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Biomedical subjects

K Adrian

Publications and source records attributed to K Adrian.

14 recordsLinked to original sources
PubMed2003

Pharmacological inhibition of plasma coagulation and platelet activation during experimental long-term perfusion.

OBJECTIVE: During extracorporeal circulation, initial contact between blood and the artificial surface of the circuit induces an overall activation of the hemostatic system. The objective of this study was to investigate the combined effect of epoprostenol (PGI (2) ), nitric oxide (NO) and nafamostat mesilate (FUT-175, a serine protease inhibitor), on plasma coagulation and platelet activation during experimental long-term perfusion. DESIGN: Two identical extracorporeal life support (ECLS) circuits were primed with fresh, heparinized human blood, and circulated for 24 h. FUT was given with a bolus dose of 85 mg/l blood at the initiation of the experiment and thereafter as a continuous infusion of 14 mg/l/h. PGI (2), at a rate of 2.4 microg/l/h, was also administered to the experimental circuit, and 120 ppm NO gas was added to the oxygenator sweep gas. The other circuit was used as a control. RESULTS: Higher platelet count and platelet membrane expression of GPIb were found in the experimental circuits as compared with control circuits. The levels of thrombin/antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2) increased significantly over time in the control circuits but remained low in the experimental circuits. Plasma levels of plasminogen activator inhibitor 1 (PAI-1) decreased rapidly in both circuits but were higher in the control circuits at each time point studied. CONCLUSION: The activation of platelets and of the coagulation system encountered during extracorporeal perfusion is consistently inhibited by a combination of PGI (2), NO and FUT-175. The combination of these drugs appears to be more effective than each drug separately.

Antithrombin III↗
PubMed2000

Expression of purinergic receptors (ionotropic P2X1-7 and metabotropic P2Y1-11) during myeloid differentiation of HL60 cells.

The expression of human purinergic P2 receptors (P2X1-7 and P2Y1-11) as well as the ecto-enzymes apyrase (CD39) and 5'-nucleotidase (CD73) was investigated on the nucleic acid level during granulocytic and monocytic differentiation of HL60 cells and on peripheral human blood leukocytes. RT-PCR and dot-blot hybridization assays indicated that mRNA transcripts of all analyzed P2 receptors apart from the P2X3 receptor were expressed during myeloid development of HL60 cells, showing a distinct regulation during the course of differentiation. In blood leukocytes, transcripts of P2X5, P2X7 and all P2Y receptors, except for P2Y6, receptor were found. CD39 and CD73 showed a marked upregulation during myeloid maturation. Functional analysis of P2 receptor-mediated intracellular Ca(2+)-increase after stimulation with ATP revealed no change during granulocytic differentiation, but showed a strong attenuation in both potency and efficacy during monocytic development of HL60 cells.

5'-Nucleotidase↗
PubMed2000

Hybrid cell vaccination for cancer immune therapy: first clinical trial with metastatic melanoma.

Hybrid cell vaccination is a new cancer immune therapy approach that aims at recruiting T cell help for the induction of tumour specific cytolytic immunity. The vaccines are generated by fusion of the patients' tumour cells with allogeneic MHC class II bearing cells to combine the tumour's antigenicity with the immunogenicity of allogeneic MHC molecules. Safety and anti-tumour activity of this treatment were assessed in a clinical trial that has yielded one complete and one partial remission, and 5 cases of stable disease among 16 patients with advanced stage metastatic melanoma. As evidenced by histology, the vaccination induced T cell relocation into tumour nodules. Stable disease could be maintained by repeated booster injections for more than 24 months in some patients. The side effects were minor. Occasional occurrences of vitiligo spots after vaccination were indicative of a restricted therapy induced auto-immune reactivity. The results suggest that hybrid cell vaccination is a safe cancer immune therapy potentially effective for induction of acute anti-tumour response as well as long-term maintenance.

Adult↗
PubMed2000

Influence of hemofiltration on plasma cytokine levels and platelet activation during extra corporeal membrane oxygenation.

