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Biomedical subjects

F Markwardt

Publications and source records attributed to F Markwardt.

335 records · Page 19Linked to original sources
PubMedDate not supplied

Influence of ion channel blockers on proliferation and free intracellular Ca2+ concentration of human keratinocytes.

The proliferation of in vitro cultivated keratinocytes from the HaCaT cell line while under the influence of different ion channel blockers, i.e. calcium channel blockers tetraethylammonium (TEA) and the nonspecific anion channel blocker 4',4'-diisothiocyanato-stilbene-2-2' disulfonic acid (DIDS) was investigated. There were changes in proliferation of the keratinocytes brought on by TEA and DIDS. It can be assumed that the effects of TEA on proliferated keratinocytes lead to a temporary arrest of cells in the G(1)-phase of the cell cycle. The change in the extracellular K+ concentration ([K+]e) had no influence on the proliferation of keratinocytes. During the entire course of investigations, the adding of DIDS leads to an increase in proliferation. Proliferation of keratinocytes is known to be greatly dependent on intracellular Ca2+ content ([Ca2+]i). The blocking of ion channels with TEA or DIDS does not lead to a change in the free [Ca2+]i. Also a change in the [K+]e does not lead to a displacement of the [Ca2+]i of keratinocytes.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMedDate not supplied

Characterization of large-conductance Ca2+-dependent and -independent K+ channels in HaCaT keratinocytes.

To characterize ion channels expressed in cell membrane of human keratinocytes, patch-clamp recordings were carried out in HaCaT cells. Two types of large-conductance K(+) channels (about 250 pS) were measured. One type was activated by micromolar concentrations of intracellular Ca(2+) ions ([Ca(2+)](i)) and membrane depolarization, the other was [Ca(2+)](i) independent. The channels were neither dependent on intracellular ATP nor Mg(2+) nor on membrane stretch. We conclude that HaCaT keratinocytes express Ca(2+)-dependent maxi K(+) channels and still unknown large Ca(2+)-independent K(+) channels. These K(+) channels may affect the proliferation and differentiation of human keratinocytes by the influence on the resting potential, which may control the Ca(2+) influx across the cell membrane.

Calcium Signaling↗
PubMedDate not supplied

A recombinant hirudin (IK-HIR02) in healthy volunteers. I. Effects on coagulation parameters and bleeding time.

The pharmacodynamic effects of different intravenous and subcutaneous doses of a recombinant hirudin (r-hirudin; IK-HIR02) on clotting parameters and bleeding time were investigated in 24 healthy volunteers in a bicenter study. Single intravenous bolus injections of 0.1, 0.2 and 0.3 mg/ kg IK-HIR02 caused a prolongation of thrombin time (TT) and aPTT in a dose-dependent manner and led to an increase in hirudin plasma levels > 6 micrograms/ml. The plasma half-life of IK-HIR02 was calculated as 1.3 h. A continuous infusion of 0.03 mg/kg/h of IK-HIR02 for 4 h significantly prolonged TT and aPTT. At the end of the hirudin infusion, a mean plasma level of 0.19 +/- 0.13 microgram/ml was measured. Single subcutaneous doses of 0.1, 0.25 and 0.5 mg/kg markedly prolonged the coagulation tests. The highest increase in hirudin plasma levels was found 2 h after injection. At this time the aPTT was doubled after 0.5 mg/kg. After repeat subcutaneous injections of 0.3 mg/kg b.i.d., aPTT was doubled, and TT increased to about 200 s, 2 h after the injections. At this time the mean plasma level was 0.5-0.6 microgram/ml. There was no cumulative effect after multiple injections. Bleeding time was not changed after the 4-hour intravenous infusion and after repeat subcutaneous injections of 0.3 mg/kg IK-HIR02. Bleeding time was moderately but significantly prolonged after the highest single intravenous and subcutaneous hirudin doses tested. Other than very minor local bleeding in some volunteers, IK-HIR02 was well tolerated. Biochemical blood and urine parameters did not change. In conclusion, r-hirudin (IK-HIR02) obtained by a new technique was well tolerated in healthy volunteers after single intravenous and subcutaneous injections, after repeat subcutaneous doses and during continuous intravenous infusion. Measurement of aPTT and anti-IIa activity, using a chromogenic substrate test, can be used to monitor hirudin effects if doses similar to those tested here are administered.

