Long-term negative feedback effects of oestrogen and progesterone on the pituitary gland of the long-term ovariectomized ewe

1989 ◽  
Vol 120 (2) ◽  
pp. 207-214 ◽  
Author(s):  
I. J. Clarke ◽  
J. T. Cummins ◽  
M. E. Crowder ◽  
T. M. Nett
Keyword(s):  
Plasma Concentrations ◽  
Pulse Amplitude ◽  
Pituitary Surgery ◽  
Pulse Frequency ◽  
Term Treatment ◽  
Gnrh Receptors ◽  
Long Term Treatment ◽  
Group 3 ◽  
Group 2

ABSTRACT The effects of long-term treatment with physiological doses of oestradiol or oestradiol plus progesterone on plasma gonadotrophin levels and pituitary content of LH and gonadotrophin-releasing hormone (GnRH) receptors were studied in ovariectomized–hypothalamo-pituitary disconnected ewes given 250 ng pulses of GnRH every 2 h (i.v.). A pilot experiment showed that 3 cm long Silastic implants (s.c.) reduced both LH pulse frequency and pulse amplitude in long-term (> 6 months) ovariectomized ewes. The main experiment was conducted over 3 weeks in ovariectomized–hypothalamo-pituitary disconnected ewes that had received pulsatile GnRH replacement for 1 week after pituitary surgery. Group 1 (n = 5) received GnRH pulses alone throughout the study. Group 2 (n = 6) received oestradiol in week 2 and oestradiol plus progesterone in week 3 and in group 3 (n = 6) the steroid treatments were reversed. Oestradiol reduced (P < 0·05) the mean (± s.e.m.) amplitude of LH in pulses in group 2 (from 8·2 ± 1·6 to 5·0 ± 0·5 μg/l) and group 3 (from 11·6 ± 1·2 to 9·3 ±1·0 μg/l); an additional effect of progesterone was seen in group 2 but not group 3. The amplitudes of the LH pulses did not change in the control ewes. Plasma concentrations of FSH were reduced by approximately 50% by the oestradiol treatments with no additional effects of progesterone. There was no effect of steroidal treatment on pituitary content of LH or pituitary levels of GnRH receptors. We conclude that long-term oestradiol treatment, with or without progesterone, reduces plasma amplitudes of LH pulses by a direct pituitary effect, but the magnitude of this effect was less than that observed on GnRH secretion in short-term ovariectomized ewes in an earlier study. The reduction in plasma LH pulse amplitude is not due to a direct pituitary effect of these steroids on GnRH receptor number. Journal of Endocrinology (1989) 120, 207–214

scholarly journals The role of an herbal agent in treatment for Escherichia coli induced bacterial cyctitis in rats

2017 ◽  
Vol 89 (2) ◽  
pp. 134
Author(s):  
Murat Tuken ◽  
Mustafa Zafer Temiz ◽  
Emrah Yuruk ◽  
Asuman Orcun Kaptanagasi ◽  
Kayhan Basak ◽  
...  
Keyword(s):  
Drinking Water ◽  
Term Treatment ◽  
E Coli ◽  
Group 4 ◽  
Long Term Treatment ◽  
Histopathological Evaluation ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Objectives: The aim of this study is to evaluate the effects of the herbal agent in the prevention and treatment of bacterial cystitis in a rat model. Material and Methods: A total of twenty-eight male Sprague- Dawley rats were divided into four groups. Group-1 constituted the control group (operated and normal saline injected into the bladder, received only drinking water for 7 days); Group-2 constituted the no-treatment group (operated, E.coli J96 strain injected into the bladder, received only drinking water for 7 days); Group-3 constituted the short-term treatment (operated, E.coli J96 strain injected into the bladder, received the herbal agent added into drinking water for 7 days) and Group-4 constituted the long-term treatment (operated, E. coli J96 strain injected into the bladder, received herbal agent added into drinking water for 14 days). At the end of the pre-defined treatment periods of duration, the rats were sacrificed, urine samples collected from the bladder for culture and bladders were harvested for histopathological evaluation. Urine culture results and histopathological findings were comparatively evaluated between the groups. Results: Urine cultures were positive for implanted E. coli strains in 0%, 85.7%, 42.8% and 0% of rats in Group 1, Group 2, Group 3 and Group 4, respectively (p = 0.001). Although histopathological evaluation revealed increased vascular dilation in the bladder specimens obtained from Group 2 and Group 3 (p = 0.028) no significant difference was noticed in level of inflammation (p = 0.610), edema (p = 0.754) and thickness of uroepithelium (p = 0.138). Conclusion: While long term (14 days) treatment with an herbal agent added into the drinking water resulted in complete clearance of urine from E. coli; shorter application of the agent revealed partial clearance. Further clinical studies are needed to support our results.

