Abstract: The present disclosure relates to organic chemistry and in particular to a series of corticotropin releasing factor type-1 (CRF1) receptor ligand compounds and compositions, as well as methods of preparation and treatment.

Abstract: The present disclosure relates to methods of treating a stimulant addiction of a patient comprising administering to a patient in need a therapeutically effective dose of a selective dopamine beta-hydroxylase inhibitor thereby decreasing stimulant reward, inducing aversion for the stimulant or preventing relapse in the patient. The disclosure further encompasses methods whereby a therapeutically effective dose of a selective dopamine beta-hydroxylase inhibitor is determined by: characterizing the genetic profile of the patient with respect to the gene encoding dopamine beta-hydroxylase, a polymorphism therein correlating to the level of endogenous dopamine beta-hydroxylase activity in the patient before administering the therapeutic agent.

Abstract: The present invention provides novel amino acid compounds useful in detecting and evaluating brain and body tumors. These compounds have the advantageous properties of rapid uptake and prolonged retention in tumors and can be labeled with halogen isotopes such as fluorine-18, iodine-123, iodine-124, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77, bromine-82, astatine-210, astatine-211, and other astatine isotopes. These compounds can also be labeled with technetium and rhenium isotopes using known chelation complexes. The compounds disclosed herein bind tumor tissues in vivo with high specificity and selectivity when administered to a subject. Preferred compounds show a target to non-target ratio of at least 2:1, are stable in vivo and substantially localized to target within 1 hour after administration. Preferred compounds include 1-amino-2-[18F]fluorocyclobutyl-1-carboxylic acid (2-[18F]FACBC) and 1-amino-2-[18]fluoromethylcyclobutyl-1-carboxylic acid (2-[18F]FMACBC).

Abstract: Various embodiments of the present invention provide a conduit device including an attaching device configured for defining a helical pathway through a tissue wall and complementary ring in cooperation for securing the device within an aperture defined in the tissue wall. Some embodiments of the present invention further provide a system for implanting a conduit device in a tissue wall. More specifically, some embodiments provide a system including a coring device for defining an aperture in a tissue by removing and retaining a tissue core and securely implanting a conduit device therein so as to provide fluid communication between a first and second surface of the tissue wall via the conduit device.

Abstract: This disclosure relates to progesterone derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation resulting from traumatic brain injury or stroke.

Abstract: mGluR5 antagonists are used for the treatment of autism. The human treated by the methods of the invention can also have fragile X syndrome, epilepsy and anxiety.

Abstract: Systems, methods and computer-readable storage mediums relate to generating an image that includes functional, anatomical, and physiological images. The generated image may be an integrated image based on the functional image on which the anatomical and physiological images are mapped. The generated image may indicate more than one location of optimal lead placement. The generated image may be useful in pre-planning cardiac intervention procedures.

Abstract: Systems, methods, and computer-readable storage media relate to generate an image series that includes a patient image and a medical image. The patient image and the medical image may be associated based on identification information.

Abstract: This disclosure relates to Hypoxia Inducible Factor-1 pathway inhibitors and uses as anticancer and imaging agents. In certain embodiments, the disclosure contemplates compounds and pharmaceutical compositions disclosed herein.

Abstract: Microfluidic devices and processes are provided that relate to microvascular-sized systems configured to identify specific pathophysiological characteristics related to the interactions between, for example, blood cells and endothelial cells combined with geometric and flow constraints of microvasculature. The device may include at least one layer, the layer including a plurality of microvascularized-sized fluidic channels, the plurality of microfluidic channels being disposed in a geometric pattern. The layer may be composed of a hydrogel and/or a silicon elastomer. The channels may include subchannels of different lengths.

