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Biomedical subjects

S Ziemer

Publications and source records attributed to S Ziemer.

45 records · Page 3Linked to original sources

Electrorotation--a new method for investigating membrane events during thrombocyte activation. Influence of drugs and osmotic pressure.

The measurement of the spin of cells in rotating high-frequency electric fields ('electrorotation') make possible the investigation of dielectric membrane properties of single cells. This method was applied to membrane permeability changes accompanying thrombocyte activation and compared with light-scattering data. Describing the dielectric behavior of platelets by a single-shell model and assuming a sufficiently low membrane conductivity of 1 X 10(-7) S/m we found for nonactivated platelets a membrane capacity of 5.5 mF/m2 and the conductivity of the internal medium was estimated to be 0.12 S/m. Upon activation, the electrorotation decreased continuously, with half-times in the range of few minutes. This could be explained assuming a 500-fold increase in membrane conductivity. The application of both local anesthetics and virostatics inhibited the decrease of electrorotation, as did hypertonic osmotic pressure. In all cases this was accompanied by inhibition of platelet aggregation. Hypotonic solutions induced self-aggregation and spontaneous loss of electrorotation. It was concluded that the increase in permeability of the granule membrane is a crucial step in the release reaction and that the electrorotation method is able to detect the incorporation of the granule membranes into the plasma membrane during activation. The advantage of this electrorotation method is that it enables measurements on a single-cell level, thus avoiding interactions between platelets.

Adamantane↗

[Status of fibrinolysis in systemic lupus erythematosus].

In patients with systemic lupus erythematosus (SLE) both a haemorrhagic diathesis and a tendency to thrombosis of the venous and arterial vessels can be observed. In the course of the disease, thrombosis of the leg or pelvic veins developed in 20 per cent of 188 patients. The levels of alpha 2-plasmin inhibitor, plasminogen, fibronectin and of factor VIII complex were increased in patients with SLE compared with a control group. Fifty per cent of the patients showed no increase in fibrinolytic activity after venous occlusion measured with the fibrin plate method. This suggests a reduced fibrinolytic capacity in SLE probably caused by alteration of the endothelial cells through immune complex vasculitis. In addition, the lupus anticoagulant and an acquired antithrombin III deficiency in nephrotic syndrome in SLE are to be considered thrombophilic mechanisms. In the individual case there is an overlapping of hyper- and hypocoagulability.

Adult↗

[A method for the cryopreservation of thrombocytes].

By using dimethylsulfoxide (0.7 mol/l) a technique of cryoconservation of thrombocyte concentrates was elaborated, with own material-technological possibilities being taken into consideration. In comparison to fresh thrombocytes the results of parameters tested in vitro reveal a mean functional ability of 50%. The survival time of cells stored in this way in vivo may be compared with fresh cells. On this basis HLA-typed single-donor pools could be established for clinical application.

Blood Platelets↗

[Further improvement of the ACD-AG protective solution for blood. III. Improvement of the oxygen transport function of erythrocytes in sorbitol xylitol pyruvate solutions with elevated Ph].

If the pH value in the ACD or in the ACD-AG storage solution is enhanced, the glucose in the autoclaving with undergo a caramelizing process. For this reason glucose was replaced by sorbite in the storage solutions with a pH value of 6.0 and additions of xylitol and pyruvate. The initial pH value in the blood amounted to 7.3. The content of 2.3 DPG of the erythrocytes remained fully preserved in the blood with sorbitol and additions of xylitol and pyruvate during the first 2 weeks of storage and decreased to 30% only in the third week. There were only slight amounts of 2.3 DPG in the ACD-AG blood at that time of storage. Up to the third week of storage the ATP content of erythrocytes as well as the haemoglobin level in the plasma revealed no essential differences between stored blood with sorbitol and xylitol as a substrate or glucose + xylitol respectively. The quick decrease of the ATP level to zero and the simultaneous strong increase of haemolysis in the sorbitol blood within the fourth week of storage is discussed in connection with a lowering of the NAD/NADH2 quotient. For the purpose of keeping the 2.3 DPG level of erythrocytes a storage solution with sorbite and xylitol (ASCX-AG-Pyr 10mM) seems to be well suited for a storing time of 2---3 weeks at first.

