University of Cincinnati's Biological Sciences Technologies Available for Licensing

109001 - A Safer Way to Treat Obesity

Kellen.Sensor@uc.edu (Kellen Sensor) — Mon, 09 Nov 2009 00:00:00 GMT

Bariatric surgery (also known as weight loss surgery) is performed on obese patients who are unable to reduce weight by dietary modifications or exercise regimens. Current bariatric surgical procedures predominantly involve removing a significant part of the stomach (such as Sleeve Gastrectomy), or partitioning the stomach with incisions and stapling. This may be achieved with or without the re-routing of the food pathway. Some of these techniques are irreversible, a fact which is troublesome in view of the increasingly younger population of potential patients. When reversible, these procedures involve a significant amount of dissection with risks of bleeding and delayed complications. There is also a possibility of gastric erosion, as in the case of gastric banding procedures.

Invention
A surgeon at the University of Cincinnati has designed a device that can overcome many of the shortcomings of current bariatric surgical procedures. The device is flexible and can be used to replace either of the currently used procedures.
The invention has the following advantages over current procedures:

Reversibility

Preservation of gastric integrity

Minimal surgical dissection and reduced operating time

Compatibility with a laparoscopic approach

Further information regarding this invention can be obtained under a Confidential Disclosure Agreement.

106026 - Molecular Profiling of Thyroid Cancer

Kellen.Sensor@uc.edu (Kellen Sensor) — Mon, 02 Nov 2009 00:00:00 GMT

This invention provides methods for characterizing thyroid tissue by detecting the gene expression levels for certain genes, such as kallikrein 10 and claudin 1, among others. This provides a novel approach for detecting thyroid carcinomas by detecting altered gene expressions in thyroid tissue samples (relative to expression levels in normal thyroid tissues). Furthermore, the level of specific gene expression can be used to discriminate between the different types of thyroid cancer e.g., papillary versus follicular.

090003 - Item Number 148 - Analysis Of Whole Blood

pinskig@uc.edu (Geoffrey Pinski) — Mon, 19 Oct 2009 00:00:00 GMT

The existence of infectious diseases, and particularly AIDS, presents a hazardous situation for the laboratory and clinical personnel whose responsibility it is to analyze contaminated blood samples for analytes unrelated to these diseases.
This has given rise to the creation of "Universal Precautions" which have further increased the difficulties of handling and the complexity of the processing procedures. This is a major problem, for hundred of millions of clinical tests are run annually in the USA alone using blood as the sample source, and it has been estimated that as much as 7% of all such specimens contain HIV, the causative agent for AIDS. It is clear that advances which reduce the number of procedural steps offer both increased safety and decreased assay time.
The development at hand provides a straightforward and inexpensive method for the quantitative assay of analytes contained in whole blood. No pretreatment of the blood, converting it to serum or plasma, is necessary. Any analyte that can be coupled to the co-factor NADH can, in principle, be quantitated. Scores of such coupled assays have been described. Proof of principle has been established initially with the therapeutic drug, phenytoin.
The nature of this new development is such that the following advantages are enjoyed:

The sampled volume of blood is small, lessening trauma and disposal problems.
The technology requires minimal sample handling, thereby lessening personnel exposure.
Procedural simplicity also results in time savings, making this development appropriate for stat and patient bedside testing.

104010 - Compounds to Treat Cardiovascular Ischemia and promote Wound Healing

Ellen.Monson@uc.edu (Ellen Monson) — Mon, 24 Aug 2009 00:00:00 GMT

Cardiovascular ischemia is a leading cause of illness and death in the United States. A number strategies including prevention through diet, exercise and lipid-lowering drugs, and medical intervention via angioplasty, stent placement and surgery are being used to alleviate the ischemic conditions. In addition, pro-angiogenesis compounds have also been used to enhance blood flow through collateral vessel formation. However, these treatments remain inadequate because of the complications associated with these strategies. Moreover, pro-angiogenesis factors, vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (BFGF), used to enhance blood flow in ischemic tissues have also been associated with pathological angiogenesis and/or the proliferation of tumor cells. The latter observation warrants the development of novel compounds that would specifically promote angiogenesis in ischemic tissues.
Neuropeptide Y (NPY) is a 36-residue peptide amide originally isolated from porcine brain. It is abundantly present in the sympathetic nervous system surrounding the heart and blood vessels, and also present in endothelial cells and platelets. Recent investigations using rat hind limb ischemic model, mouse corneal micro-pocket assay and chicken embryonic chorioallantoic membrane assay have unequivocally shown that NPY exhibits a powerful angiogenisis effect. Moreover, NPY has also been shown to promote wound healing, a process dependent on angiogenesis. These actions of NPY are mediated by Y2 receptor subtypes because: 1) NPY did not exhibit angiogenic activities in Y2 receptor deficient mice; 2) [Leu31, Pro34]NPY, which does not bind to Y2 receptor, had no angiogenesis effect.
It is therefore clear that NPY Y2 receptor selective agonists will ultimately be used to treat cardiovascular ischemia and promote wound healing. In this regard, we have developed highly selective and potent (Ki = 1 nM) lower molecular weight Y2-receptor agonists based on PYY(22-36) and PYY(25-36) (US Patents: 5604203 & 6046167), and shown that they exhibit to potent and prolong in vivo activities (J Med Chem 49:3420-3427; 2000; Dig Dis Sci. 44:643-648; 1999). We are now looking for partners to develop these compounds as drugs to treat cardiovascular ischemia, Peripheral arterial disease (PAD), and to promote wound healing.
Advantages

Lower molecular weight compounds- will be economical to develop into drugs.
Highly potent and selective- will be active at lower doses & little or no side effect expected.
Relatively stable- long acting.

103020 - A Family of Therapeutic Delivery Systems

Ellen.Monson@uc.edu (Ellen Monson) — Mon, 24 Aug 2009 00:00:00 GMT

The present invention is in the fields of molecular biology, biochemistry and pharmaceuticals. In general, the invention provides compositions for the cellular delivery of nucleic acids, polypeptides and/or molecular complexes comprising nucleic acids and polypeptides, and methods of making and using such compositions. The present invention provides a new class of non-viral transduction vectors that can be used for both in vivo and in vitro applications. This includes unique polycationic polymers that can associate with many suitable bioactive molecules, including proteins and other compounds that posses multiple cationic sites. The polymer can act as a delivery vehicle for the associated bioactive molecule, in vivo or in vitro, to the cells of interest for the bioactive molecule. In one embodiment, the present invention provides for a new series of polyamides for use as gene delivery agents. Also disclosed are methods of using the polymers to bind products, e.g., oligonucliotides, and facilitate cellular uptake. In one embodiment, the invention provides for the in vitro delivery of plasmid DNA into cells. The present also provides for the use of these polymers for the delivery of a nucleic acid is biologically active into a cell.
Advantages
The polymers are nontoxic and suitable for (highly efficacious ) drug delivery, efficient intracellular gene delivery, as well as delivery of DNA, RNA, SiRNA and oligonucleotides. One family of polymers is completely biodegradable, yielding glucose and an oligoamine monomer that is similar in chemical structure to that found in the body. The polymers are suitable for noncovalent attachment of targeting agents for cell-type specific delivery.
Areas of Application
Both the polymers and the oligonucleotide decoys have clinical applications, either separately or in combination (i.e., with the polymer delivering the decoys into cells). The polymers also have applications as reagents for in vivo and in vitro delivery of bioactive molecules. Favorable in vitro test results have been achieved in a variety of primary cell lines. The oligonucleotides, both separately and with the polymers as a delivery vehicle, are being studied for treatment of myocardial ischemia/reperfusion.

106082 - Structure of human platelet glycoprotein VI: A novel target for anti-thrombotic agents

Ellen.Monson@uc.edu (Ellen Monson) — Sun, 23 Aug 2009 00:00:00 GMT

In a recently published paper, Dr. Andrew Herr and colleagues at the University of Cincinnati developed a protocol for the expression, purification, and refolding of the collagen-binding domain of human GPVI. The crystal structure of this refolded GPVI domain was solved to 2.4 Å resolution. GPVI formed a back-to-back dimer in the crystal, consistent with several studies suggesting GPVI was dimeric on the platelet surface. These data also revealed an unusual groove on the surface of GPVI that computational docking programs and published mutagenesis studies strongly suggest is the collagen binding site.
This technology – a refolding protocol capable of generating milligram quantities of pure GPVI and the coordinates of the atomic structure of GPVI – provides critical information for the design and development of GPVI inhibitors as new therapies for human disease.A patent application has been filed. The University of Cincinnati is seeking industry partners for the development of GPVI inhibitors as novel therapeutics.

109009 - Test for Determination of Therapy for Heart Failure Patients in the ER

Ellen.Monson@uc.edu (Ellen Monson) — Mon, 10 Aug 2009 00:00:00 GMT

Patients with cardiomyopathy, a term which pertains to the diseases of the heart muscle, are often at risk of arrythmia, sudden cardiac death, or both. There may be different cardiomyopathic conditions including acute heart failure and chronic cardiomyopathies. One of the components of the heart muscle is the protein known as tropomyosin (TM) which is encoded by four genes (TPM1-4). The differential expression of the various forms of this protein have been shown to be important in cardiomyopathies.

Invention

Dr. Wieczorek and colleagues at the University of Cincinnati have discovered that one of the isoforms of tropomyosin 1,TPM1 kappa (TPM1k), which is expressed in heart muscle fibers, is differentially regulated in cardiomyopathic conditions. Specifically, they have shown that TPM1k levels are differentially expressed in acute versus chronic cardiomyopathies. The inventors have discovered that patients with acute heart failure have decreased levels of TPM1k while patients with chronic cardiomyopathy show increased TPM1k levels (1). The use of this information can be potentially used to test patients that are rushed into emergency room with heart failure in determing the appropriate therapy for their condition. Currently, ER physicians have to rely on patient histories to make such a determination.

