CIRCA-ANNUAL RHYTHMS OF PROLACTIN SECRETION IN EWES AND THE EFFECT OF PINEALECTOMY

1980 ◽  
Vol 84 (1) ◽  
pp. 83-89 ◽  
Author(s):  
C. J. MUNRO ◽  
K. P. McNATTY ◽  
L. RENSHAW

Changes in the plasma concentration of prolactin in intact, pinealectomized, shampinealectomized, ovariectomized and hysterectomized ewes were investigated over a period of 11 months. The concentrations of prolactin were consistently low (<20 ng/ml) during the winter months (short photoperiod) in the intact, sham-pinealectomized, ovariectomized and hysterectomized animals. In contrast, the concentrations of prolactin were consistently raised (> 50 ng/ml) during the summer months (long photoperiod) in the same groups. During the transitional period from winter to summer the concentrations of prolactin were correlated with the reproductive status of the animals. In the pregnant animals, the prolactin concentrations increased from low values during pregnancy to high values at parturition. During lactation, the concentrations of prolactin in these animals remained high, although they were lower than those found subsequently during the summer months when the ewes were no longer lactating. In the non-pregnant ewes (i.e. the ovariectomized and hysterectomized animals), the prolactin concentrations increased more gradually during the transitional period from winter to summer than was the case in the parturient animals. In the pinealectomized ewes, the plasma concentrations of prolactin were raised throughout the year, irrespective of whether the animals were pregnant, lactating or in anoestrus. In these animals, the only occasion when prolactin concentrations were consistently low was during the mid-winter period, although they were also low at times during the period of oestrous activity. It was concluded that the circa-annual pattern of prolactin concentrations in ewes is primarily determined by the photoperiod, and that the pineal gland in the ewe is an important translator of the photoperiod. Parturition and suckling have important, but secondary, influences. Moreover, it was concluded that the secretions from the reproductive tract and the seasonal variations in temperature normally have little influence by themselves on the circa-annual rhythm of prolactin.

1987 ◽  
Vol 65 (4) ◽  
pp. 833-836 ◽  
Author(s):  
C. Haldar-Misra ◽  
M. Srivastava

The role of the pineal gland in mediating the effects of photoperiod on the reproductive axis is not well established in tropical mammals. Indian palm squirrels (Funambulus pennanti) were exposed to experimental long (16L:8D) and short (6L:18D) photoperiods. It was observed that the testes regressed in response to short photoperiod, while during the long photoperiod the gonads were active. When squirrels were maintained for a long experimental period (130 days) under the short photoperiodic schedule (6L:18D), gonadal regrowth eventually occurred even though the photoperiod was the same one that initially induced testicular regression. Pinealectomized animals maintained the gonadal activity even in short photoperiod, suggesting that the effect of photoperiod is mediated through the pineal gland.


2012 ◽  
Vol 507 (1) ◽  
pp. 16-21 ◽  
Author(s):  
E. Díaz ◽  
N. Vázquez ◽  
C. Fernández ◽  
V. Jiménez ◽  
A. Esquifino ◽  
...  

2020 ◽  
Vol 21 (2) ◽  
pp. 126-131
Author(s):  
Bhuvanachandra Pasupuleti ◽  
Vamshikrishna Gone ◽  
Ravali Baddam ◽  
Raj Kumar Venisetty ◽  
Om Prakash Prasad

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.


2020 ◽  
Vol 21 (8) ◽  
pp. 744-750 ◽  
Author(s):  
Hongyang Li ◽  
JingyaWei ◽  
Fengtao Ma ◽  
Qiang Shan ◽  
Duo Gao ◽  
...  

In-depth studies have identified many hormones important for controlling mammary growth and maintaining lactation. One of these is melatonin, which is synthesized and secreted by the pineal gland to regulate circadian rhythms, improve antioxidant capacity, and enhance immunity. Prolactin is secreted by the pituitary gland and is associated with the growth and development of mammary glands as well as initiation and maintenance of lactation. The hypothalamus-pituitary system, the most important endocrine system in the body, regulates prolactin secretion mainly through dopamine released from tuberoinfundibular dopaminergic neurons. This review provides a reference for further study and describes the regulation of lactation and prolactin secretion by melatonin, primarily via the protection and stimulation of tuberoinfundibular dopaminergic neurons.


2020 ◽  
Vol 16 ◽  
Author(s):  
Xi He ◽  
Wenjun Hu ◽  
Fanhua Meng ◽  
Xingzhou Li

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.


2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 128-128
Author(s):  
Hannah Speer ◽  
Hannah Riley ◽  
Robert Cushman ◽  
Harvey Freetly ◽  
Mary Drewnoski

