Misoprostol as agonist of IP2 receptor.

Fourteen patients with peripheral vascular disease received 200 microg of misoprostol 3 times a day during one month. The therapy with misoprostol caused clinical and biochemical improvement in all 14 patients. An elongation of pain free and maximum walking distance, shortening of pain duration and increase in arterial blood flow in both calves were observed. At the same time an activation of the fibrinolytic system, rise in the platelet aggregate ratio and increase in cAMP levels were noticed. It is suggested that misoprostol in human being caused rather activation of IP2 receptor.

Plasma and urine pharmacokinetics of the dopamine agonist alpha-dihydroergocryptine in patients with hepatic dysfunction.

OBJECTIVE: The aim of this study was to evaluate the pharmacokinetic behavior of unchanged alpha-dihydroergocryptine (DHEC, Almirid, Desitin Arzneimittel GmbH, Hamburg, Germany, under licence of Polichem S.A., Luxembourg) and total DHEC (unchanged DHEC and pooled metabolites) in plasma and urine in patients with impaired hepatic function, following administration of single oral doses. METHODS: The study was carried out according to an open, uncontrolled, parallel-group design, investigating two study groups: patients with hepatic dysfunction, i.e. with evidence of stable cirrhosis (n = 10) and age- and sex-matched healthy subjects (n = 8). Each subject received a single dose of 20 mg DHEC. Blood samples were taken at specified intervals up to 72 h after dosing and urine was collected fractionally for 24 h. Concentrations of unchanged DHEC were determined by RIA and concentrations of total DHEC (unchanged and pooled metabolites) by EIA. RESULTS: The plasma and urinary pharmacokinetics of DHEC and its metabolites were characterized by large variability. In patients with impaired hepatic function, the geometric mean Cmax and AUC(0-infinity) values for unchanged DHEC were 571.3 pg/ml (CV: 0.87) and 4038 pg x h/ml (CV: 1.04) and were approximately 2 times (2.04, 95% CI: 0.93 to 4.46 and 2.11, 95% CI: 0.58 to 7.73 for Cmax and AUC(0-infinity), respectively) larger than those measured in age-matched healthy controls. The 24-hour urinary excretion was approximately 3 times (3.41, 95% CI: 0.95 to 12.21) higher in patients with hepatic dysfunction. Similar results were obtained for total DHEC. CONCLUSIONS: The results reflect an increased systemic exposure in patients with impaired hepatic function which is not due to a reduced urinary excretion/elimination or reduced renal clearance. The most likely mechanism involved is a reduction in pre-systemic biotransformation. The observed range of effects on the pharmacokinetics of DHEC in patients with compromized hepatic function does not suggest the need to revise the dosage recommendations, since treatment with DHEC is generally started with low doses and is slowly up-titrated according to the individual response and the occurrence of adverse effects. Nevertheless, lower maintenance doses are likely to be achieved.

[Evaluation of fraxiparine efficacy in the treatment of retinal vein occlusion]. / Ocena skutecznosci fraksyparyny w leczeniu niedroznosci zyl siatkówki.

PURPOSE: To evaluate the efficacy of Fraxiparine in the treatment of central retinal vein occlusion and retinal branch vein occlusion. METHODS: 30 patients were treated. Fraxiparine (Sanofi-Pharma) was injected subcutaneously in doses of 7.5 thousand units twice daily for 10 days and once daily for 18 days. In 19 cases central retinal vein occlusion was observed and retinal branch vein occlusion in 11 cases. Mean follow-up was 15 months (range 10-35 months). Ophthalmological examination including fluorescein angiography was performed before and after therapy. RESULTS: Improvement of visual function and condition of retina after therapy was observed in about 50% of cases. In 16 patients laser photocoagulation applied for neovascularisation or retinal edema was necessary.

Treatment of peripheral vascular disease with misoprostol (Cytotec): a pilot study.

