Prostaglandins and medicine最新文献

In anaesthetized open-chest dogs, cardiac arrhythmias (CA) were induced by cumulative intravenous doses of aconitine or ouabain. Aconitine in a dose which did not induce CA had no influence on the PGE and PGF_2a effluxes into coronary sinus blood (CSB), whereas the PGE efflux into CSB increased after a subtoxic dose of ouabain. However, both PGE and PGF_2a effluxes were increased, when CA had developed. During aconitine induced CA, the PGE efflux was 6.5-fold and that of PGF_2a had increased by 80 %. During ouabain induced CA, the effluxes of both PGs were about 3-fold. Propranolol and lidocaine decreased the PGF_2α efflux into CSB by about 50 % and the PGE efflux was doubled after lidocaine and decreased after propranolol by about a third. The increased PGE efflux into CSB during CA was normalized after propranolol and quinidine if the CA was abolished or the cardiac rhythm improved. Lidocaine did not modify the increase in PGE efflux, despite the abolishment of CA. The increase in PGF_2α efflux was not influenced by antiarrhythmic drugs. The cyclic AMP and cyclic GMP in CSB remained unchanged during ouabain induced arrhythmias or after propranolol. The increased efflux of PGE into CSB during aconitine and ouabain induced CA and its abolishment by propranolol support the hypothesis that PGE participates in the modulation of increased sympathetic tone during CA.

In 30 patients after kidney transplantation, 6-oxo-PGF_1∝ was examined in unextracted plasma by a specific radioimmunoassay. The material was divided into three groups. Patients with acute transplant rejection showing the highest 6-oxo-PGF_1∝-levels, patients with delayed transplant rejection having significantly lower plasma values and a third group of patients with stable transplant function. In these patients the plasma 6oxo-PGF_1∝-values were below the lower limit of detection (70 pg/ml). The enchanced 6-oxo-PGF_1∝ during rejection crisis could be interpreted as a self protection meachanism of vascular tissue which is, however, not sufficient in many cases, to prevent the irreversible rejection of the transplant.

This study was performed on 20 children with congenital heart defect and left-to-right shunt. These patients were divided into two groups. Group I consisted of 10 patients with normal pulmonary arterial pressure while group IT consisted of 10 patients with pulmonary hypertension. Prostaglandin Like Materials (PLMs) in pulmonary venous and arterial blood which were taken during cardiac catheterization were extracted and biologically assayed for Prostaglandin-Like Activities (PGLA) on rat stomach fundus. In all patients of group I, the ratio of pulmonary venous to pulmonary arterial PGLA levels (PV/PA-PGLA) was found to be less than one. However in group IT, this ratio was less than one in only two patients. In 8 out of the patients in group II, the ratio was either 1 or greater. These data confirmed the early concepts suggesting the role of prostoglandins (PG) in regulating normal pulmonary circulation. In addition these data have suggested that PGs may have an important role in the development of pulmonary hypertension in some cardiac patients.

The sensitivity and contractility of isolated canine renal arteries (RA) and renal veins (RV) to primary prostaglandin compounds (PG) was studied. Studies were also undertaken to determine whether specific receptors for PGs exist in RA and RV.RA and RV exhibited potent concentration-dependent contractile responses to all the primary PGs studied, including PGA₁, PGA₂, PGB₂, PGD₂, PGE₁, PGE₂, PGF_1∝ and PGF_2∝. The contractile sensitivity (based on EC50's) of canine RA to PGs was. PGB₂ > PGB₁ ⋟ PGE₂ > PGF_2∝ ⋟PGA₂ ⋟ PGD₂ ⋟ PGA₁ > PGF_1∝ > PGE₁, whereas for RV it was:PGB₂ > PGB₁ ⋟ PGD2 = PGF_2∝ > PGA₂ = PGA₁ > PGE₂ >>> PGF_1∝ = PGE₁.In terms of the ability to generate a maximum contractile response on RA, PGB₂ was the most potent and PGDthe least potent, whereas for RV PGF_2∝ and PGB₂ was the most potent and PGF_1∝ and PGE the least potent. Canine RA failed to elicit any consistent relaxant responses to PGE₁, PGE₂, PGA₁, and PGA₂. Renal veins, however, in which tone was induced by either PGs or serotonin responded with concentration-related relaxations to PGE₁; other primary PGs did not induce relaxations on isolated RV. Use of specific pharmacologic antagonists (for catecholamines, serotonin, acetylcholine and histamine) failed to interfere with any of the PG responses. The data indicate that RA and RV: a) can exhibit differential responses to primary PGs; b) exhibit structure-activity relationships for the contractile action of PGs; and c) appear to have specific receptors for primary PGs which primarily subserve contraction.

Ca²⁺ at 2mM concentration stimulates the release of saturated and unsaturated fatty acids from intact washed platelets incubated at 37°C with stirring. Aspirin at a concentration of 0.4mM inhibits both cyclo-oxygenase activity and fatty acid efflux induced by Cat+. Thus, in intact washed platelets, aspirin reduces formation of cyclo-oxygenase products by direct inhibition of the enzyme and by reducing the availability of precursor arachidonate.

Bartter's syndrome is a state associated with hyperprostaglandinemia and high urinary excretion of prostaglandin derivatives. Because of numerous reports on prostaglandins acting as local modulators of the immune system, we have studied parameters of phagocytic function and of cellular and humural immunity in four patients with this disease.

An augmentation in chemotaxis was identified in Bartter's syndrome neutrophils. Despite some minor deviations in other parameters measured, no other gross derangement in immune function could be identified.

Several prostaglandins of the E and F series are now known to be involved in reproduction and developmental events. However, there is as yet no such evidence for any of the other arachidonate metabolites. Thromboxane B2 is the stable metabolic end product of the biologically active but unstable intermediate thromboxane A. Administered to developing chick embryos at 48 and 72 hours incubation, thromboxane B₂ caused growth retardation and induced a high incidence of anomalies, in particular,everted viscera.

The effect of prostaglandins (PGs) and other compounds on human serum oxytocinase (EC 3.4.11.3) activity in vitro was studied by a sensitive assay using S-berizyl-l-cysteine-p-nitroanilide as substrate. PGE₁, PGE₂ and PGF_2α significantly inhibited serum oxytocinase activity in a dose-related manner and in decreasing order of potency. cGMP, 8-bromo-cGMP, indomethacin, polyphloretin phosphate, hypertonic saline and urea were also active. cAMP, db-cAMP, 8-bromo-cAMP, db-cCMP, 5′-AMP, 5′-ADP, 5′-ATP, 5′-GDP, 5′-GTP, aspirin, sodium salicylate, paracetamol, theophylline and IBMX did not inhibit the enzyme activity. The results suggest that the oxytocic action of prostaglandins may be due, at least in part, to an inhibition of oxytocinase activity.

Infusion of 100 or 200 ng/min of Prostaglandin El (PGEl) or of 100 ng/min of PGE2 increased serum parathyroid hormone (PTH) in the rat. These infusions, however, had no significant effect on serum calcitonin (CT). Administration of 10 mg/kg of indomethacin for 3 days had no significant effect on basal serum PTH, CT or Calcium (Ca). EDTA infusion increased serum PTH to a similar degree in the vehicle- or indomethacin-treated rats. Therefore, endogenous prostaglandins do not appear to play a role in the secretion of PTH or CT.