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D Seiffge

Publications and source records attributed to D Seiffge.

At least 37 records · Page 2Linked to original sources

[Thrombotic reactions of vascular anastomoses: comparison of model studies with experimental findings].

The areas of predilection for atherosclerosis and thrombosis in the vascular system are characterized by curvature, branching, bifurcation or embankment. We have investigated induced thrombus formation at arteriolar bifurcations with migrating stagnation points and local vortex flow. Thrombogenic endothelial lesions were produced in rat mesenteric arterioles by argon laser injury or by photochemical reactions (using FITC-dextran 70). The following items have been evaluated: local red blood cell velocity, geometry of the vessel, localization of the first thrombus growth. The first appearance of thrombus formation at presumably (re-) attachment points at bifurcations in the microcirculation could be directly demonstrated by intravital microscopy.

Animals↗

Purification of 7 alpha-hydroxysteroid dehydrogenase from Escherichia coli strain 080.

Purification studies of 7 alpha-hydroxysteroid dehydrogenase (7 alpha-HSDH) (EC 1.1.1.159) from Escherichia coli 080 showed that 1.59-fold purification could be achieved by heating (60 degrees C for 10 min) the ultracentrifuged enzyme preparation, and 6.46-fold purification was achieved by subsequent precipitation with ammonium sulfate. Further purification on Sephadex G-100 gel gave 10.1-fold purification. After pooling and concentrating the active fractions obtained from the Sephadex G-100 filtration, an 11.1-fold purification was achieved using DEAE-cellulose chromatography. The purified enzyme produced a single band on polyacrylamide gel electrophoresis and its molecular weight was determined to be 54,000. The enzyme was immunogenic and showed immunoprecipitation with homologus antisera.

Chromatography, DEAE-Cellulose↗

Stimulatory effects of vascular prostaglandins on the antiaggregatory activities of pentoxifylline acetylsalicylic acid combinations in vitro.

Pentoxifylline, Acetylsalicylic acid (ASA) and particularly both drugs in combination are known as active platelet inhibitors in pharmacological models in vivo. However, rather high amounts of these drugs are necessary to demonstrate inhibitory effects on the aggregation of human platelets in vitro, where no vessel walls are present. Surprisingly, these weak effects could be enhanced by the addition of external prostaglandins (prostacyclin (PGI2) and prostaglandin E1 (PGE1] into the in vitro system. Ternary combinations consisting of pentoxifylline, ASA and PGI2 exhibited the most impressive synergistic effects. Thus our study highlights the contribution of prostaglandins, especially of the natural vascular platelet inhibitor PGI2, for the display of the antiaggregatory potency of such drug combinations.

Alprostadil↗

Surprising effects of the sequential administration of pentoxifylline and low dose acetylsalicylic acid on thrombus formation.

The effect of the combined oral administration of pentoxifylline (pof) and low dose acetylsalicylic acid (ASA) was evaluated with the help of the laser-induced thrombosis in rat mesenteric arterioles. Laser-induced thrombosis is inhibited in a dose-dependent way by both drugs. The administration of ASA, either simultaneously with or 1 hour prior to pof, does not show any effects in the laser model. On the contrary, the administration of pof followed 1 h later by ASA not only exhibited a significant effect but also produced a supraadditive inhibition of the laser-induced thrombus formation. Specific investigations concerning the time interval between the administration of both drugs determined that a significant effect can be achieved only after an interval of 30 to 90 minutes (principle of HWA 5112). The striking results could also be shown in diseased animals after sequential chronic administration of pof 1 h prior to ASA. HWA 5112 exhibits significant effects on laser-induced thrombus formation in the following chronic animal models: 1. adjuvant arthritic rats, 10----1 mg/kg for 21 days; 2. spontaneously hypertensive stroke-prone rats, 10----1 mg/kg three times within 24 h; 3. cholesterol-induced atherosclerosis in rabbits, 10----1 mg/kg for 14 days. The reported data clearly demonstrate that the sequential drug administration of first pentoxifylline followed 30 to 90 min later by ASA exhibits a supraadditive antithrombotic effect.

Administration, Oral↗

Influence of ADP, blood flow velocity, and vessel diameter on the laser-induced thrombus formation.