Advantages:

- allows physicians to rapidly make more informed decisions regarding patient therapy, leading to better disease management

More information can be obtained under a confidentialilty disclosure agreement.

108070 - A Method of Improving the Efficacy of Currently Available Asthma Drugs

Ellen.Monson@uc.edu (Ellen Monson) — Mon, 10 Aug 2009 00:00:00 GMT

Asthma is a chronic disease which affects over 100 million people globally. Approximately 5-10 million adults and 10-15 million children worldwide suffer from asthma; and its incidence continues to grow at around 5%-6% per annum. Over 18 million Americans have asthma, but only around 60% of US sufferers are treated. US asthma prevalence rates have risen by almost 50% in the ten years ending 1994 and are expected to increase by 20%-50% every ten years.

Asthma involves the contraction of the bronchial smooth muscle and the narrowing of the airway. This together with airway mucus accumulation and edema, results in breathing difficulties in the patient. A standard component of asthma therapy includes the inhalation of beta-adrenergic agonists, such as salbutamol and related compounds. These compounds activate ß2-adrenergic receptors on bronchial smooth muscle cells, triggering an increase in cyclic AMP that leads to smooth muscle relaxation, ultimately making it easier for the patient to breathe. However, while generally beneficial for most patients, ß-agonists may sometimes fail to fully relieve bronchospasm in asthmatics with severe disease or during severe asthma exacerbations.

Invention
Drs. Reszka , McGraw and Britigan at the University of Cincinnati have uncovered a mechanism that may decrease ß2-agonist efficacy during severe asthma exacerbations. Furthermore, they have exploited this mechanism to invent novel methods for potentially maintaining the potency of these drugs. The invention offers the following advantages:

the invention can render current inhalation therapies more effective in the alleviation of asthma symptoms
the invention can potentially provide a more reliable way of controlling asthma by this class of compounds.

More information is available under a confidentiality disclosure agreement.

109100 - Method of Detection of Heparin Adulteration

pinskig@uc.edu (Geoffrey Pinski) — Wed, 01 Jul 2009 00:00:00 GMT

Dr. Stalcup and her laboratory have developed a specific, rapid, and cost-effective assay of heparin based on the induction of a unique spectroscopic signal into a chemical probe.

Background:Recent episodes of heparin adulteration resulted in numerous reports of severe adverse reactions and more than 80 deaths. The molecular weight range of heparin and the natural variation in both degree and sites of sulfation make a specific assay by conventional means difficult, expensive, time-consuming, and not easily interpreted. Some markers of adulteration may be detected by mass spectrometry and nuclear magnetic resonance. Originally, the most definitive assay was clotting time. However, unscrupulous suppliers exploited the non-specific nature of clotting-based assays by adding semi-synthetic analogues with heparanoid activity. Indeed, the FDA recently identified oversulfated chondroitin sulfate (OSCS) as a likely adulterant. The proposed work addresses the urgent need for improved technologies for rapid screening of heparin samples.

The UC discovery is that complexation between heparin and a judiciously selected probe analyte will perturb the spectroscopic signal of the probe, and that the extent of this perturbation is related to heparin concentration expressed as equivalent disaccharide. Unlike most polysaccharides, heparin is not only sulfated, but has a unique helical structure. We exploit this unique feature. Chondroitin sulfate and other sulfated polysaccharides do not respond to our chemistry and can’t be used to generate false positive heparin activity in our assay.

Advantages:
The advantages of our rapid assay is that it:

is robust
is inexpensive
is easy to use
can rapidly identifies likely compromised lots
can drastically reduce the number of samples requiring MS or NMR analysis.

109030 - Test to Determine Susceptibility to Aggressive Forms of Colon Cancer

Ellen.Monson@uc.edu (Ellen Monson) — Wed, 03 Jun 2009 00:00:00 GMT

Colorectal cancer is the second leading cause of cancer-related deaths in the US and is also amongst the most diagnosed cancers nationwide. In 2008, the number of cases of colorectal cancer was estimated to be approximately 149,000 cases in the US. Risk factors for colorectal cancers include age (50+ increases risk), presence of polyps, consumption of high fat diets, family history (genetic composition), and the presence of ulcerative colitis or Crohn's disease. Of these, genetics may be the contributing factor in approximately 30% of the patients diagnosed with colorectal cancer. Approximately 45,000 patients estimated to be diagnosed with colorectal cancer in 2008 may have the disease which may be attributable to genetic variations. Expression levels of specific genes may predispose individuals to certain forms of cancer, and the determination of expression profiles may be useful in the management of the disease.

One such gene is the AMACR gene which regulates the breakdown of branched-chain fatty acids, which are found in herbivorous animals. Previously, it has been shown that these fatty acids, present mainly in red meats and dairy products, can accelerate tumor progression.

Invention

Dr. Shuk-mei Ho and colleagues at the University of Cincinnati have discovered deletions at specific regions in the promoter of the AMACR gene results in abnormal gene expression, and such gene expression in individuals may predispose them to a more aggressive type of colon carcinoma. Hence individuals can be tested for the presence of these deletions resulting in the abnormal expression of the AMACR gene.

This invention may afford the following advantages:

Can potentially form the basis of a test for deletions which will allow physicians to determine the prognosis of some forms of the disease and manage the disease accordingly
Technology may potentially lead to the avoidance of unnecessary aggressive therapy and its attendant side effects in some patients.

More information is available under a confidential disclosure agreement.

109003 - A Test for Prostate Cancer with Better Sensitivity and Specificity

Ellen.Monson@uc.edu (Ellen Monson) — Wed, 03 Jun 2009 00:00:00 GMT

In the US, prostate cancer is the most common type of cancer in men. Prostate cancer is aggressive in some men while it is more slow-growing and less problematic in others. Most men nowadays are diagnosed with prostate cancer earlier than before, when the disease is diagnosed in a non-metastasized form. This is due to the wide-spread use of tests such as the serum prostate-specific antigen (PSA) at earlier stages. However, as elevated serum PSA levels may be due to non-cancerous conditions such as benign prostate hyperplasia (BPH), acute urinary retention, perineal trauma, and prostatitis, this test is not very specific for the detection of prostate cancer. Furthermore, increased levels due to these conditions may mask PSA originating from any small cancer foci.

Taken together, these reasons may be responsible for low levels of sensitivity and specificity of PSA tests. Hence, the risk for prostate cancer can be present at a wide range of serum PSA levels. As a consequence, men with elevated serum PSA must undergo biopsies to further confirm or rule out the presence of prostate cancer. Given that 1 million men with elevated serum PSA tests undergo biopsies annually, but only 25% of these are diagnosed with cancer, a more sensitive and specific test would be significantly beneficial.

Invention

Dr. Shuk-mei Ho and colleagues at the University of Cincinnati have designed an assay which provides greater diagnostic accuracy than the PSA test. It also has better sensitivity and specificity than that of many other commercially available tests involving other biomarkers. This assay has been tested in a study comprising of 92 patients. The sensitivity and specificity of this test was 81% and 84% respectively.

The test affords the following advantages:

Is potentially simple to perform
Is non-invasive and does not require blood draw
Has higher sensitivity and specificity compared to many tests currently available
Can potentially be used to rule out unnecessary, painful follow-up biopsies especially in older patients (70+ yrs)

More information can be obtained under a confidential disclosure agreement.

107093 - Novel Molecules for Shiga Toxin Detection

Ellen.Monson@uc.edu (Ellen Monson) — Wed, 03 Jun 2009 00:00:00 GMT

Shiga toxin producing Escherichia coli (STEC), including E. coli O157:H7, are emerging pathogens of major importance. E. coli O157:H7 alone causes an estimated 70,000 cases of disease per year in the United States. Disease caused by E. coli O157:H7 is characterized by diarrhea, hemorrhagic colitis, and the potentially fatal complication, hemolytic uremic syndrome (HUS). Shiga toxin (Stx) is a major virulence factor of E. coli O157:H7 and has been included as a Select Agent of Biothreat agent list.

The pathogenic potential of an E. coli isolate is dependent on the type of Shiga toxin it produces. There is an urgent need for diagnostic agents that can discriminate between Stx1 and the deadlier form, Stx2, for effective intervention and the prevention of future outbreaks. Furthermore, closely related variants of Stx2 also differ in pathogenic potential. Commercially available diagnostic tests for Shiga toxin distinguish between Shiga toxin variants based on antigenic differences, not pathogenic potential. Thus, a test that distinguishes between Shiga toxin variants based on pathogenic potential represents significant advancement in diagnostic and therapeutic value for affected patients.

Invention

Researchers at the University of Cincinnati have developed novel, glycoconjugate ligands which mimic the natural receptors and exhibit specific and differential binding toward Shiga toxin variants based on biological activity. These glycoconjugates can be used as robust, specific, high affinity ligands for the detection and possibly treatment of Shiga toxin mediated disease. Additionally, the methods used to make and screen these glycoconjugates represent a platform technology that can be applied to many other toxins, viruses and bacteria. A patent application has been filed that includes novel compositions, methods for making and methods for screening glycoconjugates.

Advantages

Glycoconjugates distinguish Shiga toxin variants based on biological activity, not antigenicity and unlike antibodies, glycoconjugates are insensitive to genetic drift.
Glycoconjugates can be used in several assay platforms including ELISA and sensor arrays.
Glycoconjugates have superior thermal and chemical stability compared to antibodies.
No cross reactivity or false positives are expected with this class of compounds.

