Ovine corticotrophin-releasing factor in dogs: dose-response relationships and effects of dexamethasone

1986 ◽  
Vol 112 (1) ◽  
pp. 12-19 ◽  
Author(s):  
R.J. Kemppainen ◽  
D. V. Filer ◽  
J. L. Sartin ◽  
R. B. Reed
Keyword(s):  
Dose Response ◽  
Plasma Cortisol ◽  
Peak Plasma ◽  
Cortisol Response ◽  
Corticotrophin Releasing Factor ◽  
Pre Treatment ◽  
The Relationship ◽  
Dose Dependent ◽  
Response Area ◽  
Stimulation Of

Abstract. Dose-response relationships between iv bolus injections (0, 0.1, 1 or 10 μg/kg) of synthetic ovine corticotropin-releasing factor (oCRF) and plasma immunoreactive (i) ACTH and cortisol concentrations were examined in healthy, conscious dogs. All doses of oCRF resulted in elevated plasma iACTH and cortisol levels over those of the controls. Maximum (or Peak) plasma iACTH concentrations were generally observed 20–30 min after oCRF and the magnitude of these peaks was a linear function (P<0.001) of the logarithm of the oCRF dose. The time of peak cortisol concentrations was more variable but the peak cortisol level was also linearly related (P< 0.001) to the logarithm of the oCRF dose. An estimate for the response areas for both hormones demonstrated a quadratic (P < 0.05) relationship with the logarithm of the oCRF dose. The relationship between oCRF and the iACTH response suggested a progressively greater response at increasing oCRF doses while a maximally effective oCRF dose was predicted in the cortisol response area relationship. Graded (0, 0.01, 0.1 or 1 mg/kg) bolus doses of dexamethasone produced a dose-dependent (P < 0.03) decline in baseline plasma iACTH levels and a non-dosedependent suppression in baseline plasma cortisol. Pre-treatment with 0.001 mg dexamethasone/kg 4 or 8 h before injection of 1 μg oCRF/kg did not alter the plasma iACTH or cortisol response; however, 0.1 mg dexarhethasone/kg administered at these times totally abolished the responses to oCRF. An intermediate dose (0.01 mg/kg) of dexamethasone inhibited the plasma iACTH response by an average of 79% (P<0.01) when administered 4 h before oCRF, but did not significantly alter this response when given 8 h prior to oCRF. The plasma cortisol response to oCRF was inhibited (P < 0.01) when 0.01 mg dexamethasone/kg was given as a 4 h, but not as a 8 h, pre-treatment. Iv administration of oCRF produces a profound, dose-dependent stimulation of the pituitary-adrenocortical axis of dogs and should prove useful in studies of this system.

The Regulatory Role Of Camp In Induction Of Human Platelet Receptor For Fibrinogen

1981 ◽  
Author(s):  
S E Graber ◽  
J Hawiger
Keyword(s):  
Human Platelets ◽  
Membrane Receptor ◽  
Fibrinogen Receptor ◽  
Fibrinogen Binding ◽  
Platelet Receptor ◽  
The Relationship ◽  
Camp Levels ◽  
Dose Dependent ◽  
Stimulation Of

Membrane receptor for fibrinogen plays an essential role in adhesion and aggregation of human platelets by allowing fibrinogen to bridge two or more platelets together. Whereas in normal, unstimulated platelets fibrinogen receptor is not available, it becomes mobilized upon stimulation of platelets with thrombin, ADP, and other stimuli. The mechanism(s) regulating availability of membrane receptor for fibrinogen remains unknown. Following our recent demonstration that prostacyclin (PGI2) prevents mobilization of fibrinogen receptor by thrombin and ADP (Nature 1980, 283,195), we investigated the relationship between cAMP levels and fibrinogen receptor availability. Platelets separated from plasma proteins were briefly exposed to a low thrombin concentration (0.05 U/ml) followed by hirudin to inactivate free thrombin. Binding of 125I-fi- brinogen and cAMP levels were determined in parallel samples. A dose-dependent rise in platelet cAMP levels from 3.3 pM to 10.3 pM/108 platelets in response to PGI2 (3×10-9M - 3×108M) was accompanied by a corresponding inhibition of 125I-fibrinogen binding. The degree of the cAMP increment correlated with binding inhibition (r=0.96). The inhibition of 125I-fibrinogen binding by PGI2 was sustained up to 120 min and was paralleled by a persistent rise in cAMP level. Stimulation of platelet cAMP synthesis “from within” by a ribosylation of the nucleotide regulatory component with subunit A1 of cholera toxin also increased cAMP levels and inhibited fibrinogen receptor mobilization.These results provide evidence that “up and down” regulation of fibrinogen receptor in platelets is linked to changes in cAMP levels induced by different types of adenyl cyclase antagonists and agonists.

