Kaolin, used to trigger coagulation in thrombin generation test, increases sensitivity of the method in hemophilia patients.

: Thrombin generation test (TGT) is well established tool to research blood coagulation in plasma of hemophilia patients. Traditionally coagulation in this test is triggered by a tissue factor (TF), an extrinsic coagulation pathway activator. However, it is known that disorders of the intrinsic pathway are most important for coagulation in hemophilia. In this study, we hypothesized that triggering coagulation via the intrinsic pathway could increase a sensitivity of the TGT to monitor hemophilia treatment. The aim of this study was to compare thrombin generation in hemophilia A patients with inhibitors to factor VIII before and after infusion of bypassing agent [recombinant-activated factor VIIa (rVIIa)] using standard activation of coagulation by TF or by kaolin, an activator of coagulation by intrinsic pathway. Endogenous thrombin potential (ETP) in nine patients was measured. ETP before (ETP0) and 60 min after rVIIa infusion (ETP60) were compared. It was shown that ETP0 and ETP60 were significantly different when using any coagulation activator (paired Student's t test, P = 0.017 and 3.7 × 10 for clotting activation by TF and kaolin, respectively). The ratios of ETP60/ETP0 were 1.2 ±â€Š0.2 or 30.0 ±â€Š22.4 (mean ±â€ŠSD, n = 9) for coagulation activated by TF or kaolin, respectively, and were significantly different (paired Student's t test, P < 0.005). The TGT clearly distinguished between ETP0 and ETP60 in the case of any coagulation activator, but ETP increasing after rVIIa infusion was significantly higher when activated with kaolin. This provided increased sensitivity of this method for monitoring hemophilia therapy.

Fe-HBED Analogs: A Promising Class of Iron-Chelate Contrast Agents for Magnetic Resonance Imaging.

Contrast-enhanced magnetic resonance imaging is an essential tool for disease diagnosis and management; all marketed clinical magnetic resonance imaging (MRI) contrast agents (CAs) are gadolinium (Gd) chelates and most are extracellular fluid (ECF) agents. After intravenous injection, these agents rapidly distribute to the extracellular space and are also characterized by low serum protein binding and predominant renal clearance. Gd is an abiotic element with no biological recycling processes; low levels of Gd have been detected in the central nervous system and bone long after administration. These observations have prompted interest in the development of new MRI contrast agents based on biotic elements such as iron (Fe); Fe-HBED (HBED = N,N'-bis(2-hydroxyphenyl)ethylenediamine-N,N'-diacetic acid), a coordinatively saturated iron chelate, is an attractive MRI CA platform suitable for modification to adjust relaxivity and biodistribution. Compared to the parent Fe-HBED, the Fe-HBED analogs reported here have lower serum protein binding and higher relaxivity as well as lower relative liver enhancement in mice, comparable to that of a representative gadolinium-based contrast agent (GBCA). Fe-HBED analogs are therefore a promising class of non-Gd ECF MRI CA.

Synthesis, characterization and cytotoxicity studies of palladium(II)-proflavine complexes.

An investigation of the reaction of Pd(II) complexes with proflavine (3,6-diaminoacridine) resulted in the isolation of the compounds [Pd(terpy)(proflavine)](NO(3))(HSO(4))*3H(2)O, 1, (terpy = 2,2':6',2″-terpyridine), [Pd(en)(proflavineH))](NO(3))(SO(4)), 2, (en = ethylenediamine), and [Pd(proflavineH)Cl(2)](SO(4))(0.5)*H(2)O, 3. They have been isolated and characterized by NMR, IR, and electro-spray ionization mass spectrometry techniques and by elemental analyses. The proflavine was bonded to the Pd(II) through the endocyclic nitrogen in 1, but through the proflavine NH(2) in 2. Compound 3 appeared to be polymeric in the solid state with a 1:1 mole ratio of Pd(II):proflavine. Upon solution of 3 in DMSO, two unique species were formed. In one species the Pd(II) was bonded to two proflavines through the endocyclic nitrogen (1:2 mole ratio) and in the other species, a Pd(II) was bonded to each NH(2) group of a single proflavine (2:1 mole ratio). Molecular modeling of the equilibrium geometry by Spartan 8 produced structures which were consistent with the experimental data on the solutions of the three compounds. In vitro cytotoxicity testing against two breast cancer cell lines and one ovarian cancer cell line showed that compounds 1 and 3 had significant activity.