Abstract 9411: Urine Aquaporin-2 Level is a Novel Marker for the Better Prognosis After Long-Term Tolvaptan Treatment in Patients With Advanced Heart Failure

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Teruhiko Imamura ◽  
Koichiro Kinugawa ◽  
Takeo Fujino ◽  
Toshiro Inaba ◽  
Hisataka Maki ◽  
...  
Keyword(s):  
Heart Failure ◽  
De Novo ◽  
Collecting Duct ◽  
Initial Response ◽  
Aquaporin 2 ◽  
Long Term Treatment ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Introduction: Preserved function of collecting duct is essential for the response to tolvaptan (TLV), and urinary level of aquaporin 2 (U-AQP2) can be a marker for vasopressin-dependent activity of collecting duct. Hypothesis: Higher levels of U-AQP2 in proportion to plasma levels of vasopressin (P-AVP) may be associated with better initial responses to TLV and eventually result in the improved prognosis after long-term treatment of TLV. Methods: Consecutive 60 in-hospital patients with stage D heart failure (HF) who received TLV on a de novo basis were enrolled during 2011-2013. We also selected 60 HF patients by propensity score matching who were hospitalized during the same period but never treated with TLV. Events were defined as death and/or HF re-hospitalization. Results: TLV (3.75-15 mg/day) was continuously administered except death or ventricular assist device implantation occurred. There were 41 patients (group 1) who had increases in UV over the first 24 h after TLV initiation, and all of them had U-AQP2/P-AVP ≥0.5 х103 with higher U-AQP2 levels (5.42 ± 3.54 ng/mL) before TLV treatment. On the other hand, UV rather decreased even after TLV initiation in 19 patients over the first 24 h (group 2). Those in the group 2 universally had U-AQP2/P-AVP <0.5 х103, extremely low U-AQP2 levels (0.76 ± 0.59 ng/mL, p<0.001 vs. group 1), and similar P-AVP with the group 1 at baseline. The 41 and 19 patients without TLV treatment (group 3 and 4) were respectively matched to the group 1 and 2 by propensity scores. Interestingly, every patient in the group 3 had U-AQP2/P-AVP ≥0.5 х103, and vice versa in the group 4. Among the four groups, congestion-related symptoms were only improved in the group 1 after 1 month of enrollment. The patients in the group 1 had significantly better event-free survival over 2-year by TLV treatment compared with the group 3 (76% vs. 43%, p<0.014). In contrast, the patients in the group 2 and 4 had very poor prognoses regardless of TLV treatment (7% vs. 11%, p=0.823). Conclusions: U-AQP2/P-AVP is a novel predictor for the initial response to TLV in HF patients. Patients with higher U-AQP2/P-AVP may enjoy a better prognosis by long-term TLV treatment probably due to efficient resolution of congestion.

