Allosteric Inhibition as a New Mode of Action for BAY 1213790, a Neutralizing Antibody Targeting the Activated Form of Coagulation Factor XI.

Factor XI (FXI), the zymogen of activated FXI (FXIa), is an attractive target for novel anticoagulants because FXI inhibition offers the potential to reduce thrombosis risk while minimizing the risk of bleeding. BAY 1213790, a novel anti-FXIa antibody, was generated using phage display technology. Crystal structure analysis of the FXIa-BAY 1213790 complex demonstrated that the tyrosine-rich complementarity-determining region 3 loop of the heavy chain of BAY 1213790 penetrated deepest into the FXIa binding epitope, forming a network of favorable interactions including a direct hydrogen bond from Tyr102 to the Gln451 sidechain (2.

Skin Wound Repair Is Not Altered in the Absence of Endogenous AnxA1 or AnxA5, but Pharmacological Concentrations of AnxA4 and AnxA5 Inhibit Wound Hemostasis.

Skin injury induces the cell surface exposure of phosphatidylserine (PS) on damaged and dying cells to activate coagulation and repair processes. Annexins can bind to PS and may modulate the healing response. Here, we determine the relevance of annexins for skin wound healing using AnxA1- and AnxA5-deficient mice and recombinant annexins with distinct PS binding properties.

Modeling ligand recognition at the P2Y12 receptor in light of X-ray structural information.

The G protein-coupled P2Y12 receptor (P2Y12R) is an important antithrombotic target and of great interest for pharmaceutical discovery. Its recently solved, highly divergent crystallographic structures in complex either with nucleotides (full or partial agonist) or with a nonnucleotide antagonist raise the question of which structure is more useful to understand ligand recognition. Therefore, we performed extensive molecular modeling studies based on these structures and mutagenesis, to predict the binding modes of major classes of P2Y12R ligands previously reported.

Competitive mode and site of interaction of ticagrelor at the human platelet P2Y12 -receptor.

Background: The G-protein-coupled P2Y12 -receptor plays a crucial role in platelet aggregation. Recently, ticagrelor was licensed as the first perorally active and reversible P2Y12 -receptor antagonist.

Objective: The present study investigated the site and the antagonistic mode of action of ticagrelor at wild-type or mutant human P2Y12 -receptors.

A role for coagulation factor Xa in experimental pulmonary arterial hypertension.

Aims: Anticoagulation with warfarin is recommended for the treatment of patients with pulmonary arterial hypertension (PAH). However, the therapeutic benefit of anticoagulation has not yet been demonstrated experimentally or clinically. Here, rivaroxaban, an oral, direct factor Xa (FXa) inhibitor, was compared with warfarin and enoxaparin in the prevention of right ventricular (RV) dysfunction and hypertrophy in the monocrotaline (MCT) model of pulmonary hypertension.

[Regulation (EC) No. 1394/2007 on advanced therapy medicinal products : Incorporation into national law].

Regulation (EC) No. 1394/2007 has created a new legal framework for advanced therapy medicinal products (gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineered products). The Regulation is directly applicable in the Member States of the European Union and, in principle, requires no incorporation into national law.

In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939--an oral, direct Factor Xa inhibitor.

BAY 59-7939 is an oral, direct Factor Xa (FXa) inhibitor in development for the prevention and treatment of arterial and venous thrombosis. BAY 59-7939 competitively inhibits human FXa (K(i) 0.4 nm) with > 10 000-fold greater selectivity than for other serine proteases; it also inhibited prothrombinase activity (IC(50) 2.

Volume and enthalpy changes after photoexcitation of bovine rhodopsin: laser-induced optoacoustic studies.

Laser-induced optoacoustic measurements were performed with bovine rhodopsin in the temperature range 5-32 degrees C in its natural environment (i.e., in washed membranes) as well as solubilized in dodecyl-beta-D-maltoside.

Application of impediometry to rapid assessment of liquid culture media.

The impedance method provides as unique opportunity to determine microbial activity and kinetics. Since the metabolic processes depend on the nature and quality of the culture medium, impediometry allows the assessment of liquid culture media. Impedance microbiology represents an approach to quantitative microbiology.

[The use of impedance measurements in medical microbiology].

The versatility of the impedance method makes it a valuable tool in clinical microbiology. Impedance can be used to estimate total number of bacteria or to determine bacterial susceptibility to antimicrobial agents. The impedance method provides a unique opportunity to determine microbial activity and kinetics.

[Changes in the pharmacokinetics of gentamycin during nephrotoxic therapy].

Nephrotoxicity secondary to aminoglycoside antibiotic therapy is a well-known complication in clinical medicine. We have analysed the influence of a 10-day gentamicin treatment with 3.40 mg/d on pharmacokinetic parameters and renal excretion of electrolyses and beta-NAG in 10 patients (9 female, 1 males) with UTJ.

Improved specificity in gentamicin bioassay.

An optimized bioassay for determination of gentamicin concentrations in serum of patients is presented. It was possible to enhance the exactness and representibility of the bioassay by means of a standardized methodical process, a suitable arrangement of the assay and reading at fifteen-fold enlargement. A systematic arrangement of the assay with randomized blocks is a safeguard against larger errors during the assay.

[Fast physiochemical methods for the detection of bacteria in the urine].

Physiochemical methods permit quantitative determinations of bacteria within 3 to 6 hrs and offer possibilities of automation in clinical bacteriology. The results photometrical bacteriuria-screening and electrochemical rapid method of oxygen partial pressure measurements in culture medium in comparison with conventional culture urine processing are presented. The method of impedance measurements is introduced in brief.

Bacteriuria screening and antimicrobial susceptibility testing of aerobic bacteria by an electrochemical method.

A method is described for detecting significant bacteriuria and determination of minimal inhibition concentrations (MIC's) of aerobically growing bacteria by using electrochemical electrodes to measure changes of oxygen tensions in liquid nutrient media resulting from bacterial growth. Urine specimens (n = 577) were screened electrochemically, parallel investigations were performed by standard culture methods and by photometrical measurements. All the specimens showing significant bacteriuria in standard culture were selected within 3.

In vitro sorption of aluminum complex to guinea pig stratum corneum.

The sorption of aluminum complexes to guinea pig stratum corneum has been studied using our previously described fluorometric and atomic absorption spectrophotometric procedures. The sorption, desorption, and binding properties of the two aluminum systems most often used in topically applied antiperspirants, aluminum chloride and aluminum chlorohydrate, Al2(OH)5Cl . 2H2O were examined as a function of aluminum concentration, sorption time, state of hydration, and for various delipidized tissue specimens.

Growth of Oxalic Acid Single Crystals from Solution: Solvent Effects on Crystal Habit.

Single crystals of oxalic acid dihydrate are difficult to grow from pure water solution, but good single crystals of the material may be obtained by growth from mixtures of acetone and water. The solvent markedly affects the crystal habit. Crystals grown in mixtures of acetone and water develop the prismatic habit, while those grown in water alone develop the tabular or equant habit.