Search PubMed⌕ Search

Biomedical subjects

W Rogatti

Publications and source records attributed to W Rogatti.

At least 37 records · Page 2Linked to original sources
PubMed1992

Prostaglandin (PG) E1 and 13,14-dihydro (DH) PGE1 are diminishing radiation-induced arterial damage.

Rabbit abdominal aorta was irradiated with single or repeated doses up to 10 Gy. The rabbits were killed at different time intervals after irradiation. 5 micrograms/kg x 6/hr PGE1 or its biologically active metabolite 13,14-DH-PGE1 were administered either 6 hours before or 6 hours after irradiation. The administration of both PGEs reduced radiation-induced mitotic activity (3H-thymidine incorporation) and extracellular matrix [collagen-(14C-proline) and glycosaminoglycan (35-S-sulphate)]-formation as determined by means of autoradiography. The initial peak increase in vascular PGI2-synthesis was partly abolished, while the long lasting depression was less pronounced. 13,14-DH-PGE1 was only slightly less active as compared to the parent compound. Pre-radiation treatment was more effective than post-irradiation therapy. These findings suggest that both the PGs exert significant radiation-protective actions on the arterial wall.

Alprostadil↗
PubMed1992

Synergism between PGE1-metabolites(13,14-dihydro-prostaglandin E1, 15-keto prostaglandin E1, 15-keto-13,14-dihydro-prostaglandin E1) and nitric oxide (NO) on platelet aggregation.

A synergistic antiplatelet effect between prostaglandins (PG), cAMP-stimulators and nitric oxide (NO), a cGMP-stimulator, has already been described. Data on a synergism between NO and the metabolites of PGE1, however, are lacking so far. We therefore tested the antiplatelet activity of the metabolites of PGE1 alone and their synergism with NO on human platelets of 8 healthy volunteers in vitro. 13,14-DH-PGE1 (ID 50 = 10.8 ng/ml platelet rich plasma (PRP)) was the only PGE1 metabolite inhibiting the ADP-induced platelet aggregation, its efficacy being 76.4% of the parent compound PGE1 (ID 50 = 8.25 ng/ml PRP). NO (ID 50 = 0.52 microM) also inhibited platelet aggregation. The combined addition of 13,14-dihydro-prostaglandin E1 (13,14-DH-PGE1) and NO caused an additive effect. The other PGE1-metabolites tested, 15-keto prostaglandin (15-K-PGE1) (ID 50 = 16.2. micrograms/ml PRP) and 15-keto-13,14-dihydro-prostaglandin(15-K-13,14-DH-PGE1) (ID 50 = 14.8 micrograms/ml PRP), neither had any relevant antiaggregatory capacity themselves nor a synergistic effect with NO. These findings could be of clinical relevance as a NO-synergism may occur not only with therapeutically administered PGE1 but also with its biologically active metabolite 13,14-DH-PGE1.

Adult↗
PubMed1991

Interaction between prostaglandin E1 and nitric oxide (NO).

A synergistic antiplatelet effect between prostaglandin I2 (PGI2), a cAMP-stimulator, and nitric oxide (NO), a cGMP-stimulator, has been described. Data on a PGE1-NO interaction, however, are lacking so far. We therefore examined the question in healthy volunteers, whether a similar synergism exist between PGE1 and NO on human platelets in vitro. Each of the substances alone caused a dose-dependent inhibition of ADP-induced platelet aggregation, PGE1 (1ng/mlPRP) reduced platelet aggregation by 27.8 +/- 14.6%, NO (0.3%) by 26.7 +/- 25.5%. The combination of these compounds caused an additive effect resulting in a reduction of 40.6 +/- 23.5%. The findings indicate that PGE1 (like PGI2) and NO have a synergistic antiplatelet action. The concomitant treatment with both compounds offers an interesting concept for clinical therapy.

