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Biomedical subjects

J Malyszko

Publications and source records attributed to J Malyszko.

69 records · Page 4Linked to original sources
PubMed1993

Serotonergic mechanisms are involved in the hemostatic action of erythropoietin in uremic patients.

Recombinant human erythropoietin was administered to 12 patients with end-stage renal failure on long-term hemodialysis. They responded to the therapy with a shortening of the prolonged bleeding time, starting from the 1st week of therapy, before a significant increase in hemoglobin concentration was achieved. We also observed an increase in the activity of tissue plasminogen activator and a decrease in the activity of its inhibitor. There were no changes in platelet count but a significant increase in blood and platelet serotonin concentration was found. The shortening of the prolonged bleeding time before the correction of the anemia correlated with the rise in blood and platelet serotonin concentration during erythropoietin therapy. We suggest the possible involvement of an serotonergic mechanism in the hemostatic action of recombinant human erythropoietin.

Adult↗
PubMed1993

Serotonergic measures in blood and brain and their correlations in rats treated with tranylcypromine, a monoamine oxidase inhibitor.

Tranylcypromine, a monoamine oxidase inhibitor, was administered to male Wistar rats in order to investigate its effects on blood and brain serotonin related substances after 1, 4, and 24 h following injection and possible relations between serotonergic measures in central nervous system and periphery. The dose of the drug tested was responsible for an increase in blood serotonin with a simultaneous fall in its metabolite 5-hydroxyindoleacetic acid (5-HIAA) compared to either pretreatment or control values. These changes were the most marked after 4 and 24 h following tranylcypromine injection. Almost all brain areas studied (cerebellum, medulla, hypothalamus, striatum, midbrain, hippocampus, and cortex) were to be affected by monoamine oxidase inhibitor treatment. They exhibited a rise in serotonin content starting from 1 h after drug administration and lasted in many parts of the brain up to 24 h, which was accompanied by a parallel fall in 5-HIAA level. All these changes were significant when compared to baseline and control values. Alterations in blood serotonin correlated positively with changes in brain serotonin and negatively with brain 5-HIAA, while the opposite pattern of correlations was found regarding blood 5-HIAA and the content of serotonin and 5-HIAA in various brain areas studied. This pattern of correlations speaks in favor of an existence of mutual relations between blood and brain serotonin related substances. Our results suggest that blood serotonin and 5-HIAA may serve as an index of monoamine oxidase inhibitor action on the central serotonergic system.

Animals↗
PubMed1992

A single mRNA, transcribed from an alternative, erythroid-specific, promoter, codes for two non-myristylated forms of NADH-cytochrome b5 reductase.

Two forms of NADH-cytochrome b5 reductase are produced from one gene: a myristylated membrane-bound enzyme, expressed in all tissues, and a soluble, erythrocyte-specific, isoform. The two forms are identical in a large cytoplasmic domain (Mr approximately 30,000) and differ at the NH2-terminus, which, in the membrane form, is responsible for binding to the bilayer, and which contains the myristylation consensus sequence and an additional 14 uncharged amino acids. To investigate how the two differently targeted forms of the reductase are produced, we cloned a reductase transcript from reticulocytes, and studied its relationship to the previously cloned liver cDNA. The reticulocyte transcript differs from the liver transcript in the 5' non-coding portion and at the beginning of the coding portion, where the seven codons specifying the myristoylation consensus are replaced by a reticulocyte-specific sequence which codes for 13 non-charged amino acids. Analysis of genomic reductase clones indicated that the ubiquitous transcript is generated from an upstream "housekeeping" type promoter, while the reticulocyte transcript originates from a downstream, erythroid-specific, promoter. In vitro translation of the reticulocyte-specific mRNA generated two products: a minor one originating from the first AUG, and a major one starting from a downstream AUG, as indicated by mutational analysis. Both the AUGs used as initiation codons were in an unfavorable sequence context. The major, lower relative molecular mass product behaved as a soluble protein, while the NH2-terminally extended minor product interacted with microsomes in vitro. The generation of soluble reductase from a downstream AUG was confirmed in vivo, in Xenopus oocytes. Thus, differently localized products, with respect both to tissues and to subcellular compartments, are generated from the same gene by a combination of transcriptional and translational mechanisms.