Adenosine Triphosphate↗

Intravenous administration of recombinant adenoviruses causes thrombocytopenia, anemia and erythroblastosis in rabbits.

BACKGROUND: Recombinant adenoviruses are highly efficient gene transfer vehicles but their administration to mammals is accompanied by a strong inflammatory response. The present study reports additional side effects observed during adenoviral gene transfer studies in rabbits. METHODS: Hematological and serological parameters, the course of viremia and the organ distribution were analyzed after in vivo administration of E1-deleted adenoviruses in rabbits. RESULTS: The systemic administration of a therapeutic dose of 5 x 10(11) infectious particles/kg (infusion time 20 min) led to an average reduction of 80-90% in the platelet count within 48 h. Full recovery took 10-14 days. Virus administration induced a strong but transient erythroblastosis (peaking 24 h after administration) which settled 48 h later. Normochromic anemia occurred over the next 10 days with hemoglobin levels dropping by about 40% to reach the lowest level 10 days after administration and taking two months for full recovery. Dose-dependent thrombocytopenia was also found in mice, but neither erythroblastosis nor anemia was observed (in equivalent doses). The hematological findings did not improve after local injection via the portal vein. Local and systemic administration led to a comparable course of viremia. Only minor differences were found in the biodistribution of viruses between local and systemic administration. Large amounts of viral DNA and transgene expression were found in the lungs, the kidneys and the ovaries, even after local administration via the portal vein. CONCLUSIONS: Local intravenous injection via the portal vein does not prevent systemic spread of viral vectors and the occurrence of vector-related side effects. The hematological changes observed in rabbits suggest the need for careful monitoring of hematological and rheological parameters in clinical trials.

Adenoviridae↗

Design of a prospective neonatal cohort study of homozygous and double heterozygous factor V Leiden and factor II G20210A.

BACKGROUND: Factor V Leiden (FVL) and Factor II (FII) G20210A represent common risk factors for thromboembolic (TE) events. In children, both venous and arterial TE-events have been associated with the presence of FVL and FII G20210A. In most heterozygous children with TE-events other prothrombotic factors can usually be identified. Case reports of children with homozygous FVL, including 3 patients described here, suggest that this genotype may convey a particulary high risk. However, prospective data about the type and frequency of TE-events in such children are lacking. STUDY DESIGN: We have initiated a prospective neonatal cohort study for the homozygous and double heterozygous genotypes for FVL and FII G20210A. The probands and the heterozygous controls are identified by neonatal screening that involves > 98% of the children born in Berlin and are followed up in a special out-patient clinic to document details of the clinical history, developmental parameters and the occurrence of TE-events. CONCLUSIONS: This study will provide controlled and unbiased information about the clinical significance of the homozygous and double heterozygous genotypes of these mutations.

Blood Coagulation Disorders↗

Peri-operative decreased cAMP levels in long-term alcoholic patients.

Long-term alcoholic patients have a five-fold higher risk of post-operative bleeding complications compared with nonalcoholic individuals. Serotonin increases and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) decrease platelet aggregation. We examined the platelet-rich plasma levels of these substances and agonist-induced platelet aggregation in long-term alcoholic patients before and after surgery. Thirty-three consecutive patients (13 long-term alcoholics and 20 non-alcoholics) scheduled for tumour resections of the upper digestive tract were included in the study. The levels of cAMP were significantly decreased before and after surgery in long-term alcoholic patients, but there were no significant differences in cGMP and serotonin levels in alcoholic compared with non-alcoholic patients. In contrast to previous studies, no significantly altered aggregation responses in long-term alcoholics were found. A possible explanation is decreased inhibition through diminished cAMP levels; cGMP and serotonin do not seem to influence peri-operative haemostasis.

Aged↗