OBJECTIVE: Extra corporeal circulation of human blood is used daily in lifesaving procedures such as open-heart surgery and extracorporeal membrane oxygenation (ECMO). But extracorporeal circulation also induces activation of various cascade reactions in the blood. The objective of this study was to evaluate the effects of hemofiltration on cytokine release and removal as well as on platelet activation and consumption. MATERIAL AND METHODS: Two complete ECMO systems, each of them holding a hollow fiber oxygenator, a bladder box, PVC tubing and a roller pump were perfused for 24 h with fresh, heparinized human blood. A hemofilter was added to one of the paired systems. Blood samples were collected from both circuits before start, and at 0.5, 1, 3, 12 and 24 h of perfusion. A total of 8 paired experiments was performed. RESULTS: The plasma concentration of interleukin (IL)1beta, IL-6 and IL-8, as well as of IL-1 receptor antagonist (IL-1ra) increased over time in both systems, but consistently lower levels were observed in the filter circuits compared to the controls. Only minor parts of these cytokines could be assayed in the ultrafiltrate. No significant difference in platelet count and platelet membrane expression of glycoprotein Ib was observed between the circuits. CONCLUSIONS: By adding a hemofilter to the ECMO circuit, it is possible to reduce the plasma concentration of interleukins without significantly affecting platelet activation and consumption.

Cytokines↗
PubMed1999

The effect of epoprostenol on platelet activation and consumption during experimental extracorporeal perfusion.

Hemorrhages are major complications experienced in 10-35% of neonates treated with extracorporeal life support (ECLS). The increased bleeding tendency is partly due to an ECLS induced thrombocytopenia and impaired platelet function. In the present study, we evaluated the effect of epoprostenol on the ECLS induced platelet consumption and activation. In terms of the methods, identical in vitro ECLS circuits were primed with fresh heparinized human blood and circulated for 24 h. Epoprostenol (2.4 microg/L blood/h) was added to one of the circuits in each pair. In total, 6 paired experiments were performed. The platelet count, neutrophil count, plasma concentration of hemoglobin, and platelet membrane expression of glycoproteins (GP) Ib and IIb/IIIa were assayed before the start and at 0.5, 1, 3, 12 and 24 h of perfusion. Higher platelet counts were observed in the experimental circuits. However, no difference in the platelet membrane expression of GPIb and GPIIb/IIIa could be observed between the circuits. In conclusion, epoprostenol reduces platelet consumption during ECLS without affecting the membrane expression of GPIb and GPIIb/IIIa.

Analysis of Variance↗
PubMed1998

Induced cell trauma during in vitro perfusion: a comparison between two different perfusion systems.

The purpose of this study was to compare blood cell activation during in vitro long-term perfusion using 2 parallel in vitro extracorporeal membrane oxygenation (ECMO) systems. We compared two substantially different perfusion systems, an assistance respiratoire extra corporelle (AREC) system on one hand, containing an AREC pump, silicon tubing, and a hollow-fiber oxygenator, and a centrifugal pump system, on the other hand, containing a Biomedicus centrifugal pump, PVC tubing, and a membrane oxygenator. We measured the platelet count using an automated blood cell counter. Platelet activation was evaluated using a flow cytometric technique for the platelet membrane expression of glycoproteins and ELISA for the plasma concentration of beta-thromboglobulin (beta-TG), a platelet specific protein released into the blood upon platelet activation. The neutrophil count was assayed using an automated blood cell counter and the plasma concentration of cytokines using an ELISA kit. A significant difference between the two systems was observed in terms of the platelet membrane expression of glycoprotein (GP)Ib (p=0.0001) and GPIIb/IIIa (p=0.0037), indicating a lower degree of platelet activation in the AREC system. The concentration of neutrophils was significantly lower in the centrifugal system (p=0.002) compared to the AREC system. The neutrophil membrane expression of CD11b was significantly lower (p=0.0067) in the AREC system, indicating a lower degree of neutrophil activation compared to the centrifugal pump system. A significantly lower degree of hemolysis, as expressed by plasma hemoglobin, was observed in the AREC pump system (p=0.0491). In conclusion, lower degrees of the platelet membrane expression of GPIb and GPIIb/IIIa and of the neutrophil membrane expression of CD11b were observed in the AREC system, indicating a lower degree of platelet and neutrophil activation in this system. No significant difference between the two systems as to the plasma concentration of interleukin (IL)-1beta, IL-6, or IL-8 could be recorded. Further studies are warranted to specify the role of each individual component of the two systems.

