Regulation of the seasonal cycle of β-endorphin and ACTH secretion into the peripheral blood of rams

1990 ◽  
Vol 124 (3) ◽  
pp. 443-454 ◽  
Author(s):  
E. Ssewannyana ◽  
G. A. Lincoln ◽  
E. A. Linton ◽  
P. J. Lowry
Keyword(s):  
Plasma Concentration ◽  
Pituitary Gland ◽  
Plasma Levels ◽  
Seasonal Cycle ◽  
Plasma Concentrations ◽  
Pituitary Hormones ◽  
Similar Treatment ◽  
Corticotrophin Releasing Factor ◽  
Differential Control ◽  
Autumn And Winter

ABSTRACT In a group of 12 adult Soay rams living outdoors near Edinburgh there was a conspicuous seasonal cycle in the peripheral plasma concentrations of β-endorphin, ACTH and cortisol. The concentration of all three hormones increased 5- to 20-fold from winter to summer; the seasonal maximum occurring from May to July for ACTH and cortisol and in August for β-endorphin. At the peak of the cycle the ratio of β-endorphin to N-acetyl-β-endorphin was 22:1. The regulation of the seasonal cycle was investigated in a series of five experiments involving treatments with arginine vasopressin (AVP), corticotrophin-releasing factor (CRF) and the synthetic glucocorticoid, dexamethasone. Injection of AVP i.v. induced a dose-dependent increase in the plasma concentration of β-endorphin (AVP doses of 0, 0·07, 0·33 and 1·67 μg/kg). AVP (0·33 μg/kg) and CRF (1·67 μg/kg) given alone or in combination (equimolar doses), induced an increase in the plasma concentrations of β-endorphin and ACTH in spring, summer, autumn and winter, and produced a synergistic response when given together. The responses varied with season and were greatest in summer and autumn at the time of the seasonal increase in endogenous secretion. Dexamethasone injected i.v. at 68·04 μg/kg produced a decrease in the plasma concentrations of β-endorphin and ACTH, and the responses were also greatest in summer and autumn. A similar treatment with dexamethasone blocked the AVP-induced increase in the plasma levels of β-endorphin, indicating an action of dexamethasone on the pituitary gland. Administration of ACTH (0·33 μg/kg; i.v.) to rams pretreated with dexamethasone stimulated an increase in the plasma concentration of cortisol; this response varied with season, being greatest in spring at the time of the peak in the seasonal cycle in cortisol secretion. The administration of β-endorphin (0·33 pg/kg) failed to induce an increase in the plasma levels of cortisol at any season. Analysis of the hormone profiles in the control rams based on blood samples collected every 10 min for 8 h revealed pulsatile variations in the plasma concentration of ACTH; some of the spontaneous ACTH peaks were correlated with β-endorphin peaks. From these results in the Soay ram, we conclude that β-endorphin and ACTH are co-secreted from the pituitary gland following stimulation by AVP and CRF, and that adrenal glucocorticoids stimulated by ACTH can act in a negative feedback role at the level of the pituitary gland to inhibit the release of both β-endorphin and ACTH. These acute studies indicate a parallel control of β-endorphin and ACTH at all stages of the seasonal cycle, and a seasonal change in the secretion of AVP and CRF from the hypothalamus may constitute the 'drive' to the seasonal cycle in both β-endorphin and ACTH. There was, however, a notable difference in the timing of the seasonal cycle in β-endorphin compared with that of ACTH, which indicates some form of differential control of these two pituitary hormones. Journal of Endocrinology (1990) 124, 443–454

Inhibitory effects of corticotrophin-releasing factor and β-endorphin on LH and FSH secretion in the lactating rat

1989 ◽  
Vol 120 (3) ◽  
pp. 509-515 ◽  
Author(s):  
K. Taya ◽  
S. Sasamoto
Keyword(s):  
Plasma Concentration ◽  
Opioid Peptides ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Rapid Decrease ◽  
Significant Decline ◽  
Plasma Prolactin ◽  
Inhibitory Effects ◽  
Corticotrophin Releasing Factor ◽  
Significant Change

