[Laboratory diagnostic with regard to new anticoagulants - monitoring and influence on coagulation tests]

New oral anticoagulants promise to overcome essential drawbacks of traditional substances. They have a predictable therapeutic effect, a wide therapeutic window, only limited interaction with food and drugs and can be administered p.o. with a fixed dose. On the other hand, knowledge on the laboratory management of new anticoagulants is limited. In the present article we discuss possible indications and available assays for monitoring of Rivaroxaban, Apixaban and Dabigatran. Furthermore, we discuss interpretation of routine coagulation tests during therapy with these new drugs.

New pansomatostatin ligands and their chelated versions: affinity profile, agonist activity, internalization, and tumor targeting

PURPOSE: Somatostatin receptor (sst) targeting is an established method to image and treat sst-positive tumors. Particularly, neuroendocrine tumors express the receptor subtype 2 in high density, but sst1, sst3, sst4, and sst5 are also expressed to some extent in different human tumors. Currently used targeting peptides mainly have sst2 affinity. We aimed at developing (radio)peptides that bind with high affinity to all receptor subtypes. EXPERIMENTAL DESIGN: Carbocyclic octapeptides were coupled with macrocyclic chelators for radiometal labeling. Affinity, internalization, and agonist potencies were determined on sst1- to sst5-expressing cell lines. Biodistribution was determined on nude mice bearing HEK-sst2 or AR4-2J and HEK-sst3 tumors. RESULTS: High affinity to all receptor subtypes was found. Y(III)-KE88 showed agonistic properties at all five sst receptor subtypes as it inhibits forskolin-stimulated cyclic AMP production. Surprisingly, very low or even absent sst2 receptor internalization was found compared with currently clinically established octapeptides, whereas the sst3 internalization was very efficient. Biodistribution studies of [(111)In]KE88 and [(67)Ga]KE88/[(68)Ga]KE88 reflected the in vitro data. In nude mice with s.c. implanted sst2 (HEK-sst2, AR4-2J)-expressing and sst3 (HEK-sst3)-expressing tumors, high and persistent uptake was found in sst3-expressing tumors, whereas the uptake in the sst2-expressing tumors was lower and showed fast washout. The kidney uptake was high but blockable by coinjection of lysine. CONCLUSION: This peptide family shows pansomatostatin potency. As radiopeptides, they are the first to show a full pansomatostatin profile. Despite some drawback, they should be useful for imaging sst2-expressing tumors with short-lived radiometals, such as (68)Ga, at early time points and for sst3-expressing tumors at later time points with longer-lived radiometals, such as (64)Cu or (86)Y.

New cytotoxic saturated and unsaturated cyclohexanones from Anthemis maritima

Two new cyclohexenones (antheminones A and B) and a new cyclohexanone, (antheminone C) along with five known compounds were isolated from the leaves of Anthemis maritima L. The structures were mainly deduced from extensive 1D and 2D NMR spectroscopy and mass spectrometry. The new compounds were tested in vitro for their cytotoxic activity against adherent and non-adherent cancer cell lines. Antheminones A and C exhibited significant antiproliferative activity against leukemia cells with IC(50) values ranging from 3.2 to 14 microM.

New respiratory enterovirus and recombinant rhinoviruses among circulating picornaviruses

Rhinoviruses and enteroviruses are leading causes of respiratory infections. To evaluate genotypic diversity and identify forces shaping picornavirus evolution, we screened persons with respiratory illnesses by using rhinovirus-specific or generic real-time PCR assays. We then sequenced the 5 untranslated region, capsid protein VP1, and protease precursor 3CD regions of virus-positive samples. Subsequent phylogenetic analysis identified the large genotypic diversity of rhinoviruses circulating in humans. We identified and completed the genome sequence of a new enterovirus genotype associated with respiratory symptoms and acute otitis media, confirming the close relationship between rhinoviruses and enteroviruses and the need to detect both viruses in respiratory specimens. Finally, we identified recombinants among circulating rhinoviruses and mapped their recombination sites, thereby demonstrating that rhinoviruses can recombine in their natural host. This study clarifies the diversity and explains the reasons for evolution of these viruses.

Influence of Particle Size of Deproteinized Bovine Bone Mineral on New Bone Formation and Implant Stability after Simultaneous Sinus Floor Elevation: A Histomorphometric Study in Minipigs

BACKGROUND Deproteinized bovine bone mineral (DBBM) is one of the best-documented bone substitute materials for sinus floor elevation (SFE). PURPOSE DBBM is available in two particle sizes. Large particles are believed to facilitate improved neoangiogenesis compared with small ones. However, their impact on the rate of new bone formation, osteoconduction, and DBBM degradation has never been reported. In addition, the implant stability quotient (ISQ) has never been correlated to bone-to-implant contact (BIC) after SFE with simultaneous implant placement. MATERIALS AND METHODS Bilateral SFE with simultaneous implant placement was performed in 10 Göttingen minipigs. The two sides were randomized to receive large or small particle size DBBM. Two groups of 5 minipigs healed for 6 and 12 weeks, respectively. ISQ was recorded immediately after implant placement and at sacrifice. Qualitative histological differences were described and bone formation, DBBM degradation, BIC and bone-to-DBBM contact (osteoconduction) were quantified histomorphometrically. RESULTS DBBM particle size had no qualitative or quantitative impact on the amount of newly formed bone, DBBM degradation, or BIC for either of the healing periods (p > 0.05). Small-size DBBM showed higher osteoconduction after 6 weeks than large-size DBBM (p < 0.001). After 12 weeks this difference was compensated. There was no significant correlation between BIC and ISQ. CONCLUSION Small and large particle sizes were equally predictable when DBBM was used for SFE with simultaneous implant placement.