The laser-induced thrombus model in rat mesenteric arterioles and venules represents a reliable and reproducible in vivo method. It is suitable for basic investigations concerning factors involved in thrombus formation as well as for testing antithrombotic effects of drugs. The laser-induced thrombus formation depends significantly on the presence of ADP, as ADP-utilizing enzymes inhibit thrombosis in the animal model. The instrumental test set-up consists of a 4 W Argon laser (Spectra Physics, Mountain View, CA, USA), a ray adaptation and adjusting device (BTG, Munich, FRG), a microscope (ICM 405, Zeiss, Oberkochen, FRG), and a video system (Sony, Japan). RBC velocity data were recorded with the help of a modified dual-slit technique (acc. to Wayland and Johnson). Results were expressed as number of laser injuries necessary to produce a defined thrombus (minimum size: 1/4 of the vessel diameter) under constant conditions (effective capacity: 30 mW, exposure time: 1/5 sec). The number of laser lesions necessary to induce a defined thrombus decreased with an increase in arteriole diameter (10 to 20 micron) but increased again in larger arterioles and small arteries (greater than 25 micron). On the arteriolar side there are significant correlation coefficients between vessel diameter and RBC velocity (r = 0.69), vessel diameter and No. of laser injuries (r = 0.70), and RBC velocity and No. of laser injuries (r = 0.71). Due to relative low flow conditions in the venules, the number of laser injuries required to induce a defined thrombus does not significantly depend on the vessel diameter.

Adenosine Diphosphate↗

Effects of propentofylline (HWA 285) on laser-induced thrombus formation in healthy and diseased rat mesenteric arterioles.

The antithrombotic effects of the xanthine derivative propentofylline (HWA 285) were investigated in the laser-induced thrombus model in healthy and diseased rat mesenteric arterioles. Laser-induced platelet thrombi were documented by the help of an intravital microscope and a video system. The statistical comparison of drug-treated and untreated animals, in respect to the number of laser shots necessary to induce a defined thrombus, served as a quantitative measure for a potential antithrombotic drug effect. Propentofylline and acetylsalicylic acid, in single dosages of 10 and 30 mg/kg orally, significantly increased the number of laser shots required to produce a defined thrombus. Moreover, the drug decreased the laser-induced thrombus formation in a chronic experiment in adjuvant arthritic rats. After oral administration of 30 mg/kg for 21 days, propentofylline and pentoxifylline reduced significantly the thrombus formation, whereas acetylsalicylic acid exerted no effect.

Animals↗

Effect of pentoxifylline on sickle cell thalassaemia: haemorheological and clinical results.

The effect of pentoxifylline on the deformability of red cells in sickle cell thalassaemia was investigated. The fluidity of the blood in sickle cell thalassaemia is disturbed and is accompanied by violent pains and irreversible tissue damage caused by capillary occlusions. After treating a 15-years-old female patient with pentoxifylline (2 g orally each day), the fluidity of the blood improved distinctly, and this correlated with a condition free of clinical symptoms. Erythrocyte filtration by Nuclepore filter increased significantly over the 6-month examination period (initial value: V rel = 0.068 +/- 0.008; after 6 months medication: 0.246 +/- 0.030). In addition, in the single-pore erythrocyte rigidometer (SER) a significantly improved passage time of individual erythrocytes could be demonstrated (initial value: 62.43 +/- 15.72 ms; after 4 weeks medication: 28.13 +/- 7.0 ms). The hitherto high number of rheological occlusions in the SER (48 +/- 30.9 from 200 individual passages) almost completely disappeared after treatment (1.7 +/- 1.2).

Adolescent↗

Red cell membrane abnormalities in two cases with a special type of a hereditary megaloblastoid hemolytic anemia.

