Developmental changes in the diurnal rhythm of secretion of corticosterone and LH in the domestic hen

1984 ◽  
Vol 101 (3) ◽  
pp. 299-304 ◽  
Author(s):  
S. C. Wilson ◽  
R. C. Jennings ◽  
F. J. Cunningham
Keyword(s):  
Plasma Concentration ◽  
Phase Angle ◽  
Diurnal Rhythm ◽  
Sexual Development ◽  
Plasma Concentrations ◽  
Transient Increase ◽  
Developmental Changes ◽  
Diurnal Changes ◽  
Pronounced Increase ◽  
Domestic Hen

ABSTRACT When diurnal changes in the plasma concentrations of corticosterone and LH were compared at various times during sexual development a diurnal rhythm in the secretion of corticosterone was most pronounced at 4·5 weeks of age in hens maintained on a schedule of 8 h light: 16 h darkness (8L: 16D) and at 8·5 weeks of age in hens maintained on 16L: 8D. At these ages the phase-angle of the rhythm in relation to the onset of darkness was 3 h earlier than had been observed in previous studies of the adult hen. The characteristics of the corticosterone rhythm changed during sexual development and diurnal changes were no longer evident in hens at 17 weeks of age at a time when prepubertal plasma concentrations of LH were maximal. However, there was a tendency for plasma concentrations of corticosterone to fluctuate diurnally in hens studied at less than 10 days before the onset of lay although not to the same extent as has previously been observed in the adult hen. This period of development was associated with a pronounced increase in the plasma concentration of progesterone. An increase in the plasma concentration of LH at the onset of darkness was observed at all ages in hens maintained on either photoschedule. In hens of 4·5–15 weeks of age maintained on 16L:8D or 8L:16D this increase in the plasma concentration of LH was sustained during the first 5 or 8–11 h of darkness respectively but at 17 weeks of age only a transient increase in LH was seen at the onset of darkness. Plasma concentrations of LH in samples of plasma taken at intervals of between 3 days and 2 weeks throughout sexual development were, until 18–19 weeks, consistently higher in hens maintained on a photoschedule of 16L:8D than on 8L: 16D. J. Endocr. (1984) 101, 299–304

Diurnal changes in the plasma concentrations of LH and hypothalamic contents of LHRH-I and LHRH-II in the domestic hen

1991 ◽  
Vol 130 (3) ◽  
pp. 457-462 ◽  
Author(s):  
S. C. Wilson ◽  
R. T. Gladwell ◽  
F. J. Cunningham
Keyword(s):  
Plasma Concentration ◽  
Diurnal Rhythm ◽  
Laying Hens ◽  
Plasma Concentrations ◽  
Posterior Hypothalamus ◽  
Anterior Hypothalamus ◽  
Diurnal Changes ◽  
The Mean ◽  
The Times ◽  
Lh Secretion

ABSTRACT Diurnal changes of LH secretion in sexually immature hens of 9, 11, 13 and 15 weeks of age consisted of 25–40% increases in the mean concentrations of LH in plasma between 15.00 and 18.00 h, i.e. between 2 h before and 1 h after the onset of darkness. During this time there was a tendency for the mean contents of LHRH-I in the anterior hypothalamus and posterior hypothalamus to increase by 21–74% and 20–56% respectively. In hens of 9 and 15 weeks, diurnal changes in the plasma concentration of LH closely paralleled those of LHRH-I content in the posterior hypothalamus. In contrast, the diurnal rhythm of LH secretion in hens of 11 and 13 weeks was more marked and plasma concentrations of LH continued to rise steeply between 18.00 and 21.00 h, i.e. between 1 and 4 h after the onset of darkness. At 11 weeks, this was associated with a reduction (P<0·01) in the contents of LHRH-I and LHRH-II, particularly in the anterior hypothalamus. In laying hens, a diurnal decline (P<0·01) in the plasma concentration of LH between 1 and 4 h after the onset of darkness was preceded by a fall (P<0·05) in the content of LHRH-I in the posterior hypothalamus and in the total hypothalamic content of LHRH-II (P<0·01). In all groups of hens, irrespective of the times of day at which tissue was taken, significant (P<0·05–<0·001) correlations between the contents of LHRH-I and LHRH-II in the anterior hypothalamus were observed. It is concluded that a diurnal rhythm of release of LHRH-I may drive the diurnal rhythm of LH secretion. Thus, in sexually immature hens of 9 and 15 weeks and laying hens in which diurnal changes in plasma LH were small there were parallel changes in the content of LHRH-I in the posterior hypothalamus. However, where the plasma concentration of LH was increased substantially, as at 11 weeks, there was a decline in the hypothalamic contents of LHRH-I. A simultaneous fall in the hypothalamic content of LHRH-II raises the possibility of a causal relationship between the activities of LHRH-II, LHRH-I and the release of LH. Journal of Endocrinology (1991) 130, 457–462

