scholarly journals Total and Free Plasma Concentrations of Progesterone, Cortisol and Oestradiol-I7ß during Pregnancy, Parturition and Early Lactation in Sows

1984 ◽  
Vol 37 (4) ◽  
pp. 267 ◽  
Author(s):  
JL Whitely ◽  
DL Willcox ◽  
JA Newton ◽  
GD Bryant-Greenwood ◽  
PE Hartmann

The total (bound plus free) concentrations of progesterone, 20a-<iihydroprogesterone, oestradiol-17{:1 and cortisol were determined in the plasma of sows at three stages during pregnancy and more intensively from 5 days pre-partum to 5 days post-partum. The free fractions of progesterone, oestradiol-17{3 and cortisol were measured in the same samples by a rate dialysis method. Up to day 110 of gestation, the amounts of free hormone in plasma did not fluctuate independently of their total concentrations. During farrowing, the total and free concentrations of progesterone and cortisol varied independently of each other, whereas total and free oestradiol-17{3 declined simultaneously. The initiation of parturition was associated with a decrease in circulating total progesterone, and was accentuated by a decrease in the free fraction (P<O� 005) so that its active free concentration was only 20% of its day 1 pre-partum value. Total and free cortisol concentrations rose rapidly during labour so that at 12-18 h after birth of the first piglet 30% of that cortisol in maternal plasma was free hormone.

1989 ◽  
Vol 120 (1) ◽  
pp. 113-117 ◽  
Author(s):  
C. Jansakul ◽  
R. G. King ◽  
A. L. A. Boura ◽  
S. P. Brennecke ◽  
G. M. Handberg

ABSTRACT Plasma concentrations of atrial natriuretic peptides (ANP) in female Wistar rats were measured by radioimmunoassay at oestrus, during pregnancy, during parturition and between 3 h and 4 days post partum. Concentrations of ANP in rats on days 10, 15 and 17 of pregnancy were not significantly different from those in non-pregnant animals in oestrus (32·5 ± 2·2 pmol/l; mean ± s.e.m., n = 9), but levels near term (days 20 and 21 of pregnancy) were reduced by approximately 50%. However, plasma concentrations of ANP at 6, 12 and 24 h post partum were approximately twice those of non-pregnant animals in oestrus, but returned to normal levels within 4 days after parturition. Maternal plasma volume increased significantly during pregnancy, and fell 15–20% 6–24 h post partum. These results suggest that the relationship between plasma volume and the plasma concentration of ANP is reset during pregnancy and changes rapidly post partum. The results do not necessarily, however, imply any changes in the relationship between atrial pressure and the concentration of ANP. Journal of Endocrinology (1989) 120, 113–117


2002 ◽  
Vol 48 (8) ◽  
pp. 1305-1313 ◽  
Author(s):  
Mads N Holten-Andersen ◽  
Ib Jarle Christensen ◽  
Hans Jørgen Nielsen ◽  
Hans Lilja ◽  
Gillian Murphy ◽  
...  

Abstract Background: We previously found differences in total concentrations of tissue inhibitor of metalloproteinases 1 (TIMP-1) in plasma from donors and cancer patients. Because TIMP-1 can exist in more than one molecular form, a new immunoassay to specifically detect free TIMP-1 was developed and concentrations were determined in plasma from healthy donors and colorectal cancer (CRC) patients. Methods: We established and validated an immunoassay for the specific measurement of free TIMP-1 that uses a polyclonal anti-TIMP-1 antibody for capture and a monoclonal anti-TIMP-1 antibody that binds only free TIMP-1 for detection of antigen. Plasma samples from healthy donors and CRC patients were assayed for free TIMP-1. Total TIMP-1 was measured by our previously published assay. Results: The mean (SD) concentrations of free TIMP-1 were similar in citrate [55.5 (11.5) μg/L] and EDTA plasma [58.9 (13.3) μg/L] from 76 donors (r2 = 0.82). In 154 donors, the ratio of free TIMP-1 [mean (SD), 64.5 (18.0) μg/L] to total TIMP-1 [83.8 (19.8) μg/L] in EDTA plasma was 0.77. Plasma concentrations of free and total TIMP-1 correlated significantly to age (free, r2 = 0.19; total, r2 = 0.27; P &lt;0.0001), increasing 50% over an age span of 45 years. Free and total TIMP-1 were significantly increased in CRC patients (P &lt;0.0001), whereas the ratio of free to total TIMP-1 (mean, 0.58) was significantly lower than in donors. Conclusions: Most of the TIMP-1 in donor plasma is present in its free form, and free TIMP-1 increases with age. Free and total TIMP-1 are increased in CRC patient plasma, but the ratio of free to total TIMP-1 is significantly lower in these patients than in donors.