ABSTRACT The roles of corticotrophin-releasing factor (CRF) and β-endorphin in the suppression of LH and FSH secretion during lactation were investigated using ovariectomized lactating rats separated from their litters overnight. Within 1 h of returning the pups to their mothers a marked fall in plasma LH concentration and a large increase in plasma prolactin were noted. However, resuckling caused no significant change in plasma concentration of FSH until 12 h after the return of the litter but a significant decline occurred thereafter. Twenty-four hours after removal of the litter, a single i.v. injection of 200 μl anti-LHRH serum caused similar changes in plasma concentrations of LH and FSH observed in nursing rats during suckling. These results suggest that the suckling stimulus itself is responsible for the suppression of LH as well as FSH, via inhibition of the secretion of LHRH. Twenty-four hours after removal of the litter, a single intracerebroventricular (i.c.v.) injection of either 10 μg CRF or β-endorphin resulted in a rapid decrease in plasma LH. Only β-endorphin caused a marked increase in plasma levels of prolactin within 1 h whereas FSH was less affected by either hormone. Repeated i.c.v. administration of 10 μg CRF or β-endorphin at 6-h intervals caused a prolonged inhibition of LH as well as FSH secretion during 48 h, with β-endorphin being less effective than CRF. These results demonstrate that the suckling stimulus alone suppressed the secretion of both LH and FSH, and suggest that this effect may be mediated by the inhibition of LHRH secretion from the hypothalamus. They also suggest that the suckling-induced inhibition of LHRH may be primarily mediated by endogenous CRF and opioid peptides. Journal of Endocrinology (1989) 120, 509–515

Pharmacokinetics and Response to Treatment Using a Combination of Fludarabine and Alemtuzumab (FluCam) in Patients with Relapsed/Refractory CLL.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4991-4991
Author(s):  
T. Elter ◽  
J. Kilp ◽  
T. Piironen ◽  
P. Borchmann ◽  
H. Schulz ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Plasma Levels ◽  
Residual Disease ◽  
Single Agent ◽  
Plasma Concentrations ◽  
Response Rates ◽  
Response To Treatment ◽  
Synergistic Activity ◽  
Refractory Disease

Abstract Combination chemoimmunotherapy regimens have shown substantial efficacy in the treatment of lymphoproliferative disorders, particularly in comparison to the efficacy of single-agent therapies. Fludarabine has become an established treatment regimen in CLL, and although overall response rates (ORR) in previously untreated patients range between 60% to 80%, patients who are refractory to fludarabine have poor outcomes. Alemtuzumab, the anti-CD52 monoclonal antibody, is the most effective single-agent therapy in CLL, and is capable of inducing minimal residual disease (MRD)-negative responses even among patients with fludarabine-refractory disease. Our previous clinical experience with the combination of alemtuzumab and fludarabine (FluCam) resulted in 83% ORR in 36 patients with relapsed/refractory CLL, with 30% achieving a complete response (CR; Elter et al J Clin Oncol2005;23:7024–7031). In addition, among 12 patients with fludarabine-refractory disease, 8 achieved responses (4 CRs), and median time-to-progression (TTP) for all patients was 13 months. In order to optimize the dose and schedule of the FluCam combination, we performed pharmacokinetic (PK) analysis of the previously reported 6-cycle regimen. PK data were collected for a 14-patient cohort that participated in the phase 2 FluCam trial. Median patient age was 60 years (range, 49–73), 9 patients had Binet C disease (5 were Binet B), and patients received a mean 2.5 prior therapies. Alemtuzumab 30 mg (after initial dose escalation) and fludarabine 30 mg/m2 were administered on days 1–3 of a 28-day cycle for up to 6 cycles. PK parameters were measured from samples collected before each subsequent cycle, and at days 1, 4, 7, 14, 21, 28, and 42, for a total of 158 patient samples, of which 120 were tested. Plasma concentration of alemtuzumab increased steadily from day 1 to day 4 of therapy to a median Cmax 1.55 mg/mL, but decreased to a median 0.145 mg/mL by 7 days after initiation of treatment. By day 21 of therapy, alemtuzumab plasma concentration decreased to undetectable levels. Because efficacy of alemtuzumab has been shown to correlate with serum levels of this antibody, significant improvement in progression free survival (PFS) may require a elevated plasma levels of alemtuzumab for the duration of the treatment cycle. Therefore, the significant responses seen in this trial can be attributed to documented synergistic activity between alemtuzumab and fludarabine, which has been demonstrated both in vitro and in vivo. Despite low CD4 counts through the duration of therapy, favorable safety results seen in the trial could be attributed to opportunity for hematologic recovery between treatment cycles. Detailed PK analysis is currently being completed and will be presented at the conference. Conclusions: Treatment with the FluCam immunotherapy combination yielded positive results among patients with fludarabine resistant/refractory CLL, a difficult-to-treat population. As shown previously, response rates correlate with higher alemtuzumab plasma concentrations. Therefore, longer PFS durations may require longer, more sustained alemtuzumab plasma levels, which may be achieved with either consolidation or maintenance.