Concentrations of luteinizing hormone and progesterone in plasma during sexual development of the Khaki Campbell duck

1982 ◽  
Vol 93 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Susan C. Wilson ◽  
T. R. Morris
Keyword(s):  
Plasma Concentration ◽  
Luteinizing Hormone ◽  
Negative Correlation ◽  
Sexual Development ◽  
Plasma Concentrations ◽  
Winter Solstice ◽  
Pronounced Increase ◽  
Threefold Increase ◽  
Lh Release

Concentrations of LH and progesterone were measured in the plasma of ducks which were, from 3 weeks of age, raised on either a constant photoperiod of 16 h light: 8 h darkness or a lighting schedule which simulated natural changes in daylength. In ducks raised on a constant photoperiod of 16 h light: 8 h darkness the plasma concentration of LH increased steeply between 7 and 3·5 weeks before the onset of lay. Concentrations of LH then declined, gradually at first, but then rapidly during the 7 days before the first oviposition in association with a pronounced increase in the plasma concentration of progesterone. During the 18 days before the first egg was laid there was a significant (P < 0·01) negative correlation between the plasma concentrations of LH and progesterone. The patterns of LH release during sexual development of ducks raised on a schedule which simulated natural changes in daylength were variable but could be categorized according to the daylength at which each duck came into lay. In ducks coming into lay soon after the winter solstice when daylength was short (8·0–8·5 h light/day) there was a pronounced 15-fold prepubertal increase in the plasma concentration of LH although in some ducks high LH levels were not maintained until 3–4 weeks before the first oviposition and were not always followed by a rise in the plasma concentration of progesterone. In contrast, in ducks coming into lay when daylength had increased to 11·0–11·5 h light/day there were only minor fluctuations in the plasma concentration of LH until a small two- to threefold increase in LH was observed during the 2 weeks before the first oviposition.

Diurnal changes in the plasma concentrations of corticosterone, luteinizing hormone and progesterone during sexual development and the ovulatory cycle of Khaki Campbell ducks

1982 ◽  
Vol 93 (2) ◽  
pp. 267-277 ◽  
Author(s):  
Susan C. Wilson ◽  
F. J. Cunningham ◽  
T. R. Morris
Keyword(s):  
Plasma Concentration ◽  
Sexual Development ◽  
Temporal Relationship ◽  
Plasma Concentrations ◽  
Egg Laying ◽  
Diurnal Changes ◽  
Ovulatory Cycle ◽  
Night Time ◽  
Khaki Campbell Ducks ◽  
Relationship Of

