Several crosslinking strategies exist to generate injectable materials. However, the vast majority of materials have very rapid gelation kinetics, which do not allow for complex injection routes via catheter where the material must remain at body temperature inside the catheter for a period of time. An example of such a delivery route is cardiac catheter delivery, where the material must remain liquid in the catheter to facilitate multiple injections to the damaged region of the heart. The delivery of injectable materials into the heart has been studied to encourage endogenous cell infiltration and repair as well as for the delivery of cells or other therapeutics. These studies have, however, largely been performed in small animals since the gelation kinetics of most injectable materials prevent cardiac catheter delivery. (more...)

Endovascular stents are used for a variety of conditions involving blood vessels, most often to reinforce a weak spot in an artery called an aneurysm. Current commercially available stents are manufactured from a variety of metals and are permanently implanted in various parts of the body. As these metal implants often result in untoward long-term effects, there has been considerable interest in the development of a "temporary" stent that dissolves safely within the body. Degradable technology has not yet received FDA approval, but testing is underway for temporary stents manufactured from "soft" metals or polylactide (PLA) polymers. However, there are several limitations with the current designs, including difficulty in deployment, slow degradation, and erosion resulting in a highly acidic environment. Treating vascular disease while minimizing side effects depends on the development of safe and effective degradable stents.   (more...)

Researchers at the University of California, Irvine have developed a new hybrid tissue that is capable of self renewal. This new hybrid tissue may be used as replacement heart valve leaflets and may also be used for other tissue constructs like blood vessels. (more...)

Functional MRI (fMRI) based on blood oxygenation level dependent (BOLD) signal changes has had an enormous impact on basic neuroscience studies but has had little impact on clinical practice. The problem is that the BOLD signal is a good indicator of where neural activity has changed in response to a stimulus but it is a poor indicator of how much it has changed in an absolute sense due to the complexity of the BOLD effect. Because the BOLD response can vary across subjects even if the underlying neural activity change is identical, we cannot establish the kind of normative data that is needed for clinical applications. For this reason, the only clinical applications of fMRI are in neurosurgery planning, because the critical question in that application is: where is the activity? There is a clear potential for much broader applications of fMRI in evaluating neurodegenerative disease, but these have not yet developed because the critical question is the harder one of: how much has activity changed? Arterial spin labeling (ASL) measures cerebral blood flow (CBF), a well-defined physiological variable and in particular a quantitative variable for which normative data can be acquired as a basis for clinical applications. However, the ASL measurement tends to be significantly noisier than the BOLD measurement. For this reason, most quantitative functional imaging studies with ASL are performed using long, simple stimuli such that measurements may be taken in an “active steady-state” and repeated to improve signal to noise ratio (SNR). This limits basic studies of brain dynamics during conditions that better approximate everyday human experience where a stimulus pattern is unknown, and also limits the complexity of neuropsychological tests that could be employed in clinical applications to assess brain function. Although the sensitivity of the ASL method can be improved with background suppression to remove tissue signal, this eliminates any information present in the BOLD signal. An important advantage of acquiring both ASL and BOLD signals is that the dynamics of the cerebral metabolic rate of oxygen (CMRO2) also can be measured. The primary challenge is then: how can we best derive quantitative measurements of CBF and CMRO2 dynamics when the driving stimulus is complex or even unknown? (more...)

Most quantitative functional imaging studies of cerebral blood flow (CBF) are performed using long, simple stimuli such that measurements may be taken in an "active steady-state" and repeated to improve signal to noise ratio (SNR). It is thus highly desirable to have a technique that could permit quantitative study of cerebral metabolic and hemodynamic activity under conditions that better approximate everyday human experience where a stimulus pattern is unknown. (more...)

There is a general need to improve the efficacy of the resuscitation programs and the survival rate of patients undergoing cardiac arrest. (more...)

Hydrogen peroxide (H2O2) is a toxic byproduct of many physiologic and pathological reactions, and elevated in a variety of conditions in which free radicals have been implicated, such as inflammation, infection, cancer, diabetes, aging, and cardiovascular disease. Most conventional methods for H2O2 detection are limited to in vitro use. Being able to detect and image elevated H2O2 levels in vivo and in situ provides accurate and real time diagnosis and monitoring of many pathologies and body’s response to perturbation. (more...)

