Increased Plasma Cortisol Concentrations Research Articles

Vasopressin-mediated adrenocorticotropin release increases plasma cortisol concentrations during cardiopulmonary resuscitation

Vasopressin is a possible stimulus for both adrenocorticotropin (ACTH) and endothelin-1 release. The aim of this study was to compare plasma concentrations of ACTH, cortisol, and endothelin-1 after epinephrine or vasopressin administration in an experimental animal model of cardiopulmonary resuscitation (CPR). Prospective, randomized, controlled animal study. A university research laboratory. Fourteen 12- to 14-wk-old domestic pigs. After 4 mins of cardiac arrest and 3 mins of external chest compression, the pigs were randomly assigned to receive either 0.045 mg/kg epinephrine (n = 7) or 0.4 units/kg vasopressin (n = 7). At 5 mins after drug administration, defibrillation was attempted. Coronary perfusion pressure, ACTH, cortisol, and endothelin-1 were measured before cardiocirculatory arrest, during CPR before drug administration, and at 90 secs and 5 mins after drug administration. Coronary perfusion pressure was comparable between groups. All seven animals in the vasopressin group survived, but only one pig in the epinephrine group survived (p = .005). ACTH and cortisol concentrations remained unchanged in epinephrine-treated animals, but increased significantly after vasopressin administration and were significantly higher than in epinephrine-treated animals 5 mins after drug administration. Endothelin-1 concentrations remained unchanged during the study period and were comparable between both groups. Vasopressin is a potent stimulus for ACTH secretion, but does not trigger endothelin-1 release from vascular cells during cardiac arrest and CPR. The increased plasma cortisol concentrations caused by the enhanced ACTH release after vasopressin may be one factor contributing to the improved outcome repeatedly observed with vasopressin in animal models of CPR.

Exogenous and endogenous corticosteroids modulate blood-brain barrier development in the ovine fetus.

We previously reported decreases in blood-brain barrier permeability in the ovine fetus at 80% of gestation after antenatal corticosteroids and shown that permeability is not reduced in newborn lambs after postnatal corticosteroids. We now test the hypotheses that exogenous antenatal corticosteroids decrease blood-brain barrier permeability at 60% but not 90% of gestation in ovine fetuses and that endogenous increases in plasma cortisol concentrations are associated with ontogenic decreases in barrier permeability during gestation. Chronically instrumented ovine fetuses were studied 12 h after the last of four 6-mg dexamethasone or placebo injections were given 12 h apart over 48 h to ewes. Fetuses at 80% of gestation from placebo-treated ewes studied under the same protocol were also included. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (K(i)) to alpha-aminoisobutyric acid. K(i) values were lower in cerebral cortex, caudate nucleus, hippocampus, superior colliculus, thalamus, medulla, and cervical spinal cord in fetuses of dexamethasone- than placebo-treated ewes at 60% but not 90% of gestation. Regional brain K(i) values demonstrated inverse correlations with increases in gestation and plasma cortisol concentrations in most brain regions. We conclude that maternal treatment with exogenous corticosteroids was associated with decreases in blood-brain barrier permeability at 60% but not 90% of gestation and that increases in gestation and endogenous cortisol concentrations were associated with ontogenic decreases in barrier permeability during fetal development.

Enhanced intestinal synthesis of polyamines from proline in cortisol-treated piglets.

This study was conducted to determine a role for cortisol in regulating intestinal ornithine decarboxylase (ODC) activity and to identify the metabolic sources of ornithine for intestinal polyamine synthesis in suckling pigs. Thirty-two 21-day-old suckling pigs were randomly assigned to one of four groups with eight animals each and received daily intramuscular injections of vehicle solution (sesame oil; control), hydrocortisone 21-acetate (HYD; 25 mg/kg body wt), RU-486 (10 mg/kg body wt, a potent blocker of glucocorticoid receptors), or HYD plus RU-486 for two consecutive days. At 29 days of age, pigs were killed for preparation of jejunal enterocytes. The cytosolic fraction was prepared for determining ODC activity. For metabolic studies, enterocytes were incubated for 45 min at 37 degrees C in 2 ml of Krebs-bicarbonate buffer (pH 7.4) containing 1 mM [U-(14)C]arginine, 1 mM [U-(14)C]ornithine, 1 mM [U-(14)C]glutamine, or 1 mM [U-(14)C]proline plus 1 mM glutamine. Cortisol administration increased intestinal ODC activity by 230%, polyamine (putrescine, spermidine, and spermine) synthesis from ornithine and proline by 75-180%, and intracellular polyamine concentrations by 45-83%. Polyamine synthesis from arginine was not detected in enterocytes of control pigs but was induced in cells of cortisol-treated pigs. There was no detectable synthesis of polyamines from glutamine in enterocytes of all groups of pigs. The stimulating effects of cortisol on intestinal ODC activity and polyamine synthesis were abolished by coadministration of RU-486. Our data indicate that an increase in plasma cortisol concentrations stimulates intestinal polyamine synthesis via a glucocorticoid receptor-mediated mechanism and that proline (an abundant amino acid in milk) is a major source of ornithine for intestinal polyamine synthesis in suckling neonates.

