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Biomedical subjects

S Bade

Publications and source records attributed to S Bade.

7 recordsLinked to original sources
PubMed2004

Does hemodilution enhance coagulability?

UNLABELLED: Recent publications reported enhanced coagulability in hemodilution determined by TEG. In contrast, earlier reports have shown prolongation of in-vivo bleeding time in anemia. In order to take a closer look at this discrepancy undiluted and diluted anticoagulated blood samples (20 % with saline solution, hydroxyl-ethyl starch 6 % (HES), autologous platelet poor plasma (PPP)) were investigated by TEG (n = 10), ball (n = 10), and hook coagulometer (n = 15) as well as tests simulating primary hemostasis ex vivo (Platelet Function Analyzer PFA-100, n = 10). RESULTS: Dilution with plasma changed TEG parameters in a way, when started by recalcification of the blood sample, which is characteristic of enhanced coagulability (r decreased in all and k in 8 of 10 samples, maximal amplitude increased in 9 out of 10). With HES, changes in TEG parameters mainly indicated reduced coagulability (k increased in 7 out of 10, MA decreased in 10 out of 10). When the coagulation was additionally activated by PTT reagent (InTEG) the TEG parameters also mainly showed hypocoagulation with the three dilution solutions. Coagulation times with ball and hook coagulometers were significantly prolonged by dilution especially with saline (+ 25 % and + 17 %, p < 0.001). Dilution always significantly (often abnormally) prolonged closure time in PFA-100 (saline + 41 +/- 18 %, PPP + 37 +/- 20 %, HES + 69 +/- 24 %) demonstrating disturbance of primary hemostasis, particularly with HES. CONCLUSIONS: From the results obtained it can be concluded that the changes in the classical TEG (without addition of PTT-reagent), suggesting an enhanced coagulability, may be caused methodically as they are also found with autologous PPP. On the other hand, a disturbance of the primary hemostasis in hemodilution has to be taken into account from the results seen with the PFA-100 and a number of published data.

Blood Coagulation↗
PubMed2001

Measurement of primary haemostasis using a pressure clamp technique.

UNLABELLED: With the PFA-100 a sensitive and specific screening test for primary haemostasis has recently become available. An important part of the device is a capillary, providing a defined haemodynamic resistance for the perfusion of the aperture. A modified method to measure platelet function (VCP2) is presented in which the capillary essentially is replaced with an 'electronic capillary' by clamping the pressure/flow relationship. RESULTS AND CONCLUSION: Closure time (CT) and blood volume (BV) as determined by PFA-100 and VCP2 correlated well within (r = 0.922 - 0.952) and between the two methods (r = 0.86). The test variability (CV) of CT could be significantly reduced in the VCP2 method (collagen/epi 3.9 vs. 5.9%, p<0.05; collagen/ADP 3.3 vs. 6.9%, p<0.001), thus considerably increasing test reliability and reducing test variance. In preliminary clinical studies the VCP2 system showed comparable sensitivity for vWD and slightly less sensitivity regarding ASA ingestion. The test spectrum of VCP2 could be extended to more thrombocytopenic samples (< or =20 000/microl) even in combination with low haematocrit levels (20%), thus perhaps permitting the determination of the bleeding risk in bone marrow hypoplasia. Additionally, the sensitivity and applicability can easily be adapted to the desired need only by software modifications.

Aspirin↗
PubMed1999

Proteolysis of SNAP-25 isoforms by botulinum neurotoxin types A, C, and E: domains and amino acid residues controlling the formation of enzyme-substrate complexes and cleavage.

Tetanus toxin and the seven serologically distinct botulinal neurotoxins (BoNT/A to BoNT/G) abrogate synaptic transmission at nerve endings through the action of their light chains (L chains), which proteolytically cleave VAMP (vesicle-associated membrane protein)/synaptobrevin, SNAP-25 (synaptosome-associated protein of 25 kDa), or syntaxin. BoNT/C was reported to proteolyze both syntaxin and SNAP-25. Here, we demonstrate that cleavage of SNAP-25 occurs between Arg198 and Ala199, depends on the presence of regions Asn93 to Glu145 and Ile156 to Met202, and requires about 1,000-fold higher L chain concentrations in comparison with BoNT/A and BoNT/E. Analyses of the BoNT/A and BoNT/E cleavage sites revealed that changes in the carboxyl-terminal residues, in contrast with changes in the amino-terminal residues, drastically impair proteolysis. A proteolytically inactive BoNT/A L chain mutant failed to bind to VAMP/synaptobrevin and syntaxin, but formed a stable complex (KD = 1.9 x 10(-7) M) with SNAP-25. The minimal essential domain of SNAP-25 required for cleavage by BoNT/A involves the segment Met146-Gln197, and binding was optimal only with full-length SNAP-25. Proteolysis by BoNT/E required the presence of the domain Ile156-Asp186. Murine SNAP-23 was cleaved by BoNT/E and, to a reduced extent, by BoNT/A, whereas human SNAP-23 was resistant to all clostridial L chains. Lys185Asp or Pro182Arg mutations of human SNAP-23 induced susceptibility toward BoNT/E or toward both BoNT/A and BoNT/E, respectively.

