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Biomedical subjects

Florian B Mayr

Publications and source records attributed to Florian B Mayr.

7 recordsLinked to original sources
PubMed2007

Ethnic differences in plasma levels of interleukin-8 (IL-8) and granulocyte colony stimulating factor (G-CSF).

Ethnic neutropenia is common in people of African descent. As interleukin-8 (IL-8) and granulocyte colony stimulating factor (G-CSF) bind to receptors on neutrophils, ethnic differences in neutrophil counts are hypothesized to result in different plasma levels of these cytokines. A prospective study was conducted in 72 healthy young volunteers. Neutrophil counts were 60% higher in Caucasians (P<0.00001). Average IL-8 and G-CSF levels were about 50% and 70% higher in African volunteers compared with Caucasian volunteers (P=0.0008 and P=0.00005, respectively). Additionally, oxidative burst capacity in stimulated neutrophils was significantly lower in volunteers of African descent (P=0.03 between both groups). In sum, lower neutrophil counts are associated with higher levels of IL-8 and G-CSF in Africans.

Adolescent↗
PubMed2006

Current developments in anti-platelet therapy.

Platelets play a life-saving role in hemostasis and blood clotting at sites of vascular injury and consequently are similarly involved in the pathological counterpart, namely thrombosis. Thus, anti-platelet therapy has become a mainstay in treatment and/or prophylaxis of conditions like myocardial infarction, stroke and other cardiovascular diseases. Acetyl-salicylic acid (ASA, aspirin) is still the most widely used agent and considered as the prototype antiplatelet drug. Since platelet activation occurs via several pathways that are not influenced by ASA, several other compounds have been developed to add to its beneficial effect. Currently four main classes of antiplatelet agents are available for clinical use: acetyl-salicylic acid (ASA), phosphodiesterase (PDE) inhibitors, thienopyridines and the intravenous GPIIb/IIIa antagonists. This article gives a concise review of these four classes of anti-platelet agents, using ASA as the reference standard.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Recombinant human antithrombin inhibits thrombin formation and interleukin 6 release in human endotoxemia.

We hypothesized that infusion of recombinant human antithrombin without concomitant heparin would have dose-dependent anticoagulant properties and potentially decrease endotoxin (lipopolysaccharide [LPS])-induced cytokine production. This was a randomized, double-blind, placebo-controlled study in parallel groups enrolling 30 healthy male volunteers. The active treatment groups received infusions of recombinant human antithrombin to increase antithrombin levels to 200% and 500% before infusion of 2 ng/kg endotoxin (LPS). Infusion of antithrombin dose-dependently decreased coagulation (P < .01 by repeated-measures ANOVA): peak levels of prothrombin fragment (1.8 nmol/L [95% confidence interval (CI), 1.3-2.3 nmol/L] in the 500% antithrombin group and 4.4 nmol/L [95% CI, 2.7-6.2 nmol/L] in the placebo group at 4 hours), thrombin antithrombin complexes (12 microg/L [95% CI, 8-16 microg/L] in the 500% antithrombin group and 34 microg/L [95% CI, 20-48 microg/L] in the placebo group at 4 hours), and D-dimer (0.2 microg/L [95% CI, 0.1-0.2 microg/L] in the 500% antithrombin group and 0.5 microg/L [95% CI, 0.4-0.7 microg/L] in the placebo group). Recombinant human antithrombin decreased peak interleukin-6 levels by 40% (222 pg/mL [95% CI, 148-295 pg/mL] and 216 pg/mL [95% CI, 112-320 pg/mL] in the 500% and 200% antithrombin groups, respectively, versus 357 pg/mL [95% CI, 241-474 pg/mL] in the placebo group; P < .001 by ANOVA). Finally, infusion of recombinant human antithrombin rapidly and transiently decreased neutrophil counts (by 19% [95% CI, 8%-30%] in the 500% antithrombin group versus 6% [95% CI, 1%-10%] in the placebo group, P = .002 by Kruskal-Wallis ANOVA) and monocyte counts (by 30% [95% CI, 16%-44%] in the 500% antithrombin group and 18% [95% CI, 9%-28%] in the 200% antithrombin group versus 8% [95% CI, 5%-20%] in the placebo group, P = .04) before LPS challenge, indicating that recombinant human antithrombin directly interacts with these leukocyte subsets. In summary, recombinant human antithrombin dose-dependently inhibited tissue factor-triggered coagulation. Effects on leukocytes and inhibition of interleukin-6 release seem to represent specific pharmacodynamic properties of recombinant human antithrombin.