Changes in imatinib plasma trough level during long-term treatment of patients with advanced gastrointestinal stromal tumors.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 306-306
Author(s):  
Y. Kang ◽  
C. Yoo ◽  
B. Ryoo ◽  
H. Chang ◽  
J. Lee ◽  
...  
Keyword(s):  
Plasma Level ◽  
Gastrointestinal Stromal Tumors ◽  
Plasma Concentrations ◽  
Term Treatment ◽  
Albumin Concentration ◽  
Stromal Tumors ◽  
Long Term Treatment ◽  
The Mean ◽  
Median Interval

306 Background: Pharmacokinetic study in patients with gastrointestinal stromal tumors (GISTs) suggested that plasma concentrations of imatinib decrease following long-term exposure. We therefore measured changes in imatinib plasma trough levels (Cmin) after long-term exposure. Methods: Between November 2009 and May 2010, follow-up (FU) imatinib Cmin was measured in 65 patients who received the same dose of imatinib for at least 9 months after a previous baseline (BL) measurement. Total 244 blood samples were obtained (127 at BL and 117 at FU) and plasma level was measured by liquid chromatography-tandem mass spectrometry. Results: Median patient age was 54 years (range, 28–76 years) and 42 (64.6%) patients were male. Sixty-one (93.8%) patients were treated with 400 mg/day imatinib and 4 (6.2%) with 300 mg/day. The median interval from initiation of imatinib to BL test was 6.4 months (range, 0.5–66.6 months), and the median interval between BL and FU test was 13.1 months (range, 9.6–18.4 months). The mean ± standard deviation imatinib Cmin was significantly higher at FU than at BL (1442 ± 693 ng/mL vs 1221 ± 624 ng/mL, p<0.001). The mean inter- and intra-subject variabilities were 49.2% and 25.5%, respectively, at BL, and 44.2% and 20.4%, respectively, at FU. Multivariate analysis showed a significant correlation between the ratio of FU to BL imatinib Cmin and that of albumin (r=-0.397, p=0.001). In per-sample analysis, imatinib Cmin was significantly correlated with age, hemoglobin, albumin, creatinine clearance, previous major gastrectomy and time between initiation of imatinib and plasma level tests. Conclusions: Steady-state imatinib Cmin did not decrease but remained stable in most GIST patients during long-term treatment. Changes in imatinib Cmin were associated with changes in albumin concentration. Monitoring of imatinib Cmin only for concerns about time-dependent decreases in imatinib exposure is not necessary. [Table: see text]

scholarly journals Systemic and presystemic conversion of carbamazepine to carbamazepine-10,11-epoxide during long term treatment

2006 ◽  
Vol 12 (1) ◽  
pp. 13-16 ◽  
Author(s):  
Pietro Fagiolino ◽  
Marta Vázquez ◽  
Ivette Olano ◽  
Aurora Delfino
Keyword(s):  
Plasma Concentrations ◽  
Chronic Administration ◽  
Hplc Method ◽  
Term Treatment ◽  
Published Data ◽  
Long Term Treatment ◽  
Important Pathway ◽  
Kinetics Of ◽  
Dose Dependent

INTRODUCTION: Carbamazepine (CBZ) undergoes biotransformation, being CYP3A4 the major cytocrome P450 (CYP) enzyme catalyzing the carbamazepine-10,11-epoxide (EPOX) formation, which is quantitatively the most important pathway in CBZ metabolism. There is evidence of dose-dependent elimination of this drug due to its autoinduction capacity. Moreover, published data showed an incomplete bioavailability of CBZ since its absorption increases when grapefruit juice was administered. Both CYP3A4 and MRP2 (located in the enterocyte) are autoinduced during long term use of CBZ. As the other enzymes involved in CBZ metabolism are negligible in the gut, presystemic biotransformation through CYP3A4 could be responsible for the bioavailability of the drug as well as EPOX formation. OBJECTIVE: The purpose of our study was to assess the importance of presystemic formation of EPOX during the autoinduction of CBZ versus the daily administered dose. PATIENTS AND METHODS: 40 adults (average age: 28 years) and 29 children (average age: 9 years) receiving CBZ as monotherapy were included in the study. CBZ and EPOX plasma concentrations were analyzed by a previous validated HPLC method. RESULTS AND CONCLUSION: The results obtained confirmed the metabolic induction after chronic administration and provided new elements to suggest a strong contribution of dose-dependent bioavailability in the non linear kinetics of CBZ.

