Prostaglandins and medicine最新文献

Prostaglandins are present in the epididymal and prostatic portions of the isolated intact and gonadectomized rat vas deferens. The concentration of PGF-like material is higher in the castrated than in the intact male rat in both portions of the vasa deferentia. The higher amount of PGF-like material observed in the castrated rat vas deferens was significantly reduced after testosterone replacement therapy, indicating that androgens could be controlling PGF production. On the other hand, the concentration of PGE-like material was significantly higher than PGF in both portions of the vas deferens and no differences were observed in those values when comparing data from intact, castrated and testosterone-treated rats. PGF-like material is likely to be androgen dependent, whereas PGE-like material is not under that hormonal control.

Propranolol stimulated prostaglandin synthesis in dog kidney, mouse adrenal, rat basophil leukemia, and mouse neuroblastoma cells, but not in bovine aorta smooth muscle or rat glial cells growing in culture. Culture fluids of propranolol treated rat basophil leukemia (RBL-1) cells reacted with anti-12-HETE plasma. The reactive HETE was not identified, although it was not 12-HETE. Indomethacin and aspirin, in the presence of stimulating levels of propranolol, inhibited the stimulated synthesis of the cyclooxygenase products but not the lipoxygenase products by the RBL-1 cells. Quinidine also stimulated prostaglandin synthesis in dog kidney and rat basophil leukemia cells, but not in mouse neuroblastoma, mouse adrenal, bovine aorta smooth muscle, rat glial, and rat pituitary cells and methylcholanthrene transformed mouse fibroblasts. Whereas quinine stimulated prostaglandin synthesis in the rat basophil leukemia cells, unlike quinidine it did not stimulate prostaglandin synthesis in the dog kidney cells.

OKY-1581, a known inhibitor of thromboxane biosynthesis, was infused intravenously in six healthy baboons anaesthetized with pentobarbitone sodium. Systemic blood pressure and heart rate were continuously recorded and the levels of plasma thromboxane B₂ and 6-keto PGF_1α were determined in samples taken before, during and after the infusion of OKY-1581. Following the infusion of OKY-1581 plasma level of TXB₂ decreased and 6-keto PGF_1α level increased in most animals. However, these changes were not consistent or dose-related and no significant effect was seen in some animals.

In 11 children in the acute phase of steady state edema in minimal change nephrotic syndrome renal prostaglandin synthesis as determined by urinary PGE₂ and PGF_2∝ excretion was evaluated. Age matched healthy children served as controls. In our patients highly significantly increased PGF_2α excretion accompanied by high urinary aldosterone excretion with normal PGE₂ were found. It is possible that abnormal prostaglandin synthesis within the kidney may play a role in pathogenesis of minimal change nephrotic syndrome.

Addition of prostaglandin E2 or inhibitors of prostaglandin biosynthesis to Mischell-Dutton cultures results in changes of immunoglobulin levels, particularly IgM, secreted into the culture supernatant. These changes in the quantity of immunoglobulin found in the supernatant are minimal in cultures containing naive cells. When BSA educated cells from C57B1/6 immunized mice were cultured, PGE was very effective in amplifying the biosynthesis of immunoglobulin when placed in culture in the presence of BSA. Whole spleen cell cultures from C57B1/6 mice immunized with sRBC also had increased immunoglobulin concentrations in culture supernatants upon exposure to PGE2 at culture initiation. However, the addition of sRBC to these cultures did not further increase immunoglobulin production. In all cases indomethacin inhibited the appearance of immunoglobulin into the supernatant by antigen educated cells. This inhibition which may be a result of inhibited immunoglobulin synthesis and not an impairment of transport, could be overcome by the inclusion of PGE2 in the cultures. PGE2 added to cultures containing cells educated against human gamma globulin caused an increase in the quantity of human gamma globulin-specific antibody in the culture supernatant while it had no effect on naive cells. These results indicate that prostaglandin metabolism may exert a greater influence on educated lymphocytes than naive lymphocytes in terms of immunoglobulin secretion and specific antibody production.

To study the production of antiaggregatory and vasodilatory prostacyclin (PGI₂) during human pregnancy and puerperium, we measured the concentrations of 6-keto-prostaglandin F_1α, the stable hydration product of PGI₂ , with specific radioimmunoassay in plasma samples from 53 women between 11 and 41 weeks of normal pregnancy, 11 puerperal women 53–60 days postpartum and 20 healthy nonpregnant control women. The levels of 6-keto-PGF_1α did not change during the course of pregnancy, and the mean (± SE) levels of 6-keto-PGFduring pregnancy (255.5 + 8.7 pg/ml) or puerperium (254.7 ± 12.3 pg/ml) were not significantly different from the mean level of 277.7 ± 10.6 pg/ml in the nonpregnant control women. There was no correlation between the 6-keto-PGF_1α concentration and pregnancy week, maternal age, parity or lactation. Thus, it is evident that PGI₂, as measured by its metabolite levels in maternal plasma, does not change during human gestation.

Based upon earlier findings of our group that not only the synthesis of antiaggregatory prostaglandins by the vessel wall is altered in atherosclerotic vascular tissue of patients, but also the sensitivity of their platelets to these prostaglandins is changed, we examined a well defined group of 50 patients with myocardial infarction before the age of 40 years. In all patients the coronary heart disease was verified by angiography. The sensitivity of the platelets was examined in relation to the smoking habit, the type and presence of hyperlipoproteinemia, one, two and three vessel disease and familial history. Except for hyperlipoproteinemia and smoking, all the patients were free of any additional risk factor. It is demonstrated that the platelet sensitivity to the antiaggregatory prostaglandins is significantly diminished in hyperlipoproteinemics in comparison to a control group.

The purpose of this study was to determine the levels of prostaglandins in ventricular cerebrospinal fluid (CSF) from severely head injured humans on successive days following injury. Sixteen samples from three patients were purified using XAD-2 and high pressure liquid chromatography and PGE₂, PGF_2α, and 6-keto-PGF_1α were quantitated utilizing deuterated internal standards and gas chromatography-mass spectrometry. Generally, the levels of PGs in ventricular CSF were found to be higher than has previously been reported for PGs in CSF from spinal taps. PG levels ranged from nondetectable to 11.8, 3.3 and 27.3 ng per ml for PGE₂, PGF_2α, and 6-keto-PGF_1α, respectively. However, in one sample, PG levels were much higher than this range and approached the levels found in human cortical tissue. Analysis of red and white blood cell numbers in the CSF sjkwed no relationship between cell numbers and prostaglandin levels. this study confirms a previous report that 6-keto-PGF_1α is the major prostaglandin in CSF and demonstrates that PG levels in ventricular CSF from head traumatized humans can be greatly elevated.

Various therapies during early hours of acute myocardial infarction (AMI) have been suggested to protect ischemic myocardium and reduce infarct size. Despite reports that prostaglandins (PGs) are released during myocardial ischemia, and that prostacyclin (PGI2) and thromboxane A₂ (TXA₂) have opposing effects on vasomotion and platelet aggregation, the physiologic roles of PGs, PGI2 and TXA₂ in AMI have not been clearly defined. However, in pharmacologic doses, experimental evidence suggests that vasodilator PGs might be beneficial, and vasoconstrictor PGs might be deleterious, in AMI. Recent recognition that coronary spasm is frequent in AMI has led to the notion that an increased PGI₂/TXA₂ ratio might be desirable. Thus, exogenous PGEl, exogenous PGI2 or its more stable analogs, drugs that stimulate PGI2 release, and inhibitors of TXA₂ and harmful PGs are potential agents for protective therapy in AMI.