SSR182289A enhances thrombolysis induced by fibrinolytic agents in rabbit models of venous and arterial thrombosis.

Background And Objectives: The purpose of this work was to investigate whether thrombolysis induced by recombinant tissue plasminogen activator (rt-PA) or streptokinase (SK) was enhanced in different rabbit models of thrombolysis by SSR182289A, a novel synthetic direct thrombin inhibitor which has been shown to possess potent antithrombotic properties in several experimental animal models.

Methods And Results: Human rt-PA alone (0.125 mg kg(-1) h(-1) for 2 h) induced a significant thrombolysis (18%, P < 0.

SSR182289A, a selective and potent orally active thrombin inhibitor.

SSR182289A 1 is the result of a rational optimisation process leading to an orally active thrombin inhibitor. The structure incorporates an original 2-(acetylamino)-[1,1'-biphenyl]-3-sulfonyl N-terminal motif, a central l-Arg surrogate carrying a weakly basic 3-amino-pyridine, and an unusual 4-difluoropiperidine at the C-terminus. Its synthesis is convergent and palladium catalysis has been employed for the construction of the key C-C bonds: Suzuki coupling for the bis-aryl fragment and Sonogashira reaction for the delta- bond of the central amino-acid chain.

Effects of SanOrg123781A, a synthetic hexadecasaccharide, in a mouse model of electrically induced carotid artery injury: synergism with the antiplatelet agent clopidogrel.

SanOrg123781A is a synthetic hexadecasaccharide that displays antithrombin-dependent inhibition of factor Xa and thrombin and potent antithrombotic effects. The antithrombotic activity of SanOrg123781A has been studied in a new mouse model of arterial thrombosis, where thrombus formation was induced by the application of an electrical current to the adventitial surface of a carotid artery. In this model, antiplatelet agents such as the ADP-receptor antagonist clopidogrel (30 mg/kg, p.

Population demographics and socioeconomic impact of osteoporotic fractures in Canada.

Through a survey of the literature and an analysis of selected national and regional statistics, a review of the incidence of osteoporosis and its consequences was performed. Results illustrate that the consequences of osteoporosis are preventable and should sensitize clinicians to the importance of early detection and the identification of risk factors for disease prevention and to early treatment once disease has been established. A marked increase in the annual incidence of hip fractures in all Canadians is noted.

Antithrombotic properties of SSR182289A, a new, orally active thrombin inhibitor.

N-[3-[[[(1S)-4-(5-Amino-2-pyridinyl)-1-[[4-difluoromethylene)-1-piperidinyl]carbonyl]butyl]amino]sulfonyl][1,1'-biphenyl]-2-yl]acetamide hydrochloride (SSR182289A) is a novel, potent, and selective thrombin inhibitor. We have examined the antithrombotic properties of SSR182289A administered by i.v.

Antiplatelet and antithrombotic activity of SL65.0472, a mixed 5-HT1B/5-HT2A receptor antagonist.

The antiplatelet and antithrombotic activity of SL65.0472 (7-fluoro-2-oxo-4-[2-[4-(thieno [3,2-c]pyrin-4-yl) piperazin-1-yl]ethyl]-1,2-di-hydroquinoline-acetamide), a mixed 5-HT1B/5-HT2A receptor antagonist was investigated on 5HT-induced human platelet activation in vitro, and in rat, rabbit and canine platelet dependent thrombosis models. SL65.

Sleep in menopause: differential effects of two forms of hormone replacement therapy.

Objectives: The aim of the present study was to evaluate differences between two regimens of estrogen/progestogen replacement therapy on nocturnal sleep in postmenopausal women.

Methods: Twenty-one (21) postmenopausal women were studied. They were randomized into two treatment groups: (1) estrogen (Premarin 0.

Pharmacological profile of SL 59.1227, a novel inhibitor of the sodium/hydrogen exchanger.

1. The NHE1 isoform of the Na(+)/H(+) exchanger plays an important role in the regulation of intracellular pH and in cardiac cell injury caused by ischaemia and reperfusion. SL 59.

Comparison of transdermal and oral sequential gestagen in combination with transdermal estradiol: effects on bleeding patterns and endometrial histology.