CHANGES IN PLASMA LEVELS OF PROLACTIN AND LH INDUCED BY LUTEOLYTIC OR LUTEOTROPHIC TREATMENT IN INTACT CYCLING SHEEP AFTER SECTION OF THE PITUITARY STALK

1973 ◽  
Vol 73 (4) ◽  
pp. 625-634 ◽  
Author(s):  
G. Kann ◽  
R. Denamur
Keyword(s):  
Pituitary Gland ◽  
Plasma Levels ◽  
Limit Of Detection ◽  
Oestrous Cycle ◽  
The Other ◽  
Pituitary Stalk ◽  
Similar Treatment ◽  
Luteal Regression ◽  
Gonadotrophin Secretion ◽  
Major Increase

ABSTRACT Oestradiol has been shown to cause either premature luteal regression or prolonged luteal maintenance depending on whether it is administered early or late in the oestrous cycle. Although these effects are not observable in the absence of the uterus, it was considered desirable to examine the possibility that the pituitary gland as well as the uterus may be involved in this phenomenon. Accordingly, plasma LH and prolactin concentrations were studied in sheep treated with oestradiol from day 3 (luteotrophic action) or day 11 (luteolytic action) with and without pituitary stalk section. Plasma LH fell below the limit of detection (0.3 ng/ml) in the plasma of sheep after pituitary stalk section, whether or not oestradiol had been administered. In the intact ewe, oestradiol given from day 3 resulted in luteal maintenance associated with a significant increase in the secretion of plasma LH and prolactin. However, similar treatment in the stalk sectioned ewe also resulted in luteal maintenance without any major increase in gonadotrophin secretion. On the other hand, when oestradiol was given from day 11, there was no evidence either from the intact or the stalk sectioned sheep that the pituitary contributed to the luteolytic action of oestradiol may possibly have a pituitary component, the luteolytic action is probably mediated solely by the oestrogenic action on the uterus.

Changes in the hypothalamic contents of LHRH-I and -II and in pituitary responsiveness to synthetic chicken LHRH-I and -II during the progesterone-induced surge of LH in the laying hen

1990 ◽  
Vol 127 (3) ◽  
pp. 487-496 ◽  
Author(s):  
S. C. Wilson ◽  
R. A. Chairil ◽  
F. J. Cunningham ◽  
R. T. Gladwell
Keyword(s):  
Plasma Concentration ◽  
Pituitary Gland ◽  
Laying Hens ◽  
Plasma Concentrations ◽  
Posterior Hypothalamus ◽  
Anterior Hypothalamus ◽  
Significant Fall ◽  
Basal Plasma

ABSTRACT The contents of LHRH-I and -II in the anterior hypothalamus and posterior hypothalamus (including the mediobasal hypothalamus and median eminence) were measured at 90, 180 and 360 min after the i.m. injection of laying hens with progesterone. Whilst no changes were observed in the content of LHRH-I in the anterior hypothalamus, LHRH-I in the posterior hypothalamus tended to fall at 90 and 180 min after injection of progesterone in hens maintained on 16 h light:8 h darkness (16L:8D) and 8L:16D respectively. Pretreatment of laying hens with tamoxifen significantly increased the hypothalamic contents of LHRH-I and -II, raised the basal plasma concentration of LH and modified the LH response to progesterone injection. In hens in which tamoxifen prevented an increase in the plasma concentration of LH after progesterone injection, the content of LHRH-I in the posterior hypothalamus remained unchanged. In contrast, in hens in which progesterone stimulated a steep increase in LH within 90 min, there was a pronounced and significant fall in LHRH-I content of the posterior hypothalamus. No change in the hypothalamic content of LHRH-II was observed during the progesterone-induced surge of LH until plasma concentrations had attained maximal values or started to decline. Then, in hens maintained on 16L:8D, a significant fall in the content of LHRH-II in the anterior hypothalamus was found at both 180 and 360 min after injection with progesterone. Tests in vitro and in vivo of the responsiveness of the pituitary gland to synthetic LHRH-I and -II revealed no change at 90 min after injection of laying hens with progesterone, when plasma concentrations of LH were increasing, but a pronounced reduction when plasma LH concentrations were maximal or falling. These results suggest that LHRH-I mediates in the progesterone-induced increase in the plasma concentration of LH. Although the subsequent decline in plasma LH was associated with a reduced responsiveness of the pituitary gland to LHRH, a significant correlation between the contents of LHRH-I and -II in the anterior hypothalamus and a fall in the hypothalamic content of LHRH-II when plasma LH was maximal or declining allows the possibility of an involvement of this peptide in the neuroendocrine events preceding ovulation. Journal of Endocrinology (1990) 127, 487–496