Treating blood loss with cell free oxygen carrier (artificial blood) is essential to maintain oxygen supply to the patient as well as prevent the collapse of capillaries. Effective substitution by artificial blood hinges on oxygen delivery, blood-gas and pH balance, and carbon dioxide removal. Therefore it is important to monitor the efficacy of the artificial blood or compare the efficacy of different types of them. (more...)

Cardiovascular disease is the most expensive and prevalent medical conditions in the U.S., costing $95.6 billion and 860,000 lives every year, respectively. 46% of the cardiac deaths occur outside of the hospital; this is partly due to the fact more than 90% of the strokes and 50% of the heart attacks are asymptomatic and have delay in diagnosis and treatment. Imaging procedures such as ECG are not effective in diagnosing such silent episodes. Therefore there is an unmet need for diagnosing silent heart diseases with specific biomarkers. (more...)

Hypertension affects about one in three adults in the United States. Hypertension increases risk of serious health issues, including heart attack, stroke and kidney failure. Approaches to manage hypertension may vary by individual and with differing success. Medications are available, but not all medications are suitable for all patients. Accordingly, new anti-hypertension medications may benefit patients. There are proteins known to reduce blood pressure when administered, however, some proteins are not suitable therapeutics due to short half-life in the body. Improving stability of suitable anti-hypertensive peptides may provide novel therapeutics to lower blood pressure. (more...)

Autoantibodies specific for malondialdehyde-modified LDL (MDA-LDL) represent potential biomarkers to predict cardiovascular risk. However, MDA-LDL is a high variability antigen with limited reproducibility. To identify peptide mimotopes of MDA-LDL, phage display libraries were screened and the specificity and antigenic properties of MDA mimotopes were assessed in vitro and in vivo. (more...)

This invention uses multi-functional magnetic imaging probes to image high risk atherosclerosis and nonatherosclerotic sites such as areas of cancer, infection, immunological conditions and inflammation. The invention incorporates the use of micelles containing the manganese to which are attached to oxidation specific antibodies. This multi-functional particle is injected intravenously and will enter an area of atherosclerotic plaque in the vessel wall or other site of inflammation (primary or metastatic cancer, liver disease, arthritis, Alzheimer's, macular degeneration, etc.) and the antibody will direct the micelle with the manganese to an oxidation specific epitope. Once it binds, the micelle will be taken up into a macrophage. Lysosomal enzymes in the macrophage will then cleave the manganese off the micelle which greatly enhances its relaxivity, which is a key part of the invention, that then allows the manganese to be detected by molecular bio-magnetic resonance imaging (MRI).The unique aspect of this invention is the fact that manganese is normally not easily visible by MRI when it is complexed to another carrier. However, manganese is visible to MRI when it is in a free state. Because free manganese cannot be injected for specific localization, it must be complexed to a carrier that will do two things: 1) deliver the manganese to a specific targeting area, which in this case is via the oxidation specific antibody and 2), have a mechanism by which the manganese is released to be seen with MRI techniques. This invention has these two novel aspects of using a targeting agent to deliver the manganese and through the natural pathophysiology of atherosclerosis allowing the manganese micelle to be taken out by macrophages and subsequently released in the macrophage. This results in a macrophage specific imaging. Since macrophages are associated with unstable atherosclerotic lesions and all areas of inflammation, this technique may allow a novel approach to image macrophage activity and therefore lesions that would predict higher cardiovascular risk. (more...)

Anthracyclines are the most commonly prescribed chemotherapeutic agent for their effectiveness in treating cancer.  However use of anthracyclines can have the severe, adverse effect of cardiac toxicity leading to cardiomyopathy and clinical heart failure.  Currently available medications to counteract anthracycline-induced cardiotoxicity either do so at the cost of anti-tumor activity, or there is insufficient clinical trial data to support their efficacy in preventing cardiotoxicity.  Thus widespread use of these compounds is limited.    There is a clinical need for a pharmaceutical compound that can prevent and/or treat the cardiac side effects of anthracyclines while maintaining their anti-tumor activity. (more...)

