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R Wallin

Publications and source records attributed to R Wallin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of in vitro stability of dietary fish oil on lipid peroxidation and prostanoids in vivo.

Dietary supplementation of rats with fish oil for 18 days resulted in signs of lipid peroxidation, with increased malondialdehyde production in plasma and myocardium. This increase in malondialdehyde could be completely prevented by supplementing the fish oil with a new natural antioxidant mixture (Pufanox) which is known to markedly increase the in vitro stability of fish oils. Addition of Pufanox to fish oil also tended to increase the ratio between the vasodilator prostacyclin and the vasoconstrictor thromboxane A2. The concentration of vitamin E decreased, both in plasma and in the heart after the period of fish oil ingestion, indicating that the fish oil used contained too little vitamin E. Plasma cholesterol and triglyceride levels decreased markedly after fish oil supplementation but with no apparent difference between fish oil with or without Pufanox, probably due to the insufficient content of vitamin E. The results obtained emphasize the importance both of the in vitro stability of the fish oil given and of the amount of vitamin E added.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Warfarin resistance is associated with a protein component of the vitamin K 2,3-epoxide reductase enzyme complex in rat liver.

Warfarin, the most used drug in the world in long-term anticoagulation prophylaxis, targets the vitamin K 2,3-epoxide reductase (VKOR) of the vitamin K cycle in liver. Recently, the enzyme has been identified as a multicomponent lipid-protein enzyme system in the endoplasmic reticulum (ER) membrane (17). As the first step towards understanding genetic resistance to warfarin, we present in this paper data on VKOR from normal and a strain of warfarin resistant laboratory rats maintained in the United States. Metal induced in vitro assembly of the enzyme complex demonstrates that the glutathione-S-transferase (GST) enzyme component of the complex loses its GST activity upon formation of VKOR. Less VKOR activity is measured upon assembly of the complex from warfarin resistant rats. The GST activity measured in warfarin resistant rats, before assembly of the complex, is 10-fold less sensitive to warfarin inhibition than the GST activity measured in normal rats. Microsomal epoxide hydrolase (mEH) is the second component of VKOR. When incubated with the components of VKOR before assembly of the complex, antibodies raised against mEH prevented formation of the enzyme complex. Sequencing of mEH cDNAs from normal and warfarin resistant rats revealed identical sequences. The data suggest that the mutation responsible for genetic warfarin resistance is associated with the GST component of VKOR.

Animals↗
PubMed1997

Assembly of the warfarin-sensitive vitamin K 2,3-epoxide reductase enzyme complex in the endoplasmic reticulum membrane.

gamma-Carboxylation of vitamin K-dependent proteins requires a functional vitamin K cycle to produce the active vitamin K cofactor for the gamma-carboxylase which posttranslationally modifies precursors of these proteins to contain gamma-carboxyglutamic acid residues. The warfarin-sensitive enzyme vitamin K epoxide reductase (VKOR) of the cycle reduces vitamin K 2,3-epoxide to the active vitamin K hydroquinone cofactor. Because of the importance of warfarin as an anticoagulant in prophylactic medicine and as a poison in rodent pest control, numerous attempts have been made to understand the molecular mechanism underlying warfarin-sensitive vitamin K 2,3-epoxide reduction. In search for protein components that could be involved in this reaction we designed an in vitro gamma-carboxylation test system where the warfarin-sensitive VKOR produces the cofactor for the gamma-carboxylase. Dissection of this system by chromatographic techniques has identified a member(s) of the glutathione S-transferase gene family as one component of the VKOR enzyme complex in the endoplasmic reticulum membrane. The affinity-purified glutathione S-transferase(s) was sensitive to warfarin but lost its warfarin sensitivity and glutathione S-transferase activity upon association with lipids in the presence of Mn2+ or Ca2+. In the gamma-carboxylation test system, loss of warfarin-sensitive glutathione S-transferase activity coincided with formation of the VKOR enzyme complex. It is proposed that formation of VKOR in the endoplasmic reticulum membrane resembles formation of the lipoxygenase enzyme complex where the glutathione S-transferase-related FLAP protein binds cytosolic lipoxygenase to form a membrane enzyme complex.

Animals↗
PubMed1997

Phosphatidic acid-mediated phosphorylation of the NADPH oxidase component p47-phox. Evidence that phosphatidic acid may activate a novel protein kinase.