scholarly journals Contrasting effects of different levels of food intake and adiposity on LH secretion and hypothalamic gene expression in sheep

2002 ◽  
Vol 175 (2) ◽  
pp. 383-393 ◽  
Author(s):  
ZA Archer ◽  
SM Rhind ◽  
PA Findlay ◽  
CE Kyle ◽  
L Thomas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Leptin Receptor ◽  
In Situ Hybridisation ◽  
Plasma Concentrations ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Hypothalamic Arcuate Nucleus ◽  
Lh Secretion

Body reserves (long-term) and food intake (short-term) both contribute nutritional feedback to the hypothalamus. Reproductive neuroendocrine output (GnRH/LH) is stimulated by increased food intake and not by high adiposity in sheep, but it is unknown whether appetite-regulating hypothalamic neurons show this differential response. Castrated male sheep (Scottish Blackface) with oestradiol implants were studied in two 4 week experiments. In Experiment 1, sheep were fed to maintain the initial body condition (BC) score of 2.0+/-0.00 (lower BC (LBC), n=7) or 2.9+/-0.09 (higher BC (HBC), n=9), and liveweight of 43+/-1.1 and 59+/-1.6 kg respectively. LBC and HBC sheep had similar mean plasma LH concentration, pulse frequency and amplitude, but HBC animals had higher mean plasma concentrations of insulin (P<0.01), leptin (P<0.01) and glucose (P<0.01). Gene expression (measured by in situ hybridisation) in the hypothalamic arcuate nucleus (ARC) was higher in LBC than HBC sheep for neuropeptide Y (NPY; 486% of HBC, P<0.01), agouti-related peptide (AGRP; 467%, P<0.05) and leptin receptor (OB-Rb; 141%, P<0.05), but lower for cocaine- and amphetamine-regulated transcript (CART; 92%, P<0.05) and similar between groups for pro-opiomelanocortin (POMC). In Experiment 2, sheep with initial mean BC score 2.4+/-0.03 and liveweight 55+/-0.8 kg were fed a liveweight-maintenance ration (low intake, LI, n=7) while sheep with initial mean BC score 2.0+/-0.03 and liveweight 43+/-1.4 kg were fed freely so that BC score increased to 2.5+/-0.00 and liveweight increased to 54+/-1.4 kg (high intake, HI, n=9). Compared with LI, HI sheep had higher mean plasma LH (P<0.05), baseline LH (P<0.01) and pulse amplitude (P<0.01) and showed a trend towards higher pulse frequency. Although there were no differences in final mean plasma concentrations, there were significant increases over time in mean concentrations of insulin (P<0.001), leptin (P<0.05) and glucose (P<0.001) in HI sheep. Gene expression for AGRP in the ARC was higher in HI than LI animals (453% of LI; P<0.05), but expression levels were similar for NPY, OB-Rb, CART and POMC. Thus, the hypothalamus shows differential responses to steady-state adiposity as opposed to an increase in food intake, in terms of both reproductive neuroendocrine activity and hypothalamic appetite-regulating pathways. Differences in hypothalamic gene expression were largely consistent with contemporary levels of systemic leptin and insulin feedback; however, increased nutritional feedback was stimulatory to GnRH/LH whereas constant high feedback was not. The hypothalamus therefore has the ability to retain a nutritional memory that can influence subsequent responses.

scholarly journals Can we check serum lithium levels less often without compromising patient safety?

BJPsych Open ◽  
2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Adrian H. Heald ◽  
David Holland ◽  
Michael Stedman ◽  
Mark Davies ◽  
Chris J. Duff ◽  
...  
Keyword(s):  
Term Treatment ◽  
Lithium Therapy ◽  
Target Range ◽  
First Line ◽  
Lithium Level ◽  
Testing Frequency ◽  
Long Term Treatment ◽  
Group 2 ◽  
Prevention Of Relapse

Background Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder. Aims This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases. Method We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history. Results For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency. Conclusion We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.

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