Comparative effects of UVA and UVB irradiation on the immune system of fish

Aquatic organisms can be harmed by the current levels of solar ultraviolet radiation. We have recently shown that exposure of fish to UVB irradiation alters the functioning of the fish immune system, but the effects of UVA radiation are unknown. The present study continues this work by characterizing UVA irradiation-induced immunological changes in fish. Roach, a cyprinid fish, were exposed to a single dose of either UVA (3.6 J/cm 2) or UVB (0.5 J/cm 2) irradiation. Both irradiations suppressed transiently mitogen-stimulated proliferation of blood lymphocytes. UVA, but not UVB, decreased hematocrit, plasma protein, and plasma immunoglobulin levels and increased the proportions of blood cells classified as unidentified leukocytes, possibly consisting of UVA-damaged lymphocytes. UVB, but not UVA, altered the functioning of head kidney and blood phagocytes, induced granulocytosis and lymphocytopenia in the blood and increased plasma cortisol concentration. These results imply that both UVA and UVB are potent modulators of the immune defence of fish.

Effect of cortisol on blood pressure and the renin-angiotensin system in fetal sheep during late gestation.

The effects of cortisol on blood pressure and the circulating components of the renin-angiotensin system (RAS) were investigated in sheep fetuses during late gestation and after exogenous cortisol infusion. Plasma cortisol concentration was greater in fetuses at 140 +/- 1 days of gestation (term 145 +/- 2 days) compared to those studied earlier in gestation (128 +/- 1 days), although, because of wide inter-animal variation, no differences were observed in blood pressure or plasma angiotensin II (AII), renin or angiotensinogen (Ao) concentrations. At 129 +/- 1 days of gestation, an infusion of cortisol for 5 days (2-3 mg kg(-1) day(-1) i.v.) increased plasma cortisol concentration to a value normally seen close to term. This rise in plasma cortisol was accompanied by increases in blood pressure and plasma concentrations of AII, renin and Ao. When observations from all fetuses were considered, plasma cortisol concentration correlated with plasma AII and renin, and blood pressure correlated with plasma cortisol and AII concentrations. Intravenous administration of an AII type 1 (AT(1))-specific receptor antagonist (3 mg kg(-1) GR138950) caused a reduction in blood pressure in all fetuses; the hypotensive response was greatest in fetuses studied near term and in the cortisol-treated fetuses. Overall, the magnitude of the hypotension induced by GR138950, and the concomitant rise in plasma renin, both correlated with the plasma cortisol concentration before GR138950 treatment. These findings show that, in the sheep fetus during late gestation, the RAS becomes more important in the maintenance of resting blood pressure when plasma cortisol concentration is elevated, whether endogenously or exogenously.

Cerebrospinal fluid corticotropin-releasing hormone levels are elevated in monkeys with patterns of brain activity associated with fearful temperament

Background: Asymmetric patterns of frontal brain activity and brain corticotropin-releasing hormone (CRH) systems have both been separately implicated in the processing of normal and abnormal emotional responses. Previous studies in rhesus monkeys demonstrated that individuals with extreme right frontal asymmetric brain electrical activity have high levels of trait-like fearful behavior and increased plasma cortisol concentrations. Methods: In this study we assessed cerebrospinal fluid (CSF) CRH concentrations in monkeys with extreme left and extreme right frontal brain electrical activity. CSF was repeatedly collected at 4, 8, 14, 40, and 52 months of age. Results: Monkeys with extreme right frontal brain activity had increased CSF CRH concentrations at all ages measured. In addition, individual differences in CSF CRH concentrations were stable from 4 to 52 months of age. Conclusions: These findings suggest that, in primates, the fearful endophenotype is characterized by increased fearful behavior, a specific pattern of frontal electrical activity, increased pituitary–adrenal activity, and increased activity of brain CRH systems. Data from other preclinical studies suggests that the increased brain CRH activity may underlie the behavioral and physiological characteristics of fearful endophenotype.

