Methods of Synthesis of the Ketamine Analogs (2R, 6R)-kydroxynorketamine and (2S, 6S)-hydroxynorketamine for the Treatment of Pain and other Anxiety-related Disorders

This technology includes a method for synthesizing the ketamine analogs (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine that may be useful for the treatment of pain, depression, anxiety, and related disorders. The drug ketamine was first used as an anesthetic but was found to be an effective treatment in a range of conditions, including paint, treatment-resistant bipolar depression, and other anxiety-related disorders. However, the routine use of ketamine is hindered by unwanted side effects, including the potential for abuse.

Use of the Ketamine Metabolite (R,6R)-hydroxynorketamine in Depression

This technology includes the identification and use of a ketamine metabolite, (2R,6R)-2-amino-2-(2-chlorophenyl)-6-hydroxycyclohexanone (HNK), for the treatment of depression. Ketamine is an NMDA receptor antagonist that exerts a rapid and sustained antidepressant and anti-suicidal effect. However, even low doses of ketamine has addictive and psychomimetic effects. The downstream metabolite, (2R,6R)-HNK, does not inhibit the NMDA receptor but recapitulates the antidepressant and anti-suicidal effect of ketamine.

Fluorescent Primer(s) Creation for Nucleic Acid Detection and Amplification

CDC researchers have developed technology that consists of a simple and inexpensive technique for creating fluorescent labeled primers for nucleic acid amplification. Fluorescent chemical-labeled probes and primers are extensively used in clinical and research laboratories for rapid, real-time detection and identification of microbes and genetic sequences. During nucleic acid amplification, the "UniFluor" primer is incorporated into newly synthesized double stranded DNA.

Photoinduced Electron Transfer Fluorescent Primer for Nucleic Acid Amplification

CDC scientists have developed a rapid and cost-efficient method for generating fluorescently labeled primers for PCR and real-time PCR. At present, fluorescent primers are useful for detecting and identifying microbes and specific nucleic acid sequences, amplifying nucleic acids for pyro-sequencing, determining the levels of gene expression, and many other uses. However, problems exist with current techniques used to create fluorescent primers. For one, labeling is not one hundred percent efficient, leading to inaccurate results.

Use of Detector Response Curves to Optimize Settings for Mass Spectrometry

This CDC developed optimization technology allows one to characterize the behavior of the coefficient of variation (CV) for a range of mass spectrometer machine settings. Surface-enhanced laser desorption/ionization (SELDI) and matrix-assisted laser desorption/ionization (MALDI) are used for the early detection of numerous diseases, for example cervical cancer . A critical step in the analytical process is the optimization of experiment and machine settings to ensure the best possible reproducibility of results, as measured by the CV.

Oxytocin Conditional Knockout Mouse Model for Studying Behavioral Effects

This invention relates to a novel mouse model that permits temporal and spatial inactivation of the oxytocin receptor. Oxytocin is a neurohormone that has been associated with human diseases such as autism and schizophrenia. The use of animal models to study oxytocin disease progression has been invaluable. However, existing mouse models have been limited to knockouts which leads to early mortality. Researchers at the National Institute of Mental Health (NIMH) generated the conditional oxytocin receptor knockout mice using the Cre-loxP and FLP-FRT systems.

SIRT2 Inhibitors as Novel Therapeutics for Myocardial Infarction and Ischemic Stroke and to Prevent Necrosis

Sirtuin 2 (SIRT2) inhibitors to reduce necrosis and, thereby, as novel therapeutics to treat ischemic stroke and myocardial infarction. Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion. NIH investigators have shown that the NAD-dependent deacetylase SIRT2 binds constitutively to receptor-interacting protein 3 (RIP3) and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice.

Generation of Artificial Mutation Controls for Diagnostic Testing

This technology relates to a method of generating artificial compositions that can be used as positive controls in a genetic testing assay, such as a diagnostic assay for a particular genetic disease. Such controls can be used to confirm the presence or absence of a particular genetic mutation. The lack of easily accessible, validated mutant controls has proven to be a major obstacle to the advancement of clinical molecular genetic testing, validation, quality control (QC), quality assurance (QA), and required proficiency testing.

Automated Microscopic Image Acquisition, Compositing and Display Software Developed for Applied Microscopy/Cytology Training and Analysis

Micro-Screen is a CDC developed software program designed to capture images and archive and display a compiled image(s) from a portion of a microscope slide in real time. This program allows for the re-creation of larger images that are constructed from individual microscopic fields captured in up to five focal planes and two magnifications. This program may be especially useful for the creation of data archives for diagnostic and teaching purposes and for tracking histological changes during disease progression.

Method to Detect and Quantify In Vivo Mitophagy

This technology includes a transgenic reporter mouse that expresses a fluorescent protein called mt-Keima, to be used to detect and quantify in vivo mitophagy. This fluorescent protein was originally described by a group in Japan and shown to be able to measure both the general process of autophagy and mitophagy. We extended these results by creating a living animal so that we could get a measurement for in vivo mitophagy. Our results demonstrate that our mt-Keima mouse allows for a straightforward and practical way to quantify mitophagy in vivo.