scholarly journals Graded responses of human neutrophils induced by serum-treated zymosan

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1182-1188 ◽  
Author(s):  
JC Whitin ◽  
DH Ryan ◽  
HJ Cohen
Keyword(s):  
Flow Cytometry ◽  
Membrane Potential ◽  
Fluorescent Probe ◽  
Dose Response ◽  
Dose Dependence ◽  
Human Neutrophils ◽  
Graded Responses ◽  
Dose Dependent ◽  
O2 Production ◽  
Stimulation Of

Abstract A modified zymosan preparation was used to probe the interaction of particulate stimuli with human neutrophils (PMNs). After extraction with alkali and detergent, the zymosan particles retained their ability to be opsonized in serum and to stimulate PMNs. Serum-treated zymosan (STZ) induced dose-dependent superoxide (O2-) production and membrane potential depolarization in the range of 1 to 10 mg/mL of STZ. The rate and extent of secretion of lysozyme and beta-glucuronidase were also dose-dependent in the range of 1 to 10 mg/mL of STZ. Cytochemical studies using nitroblue tetrazolium, however, showed that 92% of PMNs were stimulated to produce O2- at 0.1 mg/mL of STZ. The dose response of O2- production induced by STZ is therefore due to increasing O2- production by individual PMNs and not to the stimulation of more PMNs to produce O2-. Evidence for O2- production was found only in the area of PMN-zymosan contact, suggesting a mechanism for the graded responses of PMNs treated with particulate stimuli. In order to determine the nature of the dose dependence of depolarization (a measure of PMN activation), PMNs equilibrated with the fluorescent probe 3,3′- dipentyloxacarbocyanine were analyzed by flow cytometry. The results demonstrate that STZ induces a dose-dependent depolarization of the membrane potential of individual PMNs. These results also demonstrate that increasing concentrations of STZ can induce increasing PMN responses even when all of the PMNs have been activated. These results are consistent with the hypothesis that receptor-mediated particulate stimulation of PMNs is a phenomenon that results in graded PMN responses.

scholarly journals Dose–response and transmission: the nexus between reservoir hosts, environment and recipient hosts

2019 ◽  
Vol 374 (1782) ◽  
pp. 20190016 ◽  
Author(s):  
Tamika J. Lunn ◽  
Olivier Restif ◽  
Alison J. Peel ◽  
Vincent J. Munster ◽  
Emmie de Wit ◽  
...  
Keyword(s):  
Dose Response ◽  
Nipah Virus ◽  
Underlying Disease ◽  
Host Susceptibility ◽  
Response Models ◽  
Zoonotic Pathogens ◽  
Exposure Experiment ◽  
Reservoir Hosts ◽  
The Relationship ◽  
Dose Dependent

Dose is the nexus between exposure and all upstream processes that determine pathogen pressure, and is thereby an important element underlying disease dynamics. Understanding the relationship between dose and disease is particularly important in the context of spillover, where nonlinearities in the dose–response could determine the likelihood of transmission. There is a need to explore dose–response models for directly transmitted and zoonotic pathogens, and how these interactions integrate within-host factors to consider, for example, heterogeneity in host susceptibility and dose-dependent antagonism. Here, we review the dose–response literature and discuss the unique role dose–response models have to play in understanding and predicting spillover events. We present a re-analysis of dose–response experiments for two important zoonotic pathogens (Middle East respiratory syndrome coronavirus and Nipah virus), to exemplify potential difficulties in differentiating between appropriate models with small exposure experiment datasets. We also discuss the data requirements needed for robust selection between dose–response models. We then suggest how these processes could be modelled to gain more realistic predictions of zoonotic transmission outcomes and highlight the exciting opportunities that could arise with increased collaboration between the virology and epidemiology disciplines. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.