Author(s):  
Richard Court ◽  
Kamunkhwala Gausi ◽  
Buyisile Mkhize ◽  
Lubbe Wiesner ◽  
Catriona Waitt ◽  
...  

Aim We aimed to explore the effect of pregnancy on bedaquiline pharmacokinetics and describe bedaquiline exposure in the human milk of mothers treated for rifampicin-resistant TB, where there is no human data available. Methods We performed a longitudinal pharmacokinetic study in pregnant women treated for rifampicin-resistant TB to explore the effect of pregnancy on bedaquiline exposure. Pharmacokinetic sampling was performed at four time-points over six hours in the third trimester, and again at approximately six weeks postpartum. We obtained serial human milk samples from breastfeeding mothers, and a single plasma sample taken from breastfed and non-breastfed infants to assess bedaquiline exposure. We used liquid chromatography-tandem mass spectrometry to perform the human milk and plasma bedaquiline assays, and population pharmacokinetic modelling to interpret the bedaquiline concentrations. Results We recruited 13 women, six of whom completed the ante- and post-partum PK sampling. All participants were HIV-positive on antiretroviral therapy. We observed lower ante- and post-partum bedaquiline exposures than reported in non-pregnant controls. Bedaquiline concentrations in human milk were higher than maternal plasma (milk to maternal plasma ratio: 24:1). A single random plasma bedaquiline and M2 concentration was available in four infants (median age: 6.5 weeks): concentrations in the one breastfed infant were similar to maternal plasma concentrations; concentrations in the three non-breastfed infants were detectable but lower than maternal plasma concentrations. Conclusion We report low exposure of bedaquiline in pregnant women treated for rifampicin-resistant TB. Bedaquiline significantly accumulates in human milk; breastfed infants receive mg/kg doses of bedaquiline equivalent to maternal doses.


Reproduction ◽  
2000 ◽  
pp. 49-57 ◽  
Author(s):  
SD Johnston ◽  
MR McGowan ◽  
P O'Callaghan ◽  
R Cox ◽  
V Nicolson

As an integral part of the development of an artificial insemination programme in the captive koala, female reproductive physiology and behaviour were studied. The oestrous cycle in non-mated and mated koalas was characterized by means of behavioural oestrus, morphology of external genitalia and changes in the peripheral plasma concentrations of oestradiol and progestogen. The mean (+/- SEM) duration of the non-mated oestrous cycle and duration of oestrus in 12 koalas was 32.9 +/- 1.1 (n = 22) and 10.3 +/- 0.9 (n = 24) days, respectively. Although the commencement of oestrous behaviour was associated with increasing or high concentrations of oestradiol, there were no consistent changes in the morphology or appearance of the clitoris, pericloacal region, pouch or mammary teats that could be used to characterize the non-mated cycle. As progestogen concentrations remained at basal values throughout the interoestrous period, non-mated cycles were considered non-luteal and presumed anovulatory. After mating of the 12 koalas, six females gave birth with a mean (+/- SEM) gestation of 34.8 +/- 0.3 days, whereas the remaining six non-parturient females returned to oestrus 49.5 +/- 1. 0 days later. After mating, oestrous behaviour ceased and the progestogen profile showed a significant increase in both pregnant and non-parturient females, indicating that a luteal phase had been induced by the physical act of mating. Progestogen concentrations throughout the luteal phase of the pregnant females were significantly higher than those of non-parturient females. Parturition was associated with a decreasing concentration of progestogen, which was increased above that of basal concentrations until 7 days post partum.


2014 ◽  
Vol 306 (2) ◽  
pp. F188-F193 ◽  
Author(s):  
Timo Rieg ◽  
Takahiro Masuda ◽  
Maria Gerasimova ◽  
Eric Mayoux ◽  
Kenneth Platt ◽  
...  

In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40–50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1−/−) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose/creatinine ratios in Sglt1−/− vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1−/− vs. WT after 24 h (−33 vs. −11%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC50 for SGLT2 in mice, which were associated with FGR of 64 ± 2% in WT and 17 ± 2% in Sglt1−/−. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations ∼10-fold and reduced FGR to 44 ± 3% in WT and to −1 ± 3% in Sglt1−/−. The absence of renal glucose reabsorption was confirmed in male and female Sglt1/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50–60% of filtered glucose is excreted.