Blood Platelets↗
PubMed1998

Cytokine release during long-term extracorporeal circulation in an experimental model.

The objective of this study was to determine the degree of leukocyte activation, as measured by cytokine release, in circulating blood during experimental extracorporeal circulation. Complete in vitro extracorporeal membrane oxygenation (ECMO) circuits were used, and 9 experiments were performed. Whole blood stored at 37 degrees C was used as the control. Blood samples were withdrawn before the start of perfusion and at 24 h of perfusion. Statistically significant releases of interleukin (IL)-1beta, IL-8, and IL-1 receptor antagonist were observed in the perfusion circuits compared to both the control blood and baseline values. Also, increases in plasma tumor necrosis factor (TNF)alpha and IL-6 were seen after 24 h of perfusion although these changes did not reach statistical significance. These results indicate that extracorporeal circulation induced leukocyte activation and cytokine release. These reactions might, as an additional trauma, deteriorate the situation in an already severely ill patient. A search for methods to counteract this untoward activation seems warranted.

Adult↗
PubMed1998

The effect of albumin priming solution on platelet activation during experimental long-term perfusion.

The objective of this study was to evaluate the effect of albumin priming on platelet consumption and activation during long-term perfusion. Two identical in vitro extracorporeal membrane oxygenation circuits were used; one was primed with Ringer's solution containing human serum albumin, the other with Ringer's solution only. Fresh heparinized human blood was pooled, divided between the two systems and circulated for 24 h at 37 degrees C. Platelet count, plasma concentration of betathromboglobulin (BTG), platelet membrane density of glycoprotein (GP) Ib and of GPIIb/IIIa were assayed before the start and at 0.5, 1, 3, 12 and 24 h of perfusion. In total, seven experiments were performed. We found that during the first hour of perfusion, slightly higher platelet counts (p = 0.058) and lower BTG values (p = 0.0005) were observed in the circuits primed with albumin, compared to the control circuits. No statistically significant differences were observed for the platelet membrane expression of GPIb and GPIIb/IIIa. We conclude that albumin priming appears to transiently prevent platelet consumption and activation during long-term perfusion.

Extracorporeal Membrane Oxygenation↗
PubMed1990

Polyclonal stimulation of human B lymphocytes derived from fetal liver and spleen cells at different stages of ontogeny.

The functional capacity of human lymphocytes derived from fetal liver and spleen at different stages of ontogeny (16-34 weeks of gestation) was studied using in vitro models (increase in cell volume, [3H]thymidine incorporation, Ig secretion) reflecting various stages of activation induced by mitogens (LPS, PWM) in vitro. Lymphocytes differed in their reactivity to LPS depending on the period of intrauterine development: cells from the early liver could respond with enhanced IgM production whereas lymphocytes derived from this organ after more than 25 weeks failed. The opposite was found to apply to spleen cells: only lymphocytes derived from the organ after more than 25 weeks showed significant LPS-induced in vitro differentiation. These data were in correlation with the proliferative response to LPS. It was clear that the number of CD20-positive mature B cells in the lymphocyte preparations was not responsible for these results, since comparable yields were found throughout the period of fetal development of the liver studied, whereas in the spleen increasing numbers of B cells were seen.

B-Lymphocytes↗
PubMed1989

[The effect of the peptide dalargin on wound healing].

The wound-healing agent Dalargin, a hexapeptide and varios of its cleavage products were tested in a wound-healing model on the basis of granulation in rat. Three days after wounding (p.op.) an increase in granulation was observed at Dalargin concentrations of 10 micrograms/ml and 50 micrograms/ml. Seven days p.op. an increase was observed already at a Dalargin concentration of 5 micrograms/ml. The cleavage products of Dalargin had no stimulating effect on granulation. A histologic differentiation of the different cell parts in the granulation tissue led to an increased total number of cells. The concentration of 5 micrograms/ml induced both an increase in the number of endothelial cells and fibroblasts, the concentration of 50 micrograms/ml induced just an increase of the number of endothelial cells. The possible bases of the mode of operation are being discussed. The stimulating effect on wound healing as described could be confirmed by the results obtained in our animal experiments.

Animals↗