Case reports are presented of two related patients suffering from a hereditary megaloblastoid hemolytic anemia which at the moment cannot be categorized into one of the well-known entities. The main characteristics of the disease consisted of constant jaundice, macrocytic normochromic anemia, marked hemolysis without a substantial decrease in osmotic resistance, increased iron turnover and hepatic hemosiderosis at a relatively young age. One patient had to undergo splenectomy due to hemolytic crises, the other one cholecystectomy due to gallstones. In contrast to their uncharacteristic morphology in smear, red cells displayed highly variable forms ("lumpy", "Y", "U", drumstick forms) when examined in transmission and scanning electron microscopes. These changes corresponded well with reduced filtrability and aggregability of erythrocytes. The apparent relative blood viscosity was unchanged. The protein pattern of ghosts in SDS gel-electrophoresis revealed neither defects nor additional bands. Changes in the lipid composition of the membrane were indirectly deduced from electron spin-resonance studies, which showed an additional signal at g = 2.192. Similarly, the lipid related membrane mobility agent A2C failed to exert the usual stabilizing effect against osmotic stress. The negative surface potential, estimated by free flow electrophoresis, was only altered in the splenectomized patient. It is concluded that the primary abnormal physical properties of the enlarged red cell contribute at least in part to the marked hemolysis. The similar findings in the two related patients and the fact that the disorder was obviously congenital suggest a special subtype of a megaloblastoid hemolytic anemia.

Adolescent↗

Haemorheological studies of the sickle cell phenomenon in European red deer (Cervus elaphus).

It was demonstrated that the appearance of sickle-shaped erythrocytes can be induced by oxygenating the blood of European red deer (Cervus elaphus). The process was reversible. Blood cell counts with the exception of a slight reduction in red cell number and protein fractions did not show any abnormal values. The blood, which was examined at least 18 h after sampling, exhibited considerable deviations of blood gas values. In addition, highly significant haemorheological changes due to the sickle-shaped and oxygenated erythrocytes were detected.

Anemia, Sickle Cell↗

Effect of pentoxifylline on single red cell deformability.

In the present investigation the effect of pentoxifylline on single red cell deformability was determined. The deformability of human red blood cells were measured in a Singlepore Erythrocytes Rigidometer (SER). The new method determines optoelectronically the passage of each individual cell through a singlepore membrane (6 micrometers diameter and 50 micrometers length) under a driving pressure gradient (delta p = 100 Pa, tau = 3 Pa). Venous human blood samples were taken, prepared and divided into three samples. Sample A served as a physiological control, while to sample B and C CaCl2-solution was added. After Ca2+ stress sample C was incubated with 0.36 mmol/l pentoxifylline. The medium passage time (MPT) for sample A was 43.3 +/- 6.5 ms and for sample B 87.5 +/- 14.7 ms. The addition of pentoxifylline to the Ca2+-treated red cell suspension (sample C) reduced the MPT to 51.6 +/- 11.3 ms.

Adult↗

Filtrability investigations with red blood cell (RBC) suspensions: effects of different blood components and pentoxifylline on RBC flow rate.

RBC deformability provide an important and limitating factor in blood flow and microcirculatory perfusion. A relative great number of tests are available to estimate RBC deformability, e.g. filtration methods. We performed several tests with a filtration method (Nucleopore) whereby several basically different parameters have to be taken into consideration (driving pressure, volume of filtered suspension, number of filtered cells, flow rate and so on). We could show that RBC filtration will be influenced by the number of leucocytes and the plasma, as a great quantity of the pores will actually be plugged by the leucocytes and cell aggregation will occur due to plasma protein bridging. In order to assess RBC deformability by filtration tests, it is necessary to control all variables affecting the rheological behavior of red cells: washing and suspending in buffer, control of temperature, osmolarity and pH-values, quantification and calibration of the filter, calculation of relative flow rate (Vrel = Vsusp/Vsusp medium). Under these circumstances we tested the bloodrheological effect of pentoxifylline (Trental) on less deformable red cells. Red cell rigidification was obtained by lactacidosis or cellular ageing in buffer associated with loss in erythrocytic ATP content. A protective effect of pentoxifylline against red cell rigidification in the microfiltration test could be demonstrated.

Animals↗

Release of coagulase from staphylococci.

Immediately after inoculation with coagulase-positive staphylococci the coagulase-activity increased significantly in various culture media. The increase was much higher than the calculated coagulase-activity added with the inoculum (table 1). It appears that this release offers a possibility for the efficient production of coagulase prior to purification.

Bacteriological Techniques↗