: Twelve-year-old children born SGA had increased DHEAS and epinephrine levels in circulation. High serum cortisol concentrations are associated with high epinephrine, LDL, and total cholesterol levels. (J Pediatr 2002;141:477-82)

Optimal response criteria for the human CRH test in the differential diagnosis of ACTH-dependent Cushing's syndrome.

The CRH test is in widespread use for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS). Despite the greater availability worldwide of human-sequence CRH (hCRH), there are no large series reporting the response criteria that best discriminate between Cushing's disease (CD) and the ectopic ACTH syndrome (EC) when using hCRH, rather than ovine-sequence CRH. We have, therefore, analyzed retrospectively the serum cortisol and plasma ACTH responses to hCRH in patients with ACTH-dependent CS, to develop response criteria that best discriminate between CD and EC. One hundred fifteen consecutive patients with proven ACTH-dependent CS were studied: 101 with CD (78 females; mean age, 40 yr; range, 10-73) and 14 with EC (7 females; mean age, 46 yr; range, 32-69). The response to hCRH was also studied in 30 normal volunteers (NVs; mean age, 29 yr; range, 20-44) with no clinical evidence of CS, and the results were compared. Following basal sampling at -15 and 0 min, hCRH (100 microg iv) was administered via an indwelling forearm cannula at 0900 h and serum cortisol and ACTH were measured at 15-min intervals for 2 h. The mean basal, peak, incremental, and percentage change in the serum cortisol and ACTH at all time points, and combination of time points, were calculated and analyzed to establish the best criteria to discriminate between CD and EC, and also between CD and NVs. The mean serum cortisol concentration in samples obtained at 15 and 30 min after CRH increased by at least 14% above the mean basal in 85 of 100 patients with CD, but in none with EC, giving a sensitivity of 85% at a specificity set at 100%. In contrast, the best plasma ACTH response of a rise of 105%, calculated from the maximal rise, gave only 70% sensitivity at 100% specificity. In the NVs, the maximum cortisol at the mean 15+30 min time point was 615 nmol/liter. Using the 15 and 30 min time points as the reference point, 71 of 100 patients with CD had a rise of serum cortisol greater than 14% and also showed an absolute cortisol level more than 615 nmol/liter. Serum cortisol responses to hCRH can be used to suggest the diagnosis of CD in the majority of patients with this condition, but it should only be used in conjunction with other biochemical and imaging modalities in establishing this important diagnosis. The measurement of plasma ACTH was less helpful in making this distinction, although it may have additional value in excluding ACTH-independent causes of CS. Although we believe that bilateral inferior petrosal sinus sampling remains the single most useful test in discriminating CD from EC in patients with ACTH-dependent CS, hCRH offers rapid diagnostic information and is a useful adjunctive test in establishing the presence of a possible ectopic source.

Safety of inhaled corticosteroid therapy in young children with asthma

Physicians have had some reluctance to use inhaled corticosteroids in very young children with asthma because of the possible risks of adverse systemic effects. The purpose of this study was to evaluate the effects of fluticasone propionate on growth and adrenocortical function in young children with asthma. We performed an open, prospective study for 24 weeks of 20 children with asthma, 2.5 to 5.0 years of age, who had received fluticasone by a large volume spacer at dosages ranging from 190.50 to 565.40 microg/m2 daily. Growth was evaluated by height standard deviation scores measured by a stadiometer. Adrenocortical function was evaluated twice in each child, before and after the study, by determining fasting serum cortisol concentrations at 8 AM and also at 30 and 60 minutes after adrenocorticotropic hormone stimulation. Posttreatment values of height standard deviation scores and fasting morning serum cortisol concentrations were compared with those of 18 age-matched children, who constituted the control group. The evaluation of mean +/- SEM (and range) of height standard deviation scores revealed a significant decrease from 0.44 +/- 0.27 (-1.46 to 2.22) to 0.28 +/- 0.26 (-1.51 to 2.07; P = 0.01) at week 18 and to 0.25 +/- 0.24 (-1.90 to 2.13; P = 0.04) at the week 24 in fluticasone-treated children. At the end of the treatment, however, height standard deviation scores of these children did not differ significantly (P = 0.35) from those of the control group. Delayed growth with medium-duration treatment was not associated with alterations in serum cortisol measurements, either at baseline or after stimulation. The mean fasting morning serum cortisol concentrations did not differ significantly between the fluticasone-treated patients and the control group. Some concern prevails about the safety of medium- or long-term treatment with regularly inhaled corticosteroids in young children with asthma. The prepubertal growth may be delayed, but the effect on ultimate height remains uncertain in such children. Growth should be regularly monitored in children who begin inhaled corticosteroid therapy for mild persistent asthma at an age <5 years old.