Baseline Plasma Concentrations Research Articles

RELEASE OF PROSTACYCLIN IN VIVO AND ITS ROLE IN MAN

Concentrations of 6-oxo-prostaglandin F1α (6-oxo-PGF1α), the stable hydrolysis product of prostacyclin (PGI2) were determined in venous blood sampled from a forearm vein after dextrose (10% w/v) perfusion and after subsequent distension with physiological saline in seven healthy volunteers. 6-oxo-PGF1α was measured by gas chromatography/negative ion chemical ionisation mass spectrometry. Local release of PGI2 was demonstrated in six volunteers: in three both stimuli were effective and in three only one stimulus was effective. In seven trained athletes studied before and after vigorous exercise baseline plasma concentrations of 6-oxo-PGF1α were <1·3-3·2 pg/ml. The concentration increased after exercise in each subject (mean 10·9 pg/ml; range 5·5-18·2 pg/ml). Mild chemical and mechanical stimuli therefore can cause local production of PGI2 from human blood vessels in vivo.

Thyrotropin-releasing hormone stimulated pituitary and thyroid gland responsiveness and 3,5,3'-triiodothyronine suppression in fetal and neonatal lambs.

To evaluate the development of the pituitary thyroid axis and negative feedback control of TSH secretion, ovine TSH (oTSH) and T4 were measured by RIA in plasma samples obtained before and 15, 30, 60,120, and 240 min after an iv bolus injection of TRH in fetal lambs between 105-113 days gestation (group I) and between 125–129 days gestation (group II); newborn lambs also were injected between 7–12 days of age (group III). In each group, the TRH injection and plasmasampling protocols were repeated 14–18 h after an iv injection of T3. Plasma oTSH concentrations increased in all animals in response to TRH injection. Neither the difference between the peak and baseline plasma concentrations (ΔTSH) nor the integrated area under the plasma concentration-response curves (∫TSH) correlated with gestational age. Both responses, however, correlated with baseline oTSH concentrations (r = 0.72 and r = 0.73, respectively; P < 0.02 for both) and both (ΔTSH and ∫TSH) were significantly decreased in group III newborn anim...

Effect of thyrotropin-releasing hormone on secretion of thyrotropin, prolactin, thyroxine, and triiodothyronine in pregnant and fetal rhesus monkeys.

The effect of thyrotropin-releasing hormone (TRH) on the pituitary-thyroid axis and on prolactin secretion was studied in pregnant Rhesus monkeys during the latter period of gestation and in non-pregnant female controls. The baseline plasma concentrations of TSH, T3, T4, and prolactin (PRL) of pregnant monkeys did not differ from those of non-pregnant monkeys. After administration of TRH, plasma prolactin rose to higher levels in pregnant monkeys than in non-pregnant monkeys whereas there was a similar response of plasma TSH, T4 and T3 in both groups. The baseline plasma TSH was elevated and plasma T3 was decreased in the fetus compared with the mother. Administration of TRH iv to the maternal monkey caused a larger response in the fetal plasma TSH than in that of the mother and was followed by larger increments in plasma T4 and T3 concentrations in the fetuses than in the mothers. The larger increments of plasma TSH and thyroid hormones in the fetus compared with the mother also occurred when TRH was given iv to the fetus. There was a significant rise of plasma prolactin in both mother and fetus after administration of TRH to mother or fetus; the increase of plasma PRL was much higher in the mother than in the fetus. The data show that TRH can cross the primate placenta in either the maternal to fetal or fetal to maternal direction. The fetal thyroid of the Rhesus monkey during the latter period of gestation can release both T4 and T3 in response to TSH.

Circulating thyroid hormones and thyrotropin in adult patients with protein-calorie malnutrition.