Adult↗
PubMed1991

Formation of 13,14-dihydro-prostaglandin E1 during intravenous infusions of prostaglandin E1 in patients with peripheral arterial occlusive disease.

Formation of 13,14-dihydro-prostaglandin (PG) E1 during intravenous infusions of PGE1 in patients with peripheral arterial occlusive disease was investigated. Using both high performance liquid chromatography (h.p.l.c.) combined with radioimmunoassay and gas chromatography/triple stage quadrupole mass spectrometry (GC/MS/MS) basal levels of 13,14-dihydro-PGE1 were found to be close to or below the detection limits of the assay methods. Levels of the PGE1 metabolite increased significantly during the infusion periods and decreased after their end. Since 13,14-dihydro-PGE1, in contrast to its precursors 15-keto-PGE1 and 15-keto-13,14-dihydro-PGE1, is biologically active, its formation could contribute to the beneficial effects of PGE1 administered intravenously in patients with peripheral arterial occlusive disease.

Alprostadil↗
PubMed1991

[Prostaglandin E1 in therapy of peripheral arterial occlusive disease].

The intraarterial and intravenous infusion of prostaglandin E1 (PGE1) today is well established in the therapy of peripheral arterial occlusive disease. This review summarizes the results of pharmacological-clinical studies and the influence of PGE1 on the pathomechanism of ischaemia due to its antithrombotic, leukocyte and endothelial stabilizing properties. Clinical data available on continuous and intermittent infusion for both modes of administration are critically appraised, taking into account more recent data on active metabolites.

Alprostadil↗
PubMed1991

[Effect of intra-arterial and intravenous PGE1 infusions on transcutaneous oxygen pressure in patients with critical ischemia of the extremities].

In a randomized cross-over study 20 patients with peripheral arterial occlusive disease stage IV according to Fontaine received one i.a. infusion of 10 micrograms PGE1 in 25 ml saline over 30 min and one i.v. infusion of 40 micrograms PGE1 in 125 ml saline over 60 min. Transcutaneous PO2 was measured continuously (44 degrees C) on the forefoot and dorsum of the foot of the affected leg as well as on the forefoot of the contralateral limb. During i.a. infusion tcPO2 decreased by 73% on the forefoot combined with pain in the infused leg in 8 patients, whereas i.v. infusion induced a 83.1% increase in tcPO2. All in all i.v. PGE1 infusion resulted in a more pronounced increase of tcPO2 without causing side effects.

Alprostadil↗
PubMed1991

13,14-dihydro-PGE1, an in-vivo metabolite of PGE1, decreases mitotic activity induced by corticosteroid administration.

PGE1 has antimitotic activity by virtue of its effect in increasing cAMP in vascular smooth muscle cells. The present study compares the effect of 13,14-dihydro-PGE1 (13,14-DH-PGE1) with PGE1 in an experimental model of stress induced by desoxycorticosterone in the rabbit. 13,14-DH-PGE1 significantly inhibited the stress-induced increase in mitotic activity, measured by autoradiography as percentage of 3H-thymidine positive cells, in all 3 abdominal aortic wall layers. Administration prior to stress was more effective than after stress, while combined administration was most effective. 13,14-DH-PGE1 exerts approximately 90% of the antimitotic activity of PGE1. It seems possible that the antimitotic activity observed after administration of intravenous PGE1 is attributable in part to 13,14-DH-PGE1.

Alprostadil↗
PubMed1991

On the metabolism of prostaglandin E1 administered intravenously to human volunteers.

