The influence of stereoisomerism on the pharmacokinetics of Tc radiopharmaceuticals

The influence of stereoisomerism on the pharmacokinetics of Tc mono-oxo complexes is reviewed. Tc(V) monooxo complexes formed with N/S ligands have four donor groups from the ligands in an equatorial plane; the oxo ligand coordinates in an axial position. Stereoisomerism in Tc (V) mono-oxo complexes can be centered within the ligand (carbon atom in the chelate ring or ligating nitrogen of amine donors) or at the Tc. The metal center becomes chiral when an equatorial ligand has a head and a tail (i.e., the two ends of the ligand differ). All types of stereocenters can produce significantly different pharmacokinetic profiles for individual isomers. Thus, biological evaluation of separated stereoisomers is necessary to identify the optimal sterochemical configuration, particularly for radiopharmaceuticals targeted to receptor molecules with low specificity. Because of interspecies variation, there is ultimately no substitute for human testing. Although it is possible that the increase in non-specific binding of agents incorporating L-vs D-amino acids may more than offset any increased receptor binding, much more information is needed. Stereochemical factors can also lead to unpredictable differences in coordination geometry and thermodynamic preference of a single isomer; thus chemical characterization of stereoisomers continues to be an important component of radiopharmaceutical development.     

Thrombolytic therapy in Missouri hospital emergency departments: compliance with the National Heart Attack Alert Program guidelines

Adhesive interactions between leukocytes and endothelium are required for subsequent leukocyte extravasation toward inflammatory sites. Understanding the possible kinetic expression of vascular cell adhesion molecule-1 (VCAM-1) in the middle ear cavity during an inflammatory cascade in vivo may be important for clarifying local immunological responses in otitis media. Two inflammatory models were produced in the rat and involved acute middle ear mucosal and cutaneous inflammation induced after inoculation or intradermal injection of lipopolysaccharide (LPS). After intravenous injection of both 125I-labeled anti-VCAM-1 and 131I-labeled control monoclonal antibody (mAb), the kinetic expression of VCAM-1 in the middle ear and skin was assessed by local radionuclide uptake. The biodistribution of an 125I-labeled anti-VCAM-1 mAb as a potential detector of focal inflammation was examined in normal rats. Both inflammatory lesions were characterized by early and sustained (up to 24 h) expression of VCAM-1, with maximal expression at 4 h after LPS stimulation. The kinetics of VCAM-1 expression was similar among the middle ear mucosa or skin specimens studied and different stimulation methods. A similar biodistribution and clearance of radioactivity between 125I-labeled anti-VCAM-1 mAb and 131I- or 99mTc-labeled control mAb were observed. The present result suggest that functional VCAM-1 induced by LPS is expressed in both middle ear tissue and skin lesions and may play a role in the initial stage of inflammatory response produced. Although VCAM-1 upregulation is a very early event in the inflammatory cascade, 125I-labeled anti-VCAM-1 mAb may be useful for the early detection of focal inflammation in the middle ear.     

Separation of the enantiomers of ibuprofen and its major phase I metabolites in urine using capillary electrophoresis

This report describes a simple, rapid, automated microassay for measuring in vitro changes of oxidative burst of phagocytes following challenge with metals for orthopedic devices. The production of reactive oxygen species (ROS) by polymorphonuclear leukocytes (PMNs) was measured using 2',7'-dichlorofluorescin-diacetate (DCFH-DA) as fluorescent probe. DCFH-DA enters the cells and is oxidized by ROS to fluorescent DCF. The DCF generated was directly proportional to ROS produced intracellularly: The fluorescence intensity was read and converted to an index of ROS production by cells. In our experimental system, granulocytes (PMNs) were isolated from normal human blood and seeded in microplates. To verify if metals could influence ROS production, chromium, cobalt, nickel, molybdenum, titanium, aluminum, and vanadium prepared as aqueous extracts in phosphate-buffered saline were tested onto PMNs using phorbolmyristate acetate (PMA) as positive control. Molybdenum, aluminum, and vanadium increased ROS generation by PMNs, while signals not different from unstimulated PMNs were recorded for chromium, cobalt, nickel, and titanium. The DCFH-DA microplate-based assay provides an in vitro tool for the detection of oxygen-reactive species generated by PMNs as a response to metals.     

Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo

Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathways that act preferentially through cyclin D1. Cyclin D1 expression and the activity of its associated kinase are up-regulated in keratinocytes in response to oncogenic ras. Furthermore, cyclin D1 deficiency results in up to an 80% decrease in the development of squamous tumors generated through either grafting of retroviral ras-transduced keratinocytes, phorbol ester treatment of ras transgenic mice, or two-stage carcinogenesis.     

Numerical evaluation of the derivative of the parabolic cylinderfunction

We have presented numerically useful expressions for calculating the derivative of the parabolic cylinder function D_p'(z) for the argument z=xe^-iπ/4 and order p=-1/2+iy, with x and y real. This case is needed for calculating the currents excited on a perfectly conducting parabolic cylinder by a TE plane wave and for calculating the scattered far-field pattern     

A dilatometer for measuring autogenous deformation in hardening portland cement paste

Different techniques for measuring autogenous deformation in cement paste are discussed, and a newly developed dilatometer designed specially for measuring this deformation is described. A particular characteristic of the dilatometer is the encapsulation of the cement paste in corrugated moulds. This restricts moisture loss and ensures that the hardening cement paste suffers insignificant restraint. In addition, the encapsulation permits measurements to commence shortly after casting.     

Group codes on certain algebraic curves with many rational points

We construct a series of algebraic geometric codes using a class of curves which have many rational points. We obtain codes of lengthq ² over _q , whereq = 2q ₀ ² andq ₀ = 2 ⁿ , such that dimension + minimal distance q ² + 1 – q ₀ (q – 1). The codes are ideals in the group algebra _q [S], whereS is a Sylow-2-subgroup of orderq ² of the Suzuki-group of orderq ² (q ² + 1)(q – 1). The curves used for construction have in relation to their genera the maximal number of GF _q -rational points. This maximal number is determined by the explicit formulas of Weil and is effectively smaller than the Hasse—Weil bound.Supported by Deutsche Forschungsgemeinschaft while visiting Essen University     

Multitouch tablet applications and activities to enhance the social skills of children with autism spectrum disorders

In spite of great improvements in early diagnosis and interventions, most children diagnosed with autism spectrum disorders (ASD) are unlikely to live independently when they reach adulthood. We have been conducting research on novel computer-based interventions with the goal of promoting social skills. Working with 26 children with ASD, their teachers, and other stakeholders, we have iteratively developed a set of activities based on applications that run on multitouch tablets. Our observations suggest these activities increased pro-social behaviors such as collaboration and coordination, augmented appreciation for social activities, and provided children with novel forms of expression.