Stress hormones and the cellular stress response in salmonids

The relationship between stress protein (SP) levels and the hormonal stress response in salmonids was examined through the measurement of gill SP70 and SP30 levels together with plasma cortisol, glucose and ion concentrations, in response to handling stress (45 s holding in a net), intraperitoneal cortisol implants, and heat shock (+10 °C). Handling and cortisol implants resulted in increased plasma cortisol and glucose levels. Heat shock following handling reduced plasma [Na+] below that observed in response to the handling stress alone, and heat shock following cortisol implant significantly lowered both plasma [Cl−] and [Na+] below that of fish receiving the cortisol implant alone. Increased SP70 levels occurred 1 h following the 2 h +10 °C heat shock. Handling the fish prior to the application of heat shock suppressed the increase of SP70 levels in the gills. However, increased plasma cortisol concentrations alone did not attenuate gill tissue SP70 increase caused by heat shock. Physiological (10−7 M) and pharmacological (10−5 M) concentrations of adrenaline caused increased levels of SP70 in hepatocytes. Addition of the β-blocker propanolol blocked this response to adrenaline. The results indicate that handling procedures do not result in an increase of hsp30 or hsp70 and may suppress hsp synthesis under certain circumstances.

Maternal dexamethasone treatment in late gestation alters glucocorticoid and mineralocorticoid receptor mRNA in the fetal guinea pig brain

Development of the fetal hypothalamo–pituitary–adrenocortical (HPA) axis is critical for fetal maturation and responses to stress. Guinea pigs, unlike rats, give birth to mature young, and peak brain growth occurs around days 48–52 (75%) of gestation. There is extensive development of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) systems at the time of rapid brain growth in guinea pigs. Since approximately 10% of pregnant women are treated with synthetic glucocorticoids in late gestation, to promote fetal organ maturation, we tested the hypothesis that fetal exposure to glucocorticoids modifies developing GR and MR systems in the brain. Pregnant guinea pigs were subcutaneously injected with dexamethasone (dex; 1 mg/kg) or vehicle on days 50 and 51 of gestation (term=70 days). On day 52, guinea pigs were killed and the fetuses rapidly removed. Maternal dex treatment resulted in increased plasma cortisol concentrations in female fetuses, but decreased cortisol in male fetuses. Plasma thyroxine levels were increased in both female and male fetuses following maternal dex-treatment. Exposure to dex resulted in significant increases in MR and GR mRNA in the CA1–2 region of the hippocampus, and MR mRNA in the dentate gyrus in female fetuses. There was no effect of dex on GR or MR mRNA in the male fetuses. In conclusion, the effect of synthetic glucocorticoid on the developing brain GR and MR systems is sex-specific and is confined to very specific regions of the hippocampus. Since the hippocampus plays a central role in mediating glucocorticoid negative feedback of HPA function, alterations in the fetal development of corticosteroid receptors may form the basis of permanently modified HPA activity following fetal exposure to endogenous or synthetic glucocorticoid.

Perinatal myocardial DNA and protein changes in the lamb: effect of cortisol in the fetus.