Amino Acid Sequence↗
PubMed1990

Study on mechanisms of a haemostatic effect of 1 deamino-8-D-arginine vasopressin (desmopressin) in uraemic patients.

The effect of 1 deamino-8-D-arginine vasopressin (DDAVP) on blood platelet serotonin and some parameters of haemostasis was investigated. DDAVP was administered intravenously in a dose of 0.4 micrograms/kg BW to 16 uraemic patients maintained on chronic haemodialysis in a double-blind crossover study compared with placebo. The bleeding time was significantly shortened after DDAVP administration from 21.3 +/- 8 minutes to 11.5 +/- 6 minutes (p less than 0.001). VIII: Ag increased from 239.1 +/- 94% to 473 +/- 293% (p less than 0.01). Euglobulin lysis time was shortened from 238 +/- 101 to 148 +/- 84 minutes (p less than 0.005). The platelet serotonin level was significantly reduced from 532 +/- 141 to 366 +/- 88 ng/10(9) platelets (p less than 0.02). There were no changes in haematocrit, platelet count, VIII: C levels and blood serotonin concentrations after DDAVP administration. In placebo group there were no changes in all investigated parameters. Our data indicate that DDAVP shortens prolonged bleeding time in uraemic probably by means of the serotonergic mechanism. Further studies are needed to confirm this suggestion.

Adult↗
PubMedDate not supplied

Thrombin activatable fibrinolysis inhibitor in hypertensive kidney transplant recipients.

Kidney transplant recipients are prone to hypertension, dyslipidemia, and cardiovascular death. Hypertension is associated with hemostatic abnormalities. Thrombin activatable fibrinolysis inhibitor (TAFI) is a glycoprotein that links coagulation and fibrinolysis. The purpose of this study was to assess TAFI concentrations in renal transplant recipients in relation to blood pressure. Additionally, we evaluated thrombin activity (thrombin-antithrombin complex [TAT], prothrombin fragments 1+2 [F1+2]), thrombomodulin (TM), and the degree of plasmin generation (plasmin-antiplasmin complex [PAP]) using commercially available kits. The studies were performed on 86 renal allograft recipients (48 women, 38 men) at age range 26 to 73 years. The immunosuppressive regimen consisted of cyclosporine (CsA), prednisone, and azathioprine (n = 58) or mycophenolate mofetil (MMF; n = 28). All patients maintained sufficient and stable graft function, showing no clinical signs of rejection. In patients with hypertension (n = 68), we observed significantly higher concentrations of TAFI and of markers of thrombin generation (F1+2, TAT), and of thrombomodulin with significantly prolonged euglobulin clot lysis time (ECLT), which reflects overall fibrinolytic activity and lower fibrinolytic activity index (FAI). Both groups did not differ with respect to age, creatinine clearance, body mass index, time after transplantation, albumin, fibrinogen, and PAP. Diastolic blood pressure correlated significantly with TAFI concentrations, uric acid, and prednisone dose, whereas systolic blood pressure correlated with urea, uric acid, creatinine clearance, and MCV. Elevated TAFI concentrations and enhanced thrombin generation in hypertensive kidney transplant recipients may contribute to the hypofibrinolysis and progressive atherosclerosis in this population. Blood pressure was related to kidney function, maintenance prednisone dose, and TAFI concentration.

Adult↗
PubMedDate not supplied

Time-dependent changes in platelet aggregation, fibrinolytic activity, and peripheral serotonergic measures in rats subjected to water immersion restraint stress.

The effects of water immersion restraint stress on collagen-induced platelet aggregation in whole blood, and on the fibrinolytic and serotonergic systems in rats have been studied. One hour long stress caused a release of tissue plasminogen activator (tPA) into the blood and a shortening of euglobulin clot lysis time (ECLT), whereas restraint of longer duration was responsible for a reduction in platelet aggregation, an elevation in the activity of plasminogen activator inhibitor with a concomitant fall in tPA and a prolongation of ECLT relative to controls. Whole-blood and plasma serotonin and its metabolite 5-hydroxyindoleacetic acid were also higher in the stressed rats and whole-blood serotonin level showed a negative correlation with tPA in the stressed rats. Either stress and/or its duration are responsible for changes in both fibrinolytic and serotonergic systems.

Acute Disease↗
PubMedDate not supplied

Close relationships between serotonergic and fibrinolytic systems revealed by a monoamine oxidase inhibitor treatment in rats.