Despite recent advances in tissue engineering and regenerative medicine, ischemia related to cardiovascular disease results in the death of more than 100,000 amputations per year from peripheral artery disease (PAD) in the US alone.  Very few biomaterials have been examined and of those examined (e.g. fibrin, collagen, alginate, and Matrigel). None of these provide all the native components of the skeletal muscle extracellular matrix. Most are limited to improving growth factor and cell delivery. Currently no material meets all of the properties of an ideal scaffold, namely enhanced neovascularization to reduce the ischemic environment, better cell adhesion, survival, and maturation of endogenous or exogenously added cells. There is a need to develop improved compositions for minimally invasive tissue-engineered therapies for the treatment of critical limb ischemia. (more...)

Researchers at the University of California, Irvine have developed a novel high resolution imaging technique, referred to as Photo-Magnetic Imaging (PMI), that combines the abilities of optical and magnetic resonance (MR) imaging systems. Images are created with PMI by heating tissue with a light (e.g. laser) and measuring the resulting temperature change with MR Thermometry. This change in temperature can then be related to a tissue’s absorption, scattering, and metabolic properties. PMI addresses the limitations of current optical imaging techniques by providing a repeatable, non-contact, high resolution optical image with increased quantitative accuracy. This technique can be used for a wide-range of applications including but not limited to imaging of small animals for research purposes. This technique may also be used in imaging the tissue and organs of a patient. (more...)

Although significant efforts have been devoted to bridging the gap between synthetic nanomaterials and viable biologics, development of a bio-mimetic delivery vehicle has remained elusive. Challenges include the limited ability to reproduce a cell’s complex membrane makeup on a nanoscale substrate and the fact that most bioconjugation techniques lead to protein denaturation. Efforts to extend nanoparticle residence time in vivo have inspired a variety of strategies to bypass macrophage uptake and systemic clearance. However, none of these have been able to recapitulate what nature has already evolved as its’ own long-circulating delivery vehicles—the red blood cell (RBC). (more...)

Tachycardia is a type of abnormally fast heart beating arrhythmia-a heart rate greater than 100 beats per minute at rest, whose symptoms include palpitations, dizziness, angina, heart failure, or ultimately a heart attack. One of the commonly used non-surgical methods to treat this disease is Radiofrequency Ablation (RFA). Physicians guide a catheter with an electrode at the tip to the area of the heart muscle where there is an accessory extra pathway where heart cells give off the electrical signals that stimulate the abnormal heart rhythm. A radiofrequency energy is transmitted to the pathway and destroys carefully selected cells in a very small area. By doing so, the area stops conducting the extra impulses that cause the tachycardia. Researchers at the University of California, Irvine have developed a novel therapy modality, which combines optical coherence tomography and ultrasound with a electrophysiology catheter for real-time monitoring of the RFA treated area of the heart. The invention will provide images with high resolution and high penetration depth. (more...)

Statins are a class of small molecule drugs used for lowering blood cholesterol levels and preventing cardiovascular disease. Atorvastatin, sold by Pfizer under the trade name Lipitor, is the best-selling drug in history, with sales exceeding $11 billion in 2010. This figure is expected to drop dramatically with U.S. patent expiry and the availability of a generic version in November 2011. All statins, including atorvastatin, inhibit HMG-CoA reductase (HMGCR), an enzyme found in liver tissue that plays a key role in cholesterol production. Experimental evidence suggests that this key biochemical pathway also plays an important role in the oncogenic process, and statin administration in vivo has been shown to inhibit tumor growth. However, a number of rare but serious side effects have been attributed to statins, including muscle and liver damage. Researchers are working to identify the next generation of cholesterol-lowering small molecule drugs with greater efficacy and reduced side effects, and to understand and modulate the HMGCR pathway for cancer therapy. (more...)

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Researchers at the University of California, Irvine have developed a novel method for capturing cellular resolution images of biological tissue at depths of up to several millimeters. Conventional fluorescence detection methods utilize microscope objectives for emission light collection, a less effective approach that is only capable of imaging up to one millimeter deep.To improve upon this standard, the UC researchers minimized light losses by optimizing the system’s excitation and detection optics. (more...)