Myocardial growth during fetal life is accomplished by proliferation of the number of myocytes (hyperplasia). Shortly after birth, normal growth of the heart is predominantly due to increase in cell size (hypertrophy), and myocytes largely lose the capability to replicate. This change is characterized by a decrease in myocardial DNA concentration and an increase in protein/DNA concentration ratio. Among many of the events associated with birth is an increase in plasma cortisol concentrations in the few days before delivery of the fetus. To determine the possible role of cortisol in the postnatal change in myocardial growth, we measured DNA and protein concentrations in the free walls of the left (LV) and right (RV) ventricles in normal fetal lambs, normal newborn lambs, and in fetal lambs in which cortisone was infused for 72-80 h into the left coronary artery, which we showed does not perfuse the RV free wall. Normally, fetal RV DNA is higher than LV DNA concentration, and DNA/protein ratio is lower in RV than in LV. It is suggested that this could be related to the greater load on the RV. Postnatally, protein concentrations increase progressively, but DNA remains the same in both ventricles, and protein/DNA ratios increase. Cortisol, infused to achieve normal prenatal levels in LV myocardium, markedly decreases LV DNA without affecting RV DNA concentrations. The present study indicates that cortisol inhibits myocyte replication and that cortisol simulates the change in myocardial growth pattern normally occurring after birth. It raises concerns regarding prenatal administration of glucocorticoids to mothers to mature the fetal lungs before preterm delivery.

Behavioural, Endocrine and Cardiac Responses in Young Calves Undergoing Dehorning Without and With Use of Sedation and Analgesia

Behaviour, plasma cortisol and heart rate were measured in 4–6-week-old calves during and after dehorning with and without the use of sedation and analgesia. Six groups of eight Friesian male and female calves were studied; four groups were dehorned using an electrical cauterizing dehorner, heated to approximately 600°C. In group 1, a cornual nerve block was performed and the animals were sham-dehorned using a cold dehorner. Group 2 was treated similarly but dehorned with the heated dehorner. Group 3 received a mixture of xylazine and butorphanol intramuscularly, and were hot dehorned 20 min after the injection. Group 4 received the same sedatives–analgesics as group 3, and after 5 min also had a cornual nerve block, followed by hot dehorning 15 min later. Group 5 was hot dehorned without any form of sedation or analgesia. A sixth group of calves without any treatment or handling was used as controls for the behavioural observations.Head and leg movements during dehorning were significantly reduced when the cornual nerve was blocked. During the 4 h after dehorning, the behaviour of calves having a cornual block continued to differ from those in group 5. The cornual block prevented short-term increases in plasma cortisol concentrations and the long-term increases in heart rate seen in group 5. It was concluded that routine field use of local analgesia using a cornual nerve block improved the welfare of young calves subjected to dehorning with a hot iron.

Plasma cortisol concentrations in normal dogs given hydrocortisone sodium succinate.

To evaluate the effects on plasma cortisol concentration of a continuous infusion of a readily available steroid with equipotent glucocorticoid and mineralocorticoid effects. Plasma cortisol concentrations were measured before and regularly after hydrocortisone sodium succinate was administered as a continuous intravenous infusion over 6 h at 0.32 and 0.65 mg kg-1 h-1 to 12 healthy dogs weighing 12 to 22 kg. The infusion at both does rates produced significant and stable increases in plasma cortisol concentrations. The plateau concentrations produced by the large and small doeses were respectively above and below plasma cortisol concentrations likely to provide adequate glucocorticoid and mineralocorticoid activity in stressed dogs with significantly decreased adrenal function. This paper presents information regarding the changes in plasma cortisol concentrations in 12 normal dogs given an hydrocortisone sodium succinate infusion at two dose rates. The marked and continuous increase in plasma cortisol concentrations suggests a continuous HSS infusion may be a possible alternative to desoxycorticosterone acetate and dexamethasone in the treatment of acute adrenal dysfunction.

Adenosine modulates corticotropin and cortisol release during hypoxia in fetal sheep

Objective: This study was designed to determine the role of adenosine in the hypoxic release of corticotropin in fetal sheep. Study Design: The adenosine receptor antagonist 8-phenyltheophylline or the vehicle was infused intra-arterially to chronically catheterized fetal sheep (>0.8 term) during an hour of fetal hypoxemia (Pa O 2 ≅ 14 mm Hg). Control studies were also performed in which 8-phenyltheophylline or the vehicle was administered to normoxic fetuses. Results: 8-Phenyltheophylline abolished hypoxia-induced bradycardia and hypertension and produced a nearly 5-fold greater rise in fetal plasma concentrations of corticotropin and approximately a 3-fold greater increase in plasma cortisol levels. During normoxia 8-phenyltheophylline increased plasma cortisol concentrations by 2-fold without altering corticotropin levels, mean arterial blood pressure, or heart rate. Conclusion: Adenosine blunts fetal corticotropin release during hypoxia, which in turn reduces cortisol secretion. At lower corticotropin concentrations, adenosine also appears to dampen the cortisol response through direct effects on the adrenals. (Am J Obstet Gynecol 1999;180:1272-7.)