1990 ◽  
Vol 124 (1) ◽  
pp. 99-107 ◽  
Author(s):  
R. J. MacIsaac ◽  
R. S. Carson ◽  
A. P. Horvath ◽  
E. M. Wintour

ABSTRACT This study was designed to investigate the effects of pulsatile infusion of ACTH into ovine fetuses on the endocrine changes that precede parturition, the timing of birth and the subsequent survival of the lamb. Where appropriate, these parameters were compared with fetuses infused with pulses of saline and uninfused normal term fetuses. Ten fetuses received a 15-min infusion of synthetic ACTH(1–24) (79 ng/min) from day 125 (n=9) or day 126 (n=1) of gestation. Seven fetuses were born prematurely within 174±14 h (mean ± s.e.m.) after the commencement of the infusion, i.e. at 132 ± 0·6 days, whilst three died in utero at 130–131 days. When born all lambs could breath, walk and suckle. Of the seven premature lambs, four died 2–10 days after parturition but three survived for at least 12 months after birth. Fetuses infused with pulses of ACTH exhibited intermittent but very large increases in plasma ACTH values, with the first pulse, on day 1, increasing ACTH values from 5·1 ± 1·1 to 140 ± 31·3 pmol/l (P<0·001). At the next sampling time, ACTH values were not significantly different from preinfusion values. A similar plasma ACTH profile was observed on each subsequent day of ACTH treatment. In contrast, fetuses (n=4) infused with pulses of saline between 125 and 131 days exhibited fetal plasma concentrations of ACTH which ranged between 2 and 12 pmol/l for the majority of the time. Of the uninfused fetuses (n=8) that were studied during the last week of normal gestation, seven were born alive at 148·9± 1·0 days of gestation, whilst one lamb was stillborn at 146 days. In these fetuses, plasma concentrations of ACTH increased slowly to 35·6 ±2·4 pmol/l on the day before delivery with a further increase to 76·4± 3·9 pmol/l occurring on the day of delivery. In fetuses infused with pulses of ACTH there was also a significant (P< 0·001) increase in the fetal cortisol to corticosterone ratio from a value of 2·9 before the commencement of the infusion to 69·1 just before birth. In ewes bearing uninfused fetuses born at normal term, maternal plasma concentrations of progesterone on day 4 before delivery were significantly (P<0·05) lower than on day 5 before delivery. In comparison, in ewes bearing fetuses infused with pulses of ACTH, a significant (P<0·05) decrease from maternal plasma concentrations of progesterone on day 5 before delivery did not occur until day 1 before delivery. In ewes bearing uninfused or prematurely delivered fetuses infused with pulses of ACTH, maternal plasma concentrations of oestrogen did not significantly (P<0·01) increase until the day of parturition. It is concluded that a minimum of 6–7 days of ACTH treatment is required by the fetal adrenal for the induction of cortisol synthesis sufficient to produce the birth of viable lambs. However, premature lambs have a 57% mortality rate in the 2- to 10-day period after birth. Journal of Endocrinology (1990) 124, 99–107


2000 ◽  
Vol 43 (3) ◽  
pp. 95-101
Author(s):  
Stanislav Mičuda ◽  
Martin Hodač ◽  
Petr Pařízek ◽  
Miloslav Pleskot ◽  
Luděk Šišpera ◽  
...  

The present work was designed to determine whether the individual differences in pharmacokinetics and pharmacodynamics of amiodarone and its N-desethyl metabolite are related to cytochrome CYP3A metabolizer status. Methods: 12 cardiac patients with inducible ventricular tachyarrhythmias during the baseline electrophysiologic study were enrolled in this study. Urinary 24-hour excretion of 6β-hydroxycortisol (6β-OHC and the ratio of 6β-hydroxycortisol to urinary free cortisol (6β-OHC/UFC) were measured before the first amiodarone administration. Trough plasma concentrations of amiodarone and N-desethylamiodarone (N-DEA) were measured after 79 ± 11 days (2nd period) and after 182 ± 25 days (3rd period). Electrophysiologic effects of amiodarone therapy were established with serial electrophysiologic studies in 9 of these patients at the baseline and after 79 ± 11 days (during the second period). Results: Both the 6β-OHC excretion and 6β-OHC/UFC ratio varied approximately 6-fold between the patients. We found significant inverse correlation between the 6β-OHC excretion and the trough plasma concentrations of amiodarone at the time of the 3rd period (rs = -0.58, p < 0.05). Similarly, there was correlation between the 24-hour urinary 6β-OHC excretion and trough plasma concentrations of amiodarone during the 3rd period (rs = -0.64, p < 0.025). We were unable to detect any association between CYP3A activity and amiodarone pharmacodynamics. Conclusion: This study points toward important information value of CYP3A metabolizer status in the context of therapeutic drug monitoring of amiodarone.


2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
M. Ouidir ◽  
P. Mendola ◽  
G.M. Buck Louis ◽  
K. Kannan ◽  
C. Zhang ◽  
...  

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