Effect of acetylcholine and 5-hydroxytryptamine on the secretion of corticotrophin-releasing factor-41 and arginine vasopressin from the rat hypothalamus in vitro

1989 ◽  
Vol 122 (3) ◽  
pp. 713-718 ◽  
Author(s):  
E. W. Hillhouse ◽  
N. G. N. Milton
Keyword(s):  
Arginine Vasopressin ◽  
Bioactive Substances ◽  
Rat Hypothalamus ◽  
Corticotrophin Releasing Factor ◽  
Dose Dependent ◽  
Isolated Rat ◽  
Stimulation Of

ABSTRACT Previous studies using the isolated rat hypothalamus in vitro have shown that both acetylcholine and 5-hydroxytryptamine (5-HT) stimulate the secretion of bioactive corticotrophin-releasing factor (CRF). However, the CRF complex consists of a number of bioactive substances, and in this study we examined the effect of acetylcholine and 5-HT on the release of immunoreactive (ir)-CRF-41 and ir-arginine vasopressin (AVP) in vitro. Acetylcholine caused a dose-dependent (10 pmol–10 nmol/l) release of both neuropeptides, and the effect was partially antagonized by both atropine and hexamethonium. Nicotine (0·1–10 μmol/l) also stimulated the release of both peptides, whereas bethanacol had no effect on AVP release, but had a variable action on CRF-41 release. 5-HT caused a dose-dependent (10 pmol–1 nmol/l) stimulation of CRF-41 release without any effect on AVP release, and this effect was antagonized by cyproheptadine, suggesting the participation of specific 5-HT receptors. Journal of Endocrinology (1989) 122, 713–718

Changes in pituitary responses to synthetic ovine corticotrophin releasing factor in fetal sheep

1985 ◽  
Vol 63 (11) ◽  
pp. 1398-1403 ◽  
Author(s):  
Laurie J. Norman ◽  
Stephen J. Lye ◽  
Mary E. Wlodek ◽  
J. R. G. Challis
Keyword(s):  
Plasma Cortisol ◽  
Late Pregnancy ◽  
Sampling Interval ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Corticotrophin Releasing Factor ◽  
Spontaneous Labour ◽  
Negative Feedback Control ◽  
Relationship Of ◽  
The Relationship

The rise in cortisol in fetal sheep during late pregnancy has been related to increased responsiveness of the adrenal to ACTH. Most reports have suggested that plasma ACTH concentrations rise coincident with or after the prepartum increase in cortisol. To reexamine the relationship of cortisol with basal immunoreactive ACTH (IR-ACTH) throughout the last 40 days of pregnancy and to determine changes in fetal pituitary responsiveness during this time, we measured basal and synthetic ovine corticotrophin-releasing factor (oCRF) (10 ng – 10 μg) induced rises in ACTH and cortisol in fetal sheep at days 110–115, 125–130, and 135–140 of pregnancy. The fetuses were catheterized on day 105–120 and entered spontaneous labour at > 140 days. Basal IR-ACTH (picograms per millilitre ± SEM) rose from 16.7 ± 2.9 pg/mL at day 110–115 to 34.8 ± 8.7 pg/mL at day 141–145. There was a significant effect of time on basal ACTH concentrations with a mean increase of approximately 5 pg ACTH per millilitre of plasma per 5-day sampling interval. Plasma cortisol changed gradually between day 110 and 125 of gestation and then more rapidly to term. At day 110–115 of gestation there was no significant change in plasma ACTH after 10 or 100 ng oCRF, but there was a significant increase in ACTH after 1 μg of oCRF. Plasma cortisol did not change after any CRF injection. The change in IR-ACTH after oCRF at day 125–130 of gestation was significantly greater than that at day 110–115. Plasma cortisol concentrations were elevated following 1- and 10-μg injections of oCRF. At day 135–140, significant rises in plasma ACTH were seen in response to 1 and 10 μg oCRF, but the response was less than that at day 125–130. In contrast, the response of plasma cortisol was significantly greater than at any of the other times in gestation. We conclude the following: (i) basal ACTH concentrations rise before the major prepartum increase in plasma cortisol; (ii) pituitary responsiveness to oCRF, measured as ACTH in plasma, increases between days 110–115 and 125–130 of gestation. The ACTH response decreased at day 135–140, perhaps reflecting negative feedback control by the rising basalcortisol concentrations; (iii) adrenal responsiveness increases progressively between days 110–115 and 135–140 of gestation, as reflected by changes in the plasmacortisol concentration in response to endogenously released ACTH.

scholarly journals Salivary and plasma cortisol response to adrenocorticotropin administration in pigs

2000 ◽  
Vol 34 (2) ◽  
pp. 171-181 ◽  
Author(s):  
D. M. Bushong ◽  
T. H. Friend ◽  
D. A. Knabe
Keyword(s):  
Plasma Cortisol ◽  
Strong Relationship ◽  
Sampling Interval ◽  
Cortisol Response ◽  
Acth Stimulation ◽  
Blood Samples ◽  
Total Cortisol ◽  
The Relationship