Diurnal changes in hormonal concentrations were determined at various times during sexual development and during the ovulatory cycle of Khaki Campbell ducks raised either on a constant photoperiod of 16 h light: 8 h darkness (16L : 8D) or on a schedule which simulated natural changes in daylength. The ovulatory cycle of the latter group was studied when there were 11 h light/day and daylength was increasing. In the laying duck concentrations of LH and progesterone in the plasma rose simultaneously between 7 and 4 h before ovulation and oviposition. Preovulatory concentrations of LH and progesterone in ducks subjected to photoperiods of 16L : 8D and 11L : 13D started to increase at the onset of darkness and 2 h after the onset of darkness respectively. In ducks maintained on 16L : 8D there was a rise in the concentration of corticosterone in the plasma at the onset of darkness to attain a maximum just before the onset of light. The temporal relationship of the peak of secretion of corticosterone to the cycle of light and darkness changed during sexual development of ducks raised on 16L : 8D with a 6-h advance in the phase of the rhythm between 11 weeks of age and the onset of egg laying. Highest progesterone concentrations during the day tended to coincide with the maximal secretion of corticosterone. A monophasic diurnal rhythm in the secretion of corticosterone in 11-week-old ducks maintained on natural daylength had disappeared by 15 weeks and was not re-established by 25 weeks of age. A diurnal variation in the plasma concentration of LH was not observed in the ducks maintained on 16L : 8D, although night-time LH concentrations tended to be higher than day-time concentrations in ducks raised on natural daylength. This difference was significant at 11 weeks, and at 15, 19 and 22 weeks changes in the plasma concentrations of LH during the night tended to parallel those of corticosterone.

Maturational changes in the LH response of domestic fowl to synthetic chicken LHRH-I and -II

1989 ◽  
Vol 123 (2) ◽  
pp. 311-318 ◽  
Author(s):  
S. C. Wilson ◽  
F. J. Cunningham ◽  
R. A. Chairil ◽  
R. T. Gladwell
Keyword(s):  
Plasma Concentration ◽  
Sexual Development ◽  
Plasma Concentrations ◽  
Egg Laying ◽  
Prolonged Action ◽  
Initial Rise ◽  
Lh Release ◽  
Higher Doses ◽  
Type Response ◽  
Sustained Increase

ABSTRACT Treatment of chickens at different stages of sexual development with a single i.v. injection of synthetic chicken LHRH (cLHRH)-I or -II stimulated a rise in the plasma concentration of LH within 1 min. The activity of cLHRH-II was 1·3- to 2·7-fold greater than that of cLHRH-I in sexually immature cockerels and hens as determined by the changes in the plasma concentration of LH during the 5 or 10 min after injection. This could be attributed to both a greater effectiveness of cLHRH-II to stimulate LH release and to a more prolonged action. Thus, LH concentrations in plasma were maximal within 1–2 min of injection of all doses of cLHRH-I but within 2–5 min of injection at the higher doses of cLHRH-II. The responsiveness of the pituitary gland to cLHRH-I and -II was substantially greater in the sexually immature cockerel than in the hen and diminished during sexual development of the hen. Coincident with the onset of egg laying, the characteristics of the LH response to cLHRH-II changed to consist of an initial rise during the first 2 min, followed by a more sustained increase with LH concentrations still rising 10 min after injection. In contrast, after injection with cLHRH-I, plasma concentrations of LH rose to a peak at 2 min and thereafter declined gradually. Treatment of the sexually immature hen with oestradiol, progesterone or a combination of both steroids did not enable the expression of a laying hen-type response to the injection of cLHRH-II. It would appear, therefore, that unidentified events associated with the final stages of sexual maturation bring about changes in the mechanism of action of cLHRH-II which differ from those of cLHRH-I. Journal of Endocrinology (1989) 123, 311–318

An investigation of diurnal and cyclic changes in the secretion of luteinizing hormone in the domestic hen

1983 ◽  
Vol 98 (1) ◽  
pp. 137-145 ◽  
Author(s):  
S. C. Wilson ◽  
R. C. Jennings ◽  
F. J. Cunningham
Keyword(s):  
Luteinizing Hormone ◽  
Diurnal Rhythm ◽  
Laying Hen ◽  
Ovulatory Cycle ◽  
Pronounced Increase ◽  
Threefold Increase ◽  
Steep Decline ◽  
Cyclic Changes ◽  
Lh Secretion ◽  
Domestic Hen

The characteristics of the diurnal rhythm in the concentration of LH in plasma of the domestic hen varied according to age and duration of photoperiod. A pronounced increase in LH was observed at the onset of darkness in immature hens whether maintained on schedules of 16 h light:8 h darkness (16L:8D) or 8L:16D. During weeks 4·5–15 or −17·5 raised concentrations of LH were maintained until 6 and 12 h after the onset of darkness in hens held on 16L:8D and 8L:16D respectively. By 19 weeks of age the diurnal rhythm of LH secretion had changed to resemble more closely that observed in the laying hen. An increase in the concentration of LH in plasma at the onset of darkness was of comparatively short duration and gave way, within 2–3 h, to a steep decline before a further slight increase in LH, which tended to occur at 11–14 h after the onset of darkness. Superimposed on this diurnal rhythm of LH secretion in the laying hen were a one- to threefold increase in the concentration of LH during 8–4 h before ovulation and a much less pronounced increase in LH during 0–8 h after ovulation. The pattern of changes in the concentration of LH in plasma during the ovulatory cycle was not modified by the repeated withdrawal of blood at intervals of 2 h.