Induction of parturition in bitches with minimal side effects by two injections of a low dose of fenprostalene, a prostaglandin F2alpha analogue, and pretreatment with prifinium bromide.

An experiment using 16 Beagle bitches (aged 11 months to 6 years and 2 months) in their 56th to 58th day of pregnancy was carried out to investigate the effects of two injections of a low dose of fenprostalene, a long-acting prostaglandin F2alpha analogue, and pretreatment with prifinium bromide, a parasympathetic nerve blocking agent, on the induction of parturition and severity of side effects. The bitches were divided into three treatment groups: one injection of 5 microg/kg of fenprostalene (group I, n=5); one injection of 7.5 mg/head of prifinium bromide followed by one injection of 5 microg/kg of fenprostalene at 5 min after prifinium bromide injection (group II, n=6); and one injection of 7.5 mg/head of prifinium bromide followed by two injections of 2.5 microg/kg of fenprostalene, one injection at 5 min after prifinium bromide injection and the next at 1 hr after the fenprostalene first injection (group III, n=5). Following the injection of fenprostalene, side effects such as salivation, vomiting, colic symptoms, and watery diarrhea occurred most frequently (80-100% of cases) in group I bitches. Apart from colic symptoms, no side effects were observed in group III bitches. Group III bitches also showed the smallest increase in plasma cortisol concentration. No significant difference in the time to initiation of parturition was found between the three groups. The one-week survival rate of newborn puppies was highest in group III. The results showed that pretreatment with prifinium bromide and two injections of 2.5 microg/kg of fenprostalene can alleviate side effects following fenprostalene administration and have no adverse effect on the survival of newborn puppies, indicating that this method is a reliable and safe way of inducing parturition in bitches.

Effects of repeated jugular puncture on plasma cortisol concentrations in loose-housed dairy cows.

In three experiments, the effects of venipuncture on plasma cortisol concentrations were studied in loose-housed dairy cows. In Exp. 1, two blood samples were collected 18 min apart on three alternate days from 20 dairy cows for studying their adrenocortical response to a single venipuncture. To further evaluate the effect of cows anticipating venipuncture, in Exp. 2, 15 dairy cows were sequentially venipunctured once daily on 12 successive days in a randomized order in groups of five, starting 15 min apart. In Exp. 3, 10 primiparous cows were used on three alternate days to study habituation to serial sampling (i.e., collection of five blood samples by venipuncture, 15 min apart). In cows accustomed to handling, jugular puncture did not affect cortisol concentrations in plasma collected 18 min later. Average daily cortisol concentrations varied between 2.07 +/- .38 and 3.81 +/- .56 ng/mL in the first (t = 0) and between 1.43 +/- .15 and 2.61 +/- .72 ng/mL in the second (t = 18) blood samples. Likewise, when cows were sampled sequentially once a day, the order of sampling between and within groups did not influence (P > .05) plasma cortisol concentrations. In contrast, primiparous dairy cows that were less used to being handled showed an average increase in cortisol concentrations when five samples were collected by venipuncture 15 min apart. During successive sampling sessions, however, the cows did not decrease or increase plasma cortisol concentrations in response to repeated serial sampling at the group level (P > .05). Between individuals, the maximum effect of repeated venipuncture on cortisol concentrations (4.5 to 22.6 ng/mL), the time at which the effect reached its maximum (30 to 60 min), and the consistency of the response pattern over successive series varied largely. The results of this study show that in cows that were accustomed to handling and to being restrained, baseline cortisol concentrations can be measured in single blood samples that are collected by jugular puncture within 1 min after first approaching the cow. When successive blood samples need to be collected within 15 to 20 min, jugular puncture may induce an increase in cortisol concentration, which seems to depend on the handling experience of the animals and on individual differences.