103007 - Compositions and Methods for Targeted Drug Delivery

pinskig@uc.edu (Geoffrey Pinski) — Wed, 03 Jun 2009 00:00:00 GMT

The present invention relates to synthetic host-rotaxanes, and in particular to novel synthetic host-rotaxanes that engage in molecular recognition events with a guest molecule to yield a host-guest complex. The present invention includes methods and compositions for transporting agents and macromolecues across biological membranes.
Although recent advances in drug delivery methods have produced active peptide and protein-based drugs, the technology suffers from a lack of suitable delivery systems. Among the problems of existing delivery systems is poor absorption of peptides through cellular membranes. The host-rotaxane of the present inventions shows almost DMSO-like ability to penetrate a cell membrane and deliver desired constituents to a cell.

102080 - The Magnetic Hip Joint For Reduction of Friction

pinskig@uc.edu (Geoffrey Pinski) — Wed, 03 Jun 2009 00:00:00 GMT

When pain due to severe osteoarthritis as well as conditions such as inflammatory arthropathies, post traumatic arthritis, vascular necrosis, and childhood diseases of the hip becomes intractable and, recalcitrant to conservative non-surgical management including medication and activity modifications, total hip replacement (THR) is an extremely effective option. It relieves debilitating pain and restores function to hips. Over 120,000 total hip replacements are performed each year in the United States alone. .
However, the longevity of THR is limited by periprosthetic osteolysis. Periprosthetic osteolysis is defined as bone resorption about a prosthetic joint, which occurs as the biological response to particular wear debris from the prosthetic joint. It is the most common and most important long-term complication of THR. The failure of THR necessitates difficult revision THR.
We, at the University of Cincinnati, have developed the technology, which will make Periprosthetic osleolysis a thing of the past. The new approach developed here will prevent/reduce contact at the femoral head /acetabulum and thus significantly reduce generation of particular wear debris and its resultant periprosthetic osteolysis.

Advantages:
1. Commercialization of this technology offers great opportunity to address the needs of a vast population of patients suffering from various joint problems, which are beyond non surgical management; waiting for a solution like this one, which offers effective, long-term cure to the pain.
2. The use of magnetic levitation significantly decreases the generation of particular wear debris. Thus by elimination of particular wear debris from the femoral head/acetabulum in THR and the potential to significantly extend the clinical lifespan of THR.
3. Use of magnetic levitation eliminates/reduces the need for a revision THR. The revised THR is not just more complex, difficult and problematic than the primary THR due in great part to the loss of bone stock caused by osteolysis; its results are generally less satisfactory than primary THR.

099047 - Item Number 281 - Detection of Nucleic Acid Target Sequences by Electron Paramagnetic Resonance Spectroscopy

pinskig@uc.edu (Geoffrey Pinski) — Wed, 03 Jun 2009 00:00:00 GMT

This invention is a method for detecting the presence or absence of a target DNA sequence, within an identified region of a selected DNA molecule. The invention uses certain aspects of the polymerase chain reaction ("PCR") and ligase chain reaction ("LCR") techniques for the detection of genetic mutations in genes, particularly point mutations. The PCR reaction is carried out in the presence of nitroxide-labeled oligomers that are degraded only if hybridized to a complementary target sequence. The degradation of the nitroxide-labeled oligomers into nitroxide-labeled cleavage products results in a characteristic increase of the h-/ho ratio of the EPR signal; in the absence of a complementary target sequence the EPR signal of nitroxide-labeled oligomer remains unchanged.

In contrast to approaches based on fluorescence spectroscopy developed by others the proposed magnetic resonance detection (EPR) with nitroxide labeled oligomers offers the advantage of no interference by turbidity of the solution, no interference by the hydrophobic properties of the fluorochromes, no tedious and expensive labeled oligomer synthesis, but most importantly, no interference by potential fluorescent background signals. While the fluorescent based technology relies on some complex mechanism responsible for the increase of fluorescence in the presence of two labels (one with fluorescent and one with quenching properties) in the PCR mixture, the nitroxide-labeled oligomer based assay relies on a theoretically more readily understood EPR lineshape change (h-/ho ratio change) due to one label only, namely the nitroxide label, whereas fluorescent based assays usually require two labels. Also the EPR probes have a longer shelf-life than probes designed for fluorescence spectroscopy.

The nitroxide label methods of the invention can be used in assays to detect specific genes, gene segments and other nucleic acids. These assays can have clinical potential in a wide variety of areas such as medicine, environmental studies, biological research etc.

097032 - Item Number 274 - Self-Destructing, Controlled Release Peroral Drug Delivery System

pinskig@uc.edu (Geoffrey Pinski) — Wed, 03 Jun 2009 00:00:00 GMT

If a delivery system is provided for administering a drug at a constant rate throughout the entire gastrointestinal tract, the different absorptive rates of the various sections of the tract will result in a change in the blood levels of the delivered compound. The present invention relates to tablets that are time-controlled to release active agent at different rates in different regions of the digestive tract in order to maintain a substantially constant concentration in the blood.
The advantage of the present system is its adaptability to manufacturing on a compression coating machine, in one single step. Once the delivery system of the present invention reaches the large intestine, where absorption of drug is slower because of mucosal viscosity of the intestinal contents, the shell of the device self-destructs thus releasing the drug at an accelerated rate. The device delivers a compound in a sustained manner to the upper portion of the gastrointestinal tract and then provides a burst of release at the lower small intestine, more particularly the colon.

098021 - hBub1, Cell Cycle Checkpoint Gene

monsonek@ucmail.uc.edu (Sandip Patil) — Tue, 02 Jun 2009 00:00:00 GMT

The present invention provides therapies of human cancers which have a mutation in the hBub1 gene, including gene therapy, protein replacement therapy and protein mimetics. The invention further provides methods for the screening of drugs for cancer therapy . Finally, the invention provides methods of screening of the hBub1 gene for mutations, which are useful for diagnosing the predisposition to cancer. This invention also provides an isolated polynucleotide comprising all, or a portion of the hBub1 locus or of a mutated hBub1 locus.
Genetic analyses have identified six distinct genes (BUB1, 2, and 3 and MAD1, 2, and 3) that are important in regulating the spindle checkpoint. BUB1 encodes a protein serine/threonine kinase and is itself phosphorylated when the cell enters mitosis. A recent study shows that Bub1p activates the spindle checkpoint in the budding yeast. BUB2 is structurally related to the fission yeast cdc16 gene product, which plays an essential part in cytokinesis. BUB3, unrelated to any other known proteins, appears to be a substrate of BUB1.
This technology is patented, and we are seeking a licensee to pursue development of products based on this technology.

109034 - Innovative Method to Improve Membrane Transfer of Pharmaceutical Nanocarriers

Ellen.Monson@uc.edu (Ellen Monson) — Sun, 31 May 2009 00:00:00 GMT

Colloidal nanocarriers such as nanoparticles and liposomes have revolutionized drug delivery of potent pharmacological agents. Encapsulation of proteins, DNA, and siRNA into nanocarriers protects those therapeutic agents from rapid degradation and effectively limits toxic side effects. Despite being significantly smaller than conventional dosage forms, permeation of colloidal nanocarriers across biological membranes is negligible. Consequently, administration of these nanocarriers requires the use of a needle that may result in various complications, including life-threatening infections.

Invention:

Drs. Pauletti and Menon at the University of Cincinnati have discovered a novel technology to augment transport of pharmaceutical nanocarriers across biological membranes. This invention has the following advantages:

facilitates transcellular transport of intact, drug-loaded nanocarriers across epithelial cell barriers.
allows non-invasive, oral vaccination.
limits need for fetal injection during therapeutic intervention of the unborn child in utero.

More information is available under a confidentiality disclosure agreement.

106109 - G-Protein Coupled Receptor Kinase-5 Polymorphism

Ellen.Monson@uc.edu (Ellen Monson) — Mon, 18 May 2009 00:00:00 GMT

The present invention is directed to compositions and methods relating to a G-protein coupled receptor kinase-5 polymorphism. The methods include, for example: detecting enhanced desensitization of the beta adrenergic receptor signaling pathway in an individual, assessing partial protection against heart failure progression in an individual, and assessing an individual's response to beta-blocker therapy. The compositions include polynucleotides or fragments thereof of a nucleotide sequence encoding for a G-protein receptor kinase-5 molecule with a thymine at amino acid position 122 and oligonucleotide primers that hybridize thereto.

109036 - Methods for the Prevention of Mastitis and the Improvement of Milk Production Efficiency

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 15 May 2009 00:00:00 GMT

Bovine mastitis, a term that refers to the inflammation of the udder as a result of bacterial infection, is a problem of special concern for the dairy industry. Mastitis infections result not only in reduced milk yields but also in altered milk quality and composition. The costs related to reduced milk yields are estimated to be $102 per cow per year. Adding to these costs are the costs of discarded milk ( $24/cow/yr), the costs of premature culling and replacement of the animal ($33/cow/yr), and the costs related to treatment ($13/cow/yr) and management of the disease. It is estimated that mastitis costs the U.S. industry a total of $1.7 -2 billion per year, a figure which translates to 11% of total annual milk production. One estimate suggests that controlling mastitis to reduce its incidence to 3% of the herd can increase net income by $57 per cow per year.

The incidence of new mastitic infections is highest during the early dry period in the lactation cycle; and can be decreased by rapidly shutting down milk production during these drying-off/involution periods. Dr. Horseman and colleagues at the University of Cincinnati have discovered methods (different from those in #109004) to rapidly abrogate the production of milk during this dry-off period.

Advantages:

the approach is a preventive measure rather than treatment and management after the onset of disease
there is a potential for associated cost savings and increase in net income
reduction of mastitis in the herd results in a consequent improvement in overall milk production

For related technologies, please see 109004 and 101033. A patent for 101033 has been issued.

Current Concepts in Bovine Mastitis, 4th ed. National Mastitis Council.