We have demonstrated recently the formation of a biologically active metabolite of prostaglandin (PG) E1, 13,14-dihydro-PGE1, during intravenous infusions of PGE1 in patients with peripheral arterial occlusive disease. We have now investigated the levels of the immediate precursor of 13,14-dihydro-PGE1, the biologically inactive 15-keto-13,14-dihydro-PGE1, during intravenous administration of 20 micrograms, 40 micrograms or 80 micrograms PGE1 over a period of 60 min to human volunteers. It was found that levels of 15-keto-13,14-dihydro-PGE1, but not those of PGE1 itself, increased in a dose-dependent manner. Thus, increased formation of 13,14-dihydro-PGE1 from 15-keto-13,14-dihydro-PGE1 with increasing doses of PGE1 can be expected to occur. It remains to be investigated, to which extent formation of small amounts of 13,14-dihydro-PGE1 during intravenous infusion of PGE1 could contribute to the therapeutic effects of PGE1 in patients with peripheral arterial occlusive disease.

Adult↗
PubMed1990

Additive benefit of PGI2 and PGE1 (via different mechanisms?) on inhibition of activation of human vascular smooth muscle cells?

It seems likely that the antiplatelet action of antiaggregatory prostaglandins (PGE1, PGI2) is not the pivotal mechanism of action involved in clinical improvement of peripheral vascular disease. Based upon earlier results that both of these agents may have a certain effect on proliferation of vascular smooth muscle cells, we approached that question of an "optimal therapeutic regimen" going one step further. Patients having to undergo amputation were given a randomized "last choice" therapy with either PGI2 (once or twice a day, 6 h, 5 ng/kg/min i.v.), PGE1 (once or twice a day, 1 ng/kg/min i.a.) or a combination of both with a 6 h interval in between for 5 consecutive days. The ones who underwent surgery had a pathomorphological examination of vascular segments removed during amputation. The counting of activated smooth muscle cells indicates a significant drop induced by both of the PG's alone. A second infusion a day with the same compound, however, did not induce a further decrease in the activation state. In contrast administering the complimentary PG caused a comparable, significant decrease (p less than 0.01) in activation of smooth muscle cells in the intima and the media as well. It thus seems, that different mechanisms may be involved inducing additive therapeutic benefit. PGI2 is hypothesised to act predominantly by blocking PDGF-release and interference with PDGF, whereas PGE1 may have a more direct vascular action. From these findings, as well as the beneficial clinical results to be reported elsewhere, a combined therapy by the infusion scheme used may be the optimal one for a PG-therapy at the moment, based upon platelet and smooth muscle cell action.

Age Factors↗
PubMed1989

Beneficial effect of long-term PGE1-treatment in left ventricular heart failure.

Five male patients aged 34-47 years with congestive heart failure showed an improvement of left ventricular ejection fraction (LVEF) at rather low PGE1-doses (10-30 ng/kg/min) without affecting blood pressure or heart rate. LVEF was estimated by means of radionuclide ventriculography (RNV) prior to and during i.v.-infusion of PGE1 at increasing dose rates (10-100 ng/kg/min). Therefore, we administered to these responders PGE1 at a rate of 20 ng/kg/min i.v. continuously on a long-term basis by means of a portable infusion pump. Until up to 4 months the remarkable benefit in LVEF induced by PGE1 was still present to a comparable extent in all the patients. No rebound desensitization phenomenon occurred either on platelet activity or on LVEF. PGE1, via a more practical route of application or by a stable analogue, may be a promising therapy at this stage of cardiomyopathy (CMP).

Adult↗
PubMed1989

Efficacy and tolerability of intra-arterial and intravenous prostaglandin E1 infusions in occlusive arterial disease stage III/IV.

