Enantiomerically Pure Indazole Bioisosteres of Ifenprodil and Ro 25-6981 as Negative Allosteric Modulators of NMDA Receptors with the GluN2B Subunit.

Administration of negative allosteric modulators of GluN2B subunit-containing NMDA receptors such as Ro 25-6981 () and ifenprodil () results in neuroprotective effects. In this study, the phenol of and was replaced bioisosterically by an indazole to inhibit glucuronidation. The γ- and β-aminoalcohols and were prepared without installing a protective group at the indazole ring using the ketone as a common intermediate.

Extensive red blood cell matching considering patient alloimmunization risk.

Background And Objectives: Red blood cell (RBC) transfusions pose a risk of alloantibody development in patients. For patients with increased alloimmunization risk, extended preventive matching is advised, encompassing not only the ABO-D blood groups but also the most clinically relevant minor antigens: C, c, E, e, K, Fy, Fy, Jk, Jk, S and s. This study incorporates patient-specific data and the clinical consequences of mismatching into the allocation process.

Negative allosteric modulators of NMDA receptors with GluN2B subunit: synthesis of β-aminoalcohols by epoxide opening and subsequent rearrangement.

In order to obtain novel antagonists of GluN2B subunit containing NMDA receptors, aryloxiranes were opened with benzylpiperidines. Phenyloxiranes 6 and (indazolyl)oxirane 15 were opened regioselectively at the position bearing the aryl moiety. Reaction of the resulting β-aminoalcohols 7 and 16 with carboxylic acids under Mitsunobu conditions (DIAD, PPh) led to rearrangement and after ester hydrolysis to the regioisomeric β-aminoalcohols 9 and 18.

Indazole as a Phenol Bioisostere: Structure-Affinity Relationships of GluN2B-Selective NMDA Receptor Antagonists.

Negative allosteric modulation of GluN2B subunit-containing NMDA receptors prevents overstimulation, resulting in neuroprotective effects. Since the phenol of prominent negative allosteric modulators is prone to rapid glucuronidation, its bioisosteric replacement by an indazole was envisaged. The key step in the synthesis was a Sonogashira reaction of non-protected iodoindazoles with propargylpiperidine derivatives.

Unexpected antibody against the high-prevalence P antigen before cardiac surgery.

P is a high-prevalence antigen present in 99.9 percent of the population and is fully developed at birth. P- individuals form naturally occurring antibodies against P, which are often of immunoglobulin (Ig)M and/or IgG type, very potent in complement activation, and able to cause serious intravascular hemolytic transfusion reactions.

Mapping anticipated advantages and disadvantages of implementation of extensive donor genotyping: A focus group approach.

Background And Objectives: Current genotyping techniques allow typing of all relevant red cell, human leukocyte and platelet antigens in a single analysis. Even genetic markers related to donor health can be added. Implementation of this technology will affect various stakeholders within the transfusion chain.

Preventing alloimmunization using a new model for matching extensively typed red blood cells.

Background And Objectives: Alloimmunization is a well-known adverse event associated with red blood cell (RBC) transfusions, caused by phenotype incompatibilities between donor and patient RBCs that may lead to haemolytic transfusion reactions on subsequent transfusions. Alloimmunization can be prevented by transfusing fully matched RBC units. Advances in RBC genotyping render the extensive typing of both donors and patients affordable in the foreseeable future.

Development and validation of a universal blood donor genotyping platform: a multinational prospective study.

Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non-self-antigens is an unavoidable adverse side effect of transfusion. We describe a universal donor typing platform that could be adopted by blood services worldwide to facilitate a universal extended blood-matching policy and reduce sensitization rates.

A Conceptual Framework for Optimizing Blood Matching Strategies: Balancing Patient Complications Against Total Costs Incurred.

Alloimmunization is currently the most frequent adverse blood transfusion event. Whilst completely matched donor blood would nullify the alloimmunization risk, this is practically infeasible. Current matching strategies therefore aim at matching a limited number of blood groups only, and have evolved over time by systematically including matching strategies for those blood groups for which (serious) alloimmunization complications most frequently occurred.

Bone density in apheresis donors and whole blood donors.

Apheresis donation using citrate causes acute decrease in serum calcium and increase in serum parathyroid hormone. Long-term consequences, such as decrease in bone mineral density (BMD), are not known. In this study, we compared the BMD of 20 postmenopausal apheresis donors (mean donation number 115 times in up to 15 years) with that of 20 whole blood donors (for 15 years or more) aged 55-70.

[Diuretic resistance and mechanical ventilation in decompensated cor pulmonale: successful treatment by slow continuous ultrafiltration].

We report on a 53-year-old male patient who presented with severe dyspnea at rest and massive volume overload because of decompensated cor pulmonale. Furthermore he suffered from stage 3 chronic kidney disease. As there was diuretics resistance and carbon dioxide narcosis, he had to be intubated and ventilated.

Endocarditis in neonatal intensive care unit.

The clinical spectrum of infective endocarditis (IE) in infants is examined in four infants between 3 and 9 months of age. None of the patients had signs of IE; all four had an anatomically normal heart. Echocardiograms showed echo-dense vegetations in the left side of heart in three cases and in the right side in one.

Response of Woody Plant Communities in Power-Line Corridors to Frequent Anthropogenic Disturbance.

Ecological theory predicts that diversity should decline as disturbance frequency increases beyond an intermediate level. However, few data exist on the responses of deciduous forests to high-frequency disturbance. We compared regenerating woody plant communities in northern Kentucky power-line corridors to adjacent second-growth forests to determine if high-frequency disturbance (5-6 yr mechanical or manual cutting cycle) modifies forest development.

Habitat-Specific Resilience of the Invasive Shrub Amur Honeysuckle (Lonicera Maackii) During Repeated Clipping.

In the development of novel strategies for control of invasive plant species, researchers might first consider plant performance throughout a range of habitats and then concentrate management activities in habitats where plants are least resilient. We determined the relative resilience of forest- and open-grown populations of the invasive shrub Lonicera maackii (Caprifoliaceae) growing in northern Kentucky. Resilience was assessed by imposing a clipping regime (once each year from 1986 to 1989) during which shrub resprouting abilities were measured.

Fine root production of astringent phenolics.

Chemical quality of fine roots (<1 mm diameter) was determined over a gradient of species composition in the Mixed Mesophytic Forest Region. Ash-free nitrogen, calcium, and phosphorus concentrations of roots declined by 49, 41, and 72%, respectively, over a gradient of increasing soil acidity (pH 5.3 to 4.