Evidence for episodic but not circadian activity in plasma concentrations of adrenocorticotrophin, cortisol and thyroxine in dogs

1984 ◽  
Vol 103 (2) ◽  
pp. 219-226 ◽  
Author(s):  
R. J. Kemppainen ◽  
J. L. Sartin

ABSTRACT Concentrations of immunoreactive (i) ACTH, cortisol and thyroxine were determined in plasma samples obtained at 20-min intervals for 25 h in nine normal and two adrenalectomized dogs. The dogs were exposed to a 12 h light:12 h darkness photoperiod for 30 days before the sampling period. Episodic secretion of iACTH and cortisol was evident in each normal dog, with an average of 9·0 iACTH peaks and 10·1 cortisol peaks in a 24-h period. Levels of iACTH and cortisol were significantly correlated in each normal dog, but periods of dissociation between levels of the two hormones were apparent. A sex difference in 24-h mean iACTH and cortisol levels, numbers of cortisol peaks, and amplitude of iACTH peaks was observed, with females showing higher mean levels and greater peak frequency and amplitude in each instance. Adrenalectomy resulted in a 50- to 150-fold increase in mean iACTH concentrations with an apparent increase in iACTH peak amplitude. Cortisol levels were unchanging in the adrenalectomized dogs. Thyroxine concentrations showed episodic variation in each of the normal dogs, but the mean number of peaks (3·3/24-h period) was considerably less than for iACTH or cortisol. Female dogs had significantly higher 24-h mean levels of thyroxine than did males. No circadian rhythmicity was obvious for the plasma levels of any of the three hormones measured. J. Endocr. (1984) 103, 219–226

1987 ◽  
Vol 58 (03) ◽  
pp. 850-852 ◽  
Author(s):  
M B McCrohan ◽  
S W Huang ◽  
J W Sleasman ◽  
P A Klein ◽  
K J Kao

SummaryThe use of plasma thrombospondin (TSP) concentration was investigated as an indicator of intravascular platelet activation. Patients (n = 20) with diseases that have known vasculitis were included in the study. The range and the mean of plasma TSP concentrations of patients with vasculitis were 117 ng/ml to 6500 ng/ml and 791±1412 ng/ml (mean ± SD); the range and the mean of plasma TSP concentrations of control individuals (n = 33) were 13 ng/ml to 137 ng/ml and 59±29 ng/ml. When plasma TSP concentrations were correlated with plasma concentrations of another platelet activation marker, β-thromboglobulin (P-TG), it was found that the TSP concentration inei eased exponentially as the plasma β-TG level rose. A positive correlation between plasma levels of plasma TSP and serum fibrin degradation products was also observed. The results suggest that platelets are the primary source of plasma TSP in patients with various vasculitis and that plasma TSP can be a better indicator than β-TG to assess intravascular platelet activation due to its longer circulation half life.


1990 ◽  
Vol 124 (1) ◽  
pp. 167-176 ◽  
Author(s):  
J. H. M. Wrathall ◽  
B. J. McLeod ◽  
R. G. Glencross ◽  
A. J. Beard ◽  
P. G. Knight

ABSTRACT Two experiments were conducted to explore the effectiveness of synthetic peptide-based vaccines for active and passive autoimmunization of sheep against inhibin. In the first experiment, adult Romney ewes (n = 20) were actively immunized against a synthetically produced peptide that corresponded to the N-terminus of the α-subunit of bovine inhibin (bIα(1–29)-Tyr30). This peptide was conjugated to tuberculin purified protein derivative (PPD) to increase its antigenic properties. Control groups comprised non-immunized (n = 10) and PPD-immunized (n = 10) ewes. Primary immunization (400 μg conjugate/ewe) was followed by two booster immunizations (200 μg conjugate/ewe), given 5 and 8 weeks later. Following synchronization of oestrus using progestagen sponges, ovulation rates were assessed by laparoscopy. Weekly blood samples were taken throughout the experiment. All inhibin-immunized ewes produced antibodies which bound 125I-labelled bovine inhibin (Mr 32 000), and ovulation rate in inhibin-immunized ewes (2·15 ± 0·22; mean ± s.e.m.) was significantly (P<0·01) greater than in both non-immunized (0·90 ± 0·23) and PPD-immunized (1·20 ± 0·13) control groups. Immunization against the peptide, but not against PPD alone, resulted in a modest rise in plasma FSH, with mean levels after the second boost being significantly (P<0·025) higher (22%) than those before immunization. Moreover, when blood samples were taken (2-h intervals) from randomly selected groups of control (n = 7) and inhibin-immunized (n = 7) ewes for an 84-h period following withdrawal of progestagen sponges, the mean plasma concentration of FSH during the 48 h immediately before the preovulatory LH surge was 37% greater (P< 0·025) in immunized than in control animals. However, more frequent blood sampling (every 15 min for 12 h) during follicular and mid-luteal phases of the oestrous cycle revealed no significant differences between treatment groups in mean plasma concentrations of FSH. In addition, neither mean concentrations of LH nor the frequency and amplitude of LH episodes differed between immunized and control ewes. However, the mean response of LH to a 2 μg bolus of gonadotrophin-releasing hormone, given during the luteal phase, was significantly (P<0·05) less in immunized than in control ewes. These findings indicate that active immunization of Romney ewes against a synthetic fragment of inhibin can promote a controlled increase in ovulation rate, but this response cannot be unequivocally related to an increase in plasma levels of FSH. In the second experiment, passive immunization of seasonally anoestrous ewes (mule × Suffolk crossbred; n = 6 per group) against inhibin, using an antiserum raised in sheep against a synthetic peptide corresponding to the N-terminus of the α-subunit of human inhibin promoted a rapid (<3 h), dose-dependent rise in plasma levels of FSH which remained increased (2·5-fold; P<0·001) for up to 30 h. Plasma concentrations of LH, however, were unaffected by treatment with the antiserum. It is deduced from this observation that, even in the seasonally anoestrous ewe, the ovary secretes physiologically active levels of inhibin, which exert an inhibitory action on the synthesis and secretion of FSH. Journal of Endocrinology (1990) 124, 167–176