Two experiments were conducted to determine the responsiveness of salivary and plasma cortisol to acute (i.v.), depot (i.m.) and chronic (repeated i.m.) adrenocorticotropin (ACTH) administration in swine. In Experiment 1, barrows (castrated pigs) were assigned to one of three injection treatments: (1) saline i.m. (SHAM1 n = 2); (2) 0.75 IU/kg BW ACTH in saline i.v. (ACUTE, n = 2); (3) 2.25 IU/kg BW ACTH in gel i.m. (DEPOT, n = 3). Total cortisol concentrations were determined for concurrent saliva and blood samples. Correlations between salivary and plasma cortisol within treatments were: SHAM1, r = 0.60; ACUTE, r = 0.58; DEPOT, r = 0.79. In Experiment 2, barrows were assigned to one of two injection treatments: (1) gel i.m. (SHAM2, n = 3); (2) 2.25 IU/kg BW ACTH in gel i.m. (CHRONIC, n = 4). The injections occurred every 6 h for a total of eight injections. Concurrent saliva and blood samples were obtained every 3 h for 72 h followed by an increasing sampling interval until day 6. Overall correlations between salivary and plasma cortisol were: SHAM2, r = 0.30 and CHRONIC, r = 0.61. Experiment 1 found that the relationship between salivary and plasma cortisol was stronger during longer (DEPOT) than shorter (ACUTE) ACTH stimulation. Experiment 2 found a strong relationship between the two measurements during chronic ACTH stimulation, but that relationship weakened after ACTH stimulation ceased.

Effect of cyproterone acetate on glucocorticoid secretion in patients treated for hirsutism

1983 ◽  
Vol 104 (2) ◽  
pp. 222-226 ◽  
Author(s):  
I. M. Holdaway ◽  
M. S. Croxson ◽  
M. C. Evans ◽  
J. France ◽  
A. Sheehan ◽  
...  
Keyword(s):  
Cyproterone Acetate ◽  
Plasma Cortisol ◽  
Slight Reduction ◽  
Cortisol Response ◽  
Urinary Cortisol ◽  
Reverse Sequence ◽  
Urinary Cortisol Excretion ◽  
The Mean ◽  
Pre Treatment ◽  
Adrenal Glucocorticoid

Abstract. The effect of cyproterone acetate (CA) on adrenal glucocorticoid secretion was studied in 35 women with hirsutism. Patients were treated for 9 months with 100 mg CA orally 10 days each month, administered in reverse sequence with 21 days of a combination oral contraceptive containing 50 μg ethinyloestradiol and 2 mg CA. During treatment one patient had a mildly impaired plasma cortisol response to insulin-induced hypoglycaemia and 2 patients showed slight reduction of the plasma cortisol response to ACTH. Responses to metyrapone were normal in all patients tested. Overall, the mean response to these tests was significantly greater during CA treatment compared with pre-treatment measurements, probably due to effects of oestrogen on cortisol-binding globulin. In all patients urinary cortisol excretion remained normal and no patient demonstrated any features of steroid insufficiency. Thus it appears that CA has no untoward effect upon glucocorticoid secretion when given in high dosage for prolonged periods to hirsute women.

Changes in circadian rhythm and suppression of the plasma cortisol level after prolonged stress in the sheep

1985 ◽  
Vol 110 (4) ◽  
pp. 540-545 ◽  
Author(s):  
F. Przekop ◽  
E. Stupnicka ◽  
E. Wolińska-Witort ◽  
K. Mateusiak ◽  
B. Sadowski ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Cortisol Level ◽  
Plasma Cortisol ◽  
Plasma Cortisol Level ◽  
Diurnal Variations ◽  
Cortisol Response ◽  
Time Of Application ◽  
Prolonged Stress ◽  
Similar Decrease ◽  
Stimulation Of

Abstract. Diurnal variations in the plasma cortisol level were studied in anoestrous, pro-oestrous and pregnant ewes subjected to weak electric stimulation of the forelimbs 9 h daily for 3 consecutive days. In non-pregnant ewes the cortisol level rose on each of the 3 days when the stimulation was applied and then decreased on the day following the stimulation. A similar decrease in plasma cortisol concentrations in pregnant ewes appeared on the second day of footshocking. The acrophase of the circadian rhythm on electrostimulation days was synchronous with the time of application of footshocks; therefore, in stimulated ewes it was significantly accelerated compared to the prestimulatory day. A decrease in the plasma cortisol level in pro-oestrous and pregnant ewes was accompanied by disappearance of its normal rhythmicity. Since a normal plasma cortisol response to exogenous corticotrophin was noted after 3 days of foot-shocking it seems unlikely that the decrease in the cortisol level after prolonged stress was caused by exhaustion of the adrenal cortex. Some central mechanisms which could account for the biphasic changes in the plasma cortisol level and for disturbances of the hormone diurnal rhythmicity under conditions of prolonged stress are discussed.