Cerebral ischemia, or damage to tissue due to reduced blood supply, can quickly lead to organ dysfunction and cell death. Cerebral ischemia can lead to stroke, which when not treated in a timely fashion, can cause permanent neurological impairments and death. Normal cerebral blood flow (CBF), when at rest and awake, is around 45 to 60 mL/100g/min. When CBF drops below 10 mL/100g/min, the threshold for energy and ion homeostasis, a cascade of metabolic events is induced, ultimately leading to cellular death. If regional CBF (rCBF) stays below this threshold for prolonged periods the brain damage can be irreversible, but if rCBF is increased before such progression to necrosis then proper brain function and structure can be restored. Therefore, this clinically relevant "therapeutic window" allows the opportunity to improve the outcome of stroke by increasing CBF. Current options for stroke treatment include maintaining cerebral perfusion pressure (CPP), augmenting blood flow, and lowering cerebral metabolic rate. These are all, however, limited by a specific clinical context and inconclusive efficacies. None directly addresses enhancement of penumbral blood flow, the blood flow in the area surrounding the damaged tissue. Additionally, none of the methods considers cerebral vascular collapse as the mechanism for restricted arterial blood flow to the brain nor do they aim to minimize the effects of vascular collapse or cerebral blood flow diversion. Cerebral vessels collapse when external pressure exceeds intravascular pressure. Accordingly, when the intravascular pressure rises, the vessels reopen and their diameter increases. Although the concept of abolishing blood diversion by increasing venous pressure has been previously described it has never been applied to patients where venous steal exists, that is, where blood has been diverted from where it is needed such as occurs in a stroke. It would be desirable to improve existing methods and apparatus for treating acute and chronic ischemic conditions in the brain, particularly acute ischemic stroke. (more...)

Surface patterning for single-cell culture is of great importance in studies dealing with cell shape and microenvironment effects on the motility, migration, proliferation, and differentiation of cells.  These patterning techniques are key to effective cell printing needed for future medical advancements, such as 3D printing of artificial organs, tissue regeneration, and tissue engineering.  Despite advances in surface patterning methods, important material surfaces such as glass cannot be easily patterned with established printing methods without prior surface modification. Investigators at University of California at Berkeley have addressed this need by developing a single-cell patterning technique.  This innovation is accomplished by coating the substrate surface with a hydrophobic film and then patterning the film surface.  This surface patterning innovation for single-cell culture was achieved by combining plasma-assisted surface chemical modification, soft lithography, and protein-induced surface activation on glass.  In a proof of concept study, the investigators have accomplished surfaces seeding with mesenchymal stem cells in serum medium, resulting in single-cell patterning.   In additional research, using a dry lithography method, hydrophilic surface patterns on polystyrene were directly applied to cell culture dishes without the requirement of clean-room facilities or chemicals that could be harmful to sensitive cells. The long-term stability of single-cell patterns on PS dish surfaces produced by the present method was accomplished in cell culture experiments with neuron stem cells (NSCs) and bovine aorta endothelial cells. (more...)

Biliary stricture is an abnormal narrowing of the bile duct causing bile to back up and spill into the blood, which can cause jaundice and, if left untreated, can cause life-threatening complications to the patient. Biliary strictures are treated with the application of a stent to manage the blocked bile flow, as employed through a percutaneous approach using a needle to puncture the skin to apply the stent. Treatment has classically been guided by whether the underlying disease process is benign or malignant. In cases of inoperable malignant disease, bare metal stents are routinely used as the desire for biliary conduit restoration outweighs their relatively poor overall primary patency due to tissue in-growth. In contrast, the poor long-term performance of metallic stents in the biliary system and their inability to be removed limits their widespread application in the treatment of benign biliary disease. Subsequently, percutaneous management has required repeated balloon dilation and long-term biliary drain placement. (more...)

UCSF inventors have developed novel approaches that accelerate wound healing and prevent infectious complications in diabetic wounds by local (intracutaneous) blockade of GC activation (more...)

UCSF inventors have developed a safe endovascular biopsy device for extraction of endothelial cells from the blood vessel wall. (more...)

Scripps Institution of Oceanography (SIO) at UC San Diego is one of the oldest, largest, and most important centers for global science research and education in the world. With the oceans covering 70 percent of the earth's surface, it is no surprise that approximately two-thirds of the world's animal phyla are found in marine environments and many are exclusively marine. SIO scientists were among the first to explore the natural product chemistry of marine organisms and this research helped to develop the field of marine natural products chemistry and the realization that the oceans harbor myriad new organic molecules with utility for the development of pharmaceuticals and other products. This research led to the discovery of hundreds of new compositions of matter for new products—some of which are already well progressed into commercial development. Two compounds are now entering phase II clinical trials. One of these, Salinosporamide A, is a potent proteasome inhibitor. The second compound, which is derived from the fungal metabolite halimide, acts as a vascular disrupting agent. (more...)