Abstract Spring-born heifers (n = 1,012) weaned at 148 ± 17 d were used in a 3-yr study to evaluate performance in winter development systems which utilized cover crop and corn residue grazing. Heifers were assigned to 1 of 3 treatments: grazing corn residue with dried distillers grains (CD) or wheat midds (CW) supplementation, or grazing late summer planted oat-brassica cover crop followed by corn residue supplemented dried distillers grains (CC). Grazing of corn residue (CD and CW) and cover crop (CC) began in early November. Supplementation during the corn residue phase was adjusted to target ~55% of mature BW (338 kg) at breeding. After 63 d, CC were moved to corn residue; on d 77 CD and CW began receiving grower ration. In mid-February (d 98), heifers were comingled and managed in a single group. Breeding season began in June and lasted for 29 d. Prior to corn residue grazing, ADG of CC was greater (0.76 kg/d; P&lt; 0.01) than CD or CW (0.58 kg/d and 0.49 kg/d, respectively). Gain during the last 35 d of the winter period for CC was 0.13 kg/d less than CW (P&lt; 0.01) but not different from CD. Overall winter ADG was greater (P&lt; 0.05) for CC (0.62 kg/d) than CD (0.53 kg/d) or CW (0.50 kg/d). Percent of mature BW prior to breeding was 52% for CC and 50% for CD and CW. May reproductive tract scores did not differ (P=0.26) between CC and CW but were greater (P&lt; 0.05) in CC than CD. Pregnancy rates were affected by treatment (P&lt; 0.01), with CC (76%) being greater than CD (68%) and CW (64%). Utilizing oat-brassica cover crops early in the winter followed by a lower rate of gain while grazing corn residue appear to be effective for developing beef heifers. USDA is an equal opportunity employer and provider.


2020 ◽  
Vol 37 (12) ◽  
Author(s):  
Hannah Britz ◽  
Nina Hanke ◽  
Mitchell E. Taub ◽  
Ting Wang ◽  
Bhagwat Prasad ◽  
...  

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.


1984 ◽  
Vol 62 (12) ◽  
pp. 1479-1486 ◽  
Author(s):  
Jean-Paul Clozel ◽  
Jacques Billette ◽  
Gilles Caillé ◽  
Pierre Théroux ◽  
Richard Cartier

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.


2015 ◽  
Vol 59 (6) ◽  
pp. 3240-3245 ◽  
Author(s):  
Kanokrat Rungtivasuwan ◽  
Anchalee Avihingsanon ◽  
Narukjaporn Thammajaruk ◽  
Siwaporn Mitruk ◽  
David M. Burger ◽  
...  

ABSTRACTTenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded byABCC2andABCC4, respectively. Genetic polymorphisms of these transporters may affect the plasma concentrations of tenofovir. Therefore, the aim of this study was to investigate the influence of genetic and nongenetic factors on tenofovir plasma concentrations. A cross-sectional study was performed in Thai HIV-infected patients aged ≥18 years who had been receiving tenofovir disoproxil fumarate at 300 mg once daily for at least 6 months. A middose tenofovir plasma concentration was obtained. Multivariate analysis was performed to investigate whether there was an association between tenofovir plasma concentrations and demographic data, including age, sex, body weight, estimated glomerular filtration rate (eGFR), hepatitis B virus coinfection, hepatitis C virus coinfection, duration of tenofovir treatment, concomitant use of ritonavir-boosted protease inhibitors, and polymorphisms ofABCC2andABCC4. A total of 150 Thai HIV-infected patients were included. The mean age of the patients was 43.9 ± 7.2 years. The mean tenofovir plasma concentration was 100.3 ± 52.7 ng/ml. In multivariate analysis, a low body weight, a low eGFR, the concomitant use of ritonavir-boosted protease inhibitors, and theABCC44131T → G variation (genotype TG or GG) were independently associated with higher tenofovir plasma concentrations. After adjusting for weight, eGFR, and the concomitant use of ritonavir-boosted protease inhibitors, a 30% increase in the mean tenofovir plasma concentration was observed in patients having theABCC44131 TG or GG genotype. Both genetic and nongenetic factors affect tenofovir plasma concentrations. These factors should be considered when adjusting tenofovir dosage regimens to ensure the efficacy and safety of a drug. (This study has been registered at ClinicalTrials.gov under registration no. NCT01138241.)


1986 ◽  
Vol 109 (2) ◽  
pp. 169-174 ◽  
Author(s):  
J. N. Hugues ◽  
A. Enjalbert ◽  
E. Moyse ◽  
C. Shu ◽  
M. J. Voirol ◽  
...  

ABSTRACT The role of somatostatin (SRIF) on adenohypophysial hormone secretion in starved rats was reassessed by passive immunization. Because of the absence of pulsatile GH secretion in starved rats, the effects of the injection of SRIF antiserum on GH levels can be clearly demonstrated. To determine whether starvation modifies the sensitivity of the adenohypophysis to SRIF, we measured 125I-labelled iodo-N-Tyr-SRIF binding. There was no difference in the dissociation constant (Kd) nor in the maximal binding capacity (Bmax) in fed (n = 15) and starved (n = 15) animals (Kd = 0·38 ± 0·09 (s.e.m.) and 0·45 ± 0·09 nmol; Bmax = 204 ± 39 and 205 ± 30 fmol/mg protein respectively). Administration of SRIF antiserum resulted in a dose-dependent increase in plasma concentrations of GH, TSH and prolactin. The minimal effective dose of SRIF antiserum was 50 μl for GH, 100 μl for TSH and 200 μl for prolactin. Our results show that: (1) starvation does not modify adenohypophysial SRIF-binding sites, (2) in starved male rats endogenous SRIF exerts a negative control on prolactin secretion in vivo and (3) sensitivity to endogenous SRIF seems to be different for each hypophysial cell type. J. Endocr. (1986) 109, 169–174


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