EFFECT OF PHOTOPERIOD ON THE CONCENTRATIONS OF CORTICOSTERONE AND LUTEINIZING HORMONE IN THE PLASMA OF THE DOMESTIC HEN

1981 ◽  
Vol 91 (1) ◽  
pp. 135-143 ◽  
Author(s):  
SUSAN C. WILSON ◽  
F. J. CUNNINGHAM
Keyword(s):  
Plasma Concentration ◽  
Luteinizing Hormone ◽  
Continuous Light ◽  
Significant Rise ◽  
Maximal Concentration ◽  
Pronounced Increase ◽  
Circadian Periodicity ◽  
Free Running ◽  
Domestic Hen

Ovipositions in hens maintained under schedules of 16 h light: 8 h darkness (16L : 8D) or 8L : 16D were restricted to a 12 h period of the day while in hens maintained on continuous light, ovipositions occurred at times throughout the whole of the 24 h day. In hens maintained in continuous light a significant rise in the plasma concentration of corticosterone was observed 11–9 h before ovulation/oviposition. In hens in 16L : 8D there was an increase in the concentration of corticosterone in the plasma during the first 1·5 h of darkness which, under that schedule, coincides with the onset of the 'open period' for the occurrence of the preovulatory release of LH. In hens ovulating the first egg of a sequence the rise in the secretion of corticosterone was only transient and levels fell as preovulatory concentrations of LH rose to a peak. However, in hens undergoing an ovulation late in a sequence or in those not expected to ovulate, the concentration of corticosterone in the plasma continued to rise to attain a maximal concentration 8 h later. In hens maintained in 8L : 16D there was a tendency for the concentration of corticosterone in the plasma to increase at the beginning of the open period, 4 h after the onset of darkness, though this rise was much smaller than that observed at the beginning of the open period of hens on 16L : 8D. A further, more pronounced, increase in the concentration of corticosterone was observed between 11 and 15 h after the onset of darkness. It is suggested that the rise in the concentration of corticosterone at 11–9 h before ovulation in hens in continuous light reflects the beginning of an open period with a free-running circadian periodicity of 26–27 h.

Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

2020 ◽  
Vol 21 (2) ◽  
pp. 126-131
Author(s):  
Bhuvanachandra Pasupuleti ◽  
Vamshikrishna Gone ◽  
Ravali Baddam ◽  
Raj Kumar Venisetty ◽  
Om Prakash Prasad
Keyword(s):  
Plasma Concentration ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Concentrations ◽  
Control Group ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Post Hoc ◽  
Hydrolysis Of ◽  
Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

Design, Synthesis, and Pharmacokinetic Evaluation of O-Carbamoyl Tizoxanide Prodrugs

2020 ◽  
Vol 16 ◽  
Author(s):  
Xi He ◽  
Wenjun Hu ◽  
Fanhua Meng ◽  
Xingzhou Li
Keyword(s):  
Plasma Concentration ◽  
Broad Spectrum ◽  
Plasma Concentrations ◽  
Antiviral Drug ◽  
Systemic Exposure ◽  
Pharmacokinetic Profile ◽  
Hydroxyl Group ◽  
First Pass

Background: The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide. Objective: Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system exposure of tizoxanide. Method: These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities. Results: The results indicated that the plasma concentration and the systemic exposure of tizoxanide (T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced by equimolar dosage of nitazoxanide. It was also found that the plasma concentration and the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide. Conclusion: Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the active ingredient tizoxanide.