108023 - Method of Preconditioning Mesenchymal Stem Cells for Use in the Treatment of Myocardial Infarction

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 15 May 2009 00:00:00 GMT

Ischemic heart disease is the leading cause of heart failure and death. Conventional therapeutic approaches for the treatment of myocardial infarction are limited to preventing the progression of ventricular remodeling and congestive heart failure. Recently, different approaches in cell therapies have gained enthusiasm as alternative treatments for repair of infarcted myocardium. Stem cell transplantation may represent a realistic strategy for reversing the deleterious effects of what has been considered irreversible damage to the heart.

Invention:
Investigators at the University of Cincinnati have developed a novel method for preconditioning mesenchymal stem cells (MSCs) that enhances their proliferation, migration, engraftment, differentiation into endothelial cells, and blood vessel formation.

In vivo, in a rat model of myocardial infarction, the method of preconditioning MSCs resulted in angiogenesis, reduced fibrosis and infarction size. Preconditioned MSCs also enhanced their angiomyogenic potential. Importantly, reconditioned MSCs induced cardiomyocyte cell- cycle reentry, which associated with improved ventricular remodeling and myocardial function.

In vitro, this preconditioning method led to increased cell migration and proliferation and promoted capillary tube formation. Additionally, preconditioned MSCs release some cytokine, chemokine and adhesion molecule, such as SDF-1a, FGF, VEGF cyclin D1, etc, which are extremely important for cell growth and repair of myocardial infarction.

Advantages:

Novel method and compounds to promote stem cell growth and differentiation.

Novel approach in promoting MSCs based repair of myocardial infarction.

The medium from preconditioned MSCs may be useful for stimulating cell growth or proliferation.

108017 - Personalized Medicine - A Test for Individualized Cardiovascular Disease Treatment Protocols Based on Beta-1 Adrenergic Receptor Haplotype

Ellen.Monson@uc.edu (Ellen Monson) — Fri, 15 May 2009 00:00:00 GMT

ß-adrenergic receptors (ß-AR's) a class of G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline (norepinephrine) and adrenaline (epinephrine). ß receptors have the subtypes ß1, ß2 and ß3. All three are linked to Gs proteins, which in turn are linked to adenylate cyclase. Agonist binding to these receptors therefore causes a rise in the intracellular concentration of the second messenger cAMP.

ß subtype1-adrenergic receptors (ß1-AR's) are expressed on a number of cell types, including cardiomyocytes, vascular smooth muscle, epithelium, renal juxtaglomerular, and adipocytes. These receptors are targets for agonists in the acute treatment of decompensated heart failure, while ß1-AR antagonists are utilized in the treatment of cardiovascular diseases such as chronic heart failure, ischemic heart disease, cardiac arrhythmias, and hypertension. However, the response to ß1-AR agonists or antagonists appears to be highly variable between individuals, which is not readily explained by clinical status or demographic characteristics. Furthermore, the inventor has previously shown that the expression of ß1-AR, and the responsiveness to stimulation, can differ substantially between healthy individuals. Such variability between individuals suggests that the receptor may be polymorphic in the population, giving rise to altered expression as well as altered physiologic or pharmacologic responsiveness.

Invention
Dr. Stephen Liggett at the University of Cincinnati has invented a method for determining whether a treatment protocol for a human patient who is suffering from heart failure, ischemic heart disease, cardiac arrhythmias, or hypertension would include the administration of a beta blocker. The method also involves identifying locations of any polymorphisms in the ß1-AR sequence from the patient's biological sample, assigning a haplotype to the ß1-AR sequence based on the locations identified, and determining whether the treatment protocol includes administration of a beta blocker to the patient based on the haplotype assigned.

The invention offers the following advantages:

the invention forms the basis of a test to determine the best treatment protocol for cardiovascular disease
treatment protocols can be potentially tailored around the patient's individual genotype. This could lead to savings in terms of both costs and time.
potentially lead to the avoidance of unnecessary side effects

093008 - Synthetic Restriction Enzymes Reagents For Rapid DNA Cleavage & Analysis

monsonek@ucmail.uc.edu (Sandip Patil) — Tue, 05 May 2009 00:00:00 GMT

We have developed a family of reagents that complex with DNA, fluoresce strongly, and rapidly cleave DNA upon irradiation with long wavelength UV light. Derivatives can be attached to DNA sequence-specific proteins, nucleotides and carbohydrates, thus having the potential for creating synthetic restriction enzymes.
The less photochemically reactive but strongly fluorescing analogs are useful in DNA sequencing and analysis work. The more photochemically reactive analogs can be used for the cleavage of DNA at specific sites as determined by the attached sequence recognition units. In addition to their use as DNA complexing and cleaving reagents, members of this versatile class should be useful as drugs for the treatment of various DNA-related diseases: e.g., in the targeting of cancers arising from the activation of oncogenes, or in the treatment of virus and retrovirus disorders such as Rous Sarcoma or AIDS. Some potential advantages of this class of molecules are:

Analogs can be prepared easily, often in only one or two steps. Many synthetic variations are possible, including chiral analogs designed to fit into the grooves of DNA. Even the chiral analogs require only about five steps - a significant improvement over existing DNA cleaving agents, which either have to be isolated from natural sources or require involved syntheses.
They bind strongly to DNA even without the attachment of water solubilizing units.
Their intense fluorescence should greatly aid in analytical work.
A few seconds of irradiation are sufficient to achieve DNA cleavage with the more photo- chemically reactive analogs.
Reaction conditions can be adjusted to achieve site-specific cleavage.
The cleavage process can also be amplified to achieve massive DNA destruction, as required for the treatment of cancer.
These compounds are not associated with heavy metals, and therefore should be less toxic than cisplatin and related anticancer drugs.

This is a research-stage project, with the potential to generate a wide range of products in a number of areas. We believe our reagents are patentable, and we are seeking a corporate partner/licensee to develop them under license from the University of Cincinnati.

109024 - A Novel Approach to Target and Control Stomach Acid

monsonek@ucmail.uc.edu (Sandip Patil) — Mon, 04 May 2009 00:00:00 GMT

Hydrogen and chloride ions are secreted in the parietal cells of the stomach and combine to form hydrochloric acid (gastric acid). While in some cases the acid can result in diseases such as peptic ulcer disease, excess acid production can result in hyperacidity and reflux disease. Peptic ulcer disease is a major cause of morbidity and can have serious complications such as bleeding and perforations. This disease is managed in most patients by the use of antisecretory therapy to inhibit the secretion of hydrochloric acid. As the acid secreted by the stomach is potentiated by histamine secreted by enterochromaffin-like cells, current antisecretory therapies suppress the production of the hydrogen ion by the blockade of the histamine-2 receptor. For example, histamine-2 receptor antagonists such as Pepcid ® and Tagment ® block the parietal cell histamine-2 receptor. Another method by which acid production is regulated is by the use of proton pump inhibitors. Proton pump inhibitors such as Prilosec® and Protonix ® irreversibly block the H+K+ ATPase which is one of the stages of H+ secretion. The third therapy available on the market for acid control is the use of antacids which directly neutralize the stomach acid.

However, many patients may suffer side-effects from these therapies, or the use of these therapies is contraindicated. Hence another target for the control of stomach acid may have breakthrough commercial potential. Furthermore, long term use of this drug may result in damage to the lining of the stomach.

Invention

Dr. Soleimani and colleagues at the University of Cincinnati have discovered a novel pathway to reduce stomach acid by targeting the chloride pathway. The newly discovered molecule, Slc26a9, is a membrane transport protein that functions as a chloride channel. The inventors knocked-out the gene encoding this protein in mice and found that the production of HCl in these mice was completely halted. Development of therapies along these lines may potentially reduce stomach acid with some of the undesirable side effects and may serve as an alternative choice for the management of disease related to the production of the stomach acid.

Advantages:

a potential alternative pathway that targets chloride production rather than the production of hydrogen ions in the regulation of stomach acid.

More information can be obtained under a confidentiality disclosure agreement.

101023 - Soluble Human Apyrase

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 24 Apr 2009 00:00:00 GMT

Blood coagulation is an essential and intricate process, which quickly leads to hemostasis (closure of an injured site with prevention of further blood loss). Undesirable blood clot formation leading to thrombosis and cardiovascular disease follows very much the same mechanism. Unfortunately, over 59 million Americans suffer from one or more forms of cardiovascular disease. In the United States, more than 2,600 Americans die each day of cardiovascular disease, making this a primary source of mortality. Although there are many factors leading to cardiovascular disease, excessive platelet activation, recruitment, and aggregation at sites of vascular injury in coronary, carotid, and peripheral arteries represents one of the major contributors to myocardial infarction and stroke. Nucleotides, such as adenosine diphosphate (ADP), are released by injured tissues and aggregating platelets and are one of the most important physiological agonists of platelet aggregation and clot formation.

A key regulator of this process is an extracellular nucleotidase (CD39 apyrase) found on the endothelial cells of the circulatory system. Well described in the cardiovasculature and nervous system, apyrases (EC 3.6.1.5) are nucleotide hydrolyzing enzymes with active sites located on the exterior of the cell surface. The endothelial cell plasma membrane apyrase CD39 (recently renamed E-NTPDase-1) has been implicated in the maintenance of normal blood fluidity through its hydrolysis of extracellular ADP. In addition, alterations in the expression levels and activity of the vascular CD39 apyrase has recently been observed after oxidative stress and endothelial cell activation, and in patients suffering from atherosclerosis. Apyrases are thus proposed to be critical for termination of purinergic receptor-mediated responses, including those of platelet activation and aggregation.