In order to investigate a possible relationship between serotonergic and fibrinolytic systems, serotonin (5-hydroxytryptamine, 5-HT) metabolism was modified by the use of a monoamine oxidase inhibitor (tranylcypromine: 10 mg/kg body weight) and its effect on the fibrinolytic system was analyzed. Tranylcypromine caused a rise in whole blood 5-HT with a simultaneous fall in 5-hydroxyindoleacetic acid. Euglobulin clot lysis time was significantly prolonged 1 and 4 h after injection and tissue plasminogen activator (tPA) activity declined 4 h following administration with a simultaneous increase in its inhibitor (PAI) activity. Blood 5-HT was negatively related to tPA (r = -0.48; p < 0.05) and positively to PAI activities (r = 0.43; p < 0.05) in tranylcypromino-treated rats, whereas there were no such correlations in solvent-treated rats.

Animals↗
PubMedDate not supplied

Plasma serotonin and platelet aggregation during ischemia-reperfusion in dogs: effect of dipyridamole and coenzyme Q10.

Platelet aggregation and plasma serotonin were studied during ischemia-reperfusion of the small intestine in dogs. Blood was withdrawn from the superior mesenteric vein before and 1 h after ischemia, then 5, 30 and 60 min after reperfusion. Dipyridamole (5 mg/kg body weight) and coenzyme Q10 (CoQ10; 10 mg/kg body weight) were administered intravenously 5 min before reperfusion, following 1 h ischemia, in order to investigate their effects on platelet function and free serotonin. Ischemia-reperfusion resulted in an increased local free serotonin concentration together with an enhanced platelet response to ADP, collagen and arachidonic acid. Administration of dipyridamole and CoQ10 prior to reperfusion prevented, at least in part, augmented platelet activation and serotonin release. It appeared that dipyridamole was more potent than CoQ10. Our results may indicate a possible protective effect of dipyridamole on enhanced platelet activation during ischemia-reperfusion in dogs.

Animals↗
PubMedDate not supplied

Comparison of hemostatic disturbances between patients on CAPD and patients on hemodialysis.

OBJECTIVE: Disturbances in hemostasis are common findings in uremic patients. Both bleeding diathesis and thrombosis are observed. The purpose of this study was to assess whether renal replacement therapy in the form of hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) affects coagulation and fibrinolysis in patients with end-stage renal failure. DESIGN: Comparison of hemostatic measures in patients on CAPD, HD, and matched healthy controls. SETTING: Department of Nephrology and Internal Medicine, Bialystok University School of Medicine. PATIENTS AND METHODS: Twenty-four HD patients and 23 CAPD patients were evaluated with respect to platelet aggregation, hemostatic parameters, serum lipids, lipoprotein(a), and cytokines [tumor necrosis factor alpha (TNFalpha) and interleukin-1 (IL-1)]. INTERVENTIONS: Four exchanges of CAPD per day, using 2.0 L dialysate over a period of 25 +/- 31 months; or 4-5 hours of HD 3 times per week for a period of 31 +/- 22 months. RESULTS: Platelet aggregation in whole blood and platelet-rich plasma was significantly impaired in both groups of dialyzed patients compared to healthy volunteers. Markers of endothelial cell injury (thrombomodulin and von Willebrand factor) were significantly higher in HD and CAPD patients compared to the control group. A similar pattern of changes was observed for lipoprotein(a), fibrinogen, tissue factor pathway activity, and factor VII activity. Activity of factor X was significantly enhanced in CAPD compared to HD patients and controls. Euglobulin clot lysis time was significantly prolonged in HD and CAPD patients over controls, being more prolonged in CAPD patients. Markers of ongoing coagulation (thrombin-antithrombin complexes and prothrombin fragments 1+2) were higher in uremic patients, significantly higher in CAPD than in HD. A marker of ongoing fibrinolysis (plasmin-antiplasmin complexes) was higher in uremic patients but was lower in CAPD than in HD patients. Concentrations of TNFalpha and IL-1 were higher in HD than in CAPD patients. CONCLUSION: Patients on CAPD showed evidence of a higher degree of hypercoagulation than HD patients.Thus, hemostatic abnormalities in end-stage renal failure may be affected to some extent by the choice of renal replacement therapy.

Adult↗