Native Urotensins Influence Cortisol Secretion and Plasma Cortisol Concentration in the Euryhaline Flounder,Platichthys flesus

Adrenocorticotrophic hormone (ACTH) and flounder urotensins I and II (UI and UII) stimulate cortisol secretion of isolated interrenal/head kidney preparations of seawater (SW)-adapted flounder. UI and UII at concentrations of 10−6and 10−7M, respectively, increased cortisol secretion when acting on SW-derived interrenal but did not affect cortisol secretion in tissue derived from freshwater (FW) fish. Combined UI and UII had no synergistic or additive steroidogenic action, but either 10−7M UI or 10−7M UII in combination with ACTH produced a very marked, additive, or synergistic steroidogenic response, most apparent on interrenal derived from FW fish. These results suggest that urotensins enhance the steroidogenic action of ACTH in flounder. In all cases, significant steroidogenesis was apparent within 1 h postperifusion of ligands. In SW-adapted flounder intraarterial infusion of UIIin vivocaused a concentration-dependent increase in plasma cortisol concentration within 1 h after infusion, while after 5 × 10−6M UI infusion a similar trend was evident but this did not achieve statistical significance. The data suggest that the caudal neurosecretory system may control interrenal cortisol secretion, to modulate cortisol secretion independently of the hypophysial axis, perhaps in response to specific stress-induced or osmoregulatory challenge.

Seasonal differences in plasma cortisol and gill corticosteroid receptors in upper and lower mode juvenile Atlantic salmon

Circulating plasma cortisol and gill corticosteroid receptors (CR) have been observed to change seasonally in conjunction with smolting in Atlantic salmon. To differentiate whether these changes are seasonal or ontogenic, juvenile Atlantic salmon parr were separated by size into upper (UM) and lower mode (LM) in September. At monthly intervals, the fish were sampled for plasma cortisol, gill Na +K +ATPase activity and CR abundance ( B max) and dissociation constant ( k D). UM were significantly larger than LM, and showed the silver appearance characteristic of smolts in April and May. Gill Na +K +ATPase activity of UM fish increased 6-fold during the spring; LM fish increased 1.5-fold. Plasma cortisol levels increased significantly (10-fold) in UM fish in May, but not in LM fish. Gill CR B max increased 5-fold over the duration of the study in both groups. CR k D was lowest in October and highest in May; a 1.8- and 2-fold increase in LM and UM, respectively. There were no significant differences in gill CR B max and k D between the two groups during the study, except in May, when k D was significantly greater and B max lower in UM than LM. Peak levels of gill Na +K +ATPase activity occur coincident with an increase in plasma cortisol concentration. Seasonal increases in CR B max and k D are similar in UM and LM fish and occur independent of smolting in juvenile Atlantic salmon. In UM fish, plasma cortisol increases in spring are concurrent with increased smolt characteristics.

Heart Rate and Stress Hormone Responses of Sheep to Road Transport Following Two Different Loading Procedures

AbstractThis study was designed to investigate the physiological responses induced in sheep (n = 18) by two different loading techniques followed by a short road journey. All animals were prepared with venous catheters, to minimize the disturbing effects of blood sampling, and nine sheep were fitted with heart rate monitors. The animals were loaded onto a transport vehicle in groups of three, alternately using a conventional tailgate ramp or a crate raised with a hydraulic lift. When all of the sheep were loaded, they were taken on a journey lasting 195min. Blood samples were collected in the home pen, directly after loading, and at 15min intervals during the journey. Measurements were made of plasma concentrations of Cortisol, prolactin and catecholamines (adrenaline and noradrenaline). The results indicated that heart rate increased during loading, regardless of the method used. No changes in concentrations of Cortisol or the catecholamines were detected, although a small increase in prolactin was noted when animals were loaded using the ramp. During transport, all sheep exhibited increases in plasma Cortisol concentrations which were greatest during the first 2h of the journey. The results suggest that, under the conditions employed in this experiment, the effects of the two loading procedures were similar and that transport appeared to be more stressful than loading.