1985 ◽  
Vol 13 (1) ◽  
pp. 68-73 ◽  
Author(s):  
G M E Janssen ◽  
J F Venema

The plasma levels of Ibuprofen were measured in five healthy subjects who took 600 mg tablets of Ibuprofen twice daily, three times daily and four times daily in a crossover study. Peak plasma levels were obtained 1 hour after the first dose in all but one subject (slow absorber), the mean peak value being 51·3 μg.ml−1 (range 39·4–63·7 μg.ml−1). After the repeated dose regimens of two, three or four times daily of ibuprofen, the peak levels achieved were in a similar range to those seen after the first dose: Twice daily 39·4–66·4 μg.ml−1 Three times daily 43·6–63·3 μg.ml−1 Four times daily 44·1–58·4 μg.ml−1 There was no evidence of accumulation of the drug and no side-effects occurred during the trial.


1986 ◽  
Vol 250 (1) ◽  
pp. E76-E81
Author(s):  
D. A. Bereiter ◽  
A. M. Zaid ◽  
D. S. Gann

The effect of rate of blood loss by acute hemorrhage (H) on adrenocorticotropin (ACTH) and cortisol plasma concentrations was assessed in anesthetized cats. Arterial blood was withdrawn at a rapid rate (10% blood vol/min) or at a slow rate (2%/min), and responses were compared across three volumes of H (10, 20, and 30% of blood vol). After rapid rate of H, ACTH increased in proportion to volume of H (r = 0.669, P less than 0.001) with a mean elevation of 124 +/- 27, 267 +/- 102, and 950 +/- 195 pg/ml for 10, 20, and 30% H, respectively. Slow rate of H evoked a significant increase in ACTH that was not proportional to volume of H (r = 0.314, P greater than 0.10), and the mean change during the post-H sampling period was 611 +/- 166, 828 +/- 302, and 1,070 +/- 239 pg/ml for 10, 20, and 30% H, respectively. Control animals showed no change in ACTH to the repeated sampling paradigm. Rapid H evoked an immediate decrease in mean arterial pressure (MAP) with a post-H recovery of MAP inversely proportionate to volume of H (r = -0.552, P less than 0.01). Slow H caused a progressive decrease in MAP with no significant post-H recovery of MAP at any volume of H. Cortisol concentration increased in proportion to volume of H after rapid H (r = 0.515, P less than 0.025), but not after slow H.(ABSTRACT TRUNCATED AT 250 WORDS)


1976 ◽  
Vol 81 (3) ◽  
pp. 673-679 ◽  
Author(s):  
Hugo Scaglia ◽  
Martha Medina ◽  
Ada L. Pinto-Ferreira ◽  
Guadalupe Vazques ◽  
Carlos Gual ◽  
...  