The efficacy and tolerability of intra-arterial and intravenous PGE1 infusions in patients with occlusive arterial disease [OAD] were studied in two independent multicentre therapeutic trials. In the first study 218 patients with OAD stage III/IV were given an i.a. infusion of 1/2 to 1 ampoule of Prostavasin (10-20 micrograms PGE1) in 50 ml physiological saline solution, once a day. 211 patients took part in the second study. Patients in stage III received one i.v. infusion of 3 ampoules Prostavasin (60 micrograms PGE1) once daily, and patients in stage IV received one i.v. infusion of 2 ampoules Prostavasin (40 micrograms PGE1) twice daily, in 100-250 ml physiological saline solution. In both studies the treatment period was 4 weeks. Both i.a. and i.v. administration afforded a significant improvement in the clinical symptoms. Ulcers healed completely in 18.6% of patients under i.a. treatment (i.v.: 10.7%) and partially healed in 38.9% (i.v.: 51.1%). 50% of the patients became pain-free in the course of i.a. treatment (i.v.: 47.7%) and, at the end of the study, 61.5% no longer required analgesics (i.v.: 48.6%). Stratification of the patients into diabetics and non-diabetics showed that in the main the therapeutic response in diabetic patients was as good as in non-diabetics, allowing for the fact that the clinical pictures were usually distinctly more severe in the diabetic patients. The adverse drug reactions were, predominantly, familiar symptoms such as redness, swelling and pain in the infused extremity and phlebitis-like redness along the course of the infused vein, gastro-intestinal symptoms and headache.

Aged↗
PubMed1988

[Fibrinolytic activity, thrombocyte function and pharmacokinetics during intra-arterial or intravenous prostaglandin E1 infusion in patients with chronic arterial occlusive disease].

Monitoring various parameters of fibrinolytic activity in 6 patients with arterial occlusive disease during intra-arterial (i.a.) or intravenous (i.v.) prostaglandin (PG) E1 infusions indicated activation of the endogenous fibrinolytic system. However, due to the small number of patients not all test parameters revealed significant changes. None of the PGE1 infusion regimens used (1.25 or 2.5 ng/kg/min i.a. or 5 or 10 ng/kg/min i.v. for 120 min in each case) led to any significant change in various parameters checked for ex-vivo platelet function. In agreement with these data the radioimmunological determination of PGE1 in venous plasma did not reveal any significant rise. On the other hand, the circulating metabolite of PGE1, 15-keto-13, 14-dihydro-PGE1, reached plasma levels which correlated well with expected theoretical values taking the infusion rate into consideration. A potential mechanism by which even low plasma concentrations of PGE1 might affect platelet function in vivo is discussed.

Alprostadil↗
PubMed1988

PGE1 reduces collagen and glycosaminoglycan synthesis in rabbit aorta.

In 18 male rabbits the influence of PGE1 on collagen and glycosaminoglycan synthesis assessed by means of the incorporation of radiolabelled precursors has been examined. It is demonstrated that PGE1 induces a 20-30% drop both in 14C-proline and 35S incorporation into the vessel wall. These findings are in line with earlier data on the inhibition of proliferation of smooth muscle cells and a decrease in mitotic activity. The results present one piece of evidence more that PGE1 is acting as an anti-atherosclerotic agent in vivo at the vascular level. This pathomechanism, as well as the fact that this vascular effect is achieved--in an animal experiment at least--via an intravenous PGE1-application, offers new basics for the treatment of atherosclerosis in man.

Alprostadil↗
PubMed1988

Effects of microencapsulated vs. enteric-coated acetylsalicylic acid on gastric and duodenal mucosa: an endoscopic study.

Two preparations of acetylsalicylic acid (ASA) were tested for their effects on gastroduodenal mucosa in a randomized crossover double-blind study that involved 12 healthy volunteers. Medication M (Monobeltin) consisted of 1,050 mg ASA provided with an enteric coat and medication C (Colfarit) consisted of 1,000 mg of a microencapsulated ASA preparation. Both drugs were taken for 6 consecutive days each. Upper gastrointestinal endoscopy was performed before and 2 and 6 days after each medication. An interval of 10 days elapsed between one treatment and the other. Gastric lesions occurred in 10 of 12 subjects taking medication M and in 11 of 12 subjects taking medication C after 2 days and were present in all subject after 6 days. Duodenal lesions were seen only in subjects taking medication C. The degree of gastric mucosal lesions based on two grading scales was not significantly different between the two treatments. Neither of the two pharmaceutical formulations of ASA provided sufficient protection for the gastric mucosa.

Adult↗