Adult↗
PubMedDate not supplied

A recombinant hirudin (IK-HIR02) in healthy volunteers. II. Effects on platelet adhesion and platelet-induced thrombin generation time.

The pharmacodynamic effects of different intravenous and subcutaneous doses of a new recombinant hirudin (IK-HIR02) on platelet adhesion, platelet-induced thrombin formation and on platelet count have been studied in 18 healthy volunteers in a bicenter study. Single intravenous bolus injections of 0.1, 0.2 and 0.3 mg/kg IK-HIR02 in 6 volunteers caused a significant dose-dependent prolongation of platelet-induced thrombin generation time (PITT) and a significant inhibition of platelet adhesion to glass. Single subcutaneous doses of 0.1, 0.25 and 0.5 mg/kg IK-HIR02 slightly prolonged PITT and inhibited platelet adhesion to glass for up to 8 h. Repeat subcutaneous injections of 0.3 mg/kg IK-HIR02 b.i.d. in 6 healthy volunteers led to a prolongation of PITT and also to a reduction of platelet adhesion. In platelet-rich plasma (PRP) from blood samples which had been collected using hirudin as anticoagulant (0.7 micrograms/ml), the platelet count was constantly higher than in citrate PRP which had been sampled at the same time. The recombinant hirudin IK-HIR02 inhibits platelet adhesion to glass and also PITT. Both effects which have not been described before are most likely due to a direct inhibition of thrombin-induced platelet activation. These effects may contribute to the antithrombotic action of hirudin and probably have to be considered when hirudin is used in higher doses as an antithrombotic agent together with platelet function inhibitors to avoid excessive bleeding.

Adult↗
PubMedDate not supplied

[Thrombolytic and pharmacodynamic properties of Aspergillus ochraceus protease].

The protease isolated from Aspergillus ochraceus exerts a strong thrombolytic action. In in vitro experiments and in tests with animals (mice, rats, dogs) it caused lysis of fibrinous clots. The thrombolytic effect of the protease is conditioned by its direct influence on the fibrin. Besides the thrombolytic action the protease, used within a definite ranges of doses, displays antithrombotic properties. The paper cites data on the acute toxicity (in mice, rats and rabbits) and on the influence of the protease on isolated organs and on the organism of the animals.

Animals↗
PubMedDate not supplied

Influence of endothelium on the vasoconstrictor effect of dihydroergotamine in the isolated rat aorta.

The vasoconstrictor effect of dihydroergotamine was studied in endothelium-containing and endothelium-denuded rat aortic rings. The integrity of the endothelium was assessed by the relaxant effect of acetylcholine on precontracted aortic rings, which was absent after removal of endothelium by mechanical rubbing or exposure to saponin. Dihydroergotamine (0.01-10 mumol/l) caused no or only a small contractile effect in the presence of endothelium, while in endothelium-denuded aortic rings a pronounced concentration-dependent increase in tension was observed. The 5-HT antagonist cyproheptadine (2 mumol/l) inhibited the dihydroergotamine-induced vasoconstriction, that means, 5-HT receptors are involved in the vasoconstrictor effect. In the presence of endothelium, the contractile effect of dihydroergotamine was enhanced by the guanylate cyclase inhibitor methylene blue (2 mumol/l) and became comparable in magnitude to that observed in deendothelialized preparations. 8-Bromo-cGMP (50 mumol/l) counteracted the potentiating effect of methylene blue. In the presence of cyproheptadine, methylene blue failed to enhance the dihydroergotamine effect. These results might explain the occurrence of undesired vasospastic effects of dihydroergotamine in arterial vessels with endothelial lesions.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMedDate not supplied

[Pharmacokinetics of 131I-streptokinase].

It has been demonstrated in mouse experiments that 131I-streptokinase undergoes rapid elimination. It has been shown as unfit as a diagnostic agent in the treatment of thromboses.

Animals↗
PubMedDate not supplied

[Effect of guanclofin on catecholamine release by the adrenal medulla].

The influence of guanoclofine, an adrenergic neurone-blocking agent, on catecholamine release from isolated perfused bovine adrenal glands was studied. Guanclofine inhibited the amine liberation induced by carbachol, aminophylline, prenylamine, and snake venoms. Guanoxane and guanethidine at equimolar concentrations were less effective. The inhibitory effect of guanclofine is assumed to be due to a nonspecific effect on the cell membrane.

Adrenal Medulla↗