PLASMA TESTOSTERONE IN BULLS

1978 ◽  
Vol 88 (4) ◽  
pp. 793-800 ◽  
Author(s):  
Anne Sundby ◽  
A. Farahat
Keyword(s):  
Dose Response ◽  
Plasma Testosterone ◽  
Similar Response ◽  
Prolonged Effect ◽  
Related Response ◽  
Pre Treatment ◽  
Dose Dependent

ABSTRACT Injections of 375–6000 IU HCG to 10 bulls, 7 months of age, gave no dose related response in plasma testosterone measured in samples collected during the following 9 h. However, an increase in the dose of HCG was followed by 1) an increase in maximal testosterone values (r = + 0.9), 2) an extension of the period between injection and maximal value, and 3) an increased duration of the response. Single iv or im injections of 6000 IU PMSG to 4 bulls led to initial elevations of plasma testosterone to about the spontaneous diurnal maxima, followed by a prolonged additional elevation to approximately 2 to 3 times this level. Values decreased to pre-treatment levels on days 16–18 following im injection and 20–22 days following iv injection. In dose-response studies 750–12 000 IU PMSG gave similar response in plasma testosterone measured in samples collected 4 and 5 h after the injection, while a dose-dependent response in plasma testosterone was found with regard to maximal values as well as duration of the effect. When comparing the plasma testosterone response following the two gonadotrophins some differences were found. Injections of 6000 IU of the two gonadotrophins showed that PMSG required longer time to cause any effect upon plasma testosterone than HCG. A dose of 375 IU HCG was sufficient to evoke a prolonged effect while 750 IU PMSG was not. However, when a sufficient PMSG dose to evoke a prolonged effect was used, the duration of the effect was markedly longer after PMSG administration than after a similar HCG-dose.

scholarly journals Graded responses of human neutrophils induced by serum-treated zymosan

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1182-1188
Author(s):  
JC Whitin ◽  
DH Ryan ◽  
HJ Cohen
Keyword(s):  
Flow Cytometry ◽  
Membrane Potential ◽  
Fluorescent Probe ◽  
Dose Response ◽  
Dose Dependence ◽  
Human Neutrophils ◽  
Graded Responses ◽  
Dose Dependent ◽  
O2 Production ◽  
Stimulation Of

A modified zymosan preparation was used to probe the interaction of particulate stimuli with human neutrophils (PMNs). After extraction with alkali and detergent, the zymosan particles retained their ability to be opsonized in serum and to stimulate PMNs. Serum-treated zymosan (STZ) induced dose-dependent superoxide (O2-) production and membrane potential depolarization in the range of 1 to 10 mg/mL of STZ. The rate and extent of secretion of lysozyme and beta-glucuronidase were also dose-dependent in the range of 1 to 10 mg/mL of STZ. Cytochemical studies using nitroblue tetrazolium, however, showed that 92% of PMNs were stimulated to produce O2- at 0.1 mg/mL of STZ. The dose response of O2- production induced by STZ is therefore due to increasing O2- production by individual PMNs and not to the stimulation of more PMNs to produce O2-. Evidence for O2- production was found only in the area of PMN-zymosan contact, suggesting a mechanism for the graded responses of PMNs treated with particulate stimuli. In order to determine the nature of the dose dependence of depolarization (a measure of PMN activation), PMNs equilibrated with the fluorescent probe 3,3′- dipentyloxacarbocyanine were analyzed by flow cytometry. The results demonstrate that STZ induces a dose-dependent depolarization of the membrane potential of individual PMNs. These results also demonstrate that increasing concentrations of STZ can induce increasing PMN responses even when all of the PMNs have been activated. These results are consistent with the hypothesis that receptor-mediated particulate stimulation of PMNs is a phenomenon that results in graded PMN responses.

Sign in / Sign up

Export Citation Format

Share Document