Interestingly, the saliva of blood-feeding (hematophagous) arthropods also contains potent soluble extracellular apyrases, designed to counteract a host’s normal blood-clotting mechanisms. Secreted by the arthropod into the host’s wound during blood-feeding, these soluble apyrases hydrolyze extracellular ADP into AMP, and thus inhibit hemostasis. In fact, research has shown that the saliva of most blood-feeding organisms such as fleas, ticks, biting midges, sand flies, and mosquitoes, contain large amounts of soluble apyrase. One of these recently cloned salivary apyrases from the bed bug Cimex lectularius appears to have related homologs in human, mouse, and several other invertebrates. The fact that a secreted apyrase from a blood-feeding insect has a counterpart in humans and other animals is of interest. The discovery of a soluble human apyrase distinctly different from the endothelial cell membrane E-NTPDase-1 apyrase may have very important implications in cardiovascular nucleotide signaling. This enzyme may represent a novel regulator of hemostasis in humans and may represent a fruitful area of research into clinically relevant areas of platelet aggregation.

107014 - Novel Wound Healing Device

Ellen.Monson@uc.edu (Ellen Monson) — Mon, 13 Apr 2009 00:00:00 GMT

A fistula is an abnormal connection or passageway between organs or vessels that normally do not connect. The Enterocutaneous (EC) fistula arises between the intestine and the skin surface and occurs most often as a complication after bowel surgery. Stool or other enteric substances pass through the fistula and pool up in a wound bed (such as may be present following surgery), thereby preventing wound healing. Such fistulas may also develop in the setting of malnutrition, cancer, and inflammatory disease. Closure of such fistulas requires intensive in-patient wound management and can take up to several months.
Physicians at the University of Cincinnati developed a novel wound separator coupled to an ostomy appliancethat physically separates the fistula from the wound bed, such that any stool, or other enteric substances, that pass through the fistula are prevented from communicating with the wound bed. As a result, healing is promoted because enteric substances are diverted from the wound bed, reducing the breakdown of soft tissue, skin, etc., and lowering the incidence of infection. The wound separator was utilized on several patients as part of a patient care customization plan. While no data was collected as part of a research study, the opinion of the treating physicians was that the device dramatically reduced healing time and no adverse effects were noted.
Advantages: Faster wound healing, decreased hospitalization times, adaptable for use with commonly used wound healing devices.

085018 - Item Number 62 - Aqueous Calcium/Phosphate For Nutritional Solutions

pinskig@uc.edu (Geoffrey Pinski) — Sat, 11 Apr 2009 00:00:00 GMT

The human diet requires sources of both calcium and phosphate ions, particularly for proper bone development. It would be desirable to have a means of providing high concentrations of both ions together in liquid form. However, these nutrients generally must be obtained from separate sources, as they are not compatible in an aqueous environment. (When water solutions containing appreciable concentrations of these ions are mixed together, the ions combine chemically to form an insoluble precipitate of calcium phosphate.)
We have now developed biologically compatible chelating ligands which will prevent calcium from precipitating in the presence of phosphate ions, but after ingestion or injection will allow the calcium to be available for biological processes. The ligands themselves are metabolizable and can serve as an added source of phosphate.
The ligands are suitable for use in nutritional beverages and other dietary supplements. They also are compatible with other components of total parenteral nutrition (TPN) solutions, useful for treating burn patients, low birth weight infants, or other patients who have difficulty ingesting food.
We are seeking a company to work with us in developing and commercializing this technology.

098015 - Item Number 262 - Block Co-Polymer Surfactant Films Which Resist Fouling

monsonek@ucmail.uc.edu (Sandip Patil) — Mon, 09 Mar 2009 00:00:00 GMT

We have discovered means by which to modify Pluronic polyols so as to render films of those surfactants totally resistant to the adsorption of proteins. The resulting surfactants should facilitate all manner of processes in which fouling due to protein build-up on a surface operating in an aqueous environment is process-limiting. Products that might benefit from this technology include hair care materials, toothpastes, household and industrial cleaning solutions, floor waxes, contact lens solutions, paints, drug-delivery media, vaccines, etc. In vivo and ex vivo blood-contacting circuitry, e.g., dialysis circuitry, heart lung bypass circuitry, circulatory prosthetics, stents, catheters, etc., should also benefit from this technology. Another potential application of these surfactants -unrelated to their ability to prevent the adsorption of proteins - is use in the formulation of the nanocircuitry of computer microchips.

109004 - Methods to increase in Milk Yield in Declining Phase and Prevention of Mastitis

monsonek@ucmail.uc.edu (Sandip Patil) — Tue, 20 Jan 2009 00:00:00 GMT

Problems of particular concern facing the dairy industry include a decline in milk production and the inflammation of the bovine udder (also known as mastitis). Both these problems can be costly for the dairy industry:

A prolonged declining phase in milk production generally follows a period of peak yield in the lactation cycle. The declining phase may typically last for most of the year (about 40 weeks). At the end of this phase, milk yield is reduced by more than 50% of peak yield.

Mastitis costs the U.S. dairy industry about $1.7 - 2 billion annually, a figure which is 11% of total annual milk production.

Dr. Horseman and colleagues at the University of Cincinnati have discovered novel methods to address both these problems. The invention consists of (1) a method of increasing milk yield during the declining phase of lactation to enhance lactation persistency and (2) a method of accelerating dry-off/involution of the mammary gland with the goal of preventing mastitic infections common during the dry-off/involution period.

Advantages:

increased milk production
reduction in the incidence of mastitis in the herd
potential reduction in time and costs related to treatment of mastitis

More information regarding this technology is available under a confidentiality disclosure agreement. Please see below for contact information.

For related technologies please see 101033 and 109036. A patent for 101033 has been issued.

106042 - Methods for Diagnosing and Treating Cancers via manipulations of a non-degradative pVHL-Rpb1 ubiquitylation pathway

Ellen.Monson@uc.edu (Ellen Monson) — Fri, 09 Jan 2009 00:00:00 GMT

The novel pathway controlling RCCC tumorogenesis involves pVHL-dependent modulation of the large subunit of RNA Polymerase II, Rpb1. Low grade oxidative stress, a common pathophysiological factor in cancer, induces multiple pVHL-dependent Rpb1 modifications including P1465 hydroxylation, phosphorylation of Serine 5 within the C-terminal domain (CTD), and polyubiquitylation which does not lead to protein degradation.
RCCC cells carrying a non-hydroxylatable Rpb1 mutant (P1465) showed significantly enhanced proliferation in culture and enhanced tumoroginesis when injected into nude mice. Human RCCC tumors show alterations in Rpb1 P1465 hydroxylation, serine 5 phosphorylation and ubiquitylation. Thus, these modifications may be very useful biomarkers for detecting cancer and assessing tumor grade. In addition, the specific hydroxylases and kinases that modify Rpb1 may be effective targets for therapeutic intervention. Work is underway to identify the Rpb1 specific modulators.

106099 - An antiandrogenic compound

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 02 Jan 2009 00:00:00 GMT

Prostate cancer is the most common cancer and the second most common form of cancer death among men in the US. Improvements in detection have led to an increasing population of patients with localized disease, but in many cases metastatic disease is present prior to diagnosis, limiting the effectiveness of surgery and radiation as treatments. There remains a significant need for additional therapeutic approaches to treatment of prostate cancer.
Advantages The compound under investigation has a chemical structure unlike any anti-androgenic therapeutics currently in clinical use. In vitro studies have demonstrated inhibition of dihydrotestosterone (DHT)-induced expression of prostate-specific antigen (PSA) in an androgen-dependent LNCaP human prostate cancer cell line. PSA expression in androgen-independent LNCaP-AI cells was also attenuated by the compound in a dose-dependent fashion. The inhibitory effects of the compound were much more potent than those of flutamide and milutamide. The compound also blocked the stimulatory effects of milutamide on PSA expression in LNCaP cells, but does not appear to have intrinsic androgen receptor (AR) agonist activity. Nuclear run-on and PSA promoter-driver luciferase assays revealed that the compound blocked DHT-induced PSA gene transcription. Consistent with these effects, the compound significantly inhibited DHT-stimulated growth of LNCaP cells. Furthermore, LNCaP cells resistant to flutamide or milutamide were as susceptible as their parental cells to the inhibitory effects of the compound on cell growth. Collectively, these data suggest that the compound is a potent inhibitor of the AR signaling axis and that potential exists for the compound as a therapy for advanced prostate cancer.

105008 - Method of Killing Cancer Cells by Neurotransmitter Inhibition

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 02 Jan 2009 00:00:00 GMT

Breast cancer is a major contributor to cancer-related mortality. Standard of Care treatments for breast cancer are fraught with inadequacies related to chemotoxicity and many patients are left with few treatment options beyond radical tissue resection and traditional or experimental therapies.
Researchers at the University of Cincinnati have discovered a novel mechanism of triggering cell death in several human breast cancer cell lines. An apoptotic mechanism has been identified for one particular line, and additional experimental avenues are being pursued to further characterize the mechanisms involved in producing cytotoxicity.

104079 - Endovascular Aneurysm Neck Closure Device

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 02 Jan 2009 00:00:00 GMT

Endovascular therapy of cerebral aneurysms by coil embolization is well accepted by the surgical community as a safe and efficiacious alternative to open surgical repair of aneurysms by traditional clip ligation methods. Coil embolization benefits the patient with reduced mortality and better short term morbidity in instances of vascular rupture and shorter hospital stays and recovery times for instances of unruptured aneurysms. Standard of Care methods involve occlusion of the anyeurysmal lumen with platinum microcoil devices. New liquid embolics are also being developed by researchers, but both suffer from high aneurysm recurrence rates due to compaction and recanalization of the defect. Open surgical repair has a much lower frequency of failure, but carries the burden of tradition surgical method risk. A new method of aneurismal occlusion that offered the durability of traditional methods, coupled with the more favorable risk profile of less invasive techniques would benefit the patient. A research physician at the University of Cincinnati has designed an intravascular device to address the need for a occlusive mechanism that achieves similar fusion and closure end points from tissue apposition and compression at the neck of the aneuryism compared with traditional open surgical approaches.

