Placental control of ovarian immunoreactive relaxin secretion in the pregnant rat.

To investigate the control mechanisms for the secretion of relaxin in pregnant rats, the effects of the fetus, placenta, and uterus were studied. Plasma immunoreactive relaxin and progesterone were measured in pregnant rats, from days 8--1 post partum. On day 16 of pregnancy, groups of animals were subjected to removal of the fetuses, conceptuses (fetuses and placentae), or uteri. To determine whether there are extraovarian sources of circulating relaxin, a group of pregnant rats was ovariectomized on day 16. Immunoreactive relaxin was undetectable in the plasma of pregnant rats before day 10, and increased to a mean concentration of 0.52 +/- 0.01 (SEM) ng/ml on day 13. In control animals, immunoreactive relaxin levels remained at about this concentration throughout the remainder of pregnancy and declined rapidly post partum. The pattern of secretion of relaxin in fetectomized animals was similar to that in controls. In contrast, a significant decline in immunoreactive relaxin was seen, within 24 h after surgery, in those animals in which removal of the conceptuses or hysterectomy was performed. In these animals, immunoreactive relaxin was undetectable within 48 h after surgery and remained undetectable throughout the experimental period. In animals that were ovariectomized, immunoreactive relaxin was undetectable 24 h after surgery. Progesterone secretion in animals that had fetectomy or removal of the conceptuses performed was similar to that in controls. These groups showed a significant decline in progesterone on day 17 of pregnancy, and progesterone continued to decline until day 1 post partum. Progesterone in hysterectomized animals declined more abruptly than in either controls or other experimental groups. Ovariectomy resulted in a prompt fall in plasma progesterone. These results indicate that in the rat, the fetus is not needed for the maintenance of relaxin secretion throughout pregnancy, the placenta controls the ovarian secretion of relaxin. The uterus does not exert a tropic effect upon relaxin secretion, no extraovarian sources of circulating relaxin exist in the rat, and there is a divergence between progesterone and relaxin secretion during rat pregnancy.

Preservative effect of combinations of acetic acid with lactic or propionic acid on buffalo meat stored at refrigeration temperature.

A silverside of buffalo was cut in 15 equal-sized steaks and divided into five groups, each group containing three steaks. The steaks from groups 1,2,3 and 4 were treated with 1, 2, 3 and 4% acetic:lactic acid combinations, respectively, and the fifth group was kept as a control. Similar treatments were also given with acetic: propionic acid mixtures. The microbial analysis and changes in colour and odour were noted at 0, 24, 72 and 168 h. The bacteriostatic and bacteriocidal action of the acid mixtures increased with increasing concentration but the effect was reduced as the time advanced. Both acid mixtures had pronounced antibacterial effect on gram negative organisms than gram positive ones. The 3% acetic: lactic acid combination showed reduction in bacterial numbers without affecting the colour and odour of buffalo meat and is recommended for decontamination and preservation of meat for up to seven days at refrigeration temperature (7 ± 1°C).

Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE inhibitor spirapril in patients with chronic liver disease.

The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensin-converting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n = 10), in patients with chronic, non-cirrhotic liver disease (n = 8) and in a control group of healthy subjects (n = 16). The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 micrograms.h.l-1, 923 micrograms.h.l-1 and 1300 micrograms.h.l-1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively. Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h-1 in patients vs. 2.00 h-1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls. Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients.

Urinary creatinine as an index of urinary excretion of estrogen in cows prepartum and postpartum.

Urine was collected from 55 cows via indwelling urinary catheters for periods of 12 h on different days (28 days prepartum to 60 days postpartum). Excretion of urinary creatinine (mg/h per kg bodyweight) among Holsteins increased from .94 on day 28 prepartum to 1.14 on day .5 postpartum and then decreased to .82 on days 30 to 45 of lactation. Excretion of creatinine among 12-h collections of urine on different days did not differ for groups of cows within periods prepartum and postpartum, and coefficients of variation within cows were 12 to 13%. Ratio of urinary estradiol (-17 alpha) to urinary creatinine was correlated (.93) more highly with its excretion based on volume of urine excreted than was its urinary concentration (.79) within periods prepartum and postpartum. Ratios of urinary metabolites to urinary creatinine rather than their concentrations should be used to express rates of excretion in cows' urine when urine excreted per hour is unknown. Moreover, daily rates of excretion of estradiol in urine can be estimated [ng estradiol/day = A X ng/mg urinary creatinine x kg bodyweight x 24 h, where A is average excretion of urinary creatinine (mg/h per kg bodyweight)] for respective days prepartum and postpartum.

Plasma levels of progesterone in pseudopregnant rabbits actively immunized with a progesterone-protein conjugate.

PIP: The effects of active immunization with a progesterone protein conjugate on plasma progesterone levels in rabbits injected with a luteinizing dose of human chorionic gonadotropin (HCG) were determined. Mature female New Zealand rabbits were used. As antigen, a hemisuccinate of llalpha-hydroxyprogesterone was linked with bovine serum ablumin using the acetic anhydride method. Nuclear magnetic resonance analysis revealed that 24 moles of the hemisuccinate were linked with each mole of the protein. The conjugate was lyophilizied and stored at 4 degrees C. For immunization, an emulsion was prepared using equal volumes of Freund's complete adjuvant and .15 m NaCl solution of the immunogen. 7 rabbits received intradermal injections and 7 received weekly sc injections for 6 weeks. Sera were collected weekly for 6 weeks. Animals with high levels of antibody production were given iv injections of 1 mg of conjugate to boost antibody titers. Pseudopregnancy was induced in 14 rabbits by iv injection of 100 IU HCG. 5 weeks after the immunization schedule was finished animals were made pseudopregnant again and daily plasma progesterone was determined. Increased levels of antibodies to progesterone were found in all immunized animals but not in controls. Plasma progesterone levels in treated animals increased to a peak on Day 9 of pseudopregnancy. On Days 0 through 10, 17, and 18 progesterone values in immunized animals were significantly (p less than .05) higher than those of controls. It is concluded that immunization of rabbits by this method lead to abnormally high levels of peripheral progesterone in pseudopregnancy. I n a subsequent study it was found that despite the high plasma progesterone concentration produced in immunized animals, these females could be successfully mated.^ieng

Radioimmunoassays for spirapril and its active metabolite spiraprilate: performance and application.

Radioimmunoassays for a nonsulfhydryl angiotensin converting enzyme inhibitor prodrug--spirapril--and its active metabolite--spiraprilate--are described. Nonextraction equilibrium assays using antibodies with a high specificity for spirapril or spiraprilate were used, with charcoal separation of bound and free tracer. Within-assay reproducibility (CV%) was less than 20% in the concentration range 0.5-40 micrograms/L for both analytes and the comparable value for between-assay reproducibility was less than 25%. Results for external quality control samples were in good agreement with the expected values of 0-250 micrograms/L (spirapril, r = 0.997) and 0-300 micrograms/L (spiraprilate, r = 0.999). Overall, samples circulated to four laboratories gave good agreement for measured values, including one center using gas chromatography-mass spectrometry analysis for the two compounds. Data are presented to show the suitability of these two assays to the measurement of spirapril and spiraprilate in clinical samples from assays to the measurement of spirapril and spiraprilate in clinical samples from dose-ranging and bioequivalence studies. Results are also shown relating drug plasma concentration data to a measurement of the pharmacodynamic effects of spiraprilate, namely inhibition of angiotensin converting enzyme activity. It is concluded that these assays have the sensitivity for use in studies to model the relationship between the pharmacokinetics and pharmacodynamics of the two compounds.