scholarly journals Physiologically Based Pharmacokinetic Models of Probenecid and Furosemide to Predict Transporter Mediated Drug-Drug Interactions

2020 ◽  
Vol 37 (12) ◽  
Author(s):  
Hannah Britz ◽  
Nina Hanke ◽  
Mitchell E. Taub ◽  
Ting Wang ◽  
Bhagwat Prasad ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Organic Anion ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Time Profiles ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Concentration Time ◽  
Anion Transporter ◽  
Physiologically Based

Abstract Purpose To provide whole-body physiologically based pharmacokinetic (PBPK) models of the potent clinical organic anion transporter (OAT) inhibitor probenecid and the clinical OAT victim drug furosemide for their application in transporter-based drug-drug interaction (DDI) modeling. Methods PBPK models of probenecid and furosemide were developed in PK-Sim®. Drug-dependent parameters and plasma concentration-time profiles following intravenous and oral probenecid and furosemide administration were gathered from literature and used for model development. For model evaluation, plasma concentration-time profiles, areas under the plasma concentration–time curve (AUC) and peak plasma concentrations (Cmax) were predicted and compared to observed data. In addition, the models were applied to predict the outcome of clinical DDI studies. Results The developed models accurately describe the reported plasma concentrations of 27 clinical probenecid studies and of 42 studies using furosemide. Furthermore, application of these models to predict the probenecid-furosemide and probenecid-rifampicin DDIs demonstrates their good performance, with 6/7 of the predicted DDI AUC ratios and 4/5 of the predicted DDI Cmax ratios within 1.25-fold of the observed values, and all predicted DDI AUC and Cmax ratios within 2.0-fold. Conclusions Whole-body PBPK models of probenecid and furosemide were built and evaluated, providing useful tools to support the investigation of transporter mediated DDIs.

Effects of diltiazem on atrioventricular conduction and arterial blood pressure: correlation with plasma drug concentrations

1984 ◽  
Vol 62 (12) ◽  
pp. 1479-1486 ◽  
Author(s):  
Jean-Paul Clozel ◽  
Jacques Billette ◽  
Gilles Caillé ◽  
Pierre Théroux ◽  
Richard Cartier
Keyword(s):  
Blood Pressure ◽  
Plasma Concentration ◽  
Refractory Period ◽  
Plasma Concentrations ◽  
Atrioventricular Conduction ◽  
Gas Liquid Chromatography ◽  
Conduction Time ◽  
Arterial Blood ◽  
Drug Concentrations ◽  
Atrial Conduction Time

Atrial and atrioventricular conduction variables were studied at control and at the end of each of six consecutive 45-min diltiazem administration periods in eight closed chest-anesthetized dogs. Diltiazem was given as a bolus (50 μg/kg, i.v.) followed by an infusion (0.5 μg∙kg−1∙min−1); doses were doubled in subsequent periods. The plasma concentrations, measured by gas–liquid chromatography, ranged from 8 to 1400 ng/mL and correlated strongly with the doses (r = 0.92; p < 0.01). The Wenckebach cycle length, basic conduction time, and functional refractory period of the atrioventricular (AV) node increased proportionally with plasma concentration (respective r = 0.90, 0.89, 0.80; p < 0.01). The minimum mean plasma concentrations affecting these variables significantly were 37, 83, and 175 ng/mL, respectively. Second or third degree AV blocks developed in all dogs for plasma concentrations between 379 and 1400 ng/mL. In four dogs which were given isoproterenol (0.2 μg∙kg−1∙min−1), these blocks disappeared within 1 min. Atrial conduction time and functional refractory period were slightly but significantly shortened by diltiazem with mean plasma concentrations of 175 ng/mL and over. His–Purkinje intervals were not significantly changed by diltiazem. Systolic and diastolic arterial pressures were decreased by diltiazem (r = −0.64, r = −0.79; p < 0.01) starting with a mean plasma concentration of 83 ng/mL. We conclude that AV nodal conduction variables are progressively prolonged with increasing plasma concentrations of diltiazem; plasma concentrations affecting blood pressure and AV nodal variables overlap; and the AV blocks produced by toxic concentrations of diltiazem can be corrected by isoproterenol.

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