Abstract: 9-aminonoscapine, prodrugs thereof, and pharmaceutically acceptable salts thereof, are disclosed. Pharmaceutical compositions including 9-aminonoscapine, and methods of preparation and use thereof are disclosed. 9-aminonoscapine is a noscapine analog that can be used to treat and/or prevent a wide variety of cancers, including drug resistant cancers, by binding tubulin and inducing apoptosis selectively in tumor cells (ovarian and T-cell lymphoma) resistant to paclitaxel, vinblastine and teniposide. 9-aminonoscapine can perturb the progression of cell cycle by mitotic arrest, followed by apoptotic cell death associated with increased caspase-3 activation and appearance of TUNEL-positive cells. Thus, 9-aminonoscapine is a novel therapeutic agents for a variety of cancers, including ovarian and T-cell lymphoma cancers, even those that have become drug-resistant to currently available chemotherapeutic drugs.

Abstract: Small molecule agonists, partial agonists, and antagonists for the TrkA receptor are described. The compounds are gambogic amines, where the carboxylic acid group of gambogic acid (CO2H) has been replaced by an amine group (CH2NR1R2). In some embodiments, the compounds selectively bind to TrkA but not TrkB or C, robustly induce its tyrosine phosphorylation and downstream signaling activation including Akt and MAP kinases. Further, they can strongly prevent glutamate-induced neuronal cell death and provoke prominent neurite outgrowth in PC12 cells. Gambogic amines specifically interact with the cytoplasmic juxtamembrane domain of TrkA receptor and trigger its dimerization. Administration of these compounds in can substantially diminishes Kainic acid-triggered neuronal cell death and decrease infarct volume in transient middle cerebral artery occlusion (MCAO) model of stroke.

Abstract: One aspect of the present disclosure encompasses methods for determining a protein kinase or phosphatase activity in a biological sample, comprising: contacting in a reaction mix a first test sample and a fluorescently-labeled peptide substrate capable of being modified by a protein phosphatase or a protein kinase, contacting the reaction mix with a TiO2 matrix, thereby partitioning fluorescently-labeled phosphorylated peptide from fluorescently-labeled dephosphorylated peptide; and determining the fluorescence of the fluorescently-labeled dephosphorylated peptide, thereby determining a protein kinase or phosphatase activity.

Abstract: This invention provides amino acid derivatives useful in detecting and evaluating brain and body tumors, including (1S,2S) anti-2-[18F]FACPC and (1R,2R) anti-2-[18F]FACPC.

Abstract: Osteoporosis, is an exceedingly common malady that leads to bone fracture and results from an imbalance in the rate of osteoblastic bone formation with respect to osteoclastic bone degradation. Nanotechnology has raised exciting possibilities for the development of novel therapeutic agents. Embodiments of the disclosure provide silica-based fluorescent nanoparticles endowed with natural bone targeting capabilities and expressing potent pro-osteoblastogenic and concomitant anti-osteoclastogenic activities in vitro and the capacity to increase bone mineral density in vivo. Embodiments of the disclosure can achieve their stimulatory effects on osteoblasts, and inhibitory effects on osteoclasts, in part by suppressing NF-KB signal transduction. Embodiments of the present disclosure provide for derivatives of silica-based nanoparticles that represent a novel class of dual anti-catabolic and pro-anabolic agents that may be applicable to the amelioration of numerous osteoporotic conditions.

Abstract: The present disclosure provides methods for inhibiting the anticoagulation effect of a thrombin inhibitor in a patient in need thereof comprising administration of a therapeutically effective amount of a variant prothrombin or thrombin that is capable of binding the thrombin inhibitor and that has reduced procoagulant activity. Variant prothrombins or thrombins of use in the methods of the present disclosure include thrombin mutants W215A, W215A/E217A, or variants thereof in which the amino acids at positions 215 and/or 217 are alanine. Methods are also provided in which the thrombin mutants are administered with an additional active agent. In one embodiment, the methods are useful in the treatment of patients in which a direct thrombin inhibitor has been administered. The present disclosure further provides a method for quantifying the concentration of an anticoagulant in the plasma or whole blood of a patient using a variant prothrombin or thrombin titration assay.