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Biomedical subjects

J Svensson

Publications and source records attributed to J Svensson.

133 records · Page 8Linked to original sources
PubMed1975

Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides.

An unstable [t1/2 at 37 degrees = 32 +/- 2 (SD) sec] intermediate, thromboxane A2, was detected in the conversion of prostaglandin G2 into 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (thromboxane B2) in platelets. The intermediate was trapped by addition of methanol, ethanol, or sodium azide to suspensions of washed human platelets incubated for 30 sec with arachidonic acid or prostaglandin G2. The structures of the resulting derivatives demonstrated that the intermediate possessed an oxane ring as in thromboxane B2 but lacked its hemiacetal hydroxyl group. Additional experiments using 18O2 or [2H8]arachidonic acid in the formation of thromboxane B2 and CH3O2H for the trapping of thromboxane A2, together with information on the t1/2 of the intermediate, indicated the presence of an oxetane structure in thromboxane A2. Incubation of arachidonic acid or prostaglandin G2 with washed platelets led to formation of an unstable factor that induced irreversible platelet aggregation and caused release of [14C]serotonin from platelets that had been incubated with [14C]serotonin. The properties and the mode of formation of this factor indicated that it was identical with thromboxane A2. Furthermore, evidence is presented that the more unstable and major component of rabbit aorta contracting substance (RCS) formed in platelets and guinea pig lung is also thromboxane A2.

Arachidonic Acids↗
PubMed1975

Prostaglandin endoperoxides IX. Characterization of rabbit aorta contracting substance (RCS) from guinea pig lung and human platelets.

Material causing contraction of the isolated rabbit aorta (rabbit aorta contracting substance, RCS) was released from guinea pig lung following perfusion with arachidonic acid and from human blood platelets after addition of thrombin to induce aggregation. Prostaglandin endoperoxides (prostaglandins G2 and/or H2) were found both in the perfusate of guinea pig lung (1-3 ng/ml) and in the medium collected after platelet aggregation (13-37 ng/ml). The contractile response of the isolated rabbit aorta to the pure prostaglandins G2 and H2 was also determined. These data combined with the quantitative analyses of the endoperoxides released from the lungs and platelets showed that only a minor part of the rabbit aorta contracting activity was due to the prostaglandin endoperoxides. The major part of the activity consisted of very unstable material. The half life of this material was about 30 s at 37 degrees whereas at this temperature the prostaglandin endoperoxides had a half life of about 5 min.

Animals↗
PubMed1974

Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins.

Methods were developed for quantitative determination of the three major metabolites of arachidonic acid in human platelets, i.e., 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (PHD). Aggregation of washed platelets by thrombin was accompanied by release of 1163-2175 ng/ml of HETE, 1129-2430 ng/ml of HHT, and 998-2299 ng/ml of PHD. The amount of PGG(2) (prostaglandin G(2)) produced as calculated from the sum of the amounts of its metabolites (HHT and PHD) was 2477-5480 ng/ml. In contrast, the amounts of PGE(2) (prostaglandin E(2)) and PGF(2alpha) (prostaglandin F(2alpha)) released were approximately two orders of magnitude lower. In this system, the prostaglandins thus exert their biological action through the endoperoxides, which are almost exclusively metabolized to nonprostanoate structures and only to a small extent to the classical prostaglandins. Platelets from subjects given aspirin produced less than 5% of the above mentioned amounts of HHT and PHD, whereas the production of HETE was stimulated about 3-fold. This provides additional evidence for our earlier proposal [Hamberg, M., Svensson, J., Wakabayashi, T. & Samuelsson, B. (1974) Proc. Nat. Acad. Sci. USA 71, 345-349] that the anti-aggregating effect of aspirin is through inhibition of PGG(2) formation.

Arachidonic Acids↗
PubMed1974

Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation.