Objective: To assess prospectively the effect on bleeding patterns, transformation of the endometrium, and rate of endometrial hyperplasia of transdermal norethisterone acetate when administered sequentially in combination with transdermal estradiol (E2), and to compare it to a regimen using oral medroxyprogesterone acetate.

Methods: Two hundred eighteen women were randomized to receive either transdermal E2 0.05 mg/day for 14 days followed by transdermal E2 0.

Inhibition of insulin release induced by galanin in the dog is not exclusively mediated by activation of ATP-sensitive K+ channels.

Exogenous galanin (9 pmol/min during 20 min i.a.) decreased insulin levels in the plasma sampled from the pancreatic vein of the blood-perfused pancreas of dogs in which ganglionic transmission and beta-adrenoceptors had been blocked.

5-HT4 receptors, present in piglet atria and sensitive to SDZ 205-557, are absent in papillary muscle.

Putative 5-HT4 receptors were investigated in isolated piglet left atria and papillary muscles. In atrial tissues, 5-hydroxytryptamine (5-HT) was a potent positive inotropic agent with a pD2 of 6.7.

Adrenergic and nonadrenergic cotransmitters inhibit insulin secretion during sympathetic stimulation in dogs.

Vascular and biochemical responses to pancreatic sympathetic nerve stimulation were investigated in the blood-perfused pancreas of anesthetized dogs. During sympathetic nerve stimulation, pancreatic perfusion pressure and norepinephrine release increased, whereas insulin secretion decreased. The latter effect did not occur after pretreatment with the alpha 2-adrenoceptor antagonist idazoxan.

Studies on the mechanisms of the development of tolerance to the hypotensive effects of fenoldopam in rats.

In pentobarbital-anesthetized rats prepared for hemodynamic measurements with Doppler flow probes, intravenous (i.v.) infusions of fenoldopam (2.

Effects of pergolide on the cardiovascular responses to sinoaortic deafferentation in dogs with intact or surgically decentralized adrenal glands.

In pentobarbital-anesthetized dogs with decentralized adrenal glands, sinoaortic baroreceptor deafferentation produced an increase in mean aortic blood pressure which reached a maximum (42 +/- 5 mm Hg, n = 6) within 5 min and then waned entirely within the subsequent 25 min. In contrast, in sham-operated dogs, the maximal pressor response due to deafferentation was of greater magnitude (63 +/- 6 mm Hg, n = 8) and of much longer duration (44 +/- 4 mm Hg, 60 min after deafferentation). Heart rate was only augmented slightly in both preparations.

Cardiovascular characterization of the DA2 dopamine receptor agonist quinpirole in rats.

In normotensive anesthetized rats, 15-min IV infusions of quinpirole (2.5-40.0 micrograms/kg/min) produced dose-related, rapidly appearing, and long-lasting decreases in mean carotid artery BP and HR.

Pharmacological, hemodynamic and biochemical mechanisms involved in the blood pressure lowering effects of pergolide, in normotensive and hypertensive dogs.

In pentobarbital-anesthetized normotensive dogs, clonidine (20.0 micrograms/kg i.v.

Comparison of natural and synthetic prostaglandin E2 tablets in labour induction.

A multicentre, randomized, double-blind trial compared the efficacy and safety of and tolerance to natural and synthetically produced prostaglandin E2 tablets in the induction of labour in 202 women. The compounds were similarly effective, inducing labour in approximately 66% of patients. The total dose required and the interval between induction and delivery were similar in the two groups, as were the Apgar scores at 1 and 5 minutes and the incidence of maternal and fetal side effects.

Preconceptional selection of fetal sex.

Background information is given on postconceptional and preconceptional methods of selecting fetal sex. Among the preconceptional methods presented are treatment of the sperm to isolate either the X or the Y chromosome, timing of insemination and the effect of ionic concentrations in the woman's body as controlled by the dietary intake of minerals. The authors studied 281 couples, 21 of whom were later excluded, who adhered to a diet specific in its amounts of calcium, magnesium, sodium and potassium.

[Antibiotics: interactions with other drugs (author's transl)].

More and more numerous each year, and only rarely beneficial, these are responsible for unexplained therapeutic failures or complications. They may occur at different levels. In the bottle of infusion fluid, the risk is that of neutralisation of varying amounts of the antibiotic.