Misoprostol, the oral analogue of alprostadil, was used to treat 20 patients (aged 40-60 years) with peripheral arterial disease (PAD) according to Fontaine's classification at stages IIa and IIb. All patients received 200 micrograms of misoprostol 3 times a day during a month. The therapy with misoprostol resulted in clinical improvement in all patients. Elongation of pain-free (before treatment: 129 m +/- 78 m; after treatment: 214 m +/- 109 m) and maximum walking distance (before treatment: 304 m +/- 169 m; after treatment: 471 m +/- 264 m) was observed. At the same time, a shortening of the duration of pain was noted (before treatment: 100 sec +/- 37 sec; after treatment: 71 sec +/- 23 sec). The ankle/arm pressure ratio (AAPR) and arterial blood flow increased in both limbs after 4 weeks of treatment. Activation of the fibrinolytic system was seen in the course of therapy (shortening of euglobulin clot lysis time (ECLT) and increase in t-PA activity). The platelets became less sensitive to ADP and collagen after intake of misoprostol. The results justify administration of misoprostol as a new therapeutic agent for the treatment of patients with PAD.

[The effect of treatment with sulphur water from the spring in Wieslaw in Busko-Solec on levels of lipids,the fibrinolytic system and thrombogenic platelet function in patients with arteriosclerosis]. / Wplyw kuracji pitnej woda siarczkowa ze zródla Wieslaw z uzdrowiska Busko-Solec na gospodarke lipidowa, uklad fibrynolityczny i trombogeneze plytkowa u pacjentów z miazdzyca.

29 patients with arteriosclerosis obliterans and elevated level of cholesterol and/or triglycerides in blood received undiluted sulphur water from the spring Wieslaw in Busko-Solec at the dose of 50 ml 3 times a day for 4 weeks. Such a treatment resulted in statistically significant decrease of blood levels of cholesterol, triglycerides and LDL cholesterol. The concentration of HDL cholesterol did not change significantly. Moreover, therapy with sulphur water resulted in decreasing of platelet aggregability evoked by ADP and collagen, spontaneous platelet aggregability and increasing fibrinolytic activity of the blood (elongation of euglobulin clot lysis time). We concluded that orally administered sulphur water from the spring Wieslaw in Busko-Solec may be an additional means of treatment of patients with arteriosclerosis obliterans and high levels of cholesterol and/or triglycerides.

Multiple fundic gland polyps in duodenal mucosa not associated with colonic polyposis.

One of extracolonic manifestations of Gardner's syndrome and familial adenomatous polyposis (FAP) are fundic gland polyps (FGP) located typically in the gastric body. Rarely FGP develop in the absence of intestinal polyposis. A case of FGP in the duodenal bulb without associated pathological changes in the large bowel has been reported.

[Misoprostol--oral prostanoid--the first clinical trial for use in patients with peripheral vascular disease]. / Mizoprostol--doustny prostanoid--pierwsza próba klinicznego zastosowania w chorobie niedokrwiennej konczyn dolnych.

Misoprostol, the oral analogue of alprostadil was used for the treatment of 20 patients (aged 40-60) with peripheral arterial disease according to Fontaine's classification at stages IIa and IIb (PAD). All patients received 200 micrograms of misoprostol 3 times a day during a month. The therapy with misoprostol resulted in a clinical improvement in all patients. Elongation of pain free (before treatment 129 m +/- 78 m, after treatment 214 m +/- 109 m) and maximum walking distance (before treatment 304 m +/- 169 m, after treatment 471 m +/- 264 m) was observed. At the same time a shortening of the pain duration was noted (before treatment 100 sec +/- 37 sec, after treatment 71 sec +/- 23 sec). The ankle/arm pressure ratio (AAPR) and arterial blood flow increased in both limbs after 4 weeks of the treatment. Activation of the fibrinolytic system was seen in the course of the therapy (shortening of euglobulin clot lysis time-ECLT and increase in t-PA activity). The platelets became less sensitive to ADP and collagen after intake of misoprostol. The results justify administration of misoprostol as a new therapeutic agent for the treatment of patients with PAD.

Treatment with L-arginine is likely to stimulate generation of nitric oxide in patients with peripheral arterial obstructive disease.

