Plasma PGE2 Concentrations Research Articles

LONG TERM PROSTAGLANDIN SYNTHESIS INHIBITORS (PGSI) AND TRACHEAL FLUID (TF) PRODUCTION IN FETAL SHEEP

In fetal sheep, TF production is relatively constant during the last month of gestation; it decreases in the few days before birth, a time when fetal plasma PGE2 concentrations ([PGE2]) are rising. Short term (12 h) infusions of PGE2 decrease TF production, suggesting that the rise in endogenous [PGE2] may be responsible for the prepartum decrease in TF production. To investigate the possible role of PGE2 in the control of TF production before birth, we studied 5 chronically catheterized fetal sheep from 131-150d gestation. In 4 animals, we infused meclofenamate (Mec), a PGSI, at 1.4-2.8 mg/h (a dose previously shown to decrease [PGE2]); the infusion was continued until birth or fetal demise (5-13d). A control animal received an infusion of vehicle only, for 11d. Each day we collected tracheal fluid from a tracheal cannula and a soft, intrauterine collection bag. TF production in experimental and control animals was similar to previously reported normal values. During the 2 days prior to birth TF production progressively decreased in all animals to 30% of the usual rate; this decrease is similar to that previously reported. Thus, Mec did not prevent the prepartum decrease in TF production. We conclude that in the last few days before birth, the rise in [PGE2] does not cause the fall in TF production. (Supported by USPHS Grant HL 27356 (Pulmonary SCOR) and ALA Fellowship Grant.)

Effect of gestational age on ductus arteriosus response to circulating prostaglandin E 2

Premature newborn lambs with a patent ductus arteriosus have higher plasma prostaglandin E2 concentrations than near-term newborn lambs with a contricted ductus arteriosus. To see whether these concentrations of PGE2 could produce patency of the ductus arteriosus, we studied eight near-term lambs (with constricted ductuses) delivered by cesarean section, paralyzed, and mechanically ventilated. After ductus arteriosus resistance and plasma PGE2 concentrations had stabilized, a continuous PGE2 infusion into the superior vena cava was started to determine threshold concentrations needed to dilate the ductus in vivo. By two hours after birth, circulating PGE2 concentrations in near-term lambs were considerably less then the threshold concentration, and the ductuses were constricted. In five premature newborn lambs, significantly lower concentrations of PGE2 were required to dilate the ductus: threshold and ED50 concentrations were one sixth and one third, respectively. In these premature lambs during the first two hours after birth, circulating PGE2 concentrations were twice as high as the calculated in vivo threshold level. Therefore, circulating PGE2 concentrations probably played a significant role in the patency of the ductus arteriosus in these premature lambs.

Prostaglandin E2 and cyclic AMP in tumor and plasma of breast cancer patients.

Prostaglandin E2 and cyclic AMP (cAMP) levels were measured in tumors and plasma of 78 patients with benign and malignant breast tumors. Two groups of malignant tissues were found, one with a high level of PGE2 (M = 55.4 pg/mg) and one with a low level (M = 10.7 pg/mg). The low level did not differ significantly from the benign tissue level (M = 8.7 pg/mg). Two malignant groups could not be detected in the plasma levels. Plasma PGE2 concentration (in form of the 13,14-dihydro-15-Keto metabolite) did not reflect the tissue levels, and no difference was found between the benign (M = 59.9 pg/ml) and the malignant (M = 62.3 pg/ml) patients, but both concentrations were higher than those of healthy controls (M = 34.4 pg/ml). The stage of the cancer, the histological classification and, most important, the period of survival, could not be related to the differences in the PGE2 tissue levels. Neither could plasma cAMP be nominated as a breast cancer market because no difference was found between the cAMP levels of benign tumor patients (M = 16.48 pmol/ml), of malignant tumor patients (M = 21.14 pmol/ml) and of healthy controls (M = 19.07 pmol/ml). The conclusion is that although high amounts of PGE2 appear in some malignant breast tumors, they do not affect the clinical situation. These results may explain the failure to treat human breast cancer patients with prostaglandin synthetase inhibitors.

The influence of diazepam administration in rats bearing the R3230AC mammary carcinoma

The growth of the R3230AC mammary carcinoma was studied in female Fisher 344 rats that were treated with diazepam. Diazepam at 250 μg/animal/day (2.5 mg/kg body weight) and 500 μg/day was administered for 4 weeks, starting 2 days before subcutaneous transplantation of uniform pieces of the tumour. Tumour size was significantly increased in the group receiving 250 μg but was below the levels observed in the saline treated controls in those given 500 μg diazepam. Plasma PGE2 and PGF2α concentrations were comparable in control and diazepam treated animals.