Adrenal function in patients with chronic renal failure

Previous studies have reported divergent findings on the function of the hypothalamic-pituitary-adrenal axis in patients with chronic renal failure (CRF). The low-dose adrenocorticotropin (ACTH) test offers the possibility of unmasking adrenal dysfunction, which might remain undiscovered using the ACTH test with the standard 250-microg dose. Furthermore, the choice of renal replacement therapy (either hemodialysis or continuous ambulatory peritoneal dialysis [CAPD]) might have an impact on adrenal function. To investigate these possibilities, ACTH tests were performed with three different doses (ie, 1, 5, and 250 microg) in 14 CRF patients and in seven healthy controls. Seven of the CRF patients were receiving chronic hemodialysis and seven were receiving CAPD. Basal plasma concentrations of cortisol were comparable in the three groups tested (5.3+/-0.4 microg/dL in the controls, 6.6+/- 0.7 microg/dL in the hemodialysis patients, and 7.9+/-1.0 microg/dL in the CAPD patients), whereas basal ACTH concentrations were significantly elevated in the CRF patients (28.5+/-3.8 pg/mL in the hemodialysis patients and 33.0+/-6.0 pg/mL in the CAPD patients) when compared with normal controls (17.0+/-1.4 pg/mL; P < 0.05). All three doses of ACTH resulted in a rapid increase of plasma cortisol concentrations that was comparable in all three groups. In the hemodialysis patients, a trend toward a diminished response to the lowest dose of 1 microg was noticed. We conclude, therefore, that adrenal response to ACTH in various doses is unaffected in CRF independent of whether hemodialysis or CAPD is chosen for renal replacement therapy. (Am J Kidney Dis 1998 Jul;32(1):52-5)

Effects of regional analgesia and/or a non-steroidal anti-inflammatory analgesic on the acute cortisol response to dehorning in calves

The effect of using a non-steroidal anti-inflammatory analgesic (ketoprofen) on the plasma cortisol response in calves dehorned with or without regional analgesia was determined. One hundred calves divided into 10 groups, four control and six dehorned, were used. Blood samples were taken before and after dehorning and plasma cortisol concentrations were measured. Dehorning caused a marked rise in plasma cortisol concentrations which returned to pretreatment levels after seven hours. The animals given ketoprofen before dehorning had a cortisol response similar to the dehorned animals for the first 1·3 hours after dehorning but then the plasma cortisol concentration returned to pretreatment levels. When animals were given a regional analgesic and ketoprofen the plasma cortisol concentrations were similar to control animals which had not been dehorned, with a small increase in plasma cortisol concentrations for the first hour after dehorning and then a rapid return to pretreatment values. This response was significantly lower than that seen in calves which received only regional analgesia. The results of this study suggest that a systemic analgesic should be combined with regional analgesia if the distress associated with dehorning is to be abolished.

Safety and tolerability of once-daily mometasone furoate aqueous nasal spray in children

Sensitive and reproducible assessments of hypothalamic-pituitary-adrenal (HPA) axis function were used to assess the systemic exposure and tolerability of mometasone furoate aqueous nasal spray (MFNS) in 96 children aged 3 to 12 years with allergic rhinitis. In the first phase of the study, older children (aged 6 to 12 years) received MFNS at 50, 100, or 200 μg or placebo once daily for 7 days, and plasma cortisol concentrations were measured by radioimmunoassay before and after treatment. Plasma cortisol concentrations were not statistically significantly different from baseline values on day 7 or day 8 (1 day after treatment was stopped). Also, the mean plasma cortisol and 24-hour urinary free-cortisol concentrations of the MFNS-treated and placebo groups were not statistically significantly different. Additionally, mometasone furoate was undetectable in almost all plasma samples collected at 0.5, 1, and 2 hours after dosing on days 1 and 7. Because these findings indicated that MFNS could be safely administered to patients aged 6 to 12 years, a more rigorous assessment was conducted in younger patients (aged 3 to 5 years). The younger patients also received MFNS at 50, 100, or 200 μg or placebo once daily, but for a longer duration (14 days). HPA axis function was determined by the response to cosyntropin stimulation on the final day of treatment. The younger patients demonstrated a normal cortisol response to cosyntropin stimulation on day 14; that is, all the patients had an increase in plasma cortisol concentration of at least 7 μg/dL to at least 18 μg/dL. Mean plasma cortisol concentrations for the MFNS-treated groups were not statistically significantly different from the mean concentration for the placebo group, either before or after cosyntropin stimulation. MFNS was also found to be well tolerated by both the younger and older children, with headache the most frequently reported adverse event in both the placebo- and MFNS-treated groups. No clinically relevant changes in the results of physical examinations, clinical laboratory determinations, or electrocardiography were noted. These results indicate that the intranasal administration of up to 200 μg of MFNS once daily for up to 14 days in children aged 3 to 12 years who have allergic rhinitis is well tolerated and does not result in clinically relevant systemic exposure.