Adult↗
PubMed2006

Coagulation interventions in experimental human endotoxemia.

Recognition of the link between coagulation activation and inflammation has led to the hypothesis that anticoagulants may be effective in the treatment of septic patients by altering the inflammatory response. However, only limited methodologies exist that can be used in human volunteers to mimic the physiologic alterations observed in critically ill patients. The human endotoxemia model represents a model of inflammation-induced tissue factor triggered coagulation activation. As it permits elucidation of a key player in this proinflammatory and procoagulant response, it serves as a useful tool to investigate novel therapeutics in a standardized setting. The aim of this review is to focus on coagulation interventions in the human endotoxemia model.

Anticoagulants↗
PubMed2005

The effects of supra-normal protein C levels on markers of coagulation, fibrinolysis and inflammation in a human model of endotoxemia.

The protein C pathway serves as a modulating system with both anti-inflammatory and anticoagulant properties and is intimately involved in the pathophysiology of inflammation and sepsis. Treatment with recombinant human activated protein C (rhAPC) can reduce the mortality of severe sepsis. We investigated whether an elevation of plasma protein C levels to supra-normal levels by infusion of a protein C zymogen concentrate has an effect on coagulation, protein C activation or inflammation in a human endotoxemia model. Eleven healthy male volunteers were enrolled in a double-blind, placebo-controlled two-way cross-over trial. Ten minutes after infusion of 2ng/kg endotoxin each volunteer received either placebo or a plasma-derived protein C zymogen concentrate (Ceprotin, Baxter) (150 U/kg as a slow bolus infusion followed by 30 U/kg/h continuous infusion until 4 hours after LPS-infusion). Protein C antigen and activity increased 4- to 5-fold after infusion of the concentrate. APC was generated during endotoxin-induced inflammation in the placebo (1.6 fold increase) and the protein C period (4.0-fold increase). The increase of APC levels correlated with the TNF-alpha and IL-6 release in both periods (r = 0.65-0.68; p < 0.05) and paralleled the protein C antigen and activity levels in the period with supranormal protein C levels. Supra normal protein C levels resulted in slightly, although non-significant, lower tissue factor mRNA expression and thrombin generation (TAT, F1+2). Systemic inflammation (TNF-alpha, IL-6) was not influenced by protein C zymogen concentrate administration. Infusion of protein C zymogen was safe and no adverse effects occurred. The increase of protein C levels several fold above the normal range resulted in a proportional increase of the APC levels, but had no major anticoagulant, anti-inflammatory or profibrinolytic effects. Low grade endotoxemia itself induces significant protein C activation, which correlates with the TNF release.

Adult↗
PubMed2004

Effects of carbon monoxide inhalation during experimental endotoxemia in humans.

Data show that carbon monoxide (CO) exerts direct antiinflammatory effects in vitro and in vivo after LPS challenge in a mouse model. We hypothesized that CO may act as an antiinflammatory agent in human endotoxemia. The aim of this trial was to study the effects of CO inhalation on cytokine production during experimental human endotoxemia. The main study was a randomized, double-blinded, placebo-controlled, two-way cross-over trial in healthy volunteers. Each volunteer inhaled synthetic air (as placebo) and 500 ppm CO for 1 hour in random order with a washout period of 6 weeks and received a 2-ng/kg intravenous bolus of LPS after inhalation. Carboxyhemoglobin levels were assessed as a safety parameter. CO inhalation increased carboxyhemoglobin levels from 1.2% (95% confidence interval, 1.0 to 1.4%) to peak values of 7.0% (95% confidence interval, 6.5 to 7.7%). LPS infusion transiently increased plasma concentrations of tumor necrosis factor-alpha, interleukin (IL)-6 (approximately 150-fold increases), and IL-8, as well as IL-1alpha and IL-1beta mRNA levels (an approximately 200-fold increase). These LPS-induced changes were not influenced by CO inhalation. Inhalation of 500 ppm CO for 1 hour had no antiinflammatory effects in a systemic inflammation model in humans, as 250 ppm for 1 hour did in rodents.

Administration, Inhalation↗