The impairment of endothelial function in hypercholesterolaemic animals and humans is known to be reversed by intravenous infusions of L-arginine (L-ARG), the precursor of NO. 22 patients with peripheral arterial obstructive disease (PAOD) received L-ARG (60 mmol) as intravenous infusions, each lasting three hours, daily for seven consecutive days. This treatment resulted in elongation of the painfree and maximum walking distances, as well as shortening of the period of time required for pain relief after walking the maximum distance. A rise in the ankle/arm pressure ratio (AAPR) was associated with an increase of arterial blood flow in both calves. The transcutaneous oxygen tension (tcpO2) in the ischaemic foot was also increased. After the 1st and the 7th infusion of L-ARG the spontaneous (PAR) as well as the ADP- and collagen-induced platelet aggregation were suppressed, the euglobulin clot lysis time (ECLT) shortened, plasma levels of platelet activator inhibitor (PAI) decreased, and cGMP levels increased. These data indicate beneficial effects of L-ARG as a therapeutic agent in patients with PAOD. We presume that in these patients high doses of exogenous L-ARG can be partially converted to NO.

Misoprostol (cytotec) in the treatment of peripheral ischaemic disease.

The stable prostacyclin analogue-iloprost and prostaglandin E1 (Alprostadil) showed a beneficial effect on activated platelets and leukocytes, and thrombocyte and leukocyte vessel interaction and damaged endothelium, improving microvascular perfusion and were useful in treatment of patients with peripheral arterial disease. The 4 weeks therapy with misoprostol caused a clinical improvement in all 14 patients and resulted in vasorelaxation and showed antiplatelet and fibrinolytic effects.

L-arginine--substrate for no synthesis--its beneficial effects in therapy of patients with peripheral arterial disease: comparison with placebo-preliminary results.

Intravenous infusions of L-arginine (L-ARG) and placebo (saline) resulted in improvement of clinical assessments, statistically significant after L-ARG but not after saline. Results of laboratory estimations for platelet and fibrynolysis changed significantly following L-ARG infusions but not after infusions of placebo. These data indicate beneficial effects of L-ARG as a therapeutic agent in patients with peripheral arterial obliterative disease (PAOD). In these patients exogenous L-ARG can be converted to NO.

[A case of high intestinal obstruction caused by mycotic bezoar of the duodenum]. / Przpadek wysokiej niedroznosci jelit wywolanej grzybiczym bezoarem dwunastnicy.

A case of the mycotic bezoar in the female patient with gastric hypersecretion is reported. The symptoms of the high intestinal obstruction accompanied underlying disease. Bezoar formed of Geotrichum candidum was fragmentated with biopsical forceps of "alligator" type. Then, natamycin was administered for 5 weeks. The patients recovered completely.

Phenazone metabolism during perfusion of isolated guinea pig liver.

After 3 hr of perfusion of isolated guinea pig liver with a medium containing 407 ng/ml of phenazone, the drug concentration in the bile was 1.5 times higher than the initial concentration in the perfusion fluid. This indicates that in addition to phenazone metabolism, liver eliminates the drug by active releasing it to the bile. The active release is responsible for depression of phenazone concentration during the perfusion in approx. 6%. The remaining loss of phenazone is due to its hepatic metabolism.

Effect of secretin on antipyrine elimination during extracorporeal perfusion of the isolated guinea pig liver.

The aim of these investigations was to elucidate in which part of the bile system (canaliculi or ductules) antipyrine is secreted actively into bile during extracorporeal perfusion of isolated guinea pig liver. Twelve perfusions were performed including 6 control and 6 with secretin. After 1, 2 and 3 hours from the onset of perfusion the perfusion fluid and bile samples were taken for determination of antipyrine concentration. It was demonstrated that secretin increases the volume of secreted bile, the concentration of antipyrine was decreased and the total amount of antipyrine eliminated with bile remained unchanged. The obtained results refute the hypothesis that antipyrine is secreted into bile in the ductular phase and suggest that this process takes place at the level of biliary canaliculi.