104041 - Management of the Newborn Experience

pinskig@uc.edu (Geoffrey Pinski) — Fri, 02 Jan 2009 00:00:00 GMT

The University of Cincinnati, lead by Ms. Barbara Gilman RN, MSN, Ms. Shirley J. Adams, RN, MSN, Ms. Elizabeth E. Weiner RN, PhD, and Jeffery Q. Adams, MSCE, has developed a two hour interactive comprehensive program for educating nurses about the newborn experience.

The program is divided into four different modules, with a number of different sections:

Immediate Care of the Newborn
1. APGAR
2. Check for Anomalies
General Assessment: Appearance, Vital Signs & Measurements
1. Determine Heart Rate
2. Cord Care
Complete Assessment: Skin, Head, Chest & Abdomen
1. Identification of Fontanels
2. Abdominal Palpation
Complete Assessment: Genitalia, Extemities, Reflexes and Gestational Age
1. A circumcision
2. Ballard chart

103036 - Novel Drug Candidates

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 02 Jan 2009 00:00:00 GMT

Pneumonia caused by Pneumocystis carinii (PcP) remains a major opportunistic infection associated with AIDS patients, even in the era of Highly Active Anti-Retroviral Therapy (HAART). In the previous 2 decades, patients with AIDS have been a primary target of PcP, the population in which it remains a leading opportunistic infection. Limited therapeutic choices and adverse reactions to the two standard treatments, trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine (Mei, Gurunathan et al., 1998), cause the clinical management of this infection to remain problematic. Moreover, side effects in almost half of AIDs patients required switching to a less effective therapy.
Despite the efforts of several in vitro and in vivo screening projects, no better treatment than TMP-SMX for PcP has been identified. Strategies to exploit the effective combination of dihydrofolate reductase inhibitor and DHPS inhibitor of the TMP-SMX combination, by substitution of each component (e.g. TMP-dapsone) have not resulted in any therapies with increased efficacy. More recently, mutations in Pneumocystis genes which are the targets of TMP-SMX, atovaquone and dapsone were similar to those conferring resistance in other organisms such as Plasmodium falciparum. Previous therapy with these agents had a strong correlation to presence of the mutation, suggesting a selective mechanism was operational. Moreover, a Pc genotype with double mutations in the DHPS gene replaced the wild type genotype (no mutations) as the predominant type in certain regions of the country (e.g. San Francisco) implying that again, a dominant selection was occurring and these organisms were being transmitted throughout the human population in these regions.
The limited repertoire, problems in tolerance, and potential emerging resistance make it necessary to identify new efficacious treatments for PcP. Drug screening and development for anti-PcP agents has taken advantage of available rodent models of PcP and short term in vitro systems. Recombinant proteins have been used in some biochemical assays when the Pc gene was cloned as in the case of dihydrofolate reductase, but this application has been rarely used due to the paucity of Pc gene sequences previously available. Researchers at UC and Xavier University of Louisiana have developed a series of novel compounds which may be useful for the treatment of viral infections, such as pneumonia and for instance, pneumonia caused by Pneumocystis carinii. In vitro evaluation of these compounds using a P. carinii ATP detection assay indicated that the bisbenzamidines of the present invention functioned as anti-P. carinii agents.

102051 - Receptor Antagonists for Affective Disorders and Addiction

Ellen.Monson@uc.edu (Ellen Monson) — Fri, 02 Jan 2009 00:00:00 GMT

1. Stress is necessary for animals including humans to adapt their behaviors and physiology to changes in both the internal and external environment. However, such stress responses that are adaptive in the short-term often come at the price of long-term mental and physical health in the form of affective disorders such as depression and post-traumatic stress disorder, systemic diseases such as colitis, hypertension, and asthma as well as neurodegenerative disease such as Alzheimer?s disease. Thus, controlling stress and the responses that it produces could be effective primary therapies for anxiety and affective disorders and adjunctive therapies for a number of other serious disorders.
2. Two important aspects of the stress response are increased activity of the hypothalamic-pituitary-adrenal axis (HPA) resulting in increased levels of circulating glucocorticoids and a variety of anxiety-related behaviors. Considerable research effort has been expended to understand the neural circuits that mediate both activation of the HPA axis and anxiety-related behaviors in the hopes of finding ways to reduce inappropriate stress that contributes to disease.
3. Using a rodent model, we have found a novel role for an identified neurochemical system and its receptor to control both ACTH and corticosterone secretion and to modulate levels of anxiety in response to diverse stressful stimuli. These results provide a viable drug target with identified chemistry for the manipulation of both levels of glucocorticoids and anxiety.

Advantages:
1. The discovery of this mechanism may lead to a more appropriate therapeutic approach for stress modulation than current treatment methods. Additionally, current treatments could be used in conjunction with this technology for a more effective remedy.
2. In addition to alleviating general anxiety, utilization of this method can effectively prevent affective disorders derived from sustained exposure to high levels of stress.

102042 - Potential Tumor Suppressor Gene

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 02 Jan 2009 00:00:00 GMT

Lung cancer is the most common cause of cancer-related deaths in the United States, and in spite of the progress that has been made in understanding the molecular biology of the disease mortality rates have not decreased significantly. To a large extent this is due to the fact that lung tumors form metastases early when the primary tumor is small and less likely to be detected. What is needed are effective systemic therapies, and diagnostic tools to detect tumors at early, pre-metastatic stages. Chromosomal deletions in tumors are usually taken to indicate the location of one or several tumor suppressor genes in the same region. We have identified a gene with several splice variants close to a chromosomal region that has been shown to be homozygously deleted in lung tumors. The first exon of the gene contains an evolutionary conserved predicted phosphorylation site for PKB/Akt, a key mediator of signal transduction processes involved in cell proliferation and survival. Using a synthetic 13-aa peptide as a substrate for recombinant PKB/Akt we have confirmed that the predicted threonine is a putative phosphorylation site for PKB/Akt. PKB/Akt can both promote proliferation and inhibit apoptosis through phosphorylation of key proteins like p21, the forkhead transcription factor, BAD, and others. Often this leads to inhibition or sequestration of the phosphorylated protein. Several other proteins known to be involved in proliferation or apoptosis, such as DAP kinase, Huntington protein, and several caspases, although not yet shown to be PKB substrates contain putative PKB phosphorylation sites. The first six exons of the gene are ubiquitously expressed in all tissues and cell lines that we have screened. Alternative splicing of the first exon creates a transcript with shorter reading frame and a different protein product. In many cell lines and tissues the last internal exon is alternatively spliced onto exons downstream of the sixth exon to generate low expression levels of numerous alternative transcripts of which many are very long and some span the minimal region of homozygous deletion mentioned above. Preliminary results indicate that these variants are differentially expressed in tumors versus normal tissue.

The significance of the various splice variants of this gene is not clear yet, but preliminary experiments indicate that they are differentially expressed in normal tissue versus tumors. If changes in expression occur early in cancer development, this could facilitate early detection of cancer, and a diagnostic procedure or kit could be developed. The fact that there is a putative PKB/Akt phosphorylation site in the first exon of our gene raises the possibility that its various splice variants function in the PKB/Akt cell survival pathway, which is up-regulated in many types of cancer. It appears to be the major pathway for survival of cancer cells. Thus our gene could become targets for new therapeutic strategies for chemotherapy and chemoprevention. We have unpublished data showing that the PKB/Akt pathway is activated in many early lesions (hyperplasia and dysplasia).

102037 - Method for Determining Dietary Fat Absorption

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 02 Jan 2009 00:00:00 GMT

The current invention is a composition used as a test meal comprising a predetermined amount of dietary fat and a predetermined amount of a non-absorbable fat marker, such as a sucrose polyester in the form of sucrose behenate. The method for measuring total dietary fat absorption by the digestive tract of a subject comprises the steps of administering ingestion of the test meal by the subject, collecting a sample of fecal matter at an interval following ingestion of the test meal, measuring the amount of the of non-absorbable fat marker recovered in the fecal sample and calculating the amount of dietary fat recovered from the test meal to determine the amount of dietary fat that was absorbed by the digestive tract of the subject. The methods of the invention can be used to diagnose malabsorption of dietary fat by the digestive tract of a subject or impairment of dietary fat digestion. The advantage of this current invention over existing tests is that patients may take only one test and only a single “marked” stool sample is required for analysis to determine the ratio of fat to marker in the stool and by comparison to the same ratio in the test meal, calculate the fraction of fat absorbed from the test meal. Sucrose behenate is an excellent marker for this purpose because it is currently consumed in food, is completely excreted, is handled by the G.I. tract as are normal dietary fats and is readily measurable by gas chromatography. Thus, this method provides a rapid and easy assessment of dietary fat absorption and avoids the cumbersome and laborious process currently in use. Investigators are currently nearing the completion of a study to compare the method with the quantitative fecal fat measurement in cystic fibrosis and have completed studies evaluating the sucrose behenate method against the quantitative fecal fat method in overweight adults taking Orlistat.

101033 - Method to Increase Milk Production

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 02 Jan 2009 00:00:00 GMT

Mammalian milk production is regulated by a feedback system in the mammary glands that results in reduced lactation when the frequency of milking is reduced. The baseline level of bovine milk production can be increased with a more frequent milking regimen, or with the administration of rBST (a recombinant bovine growth hormone) that counteracts this feedback response resulting in a boost in milk production by approximately 10 percent.

