Prostaglandins and medicine最新文献

The effects of a strenuous marathon run of 42.2 kilometers on the presence of prostaglandins in blood was investigated in 24 healthy males and females. Testosterone, FSH, LH, epinephrine, norepinephrine, dopamine, T4 and T3 were also measured. With the exercise of the marathon run, a significant elevation of plasma PGE₂, PGF_2^α and 6 keto PGFla was observed in the runners following the race. Significant increases were also noted in blood catecholamine, dopamine and testosterone levels while a significant decline in the gonadotropins, FSH and LH was observed. No changes in thyroxine or tri-iodothyronine were noted.

Prostacyclin (PGI₂) was given intravenously in doses of 1 to 5 ng/kg/min to eight consecutive patients with end stage peripheral arteriosclerosis and ischaemic ulcers. Seven patients had intense ischaemic pains. Complete or partial healing of ulcers were seen in six cases (complete in three). In those whose ulcers healed (complete or partially) relief of ulcer pain was remarkable. Acute studies of the effect of prostacyclin on skin temperature of ischaemic areas showed no correlation with clinical effects. Seven patients had more or less pronounced subjective side effects, most often flushing, nausea, headache and uneasiness. As we previously have seen equally good healing and pain relieving effects by the administration of prostaglandin E₁ without these side effects the latter compound is so far preferred in the treatment of severe peripheral artery disease. Controlled studies of the effect are needed.

Regiospecific monomethyl prostaglandin F₂α ethers (at 0–9, 0–11, and 0–15) have been prepared by total synthesis. The 9,15-bis-ether was also prepared. The 11- and 15-monoethers have been converted to the corresponding prostacyclins. Nuclear Magnetic Resonance (NMR) spectral comparisons indicate conformational changes associated with ether formation; nonetheless, the PGF₂α monoethers all retain significant biological activity: 3–420% of natural PGF₂α. The 9- and 15-methyl ethers show increased selectivity for luteolytic activity as measured in the hamster antifertility (HAF) assay. In contrast the prostacyclin ethers are essentially devoid of agonist activity on both the platelet and vasculature. Prostacyclin diastereomers [5a] also lack activity and it appears that any modification at or of the C-11 or C-15 functions reduces receptor binding by at least a factor of 100.

The effects of PGE₂ and PGEl on the response of human peripheral blood lymphocytes to Pokeweed mitogen were studied.

Addition of PGE2 inhibited IgM production. This effect was augmented by treating the lymphocytes with 2.0 ug/ml of Indomethacin. Addition of PGE, alone had little effect but augmentation of IgM production was seen in cultures where the lymphocytes had been treated with Indomethacin and PGEl then added. The results suggest that PGE₁/E₂ have a small but measurable effect on in vitro IgM production.

Three long-stay, hospitalised schizophrenics who had failed to respond adequately to conventional drug therapy were treated with gamma-linolenic acid and linoleic acid in the form of evening primrose oil. They became substantially worse and electroencephalographic features of temporal lobe epilepsy became apparent. In all three the clinical state dramatically improved when carbamazepine, the conventional therapy for temporal lobe epilepsy was introduced. It can be extremely difficult to distinguish on clinical grounds between schizophrenia and temporal lobe epilepsy, and electroencephalographic studies do not always reveal an abnormality in the temporal lobe syndrome, unless additional procedure such as sphenoidal electroencephalography is undertaken. A trial of therapy with gamma-linolenic acid may prove of considerable value in distinguishing between these two states, so allowing specific therapy to be introduced.

Pre-operative dilatation of the cervix was attempted in 223 cases prior to vacuum aspiration in patients seeking late first trimester termination beyond ten weeks. 15 Me PGF_2a was used in the form of vaginal suppositories, intramuscular and intracervical injections. Dilatation of cervix of 10 mm or more was achieved within 4 hours in 86% cases with intra-cervical injections. Gastro-intestinal disturbances caused by intra-muscular injections could be avoided by intra-cervical injections, as the amount of prostaglandin required was only 100 ugm, but the success rate was significantly lower. The success with multiple dose suppositories was 80%. There was no significant difference in the success with 1.5 mgm or 1.0 mgm dosage, but the side effects were significantly higher with 1.5 mgm suppositories.

Intra-cervical Hylase did not dilate the cervix but successfully softened it within 5 minutes to make metallic dilatation simple. The hygroscopic Isogel tents achieved dilatation of 10 mm or more in 73% of the patients in 12 hours. The tents as well as intracervical prostaglandin injection had the disadvantage of requiring an additional theatre procedure prior to suction curettage.

The metabolism of prostaglandin E₂ (PGE₂) was decreased in isolated male hamster lungs, when sulfinpyrazone was infused into the pulmonary circulation. After pulmonary injection of 20 nmol of¹⁴C-PGE₂ the amount of 15-keto-metabolites of PGE₂ was in the effluent from control lungs 4.0 ± 0.5 nmol (mean ± SEM) and in those from 20 μM and 100 μM sulfinpyrazone treated lungs 1.9 ± 0.2 nmol (2P<0.01 compared to the control) and 1.7 ± 0.4 nmol (2P <0.01), respectively.The amount of unmetabolized PGE₂ was correspondingly increased in the effluent by sulfinpyrazone. The rate of efflux of the radioactivity from the lungs was increased by sulfinpyrazone. After injection of 10 nmol of ¹⁴C-PGE₂ into the pulmonary circulation half of the injected radioactivity appeared in the effluent in 30 ± 4 sec in control and in 15 ± 0.7 sec (2P <0·01) in 20 μM sulfinpyrazone experiments. Sulfinpyrazone had no effect on the activity of 15-hydroxyprostaglandin dehydrogenase in the 100.000 g supernatant fraction of homogenized hamster lungs. Thus the decreased metabolism of PGE in the pulmonary circulation of hamster lungs is obviously not due to the inhibition of 15-hydroxyprostaglandin dehydrogenase. A more likely explanation seems to be the decreased uptake of PGE₂ into the lung cells.

17(s) methyl-ω-hamo-trans-Δ²-PGE, (ONO 1206) produced qualitatively similar effects to PGE₁ in several systems.It was 18.4 and 25.6 times respectively more potent than PGE₁ in inhibiting ADP-induced baboon and human platelet aggregation in vitro. Intravenous infusion of ONO 1206 in baboon also produced ex-vivo inhibition of ADP-induced platelet aggregation.However, this was accompanied by a significant fall in blood pressure and an increase in heart rate. The potent relaxant effect of ONO 1206 on human respiratory tract smooth muscle in vitro suggests that this compound may be a bronchodilator in man.