Phosphatidic acid (PA), generated by phospholipase D activation, has been linked to the activation of the neutrophil respiratory burst enzyme, NADPH oxidase; however, the intracellular enzyme targets for PA remain unclear. We have recently shown (McPhail, L. C., Qualliotine-Mann, D., and Waite, K. A. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 7931-7935) that a PA-activated protein kinase is involved in the activation of NADPH oxidase in a cell-free system. This protein kinase phosphorylates numerous endogenous proteins, including p47-phox, a component of the NADPH oxidase complex. Phospholipids other than PA were less effective at inducing endogenous protein phosphorylation. Several of these endogenous substrates were also phosphorylated during stimulation of intact cells by opsonized zymosan, an agonist that induces phospholipase D activation. We sought to identify the PA-activated protein kinase that phosphorylates p47-phox. The PA-dependent protein kinase was shown to be cytosolic. cis-Unsaturated fatty acids were poor inducers of protein kinase activity, suggesting that the PA-activated protein kinase is not a fatty acid-regulated protein kinase (e.g. protein kinase N). Chromatographic techniques separated the PA-activated protein kinase from a number of other protein kinases known to be activated by PA or to phosphorylate p47-phox. These included isoforms of protein kinase C, p21 (Cdc42/Rac)-activated protein kinase, and mitogen-activated protein kinase. Gel filtration chromatography indicated that the protein kinase has an apparent molecular size of 125 kDa. Screening of cytosolic fractions from several cell types and rat brain suggested the enzyme has widespread cell and tissue distribution. The partially purified protein kinase was sensitive to the same protein kinase inhibitors that diminished NADPH oxidase activation and was independent of guanosine 5'-3-O-(thio)triphosphate and Ca2+. Phosphoamino acid analysis showed that serine and tyrosine residues were phosphorylated on p47-phox by this kinase(s). These data indicate that one or more potentially novel protein kinases are targets for PA in neutrophils and other cell types. Furthermore, a PA-activated protein kinase is likely to be an important regulator of the neutrophil respiratory burst by phosphorylation of the NADPH oxidase component p47-phox.

Animals↗
PubMed1997

Human chondrocyte expression of growth-arrest-specific gene 6 and the tyrosine kinase receptor axl: potential role in autocrine signaling in cartilage.

OBJECTIVE: To determine if human articular chondrocytes express the axl tyrosine kinase receptor and its ligand Gas-6, a protein product of growth-arrest-specific gene 6, and to determine if Gas-6 and axl function in the regulation of chondrocyte growth and survival. METHODS: The presence of Gas-6 and axl was examined in situ in human articular cartilage by immunohistochemistry and in vitro in cell culture studies using primary human chondrocytes and immortalized human chondrocytes. The ability of recombinant Gas-6 to mediate adhesion of chondrocytes and to stimulate chondrocyte axl phosphorylation was determined. Studies of the role of Gas-6 and axl in cell proliferation and survival were also performed. RESULTS: Both Gas-6 and axl were detected in cartilage by immunohistochemical staining. Gas-6 and axl messenger RNA (mRNA) and protein were also detected in cultures of primary and immortalized human chondrocytes. Compared with cells cultured in medium containing 10% serum, Gas-6 mRNA levels were increased in immortalized chondrocytes cultured in serum-free medium, while axl expression decreased. Chondrocytes attached to Gas-6-coated plastic, and the attachment was blocked by a soluble Ig fusion protein containing the axl extracellular domain. Recombinant human Gas-6 and serum-free conditioned medium from primary and immortalized human chondrocyte cultures stimulated chondrocyte axl tyrosine phosphorylation. A mitogenic effect was noted both when immortalized chondrocytes were stimulated with recombinant Gas-6 or when they were made to overexpress axl by transfection. Addition of recombinant Gas-6 to serum-free medium resulted in increased survival of primary chondrocytes cultured at low density in agarose. CONCLUSION: These findings present evidence for an autocrine signaling pathway in cartilage involving Gas-6 and the axl tyrosine kinase adhesion receptor. Stimulation of axl by Gas-6 may play an important role in the control of chondrocyte growth and survival.

3T3 Cells↗
PubMed1997

The duration of action of bupivacaine, levobupivacaine, ropivacaine and pethidine in peripheral nerve block in the rat.