ABSTRACT The plasma concentrations and episodic fluctuations of immunoreactive FSH and LH as well as the pituitary sensitivity to LH-RH stimulation were evaluated in post-menopausal women. The subjects were divided into 4 groups according to age. Group 1: 60–70 years old (n=11), group 2: 70–80 years old (n=22), group 3: 80–90 years old (n=31) and group 4: 90–100 years old (n=8). Standards used in gonadotrophin radioimmunoassays included the LER-907 preparation and a pooled post-menopausal serum. Since it was found that circulating gonadotrophins have an immunological pattern different from that shown by the pituitary preparation, the results were expressed in mIU/ml calculated accordingly to the immunological behaviour of pooled post-menopausal sera. The mean (± se) plasma levels of FSH (mIU/ml) were: group 1: 105.9 ± 9.5, group 2: 149.3 ± 10.5, group 3: 124.8 ± 7.1 and group 4: 149.4 ± 25.3. The mean (± se) plasma levels of LH (mIU/ml) were: group 1: 81.9 ± 12.5, group 2: 95.4 ± 9.9, group 3: 84.3 ± 7.7 and group 4: 113.5 ± 19.1. No statistically significant differences were observed among the 4 groups. One patient from each group was randomly selected in order to evaluate their LH and FSH episodic release as well as their pituitary responsiveness to exogenous stimulation. A pulsatile plasma pattern of gonadotrophin and a normal pituitary response to LH-RH injection were observed in the 4 patients studied. The results are interpreted as demonstrating that normal pituitary gonadotrophin function and pituitary reserve and responsiveness to exogenous stimulation are maintained in women of advanced age.


1993 ◽  
Vol 128 (6) ◽  
pp. 521-528 ◽  
Author(s):  
Ali Iranmanesh ◽  
German Lizarralde ◽  
Johannes D Veldhuis

In the present study, we investigated the coordinate kinetic response of the corticotropic axis to the acute metabolic stress of hypoglycemia by applying deconvolution analysis to adrenocorticotropin (ACTH), β-endorphin and cortisol concentration-time series generated in seven normal men after intravenous administration of insulin. Hypoglycemic stress resulted in a 22-fold increase in the mean plasma concentration of ACTH to a maximum of 77±15 pmol/l, in conjunction with a 7.5-fold increase in the mean plasma β-endorphin concentration, the maximal value of which was 96±11 pmol/l. Plasma cortisol concentrations increased by 2.6-fold with a mean value of 734±14 nmol/l. Maximal plasma ACTH and β-endorphin concentrations were preceded by discrete secretory bursts with peak amplitudes of 10.5±2.7 and 10.6±2.0 pmol·I−1·min−1 (20-fold and ninefold increases compared to control), respectively. The mass of ACTH released was 114±20 pmol/l (3.4-fold increase), which corresponds to a total amount of 1.25 μg (50% of daily production and 0.5% of reported pituitary stores), assuming a distribution volume of 40 ml/kg. A total amount of 4.4±0.7 mg of cortisol was released after insulin-induced hypoglycemia, based on a mean cortisol secretory mass of 1088±137 nmol/l and a presumed 11.3-1 volume of distribution. Deconvolution-based estimates of the endogenous half-lives of ACTH, β-endorphin and cortisol were 17±0.6, 22±1.7 and 65±5.3 min, respectively. In summary, deconvolution analysis revealed a rapid coordinate activation of ACTH, β-endorphin and cortisol secretion after hypoglycemic stress, which correlated closely but temporally preceded increases in the respective plasma concentrations. Our inference that only a small fraction of pituitary ACTH content is released during hypoglycemic stress emphasizes the large reserve capability of the pituitary corticotropes. The percentage response of adrenal gland to the metabolic stress of hypoglycemia was of lesser magnitude, possibly owing to the rate-limiting properties of cortisol biosynthesis. We conclude that kinetic responses of the hypothalamic—pituitary—adrenal axis to hypoglycemic stress exhibit exquisite temporal synchrony and manifest a marked reserve capacity.


1998 ◽  
Vol 89 (4) ◽  
pp. 969-979 ◽  
Author(s):  
Christiane Drager ◽  
David Benziger ◽  
Feng Gao ◽  
Charles B. Berde

Background Previous work from the authors' group characterized a prolonged percutaneous blockade of the sciatic nerve in rats using bupivacaine-dexamethasone microspheres. The goals of the current study are to examine the (1) efficacy of bupivacaine microspheres with and without dexamethasone for intercostal blockade in sheep; (2) scaling of dose and duration with a 100-fold increase in body size from rats to sheep; (3) local toxicity and adverse systemic reactions to bupivacaine microspheres with and without dexamethasone. Methods Intercostal blocks were performed percutaneously in sedated sheep. Sensory blockade was measured at repeated time points by absent flinch response to skin pinch. Plasma bupivacaine concentrations were measured using high performance liquid chromatography. Chest wall specimens were examined by light microscopy. Results The duration of intercostal blockade increased with bupivacaine dose for animals receiving from 8 to 80 mg/kg of microspheres with and without dexamethasone. At each dose, microspheres containing dexamethasone had a longer duration of block than microspheres without dexamethasone. From 8 to 80 mg/kg, the mean duration of block with bupivacaine-dexamethasone microspheres increased from 4 to 13 days. Plasma concentrations of bupivacaine remained 10-fold below the convulsive EC50 concentration for sheep. Chest wall histology showed a significant granulomatous reaction around bupivacaine microspheres but not around bupivacaine-dexamethasone microspheres. Conclusions A single administration of bupivacaine-dexamethasone microspheres produces an effective chest wall analgesia of several days' duration. This may prove useful clinically for thoracic surgery or trauma.