We studied plasma concentrations of thyroxine (T4), triiodothyronine (T3), free T4, free T3, thyrotropin (TSH), albumin and thyroxine-binding globulin (TBG) before and following 56 to 145 days (mean, 85) of refeeding in ten Indian patients who had severe protein-calorie malnutrition (PCM). The mean baseline plasma T4 concentration of 8.2 mug per 100 ml in these patients was comparable to the corresponding post-treatment value of 7.7 mug per 100 ml. However, since the dialyzable fraction of T4 (DFT4) was considerably higher (0.048 vs 0.029%), the mean baseline plasma free T4 concentration, 3.8 ng per 100 ml, was significantly greater than the mean post-treatment value of 2.2 ng per 100 ml. The mean baseline plasma concentration of T3, 21 ng per 100 ml, was markedly lower than the corresponding value of 96 ng per 100 ml after treatment. The mean plasma concentration of free T3, 94 pg per 100 ml, was also significantly lower than the post-treatment value of 303 pg per 100 ml. This was the case even when the mean DFT3 prior to treatment was significantly higher than that following treatment (0.46 vs 0.32%). The mean baseline ratio of plasma concentrations of total T3 and T4 (T3/T4 X 100) of 0.25 was significantly lower than the corresponding normal value of 1.3 after treatment. The mean plasma TSH concentration of 6.0 muU per ml in patients prior to treatment was comparable to the mean value of 5.5 muU per ml following treatment. The mean baseline plasma concentration of TBG of 3.3 mg per 100 ml was also comparable to the mean post-treatment value of 3.6 mg per 100 ml. The data on thyroid hormone levels in PCM can be explained if there were i) a selective increase in metabolic clearance rate of T3 without a change or a decrease in that of T4 and ii) a reversible defect in extrathyroidal conversion of T4 to T3. The latter possibility appears more likely.

Hydrocortisone Suppression Test for Cushing Syndrome

To develop a reliable suppression test for corticotropin (adrenocorticotrophic hormone, ACTH) for use in patients receiving anticonvulsant drugs, we selected hydrocortisone suppression of plasma corticosterone (B), whose secretion is regulated by corticotropin, thus eliminating the drug interference observed with the dexamethasone suppression test. By estimating an 8 AM base line plasma B concentration and administering 50 mg of hydrocortisone orally at midnight, we could evaluate its effect on plasma B suppression the following morning at 8 AM. The overnight suppression tests with 1 mg of dexamethasone and 50 mg of hydrocortisone reduced the plasma B concentration to less than 50% of the base line value and to less than 120 ng/deciliter in control subjects, but they failed to result in suppression in patients with Cushing syndrome. The 1-mg dose of dexamethasone caused no suppression in patients treated with anticonvulsants, whereas following hydrocortisone, base line plasma concentrations were reduced by more than 50%. The test appears to be as reliable a screening test for Cushing syndrome in drug-treated patients as the overnight dexamethasone suppression test is in patients not receiving drugs.

Osmotic extraction of hypotonic fluid from the lungs.

After injections of sucrose, NaCl, and urea solutions, the flow of tissue fluid from the lungs amounted to 0.182, 0.216, and 0.152 x 10(-3) ml/s per mosmol/kg of concentration difference between plasma and tissues in each gram of wet tissue weight. The extracted fluid contained less than 20% of the Na(+), K(+) and urea concentrations of the plasma. It was concluded that this fluid was distinctly hypotonic in comparision with the fluids of the plasma and tissue compartments both before and after the injection of hypertonic solutions. The presence of low solute concentrations in the extracted fluid is attributed to the passage of this fluid across cellular membranes, which are relatively impermeable to small hydrophilic solutes. Movement of fluid out of the junctions appears to be less than that through the endothelial cells. It is suggested that the injected solutes rapidly leak into the junctions and consequently induce relatively little movement of water or tissue solutes out of the junctions. Concentrations of tritiated water and [(14)C]antipyrine in the extracted fluid are essentially the same as base-line plasma concentrations when the animals have been primed with these tracers. It is therefore likely that these tracers can readily traverse cellular membranes. Red cell transit through the lungs is impaired by hypertonic solutions of sucrose and NaCl with transient increases in pulmonary arterial hemoglobin concentrations of as much as 35% of base-line values.