BACKGROUND: There is a current interest in local anaesthetic drugs/formulations exhibiting long durations of sensory block and minor motor-blocking effects. OBJECTIVES: To compare the duration of sensory and motor blockade in peripheral nerve blocks induced by the new agents ropivacaine and levobupivacaine, with that of racemic bupivacaine and pethidine. METHODS: Groups of 8 male Sprague-Dawley rats were subjected to infraorbital (IONB) or sciatic nerve block (SNB) employing 0.2 ml of differently concentrated solutions of bupivacaine, levobupivacaine, ropivacaine or pethidine. The sensory blocking effect in IONB is expressed as (i) the time to elicitation of an abdominal jerk by electrical stimulation at arbitrarily chosen (threshold) intensities (IONB degree 3, 5, 8 and 10), and as (ii) the area under the curve (AUC, threshold intensities vs time). The duration of motor block in SNB is given as the time from injection to regained ability to walk and grip normally with the toes. Comparisons of the dose-effect relationships for the investigated agents were made by analysis of covariance. RESULTS: In IONB the log (dose)-log (effect) lines for bupivacaine, levobupivacaine and ropivacaine did not deviate from parallelism. The duration of sensory block induced by equimolar doses of these agents was similar, although bupivacaine exerted more pronounced effects than levobupivacaine (AUC by 25%, P=0.001; IONB degree 3 by 14%, P=0.03). In SNB only the log (dose)-log (duration) lines for bupivacaine vs levobupivacaine were found not to deviate from parallelism, both agents exerting similar durations of action. The motor-blocking effects of ropivacaine showed an inverse dose-duration relationship (P=0.019). CONCLUSIONS: Equimolar doses of the investigated local anaesthetics exerted similar durations of sensory blockade in a peripheral nerve block model in the rat.

Amides↗
PubMed1996

Processing and expression of rat and human clotting factor-X-encoding cDNAs.

The cDNA encoding clotting factor X, which participates in the middle stage of the blood coagulation cascade was cloned from a rat liver cDNA library. Sequencing of the rat factor-X-encoding cDNA revealed that this vitamin-K-dependent protein has a dibasic Arg-Arg sequence at the propeptide cleavage site, as occurs in other vitamin-K-dependent proteins. Although the human and rat deduced amino acid sequences are remarkably similar (76% identical), they do significantly differ in that human factor-X contains a unique Thr-Arg sequence at the propeptide cleavage site [Fung et al., Proc. Natl. Acad. Sci. USA 82 (1985) 3591-3595], where a dibasic sequence would normally be expected. This specific site is the recognition motif for the endoprotease, furin, which is located in the Golgi apparatus. Both rat and human cDNAs expressed in Cos-1 cells resulted in secretion of a mixture of single- and two-chain forms of factor X. The two-chain forms were devoid of the propeptide and were produced at similar rates by the transfected cells. The efficient processing of human factor X, when compared to rat factor X, may indicate that an additional protease(s), which recognizes the Thr-Arg motif, may be involved in proteolytic processing of the human enzyme.

Amino Acid Sequence↗
PubMed1996

Effects of pH and buffer capacity modulation on the analgesic efficacy of lignocaine and pethidine solutions.

BACKGROUND: Objectives were to study the effects of variations in the pH and the buffer capacity of solutions of lignocaine or pethidine on their analgesic efficacy in peripheral nerve block. METHODS: Infraorbital nerve blocks (IONB) were induced in rats during light pentobarbitone anaesthesia employing 0.2 ml of test solutions containing 10 mg center dot ml-1 of lignocaine or pethidine dissolved in normal saline, 50 mmol and 150 mmol tris-hydroxymethylaminomethane (THAM) hydrochloride (THAM center dot HCl) of pH 4.8 and 4.5, respectively, or 100 mmol THAM + THAM center dot HCl of pH 7.4. The pH of solutions in saline was varied from 3.0 to 9.3 by adding HCl or NaHCO3. The analgesic efficacy is expressed as the interval from injection to elicitation of a minimal response to electric stimulation at various intensities (threshold intensities) within the blocked area (IONB 3 to 10), and in terms of the area under the curve (AUC, threshold intensities vs. time). RESULTS: When dissolved in saline, pH 7.4, pethidine exerted more pronounced effects than lignocaine [AUC by 3.5 times (P<0.001), IONB 3 to 10 by 2.7 (P<0.05) to 3.6 (P<0.001) times]. Variations of the pH of solutions did not affect their analgesic efficacy. Lignocaine exerted more pronounced local analgesic effects when mixed with 150 mmol THAM center dot HCl than when mixed with saline (pH 7.4), but manifested even more pronounced effects when dissolved in THAM + THAM center dot HCl [AUC by 3.7 times (P<0.001), IONB 3 to 10 by 2.7 (P<0.01) to 3.8 (P<0.001) times]. When dissolved in THAM + THAM center dot HCl, the analgesic efficacy of pethidine increased by 2.0 to 2.8 times (P<0.001), as compared to a solution in saline at the same pH. CONCLUSIONS: It is concluded that variations in the pH of solutions of lignocaine or pethidine in saline does not affect the analgesic efficacy of the drugs, presumably due to the low buffer capacity of the medium, whereas when dissolved in THAM + THAM center dot HCl, their effect is enhanced.