Dr. Nelson Horseman and colleagues have discovered a new method of regulating milk production exploiting a different mechanism which does not involve the use of hormones. The researchers have identified a key component of the feedback loop that regulates milk production in the mammary gland. They have found that this intrinsic feedback mechanism can be manipulated by the use of well-characterized pharmaceuticals either alone or in combination with certain biologically active substances.

Specifically, the researchers have found that the administration of various serotonin antagonists is effective in increasing milk production. This offers several advantages such as those listed below.

Advantages:

Potential lower manufacturing costs

Absence of any compounds in milk

Reduced consumer resistance due to lack of use of hormones

Can be developed for oral administration, suggesting ease of use

Compounds by themselves have very safe and well understood pharmacological profiles

100037 - Enhanced tPA Activity and Therapy

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 02 Jan 2009 00:00:00 GMT

Researchers at UC have developed methods for inhibiting lysis of coagulated blood and reducing risk of excessive lysis comprising administration of lysis-inhibiting amounts of apolipoprotein E4, and methods for inhibiting lysis of coagulated blood and reducing risk of excessive lysis comprising administration of a specific level of a lysis-inhibiting agent wherein the specific level is based on the apolipoprotein phenotype of an individual, are provided. Methods for enhancing lysis of coagulated blood by administration of an Apo E peptide fragment to blood containing a clot lysis agent are also provided.

100021 - Peptides with Antioxidant and Antimocrobial Properties

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 02 Jan 2009 00:00:00 GMT

Research at UC has led to the development of methods of treating conditions associated with lipid oxidation or microbial proliferation which include the step of administering a composition comprising a pharmacologically effective amount of an antioxidant or antimicrobial lung surfactant protein compound. These peptides derived from lung surfactant protein compounds possess lipid oxidation inhibiting and/or antimicrobial properties.

099002 - Tramadol for Treatment Refractory Obsessive Compulsive Disorder

monsonek@ucmail.uc.edu (Sandip Patil) — Fri, 02 Jan 2009 00:00:00 GMT

Researchers at UC have found that tramadol, which is primarily used as an analgesic, provides therapeutic benefits for individuals with obsessive-compulsive (OC) spectrum disorders, including obsessive-compulsive disorder. Tramadol has been found to be particularly useful in treating individuals which are refractory to serotonin reuptake inhibitors (SRIs). Applicants have also found a surprisingly rapid onset of response in tramadol-treated individuals as compared to SRI-treated individuals, and have also found that it is possible to treat OC spectrum disorder symptoms on an as-needed basis with tramadol.

108104 - Drug/Food Self-Administration v.2.23

pinskig@uc.edu (Geoffrey Pinski) — Tue, 23 Dec 2008 00:00:00 GMT

This software and accompanying bioassay measure the pharmacodynamic (“PD”) and pharmacokinetics (“PK”) properties of a psychotropic compounds. Three properties of the compound can be measured: bioavailability, potency, and half-life. The compound’s potential for abuse/addiction can also be quantified.

Conventional analytical methods for measuring PD and PK properties are time-consuming and cumbersome. In order to measure these properties by conventional means, blood must be sampled numerous times and then later analyzed by chemists using expensive machines and complex techniques. Using conventional methods screening large numbers of compounds is expensive—approximately $100k-$500k per compound.

Conversely the bioassay and accompanying software drug compounds can be quickly, more precisely and cost-effectively analyzed. Using this system, researchers can identify compounds with the longest half-life, the greatest bioavailabilty, those that cross the blood-brain barrier, and those that are the least likely to be habit-forming. The cost of testing a single compound using this bioassay is estimated at $10k-$50k per compound.

This system relies on the pharmacological theory that competitive antagonists increase the concentration of agonist required to produce a response. The response used in this method is the satiety threshold. Increases in the satiety threshold reflect the PD potency of the antagonist in vivo. The time course of the effect reflects the antagonist PK. And the area under the time-concentration curve (AUC) following different routes of administration (e.g., i.v., subcutaneous, or intraperitoneal) measures the bioavailability of antagonists.

For the bioassay, rats are trained to self-administer indirect or direct agonists such as cocaine apomorphine. Once a baseline satiety threshold is established the rats are given doses of the compound to be evaluated. Changes in the frequency of the rats’ self-administration and satiety threshold are measured and from the changes the PK and PD of the compound are be calculated.

The sensitivity of this system is approximately 50-100 fold greater than conventional methods. Conventional methods have a typical limit of detection (LOD) of GC/MS is 1,540 nmol/kg i.v. dose, assuming a volume of distribution of 10 L/kg. This system works optimally at 20 nmol/kg i.v. dose.

Software Requirements:
MS Windows XP
MS Access
MED-PC (Software for testing and collecting data from medical devices)
MPC2XL (For transferring the contents of MED-PC® data files to Excel spreadsheets, Access databases, etc.
Sigma plot (Graphing software)

098030 - Preparative Chiral Separations

pinskig@uc.edu (Geoffrey Pinski) — Mon, 17 Nov 2008 00:00:00 GMT

Separation of enantiomers is an important topic to the pharmaceutical industry. Many of the drugs and pharmaceuticals marketed in the US and overseas have at least one chiral center (e.g. ibuprofen and propanolol). In many cases, one enantiomer has the desired pharmacological activity whereas the other enantiomer may be responsible for unwanted side effects. Thus, the development of economical methods for preparative and semi-preparative scale chiral separation is highly desirable, particularly for an R&D setting, where only small amounts of material may be required to initiate screening prior to development of a potentially more costly, less efficient stereospecific synthetic strategy.
Chiral separations are commonly performed using chiral stationary phases by liquid chromatography ("HPLC"). However, there are several disadvantages to these techniques. A large number of chiral compounds are not resolvable using any of the existing chiral stationary phases. Chiral HPLC columns are more expensive and require more careful handling than conventional columns. Column deterioration is often observed, and lot-to-lot variability in HPLC media further hampers methods development.
We have developed preparative chiral separation methods based on continuous electrophoresis using a chiral additive in the buffer.
Advantages

The method is particularly useful for water-soluble (or organic-insoluble) species, which are particularly difficult to separate by traditional methods of chiral preparative chromatography.
The application of continuous free flow electrophoresis to bulk scale chiral separations is novel and has the potential for obtaining milligram- to gram-per-hour quantities of both pure enantiomers of chiral drugs in aqueous solutions, with wide applicability for a broad range of chiral drugs from many different categories, as well as chiral intermediaries or metabolites.
The method allows for the potential recovery and re-use of the chiral selector (typically expensive and/or rare).

107055 - RB Functional Status as a Determinant for Breast Cancer Therapy

Ellen.Monson@uc.edu (Ellen Monson) — Mon, 10 Nov 2008 00:00:00 GMT

Breast cancer is the second leading cause of cancer death in US women, after lung cancer. It is estimated that about 200,000 women in the United States will be diagnosed with invasive breast cancer in 2006 and that about 40,000 women will die from the disease.
In a recently published article in the Journal of Clinical Investigation, Dr. Erik Knudsen and colleagues at the University of Cincinnati discovered a link between inactivation of the retinoblastoma (RB) tumor suppressor and the response of cancer cells to anti-tumor therapies, including anti-estrogens and DNA damaging agents.
A gene expression signature of 59 genes that are deregulated with RB loss and repressed upon RB activation was used to group breast cancer patients. Patients showing high expression of RB regulated genes, indicating loss of RB function, had increased incidence of cancer recurrence relative to patients in the medium or low level expression groups. Thus, the loss of RB function in breast cancer tumors, as assessed by the expression of 59 signature genes, correlated with decreased effectiveness of tamoxifen monotherapy.

102024 - Stress Protectors for Selenium Enriched Yeast

geoffrey.pinski@uc.edu (Dan O’Neill) — Thu, 16 Oct 2008 00:00:00 GMT

In 1996, Clark and co-workers[1] made a statistically representative study of the relationship between selenium supplementation and cancer incidence. Supplementation to the individuals was accomplished with the ingestion of selenium enriched yeast, showing a direct correlation between selenium supplementation and incidence of tumorogenic type cancers, especially prostate, colon and lung cancer. A second, narrower study[2] proved the benefits of supplementation with selenium enriched yeast for the reduction of the incidence of prostate cancer.
The selenium enriched yeast has been commercialized into tablets that can be bought in health food stores, drug stores, discount stores and supermarkets. A study by Sutton and co-workers[3] showed that the commercial selenium supplements varied in selenium species composition. Our group experimented in the preparation of selenium enriched yeast[4]. We could see in these experiments that while enriching the yeast, the selenium is toxic to the yeast resulting in a decreased yield of yeast cells. This was also found by Suhajda and co-workers[5].
The subject matter of the technology is the preparation of selenium enriched yeast with calcium or magnesium that increases the yield of the yeast up to 11% while also increasing the selenium incorporation by up to 36%.
The key benefit of the discovery is that better yields of selenium enriched yeast with a higher selenium content would be obtained with minimal investment to the current selenium enriched yeast producers.

Advantages
1. This methodology has the double advantage of increasing the yield of selenium enriched yeast and at the same time more selenium is incorporated to the yeast. This translates, at industrial level, to more product for the same amount of starting materials.
2. The protecting agents are inexpensive materials (therefore not contributing significantly to the cost of the yeast) and since these are also of nutritional importance too, they add another health attribute to the yeast.

104070 - Miniature Multisensor Catheter

pinskig@uc.edu (Geoffrey Pinski) — Wed, 15 Oct 2008 00:00:00 GMT

The novel design and miniature size of the catheter provide an adaptable platform that allows

the inclusion of other biosensors in the array, such as pH, osmolarity and temperature sensors,
use in adults and neonatal and pediatric patients,
monitoring of various regions of the body
use of a double lumen system that allows for using one catheter for sensing a physiologic parameter and the other for sampling fluids or delivering locally active drugs.