Incubation for a short time of arachidonic acid with the microsomal fraction of a homogenate of the vesicular gland of sheep in the presence of 1 mM p-mercuribenzoate followed by extraction and silicic acid chromatography yielded two prostaglandin endoperoxides. The structures of these compounds, i.e., 15-hydroperoxy-9alpha,11alpha-peroxidoprosta-5,13-dienoic acid (prostaglandin G(2)) and 15-hydroxy-9alpha,11alpha-peroxidoprosta-5,13-dienoic acid (prostaglandin H(2)), were assigned mainly by a number of chemical transformations into previously known prostaglandins. The new prostaglandins were 50-200 times (prostaglandin G(2)) and 100-450 times (prostaglandin H(2)) more active than prostaglandin E(2) on the superfused aorta strip. The half-life of the prostaglandin endoperoxides in aqueous medium (about 5 min) was significantly longer than that of "rabbit aorta-contracting substance" released from guinea pig lung, indicating that none of the prostaglandin endoperoxides is identical with this factor. Addition of 10-300 ng/ml of the endoperoxides to suspensions of washed human platelets resulted in rapid aggregation. Furthermore, platelet aggregation induced by thrombin was accompanied by release of material reducible by stannous chloride into prostaglandin F(2alpha), thus indicating the involvement of endogenous prostaglandin endoperoxides in platelet aggregation.

Animals↗
PubMedDate not supplied

Pyridine nucleotides in glucose metabolism and diabetes: a review.

Nicotinamide adenine dinucleotide (NAD) and its derivatives NADH, NADP and NADPH have regulatory functions in the generation of triose phosphates and pyruvate from glucose. In many studies of the influence of the diabetic state on relationships between pyridine nucleotide and glucose metabolism, the focus has been on the sorbitol pathway. Less attention has been paid to other aspects of the role of pyridine nucleotides in pyruvate formation from glucose, in particular the effects of the NAD precursors nicotinamide and nicotinic acid on glucose metabolism. This paper reviews current knowledge of the involvement of pyridine nucleotides and their precursors in glucose catabolism in the normal and diabetic state. Reference is also made to the following three current hypotheses for mechanisms underlying diabetic microangiopathy: 1. Chronic glucose overutilization, caused by hyperglycemia, in tissues which lack insulin receptors and therefore are freely permeable to glucose. 2. Enhancement of sorbitol pathway activity with an ensuing decrease in the ratio of NAD/NADH. 3. Enhanced utilization of both glucose and pyridine nucleotides in formation of triose phosphates and pyruvate. Therapy with NAD precursors like nicotinamide might have corrective effects on these proposed biochemical aberrations, thereby retarding progression of microangiopathy.

Animals↗
PubMedDate not supplied

Anticoagulant effects of low-molecular-weight heparin following thrombolytic therapy in acute myocardial infarction: a dose-finding study.

The aim of the present study was to gain clinical experience with different dose levels of dalteparin, a low-molecular-weight heparin, following thrombolytic therapy in acute myocardial infarction. Compared to heparin, dalteparin has a longer half-life and a greater and highly predictable bioavailability, which would suggest dalteparin to be a convenient alternative. Twenty patients with ECG signs of acute transmural myocardial ischemia received streptokinase (1.5 million IU for 60 min) and were allocated to a control group or to open treatment with 50, 75 or 100 IU of dalteparin/kg b.w. s.c. b.i.d., starting 4 h later, for 6 days. Each group consisted of 5 patients. Except for the control group, aspirin was withheld during dalteparin treatment. Anti-factor-Xa (anti-FXa) values increased dose-dependently during the first 24 h and were maintained throughout the study period. On day 6, anti-FXa levels after 100 IU/kg b.w. were 0.79 (0.59-1.00) IU/ml (median, min.-max.) 4 h after administration of dalteparin, and 0.51 (0.34-0.82) IU/ml before the subsequent dose of dalteparin. In conclusion, our results indicate that a dalteparin dose slightly higher than 100 IU/kg b.w. is required in order to obtain the presumed therapeutic range of anti-FXa (0.6-1.0 IU/ml).

Adult↗