Analgesics, Opioid↗
PubMed1995

Evidence for competition between vitamin K-dependent clotting factors for intracellular processing by the vitamin K-dependent gamma-carboxylase.

This study demonstrates an apparent competition between newly synthesized precursors of prothrombin and factor X for binding to and processing by the gamma-carboxylase in the ER membrane of hepatocytes. The precursor of factor X appears to exhibit a strong affinity for the carboxylase than the prothrombin precursor. This conclusion is supported by the findings that 1) in normal hepatocytes, the factor X precursor prevents increased prothrombin precursor binding to the ER membrane, 2) increased prothrombin binding to the ER membrane was measured in H4-II-E-C3 Reuber H-35 cells where factor X synthesis is suppressed. The variations in the concentrations of the prothrombin and the factor X precursors that were as associated with the ER membrane correlated with the available prothrombin and factor X substrate pools for the gamma-carboxylase.

Animals↗
PubMed1995

Platelet and leukocyte activation after myocardial infarction. Influence of enalapril.

In this double-blind placebo-controlled study with enalapril, 74 patients with acute myocardial infarction were followed at 0, 7, 30, 60 and 180 days after the event. Platelets and leukocytes were activated during the first 7 days. During the 6-month period fibrinogen, leukocytes, elastase, and B beta 30-43 remained elevated in 50, 15, 30 and 80% of the patients, respectively, but there was no detectable angiotensin converting enzyme activity in platelets. Enalapril did not modulate fibrinogen, leukocyte count or elastase, while B beta 30-43 peptide showed decreased levels, although the proportion of patients with values above the reference limit did not differ from placebo. In conclusion, in the 6-month post acute myocardial infarction period, while platelet function is activated only during the first week after acute myocardial infarction, fibrinogen and leukocyte function continue to be activated throughout the 6 months in a considerable proportion of patients. These signs may indicate an ongoing atherosclerotic process. Enalapril has no major influence on these reactivities.

Adult↗
PubMed1995

Aspirin does not potentiate effect of suboptimal dose of the thrombin inhibitor inogatran during coronary thrombolysis.

OBJECTIVES: Coronary artery often reoccludes after thrombolytic therapy with recombinant tissue-plasminogen activator (rt-PA). This reocclusion is thought to be due to in situ platelet activation mediated by thromboxane (Tx) A2 and thrombin; hence, aspirin and thrombin inhibitors are often used in patients with acute myocardial infarction. This study was designed to examine the modulation of coronary artery reocclusion by a novel low molecular weight direct thrombin inhibitor inogatran with or without aspirin. METHODS: 22 dogs with electrically-induced occlusive intracoronary thrombus were treated with saline (n = 7, group A), or high dose inogatran (0.25 mg/kg bolus followed by 0.6 mg/kg per h for 2 h, n = 5, group B), or low dose inogatran (0.125 mg/kg bolus followed by 0.3 mg/kg per h for 2 h, n = 5, group C), or aspirin+low dose inogatran (n = 5, Group D). Recombinant tissue-plasminogen activator (rt-PA) was infused for 20 min starting 2 min after the bolus in all dogs. Coronary artery blood flow was monitored for 120 min after rt-PA administration. RESULTS: Reperfusion rates were similar in all groups, but the time to reperfusion was shortest in group B dogs (18 +/- 2 min vs. 32 +/- 7 min in group A dogs, P < 0.05). Reocclusion rates were 80%, 0%, 50%, and 60% in groups A, B, C, and D dogs, respectively. The restored blood flow persisted for 19 +/- 10, > 120 min, 71 +/- 30 and 54 +/- 26 min in groups A, B, C, and D dogs, respectively. At the end of rt-PA infusion, prothrombin time (PT) and activated partial thromboplastin time (APTT) were increased 1.3-2 times the control value, and the changes in PT and APTT were similar in all groups. Thrombin generation and activity, assessed by rise in thrombin-antithrombin complex and fibrinopeptide A levels, and decrease in fibrinogen levels were most marked in group A dogs, and less so in group B, C and D dogs. CONCLUSIONS: These data show that high dose of direct thrombin inhibitor inogatran shortens time to reflow and abolishes coronary artery reocclusion. However, aspirin does not potentiate the effect of suboptimal doses of inogatran.