Intranasal Cocaine: Dose Relationships of Psychological Effects and Plasma Levels

1983 ◽  
Vol 12 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Craig Van Dyke ◽  
James Ungerer ◽  
Peter Jatlow ◽  
Paul Barash ◽  
Robert Byck
Keyword(s):  
Plasma Concentration ◽  
Plasma Levels ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Psychological Effects ◽  
Acute Tolerance ◽  
Lidocaine Hydrochloride ◽  
Intranasal Cocaine ◽  
Cocaine Hydrochloride ◽  
Repeated Doses

We compared the psychological effects of three doses of intranasal cocaine hydrochloride (.2, .75, and 1.5 mg/kg) with cocaine plasma concentrations in four volunteers. Intranasal lidocaine hydrochloride (.2 mg/kg) was used as a topically active placebo. Peak “high” ratings were related to both dose and peak plasma concentrations. At a given plasma concentration, “high” ratings were greater when plasma levels were increasing than when they were decreasing. This indicates that acute tolerance by tachyphylaxis occurred after single doses. The cocaine “high” was a pleasant feeling but was without distinctive sensations. The dramatic effects of intranasal cocaine on the street may be related to larger or repeated doses as well as the setting.

Part II: Biochemical changes after pituitary adenylate cyclase-activating polypeptide-38 infusion in migraine patients

Cephalalgia ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 136-147 ◽  
Author(s):  
Song Guo ◽  
Anne Luise Haulund Vollesen ◽  
Young Bae Lee Hansen ◽  
Erik Frandsen ◽  
Malene Rohr Andersen ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Plasma Levels ◽  
Intravenous Infusion ◽  
Plasma Concentrations ◽  
Pituitary Hormones ◽  
Control Group ◽  
Gene Variant ◽  
Biochemical Variables ◽  
Increased Risk ◽  
Pituitary Adenylate Cyclase

Background Intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine attacks in 65–70% of migraine without aura (MO) patients. We investigated whether PACAP38 infusion causes changes in the endogenous production of PACAP38, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), tumour necrosis factor alpha (TNFα), S100 calcium binding protein B (S100B), neuron-specific enolase and pituitary hormones in migraine patients. Methods We allocated 32 previously genotyped MO patients to receive intravenous infusion PACAP38 (10 pmol/kg/minute) for 20 minutes and recorded migraine-like attacks. Sixteen of the patients were carriers of the risk allele rs2274316 ( MEF2D), which confers increased risk of MO and may regulate PACAP38 expression, and 16 were non-carriers. We collected blood samples at baseline and 20, 30, 40, 60 and 90 minutes after the start of the infusion. A control group of six healthy volunteers received intravenous saline. Results PACAP38 infusion caused significant changes in plasma concentrations of VIP ( p = 0.026), prolactin ( p = 0.011), S100B ( p < 0.001) and thyroid-stimulating hormone (TSH; p = 0.015), but not CGRP ( p = 0.642) and TNFα ( p = 0.535). We found no difference in measured biochemical variables after PACAP38 infusion in patients who later developed migraine-like attacks compared to those who did not ( p > 0.05). There was no difference in the changes of biochemical variables between patients with and without the MEF2D-associated gene variant ( p > 0.05). Conclusion PACAP38 infusion elevated the plasma levels of VIP, prolactin, S100B and TSH, but not CGRP and TNFα. Development of delayed migraine-like attacks or the presence of the MEF2D gene variant was not associated with pre-ictal changes in plasma levels of neuropeptides, TNFα and pituitary hormones.

Epileptiform seizures in domestic fowl. VII. Plasma phenytoin concentrations and anticonvulsant activity

1978 ◽  
Vol 56 (2) ◽  
pp. 310-315 ◽  
Author(s):  
H. L. Davis ◽  
D. D. Johnson ◽  
R. D. Crawford
Keyword(s):  
Plasma Concentration ◽  
Plasma Levels ◽  
Domestic Fowl ◽  
Anticonvulsant Activity ◽  
Plasma Concentrations ◽  
Anticonvulsant Effect ◽  
Complete Protection ◽  
Intermittent Photic Stimulation ◽  
The Relationship ◽  
Epileptiform Seizures

Acute dose–response studies with phenytoin were conducted to determine the relationship between plasma levels and anticonvulsant effect in epileptic chickens. Phenytoin produced statistically significant reductions in both the incidence and severity of seizures in photosensitive epileptic chickens when the plasma concentrations exceeded 8.15 ± 0.89 μg/ml. A high correlation exists between plasma phenytoin concentrations and both the reduction in incidence or severity of seizures. However, the appearance of plasma concentration dependent neurological toxicities resulted in a failure to achieve complete protection against intermittent photic stimulation induced seizures.