1980 ◽  
Vol 86 (3) ◽  
pp. 425-430 ◽  
Author(s):  
R. E. FALVO ◽  
L. R. DEPALATIS ◽  
J. MOORE ◽  
T. A. KEPIC ◽  
J. MILLER

Blood samples, drawn every 15 days (September 1975–September 1976) from four laboratory-housed male mongrel dogs, were assayed by radioimmunoassay for levels of testosterone and LH in the plasma. The mean plasma concentrations of testosterone remained relatively constant for most of the year with the exception of a significant rise in late August and early September. Mean plasma levels of LH showed a cyclic pattern throughout the year which could be represented by a cosine function curve. However, this cyclic pattern of LH was not accompanied by cyclic changes in plasma levels of testosterone and there was no relationship between these two hormones during the period of 1 year. As the cyclic pattern of LH was altered, the plasma level of testosterone began to rise and reached its highest concentration. Since this alteration of the LH cycle occurred before the increased concentrations of testosterone, and since there was no relationship between these two hormones for the period of a year, we have concluded that there may be another hormone(s) involved which either alters the sensitivity of the canine testis to LH or alters the LH synthesis/release mechanism of the pituitary gland.


2016 ◽  
Vol 7 (2) ◽  
pp. 79-83 ◽  
Author(s):  
Siobhan H. Gee ◽  
David M. Taylor ◽  
Sukhwinder S. Shergill ◽  
Robert Flanagan ◽  
James H. MacCabe

Background: Tobacco smoke is known to affect plasma levels of some drugs, including the antipsychotic clozapine. The effects of suddenly stopping smoking on patients who take clozapine can be severe, as plasma concentrations are expected to rapidly rise, potentially leading to toxicity. A ban on smoking at South London and the Maudsley NHS Foundation Trust (SLaM) was implemented in 2014, and this was expected to affect the plasma concentrations of clozapine for inpatients at the time. This study aimed to determine whether plasma concentrations of clozapine were affected, and additionally, in line with observations from other authors, whether levels of reported violence would also be affected. Methods: The smoking habits of all patients at SLaM who smoked and were prescribed clozapine were recorded both before and after the ban. The Glasgow Antipsychotic Side Effect Scale for Clozapine (GASS-C) scale was used to evaluate side-effect burden. Clozapine doses and plasma concentrations were also collected. Results: In total, 31 patients were included in this study. The mean clozapine dose before the ban was 502 mg/day, and this did not change significantly after the ban. Similarly, there were no significant changes in clozapine or norclozapine plasma concentrations, or in GASS-C scores. There was no change in the amount of tobacco patients reported smoking before or after the ban. A modest but statistically significant reduction in violent incidences was observed. Conclusions: Our data suggest that a ban on smoking for patients taking clozapine on open wards at inpatient hospital sites had little impact on clozapine plasma concentrations, because patients continued to smoke tobacco if allowed to leave. Smoking bans may result in a reduction in violent incidences.


1980 ◽  
Vol 58 (11) ◽  
pp. 2081-2083 ◽  
Author(s):  
K.-A. Stokkan ◽  
K. Hove ◽  
W. R. Carr

Concentrations of plasma testosterone and luteinizing hormone (LH) were measured in peripheral plasma from semidomestic, rutting reindeer bulls. Although the concentrations of plasma testosterone were high and showed large variations, those of LH were low and only a few episodic bursts could be detected in hourly samples taken throughout a 48-h period. The mean testosterone concentration in three bulls differed significantly and ranked the animals according to their position in a fighting hierarchy. The mean concentrations of LH did not differ significantly. Plasma samples from one reindeer bull sampled every 20 min for periods of 3 h indicated that an increment in LH concentration preceded a peak in testosterone. No diurnal pattern in testosterone concentrations could be detected, but testosterone peaks seemed to appear about every 3–4 h. The present study thus demonstrates that a series of plasma samples throughout the day is necessary to determine a true "testosterone level" in the reindeer bull.


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