Animals↗
PubMed1994

Intracellular proteolytic processing of the two-chain vitamin K-dependent coagulation factor X.

The vitamin K-dependent clotting factors require posttranslational proteolytic processing before they are secreted by the liver into blood as mature zymogens. For most of these proteins, the sequences around the cleavage sites show a common motif (Arg-X-Lys/Arg-Arg) which define the substrate specificity for the endoprotease furin/PACE of the Golgi apparatus. In this paper, we present data which suggest that an additional Ca(++)-dependent endoprotease(s) is located in the endoplasmic reticulum, and may participate in processing of the two-chain vitamin K-dependent coagulation factor X. The single-chain 70 kDa factor X precursor in microsomes from rat liver was labeled by 14C-gamma-carboxylation and its conversion to a two-chain form followed in an incubation system with microsomal membrane fragments. A Ca(++)-dependent endoprotease(s) converted the factor X precursor to a two-chain form with a light-chain of 21 kDa. The endoprotease(s) showed little reactivity towards release of the factor X propeptide. The data provide new information about the endoprotease system in liver which participates in clotting factor proteolytic processing.

Amino Acid Sequence↗
PubMed1994

Replacement of L-Lys by D-Lys(NH2) in peptide Ala-Arg-Pro-Ala-Lys (peptide 6A) increases its coronary blood flow-promoting properties.

Peptide 6A, a degradation of B beta chain of fibrinogen, is known to increase coronary and femoral blood flow. In this study, we examined the effects of peptide 32, an analogue of peptide 6A on coronary blood flow in anesthetized dogs. Intracoronary administration of equimolar amounts of peptide 32 and peptide 6A showed a greater (p < 0.05) increase in blood flow with peptide 32. Intravenous administration of peptide 32 also resulted in greater and longer-lasting increase in coronary blood flow. The greater blood flow enhancing effect of peptide 32 than that of peptide 6A may relate to absence of its degradation by angiotensin converting enzyme.

Amino Acid Sequence↗
PubMed1994

Management ... working day of a health services manager. Plymouth Community Services NHS Trust.

Rae Wallin is Director of Personnel, Plymouth Community Services NHS Trust, a trust with 2000 staff and a budget of 40m pounds. Ideally, work and home life are strictly compartmentalised but this does not always happen in practice; there is a challenge in balancing the needs of both. Senior managers are under enormous pressure in today's NHS; for women, Opportunity 2000 has not yet really changed things.

Administrative Personnel↗
PubMed1993

Intracellular maturation of the gamma-carboxyglutamic acid (Gla) region in prothrombin coincides with release of the propeptide.

Vitamin K-dependent coagulation factors undergo several post-translational modifications before the proteins are secreted into the blood as functional zymogens of the coagulation system. The modifications include Asn-linked glycosylation, Asn/Asp hydroxylation, removal of a signal peptide for translocation of the polypeptide into the endoplasmic reticulum and removal of a propeptide which, when attached to the intracellular coagulation factor precursor, directs the protein for vitamin K-dependent gamma-carboxylation. gamma-Carboxylation of targeted Glu residues results in formation of Ca(2+)-binding gamma-carboxyglutamic acid (Gla) residues. Ca2+ binding by these residues induces a conformational change in the protein which is a necessary event for optimal activation or activity of the clotting factor in blood. In the present study we have monitored the intracellular prothrombin precursor in the secretory pathway of liver cells to determine the effect that the propeptide has on Ca(2+)-dependent folding of the protein. The data provide evidence that the Ca(2+)-induced conformational change required for activation of prothrombin coincides with release of the propeptide in the trans-Golgi apparatus of the liver cell and elucidates an important function for the endoproteinase furin in biosynthesis of vitamin K-dependent clotting factors.

1-Carboxyglutamic Acid↗
PubMed1993

Branched chain aminotransferase isoenzymes. Purification and characterization of the rat brain isoenzyme.