Association of Plasma Uremic Solute Levels with Residual Kidney Function in Children on Peritoneal Dialysis

2021 ◽  
pp. CJN.01430121
Author(s):  
Lakshmi Ganesan ◽  
Frank O'Brien ◽  
Tammy Sirich ◽  
Natalie Plummer ◽  
Rita Sheth ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Kidney Function ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Extracellular Volume ◽  
Metabolomic Analysis ◽  
Dialysis Patients ◽  
Similar Treatment ◽  
Residual Kidney Function ◽  
Uremic Solutes

Background and objectives. Residual native kidney function confers health benefits in dialysis patients. It can facilitate control of extracellular volume and inorganic ion concentrations. Residual kidney function can also limit the accumulation of uremic solutes. This study assessed whether lower plasma concentrations of uremic solutes were associated with residual kidney function in pediatric patients on peritoneal dialysis. Design, setting, participants, and measurements. Samples were analyzed from 29 pediatric peritoneal dialysis patients including 13 without residual kidney function and 10 with residual kidney function. Metabolomic analysis by untargeted mass spectrometry compared plasma solute levels in patients with and without residual kidney function. Dialytic and residual clearances of selected solutes were also measured by assays employing chemical standards. Results. Metabolomic analysis showed that plasma levels of 256 uremic solutes in patients with residual kidney function averaged 64 (51-81 IQR) percent of the values in patients without residual kidney function who had similar total Kt/Vurea. The plasma levels were significantly lower for 59 of the 256 solutes in the patients with residual kidney function and significantly higher for none. Assays employing chemical standards showed that residual kidney function provides a higher portion of the total clearance for non-urea solutes than it does for urea. Conclusions. Concentrations of many uremic solutes are lower in peritoneal dialysis patients with residual kidney function than in those without residual kidney function receiving similar treatment as assessed by Kt/Vurea.

CONCENTRATION OF PROGESTERONE IN SYSTEMIC PLASMA OF GOATS: EFFECTS OF VARIOUS ROUTES OF ADMINISTRATION

1973 ◽  
Vol 57 (2) ◽  
pp. 247-252
Author(s):  
D. S. DHINDSA ◽  
J. A. RESKO ◽  
J. METCALFE
Keyword(s):  
Plasma Concentration ◽  
Oral Administration ◽  
Silicone Rubber ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Physiological Mechanism ◽  
High Plasma ◽  
Marked Rise ◽  
Routes Of Administration ◽  
High Doses

SUMMARY The effect of various routes of administration on the plasma concentrations of progesterone was studied in Pygmy goats. Oral administration, even in extremely high doses, gave low plasma concentrations which returned to normal within 24 h. Progesterone given by subcutaneous or intra-abdominal implantation in silicone rubber (Silastic) envelopes caused a marked rise in the plasma concentration of progesterone, values reaching 10–30 ng/ml at 10–20 days but then declining. A fall in plasma concentration despite continued administration was also observed with daily intramuscular injections of large doses of progesterone. This observation suggests that some physiological mechanism prevents sustained high plasma levels of this hormone.

Desipramine Plasma Concentration and Therapeutic Response in Elderly Depressives: A Naturalistic Pilot Study

1986 ◽  
Vol 31 (8) ◽  
pp. 752-754 ◽  
Author(s):  
S.P. Kutcher ◽  
K.I. Shulman ◽  
K. Reed
Keyword(s):  
Plasma Concentration ◽  
Pilot Study ◽  
Plasma Levels ◽  
Therapeutic Response ◽  
Plasma Concentrations ◽  
Initial Results

This naturalistic pilot study of desipramine hydrochloride treatment in elderly DSM III diagnosed depressives demonstrated that therapeutic response was related to desipramine plasma levels and that a desipramine plasma concentration of 200 nmol/l significantly differentiated responders from non-responders. Plasma concentrations of 2-Hydroxydesipramine were not related to therapeutic response. This finding suggests that monitoring of desipramine plasma levels has utility in certain clinical situations. Further fixed dosage studies are necessary to confirm these initial results.

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