099033 - Transcranial Ultrasound Thrombolysis System and Methods of Treating Stroke

monsonek@ucmail.uc.edu (Sandip Patil) — Tue, 07 Oct 2008 00:00:00 GMT

Background

Approximately 700, 000 cases of stroke occur every year in the US, many of which result in death. Successful treatment of ischemic stroke, which accounts for 83% of all cases, depends on early recognition as well as treatment of the stroke within 2-4 hours of its onset. The primary approved method of treating ischemic strokes involves the use of a specific thrombolytic agent known as recombinant tissue plasminogen activator (r-tPA) by intravascular injection. However, this treatment is not commonly administered due to various factors such as delays in the recognition and diagnosis of stroke symptoms, delays in the transportation of patients to the appropriate medical facility, and the lack of availability of a specialized stroke neurologist on site. Furthermore, r-tPA administration is restricted to patients who do not have certain risk factors for bleeding. Moreover, physicians are reluctant to administer this drug due to an increased risk of an intracerebral hemorrhage.

Invention

Faculty at the University of Cincinnati have invented a system and method of treatment of ischemic stroke that overcomes the shortfalls of current treatment protocols for stroke. This consists of the use of a predetermined level of ultrasonic energy throughout the primary treatment zone covering most of the M1 and M2 branches of the middle cerebral artery in one hemisphere of the brain. A transducer is used to provide the ultrasonic energy. This system may be used in conjunction with the administration of r-tPA, which may or may not be encapsulated in microbubbles. This invention offers several advantages.

Advantages

Provides a quicker treatment of stroke as compared to current protocols

Does not require radiologic or imaging data to determine the specific location of the clot prior to treatment

Can be administered by front-line medical personnel without the presence of a specialized stroke neurologist

107054 - Novel End-Point Assay for Autophagy

Ellen.Monson@uc.edu (Ellen Monson) — Fri, 29 Aug 2008 00:00:00 GMT

Dr. Patrick Dennis at the University of Cincinnati developed a novel end-point assay for autophagy based on the observation that the BHMT (betaine homocysteine methyl transferase) enzyme is degraded via autophagy with the generation of a discrete proteolytic fragment in the lysosomal compartment (1). Dr. Dennis engineered a novel Glutathione-S-Transferase (GST)-BHMT reporter with targeted mutations that result in degradation of the fusion protein via the autophagocytic pathway. Autophagocytic degradation of the reporter leads to the generation of discrete proteolytic fragments in the lysosomal compartment, similar to native BHMT. The advantages of this autophagy assay over existing assays are 1) end-point assay rather than mid-point assay, 2) increased sensitivity and 3) less subjective and more quantifiable.

107004 - Novel Estrogen Receptor Beta (ER-ß) Isoforms as Targets for Cancer Therapeutics and other ER-ß related diseases.

Ellen.Monson@uc.edu (Ellen Monson) — Fri, 29 Aug 2008 00:00:00 GMT

Most published data on human ER-ß function/signaling have been derived from studies on ER-ß1, the originally cloned sequence. However, there are five splice-variants of ER-ß that have until recently been poorly characterized. Dr. Shuk-Mei Ho and colleagues at the University of Cincinnati isolated and expressed the full length cDNA’s for ER-ß2, ER-ß4 and ER-ß5 and examined ligand binding, dimerization, transactivation and coactivator binding. In addition, in silico modeling was performed to examine structural characteristics.
Dr. Ho’s work demonstrated that ER-ß1 is the only fully functional isoform and that ER-ß2, ER-ß4 and ER-ß5 do not have innate activities in their homodimeric forms. However, ER-ß2, ER-ß4 and ER-ß5 can heterodimerize with ER-ß1 and enhance ER-ß1- induced transactivation in a ligand dependent manner.Dr. Ho’s work provides the first evidence that ER-ß1 prefers to form heterodimers with its isoforms and the process is likely dependent on ligand type. Her work also revealed pronounced differences in expression of ER-ß isoforms in normal human cell lines/tissues and that prostate, ovarian and breast cancer cell lines have distinct expression profiles relative to the corresponding normal cell lines/tissues. This data suggests that tissue responsiveness is determined by isoform expression and that ER-ß heterodimers may provide specific, and as yet, unexplored, targets for therapeutic intervention in a variety of ER-ß related diseases.The University of Cincinnati is seeking industry partners for the development therapeutics/diagnostics related to ER-ß isoforms. A patent application has been filed.

106078 - Polo-like kinase 3 (Plk3) as a Rational Target for Anti-Cancer Therapy

Ellen.Monson@uc.edu (Ellen Monson) — Fri, 29 Aug 2008 00:00:00 GMT

A strategy for developing anti-cancer therapies is to inactivate proteins that are required for the integrity of DNA repair signaling pathways. Inactivation of such proteins may lead to greater therapeutic effectiveness of the many current cancer treatments that act by causing DNA damage, such as radiation therapy and many chemotherapeutic agents. When cells incur damage in the form of DNA double strand breaks, normal cells will arrest at various checkpoints throughout the cycle to allow for DNA repair. Several pathways are involved in a DNA damage checkpoint at the G1/S phase cell cycle boundary. One pathway is mediated by the p53 tumor suppressor. P53 induces the kinase inhibitor p21, resulting in the arrest of cells at G1/S. This pathway is compromised due to mutation or loss of p53 in about 80% of human tumors.
The regulation of a second pathway has recently been discovered in the laboratory of Dr. Peter Stambrook at the University of Cincinnati. For cells to activate the G1/S checkpoint, CDC25A phosphatase must be degraded. Using cultured mammalian cells and mouse knockout models, Dr. Stambrook’s work has demonstrated that Polo-like kinase 3 (Plk3), a member of a conserved family of serine/threonine protein kinases, is likely the principle kinase required to facilitate the degradation of CDC25A at the G1/S checkpoint.
Therefore, Plk3 is proposed as a novel target for the discovery of inhibitory molecules that would be useful as cancer therapeutics. The rationale is that most human tumors are p53 deficient and therefore one of the pathways leading to G1 checkpoint arrest is compromised. If the alternate pathway is also compromised by inhibition of Plk3 by a small molecule inhibitor, the tumors would be selectively killed or sensitized to low levels of standard chemotherapies.

104062 - Glucocorticoid Induced Receptor: A novel Neuropeptide Y “Y2-like” GPCR as a target for obesity

Ellen.Monson@uc.edu (Ellen Monson) — Fri, 29 Aug 2008 00:00:00 GMT

The glucocorticoid-induced receptor (GIR) is an orphan G protein-coupled receptor. GIR was originally identified as a stress-responsive element from the murine T-cell line WEHI-7TG and normal thymocytes treated with glucocorticoids and forskolin. The mouse and rat GIR genes show high levels of expression in the brain. GIR mRNA distribution in the rat indicates a potential role of this receptor in the control of feeding and ingestive behavior, regulation of stress and emotional behavior, learning and memory. The human GIR gene (87% identical to rodent) also shows high levels of expression in the brain.
Rat GIR exhibits highest sequence similarity to the Neuropeptide Y (NPY)-Y2 receptor (38% identity). In experiments to characterize the pharmacology of rGIR, Dr. Randy Sallee and colleagues at the University of Cincinnati, showed that NPY-Y2 selective antagonists and agonists bind to and activate rGIR in a manner similar to NPY-Y2. However, the binding profiles of NPY and Y2 selective ligands to rGIR are distinct from NPY-Y2 receptor suggesting that GIR may represent a novel neuropeptide receptor that interacts with NPY analogs. Indeed, a novel amino acid peptide, the structure of which was modeled on the Neuropeptide Y (NPY) C-terminus, binds with nM affinity to the rGIR receptor but does not bind to any known NPY receptors.Administration of this novel peptide i.c.v. to rats results in feeding inhibition.
Based on a) its distribution in feeding regulatory areas in the forebrain and brain stem, b) its interaction with compounds such as PYY3-36 and other anorectic peptides that regulate feeding, and c) its regulation by leptin, it is likely that GIR represents a novel target for the identification of potential obesity therapeutics.Dr. Sallee’s group has identified small molecule antagonists and agonists of GIR that are currently being tested in animals. These molecules can serve as the basis for the further development of novel GIR antagonists as potential appetite suppressants for the treatment of obesity.

102079 - Biomarker for Chronic Pseudomonas aeruginosa Lung Infection

Ellen.Monson@uc.edu (Ellen Monson) — Fri, 29 Aug 2008 00:00:00 GMT

P. aeruginosa is a widely distributed, opportunistic pathogen that is notorious for anti-bacterial resistance and robust metabolic adaptability. It often targets immuno-compromised individuals, as well as cystic fibrosis sufferers. In CF lung disease, P. aeruginosa takes up residence in the thickened, dehydrated, hypoxic mucus that lines the airway epithelia. Chronic lung infection of CF patients by the bacteria is the primary source of morbidity associated with the disease. In the progressive stages of the infection, the local environment that P. aeruginosa inhabits is markedly hypoxic. The bacterium adapts to this oxygen and nutrient poor milieu by shifting to an anaerobic biofilm mode. Researchers at the University have explored this mode of growth, and in the process identified a highly over-expressed marker for this state. OprF is an outer membrane protein of P. aeruginosa that is reported to play a role in cell shape and is required for growth in low salt environments. Experiments on the anaerobic planktonic and biofilm growth modes in vitro identified this protein, OprF, as being significantly over-expressed in those states. Researchers also demonstrated that Class IV CF patients have serum anti-bodies to OprF. Additional data suggests that expression of OprF in vivo is consistent with the levels found in anaerobic in vitro growth.
A reliable diagnostic marker for the transition of P. aeruginosa infection from aerobic to anaerobic biofilm phase would provide a sound clinical decision tool for the use of alternative therapeutic strategies against the infection.