Amino Acid Sequence↗
PubMed1997

Loss of in vitro cytotoxicity of cisplatin after storage as stock solution in cell culture medium at various temperatures.

BACKGROUND: Cisplatin (cis-dichlorodiammineplatinum [II]) is one of the most potent and widely used cytotoxic drugs in cancer therapy. However, in vitro cytotoxicity assays often yield diverging results. Therefore, it is believed by many investigators that cisplatin is not effective in vitro. The authors investigated whether the experimental conditions used could be responsible for the diverging results. METHODS: In vitro cytotoxicity assays were performed using the original cisplatin solution as distributed by the manufacturer or a 5-fold dilution of this in cell culture medium after storage for 2 weeks or 1 month at various temperatures (room temperature, 4 degrees C, and -20 degrees C). RESULTS: The original solution of cisplatin retained the full cytotoxic potency for at least 1 month under all storage conditions tested. The highest loss of cytotoxicity resulted from storage of cisplatin in cell culture medium in which a >7-fold increase in the concentration that inhibits 50% occurred after 2 weeks' storage at room temperature. Solutions stored in culture medium at -20 degrees C retained full cytotoxic potency. CONCLUSIONS: Cisplatin is a potent cytotoxic drug in vitro when stored under appropriate conditions. These findings are of relevance for in vitro studies with cisplatin.

Antineoplastic Agents↗
PubMed1997

New NO-donors with antithrombotic and vasodilating activities, Part 17. Arylazoamidoximes and 3-arylazo-1,2,4-oxadiazol-5-ones.

Seven arylazoamidoximes (3), six phenoxycarbonyl derivatives (4), and six 1,2,4-oxadiazol-5-ones (5) have been prepared and their structure and purity established by spectroscopy and elemental analysis. In the EI mass spectra ready elimination of NO from the title amidoximes was observed. A new addition reaction of 3a with hydrochloric acid to 4-chlorophenylhydro-azoamidoxime 7 is described. The compounds were tested for nitric oxide dependent biological properties, i.e. platelet aggregation, antithrombotic effects, and decrease in blood pressure. In arterioles of rats 5/19 compounds inhibited the formation of thrombi with a laser beam by > or = 20% 2 h after oral administration of 60 mg/kg. Among these are three amidoximes (3a, 3e, 3f), one phenoxycarbonyl derivative (4a), and one oxadiazolone (5a). With the 4-chlorophenylazoamidoxime 3c a long lasting (24 h) decrease of blood pressure in spontaneously hypertensive rats was observed. Microsomal fractions of rat liver oxidize arylazoamidoximes and generate nitric oxide (e.g. 3a and 3b). NO was measured by the oxyhemoglobin assay. The influence of SOD, pretreatment of the rats with dexamethasone, as well as kinetic parameters were determined. Type 3 compounds, therefore, are a new class of NO donors. Type 4 and 5 compounds function as their prodrugs.

Animals↗
PubMed1996

New NO-donors with antithrombotic and vasodilating activities, Part 16. 3-Amino-1,2,4-oxadiazol-5-ones as prodrugs for hydroxyguanidines.

Nineteen 4-substituted 1,2,4-oxadiazol-5-ones (6a-s) were prepared as prodrugs for lipophilic hydroxyguanidines which should be metabolized in vivo to nitric oxide. This hypothesis was tested indirectly by measuring the antithrombotic properties of these compounds 2 h after oral administration to rats (60 mg/kg). In mesenteric arterioles seven compounds moderately (> or = 10%) inhibited the formation of thrombi by a laser beam. Maximum effects were observed in 6c (4-pentyl) and 6f (4-benzyl). The lack of activity in the corresponding 2-pentyloxadiazolone 10c, where no formation of nitric oxide seems possible, indirectly suggests that the antithrombotic properties of the title compounds could be mediated by the in vivo formation of nitric oxide.

Animals↗