This paper presents the first complete purification of the branched chain aminotransferase (EC 2.6.1.42) from rat brain cytosol (BCATc). On sodium dodecyl sulfate-polyacrylamide gel electrophoresis the enzyme appeared as a single band with a molecular mass of 47 kDa; however, gel exclusion chromatography suggested that BCATc is a dimer. Comparison of tryptic peptide maps of BCATc and the mitochondrial form of the enzyme (BCATm) indicated that they are different proteins. Experiments with protein labeling reagents, in particular sulfhydryl reagents, also suggested that there may be some distinct structural differences in BCATc and BCATm. Nevertheless, BCATc and BCATm showed similar specificities for amino acid and alpha-keto acid substrates. Both enzymes transaminated branched chain amino acids, their straight chain analogs, L-alloisoleucine and glutamate. A broader range of alpha-keto acids than amino acids was accepted as substrate including alpha-ketobutyrate and the alpha-keto acid of methionine. Both enzymes exhibited ping-pong kinetics with apparent Km values for leucine and isoleucine of about 1 and 5 mM for valine, respectively. Km values for alpha-ketoglutarate ranged from about 0.6 to 3 mM depending on the amino acid substrate. Polyclonal antibodies were raised in rabbits against purified BCATc. BCATc antiserum neutralized branched chain aminotransferase activity in rat brain cytosol but did not affect the activity in a heart mitochondrial extract. However, immunoblotting showed that BCATc and BCATm do share common epitopes since BCATm antiserum recognized BCATc on the immunoblots. The tissue distribution of BCATc was examined using BCATc and BCATm antisera. These data showed that BCATc was found in adult and fetal rat brain, cultured cells from fetal rat brain cortex, ovary, and placenta. Brain had the highest activity followed by ovary, fetal brain, and placenta. BCATc was not found in fetal liver, adult rat liver, or a rat hepatoma cell line. These data provide clear evidence that BCATc, unlike BCATm, is restricted to several highly specialized tissues.

Animals↗
PubMed1993

Streptokinase, but not tissue plasminogen activator, attenuates platelet aggregation in patients with acute myocardial infarction.

OBJECTIVES: To investigate if tissue plasminogen activator (tPA) and streptokinase given during acute myocardial infarction (AMI) have different effects on platelet aggregation which could contribute to the higher reocclusion rate observed after tPA. DESIGN: Open labelled on consecutive patients. SETTING: Coronary care unit. SUBJECTS: Twenty patients with chest pain and ST elevations on an electrocardiogram suggestive of AMI. INTERVENTIONS: Ten patients were treated with tPA (100 mg 3 h-1), 10 patients with streptokinase (1.5 x 10(6) IU 1 h-1). MAIN OUTCOME MEASURES: Before, immediately after and 24 h after fibrinolytic therapy, platelet aggregation was estimated with filtragometry and whole blood aggregometry. Fibrinogen, beta-thromboglobulin, elastase and the fibrinogen-derived peptide B beta 30-43 were also measured. RESULTS: The groups were comparable at baseline. Directly after treatment, streptokinase prolonged aggregation time in filtragometry with 112 +/- 140 s (P < 0.03) and reduced conductance in whole blood aggregometry by 6.2 +/- 6.1 omega (P < 0.03), both tests indicating inhibited platelet function. Fibrinogen decreased 2.5 +/- 1.0 g l-1 (P < 0.02). In the tPA-treated group corresponding changes were 68 +/- 225 s (NS) and 2.5 +/- 7 omega (NS) with no significant reduction in fibrinogen. After 24 h, at which time every patient was on acetylsalicylic acid, aggregation was inhibited in both groups as measured by aggregometry. Directly after fibrinolytic treatment, neutrophils were similarly activated in both groups with increments of elastase and B beta 30-43 by 26 +/- 46 micrograms l-1 (P < 0.03) and 280 +/- 381 pmol l-1 (P < 0.03) respectively (streptokinase) and by 12 +/- 6 micrograms l-1 (P < 0.02) and 919 +/- 856 pmol l-1 (P < 0.02) respectively (tPA). CONCLUSIONS: Despite similar degrees of platelet and leucocyte activation, streptokinase but not tPA treatment appears to inhibit platelet aggregation. One possible reason could be a streptokinase-induced pronounced decrease of fibrinogen and increase of fibrinogen split products. Therefore, further development of adjuvant antiplatelet therapy could be of clinical importance.

Aged↗