Cardiac dysfunction is the leading cause of death (> 50%) in diabetic and pre-diabetic population. However, the specific molecular mechanisms underlying diabetic heart failure remain largely unknown. To date, there is no heart failure diagnostic method or treatment specific to diabetes, even though diabetic heart failure has a poor prognosis. Researchers at University of California, Davis have indentified the islet amyloid polypeptide (IAPP) oligomer, a toxic entity causally implicated in dysfunction of pancreatic β-cells and development of type-2 diabetes mellitus (T2DM), as the primary molecular pathogen linking T2DM to heart failure. UC Davis researchers have discovered that secretory dysfunction of pancreatic β-cells leading to the formation of IAPP toxic oligomers results in a feed forward process, whereby the secretion of these toxic entities in the blood causes additional damage in organs other than pancreas, including heart and kidneys. Thus, these toxic oligomers represent pathogens of diabetic cardiac dysfunction. Researchers have shown that accumulation of IAPP toxic oligomers in the heart triggers a cascade of structural and physiological changes within myocytes culminating in heart failure. The discovery that the IAPP toxic oligomer is a biomarker of heart failure in T2DM has immediate relevance in the diagnosis and prognosis of cardiac dysfunction in T2DM and pre-diabetic patients. The UC Davis researchers’ findings reveal that the toxicity associated with accumulation IAPP oligomers in the heart manifests starting from early pre-diabetes. Thus, these oligomers may represent an effective target for diagnostic purposes and therapeutic strategies. (more...)

UCSF researchers have discovered a novel prognostic biomarker of heart tissue health for assessment of risk of cardiac mortality and the need for a heart transplant vs. LVAD implantation in end stage heart failure.  The test would also help clinicians monitor improvement after LVAD implantation.  (more...)

Heart disease remains by far the major cause of morbidity and mortality in the US and other Western countries. Effective treatments for coronary artery disease (CAD) include statins and blood pressure medications. However, therapies involving different treatment strategies are needed to enhance clinical outcomes for heart disease patients. Researchers at UCLA have identified a 5-Lipoxygenase (5LO) as a possible target for pharmaceutical intervention in CAD. The gene may further be used as a genetic diagnosis of individuals with predispositions to CAD. (more...)

The cellular destruction that accompanies myocardial ischemia, infarction and reperfusion is thought to be related in large part to intracellular overload of calcium. Uncontrolled Ca++ influx, which is thought to occur through calcium leak channels, leads to progressive metabolic and functional failure of cells, and eventually to cell death. (more...)

Strokes are the most common life-threatening neurological disease, and are the third leading cause of death in developed countries after heart disease and cancer. Approximately 6-8 percent of all strokes results from non-traumatic subarachnoid hemorrhage, a condition where blood leaks from the cerebral vasculature into the subarachnoid space. About 8 percent of subarachnoid hemorrhages result from rupture of an intracranial aneurysm. Ruptured intracranial aneurysms are associated with a high rate of mortality. Approximately 15% of the patients die soon after the initial rupture. An additional 20 to 30% of the patients die during the first 2 weeks following the initial rupture. Rebleeding is one of the major causes of death in the patients who survive the initial hemorrhage. In addition to the high mortality rate associated with ruptured intracranial aneurysms, there is also a high morbidity rate among patients who survive the rupture long term. Almost two-thirds of patients well enough to be discharged home after surgical obliteration of the aneurysm have a residual neurological deficit. (more...)

The Myeloperoxidase (MPO) enzyme aids in the defensive properties of phagocytic cells of the human immune response. Prevalent in neutrophils and monocytes/macrophages, MPO generates a variety of oxidative processes which aid in the defensive mechanism of the host. Due to the fact that these cells are usually the primary responders to a diseased state, their defensive enzymes are often non-specific. In turn, the oxidative enzymes generated by MPO, may potentially play a role in the disease processes. (more...)

  BACKGROUND: Cardiovascular disorders are leading causes of death worldwide and products have been developed to treat several of their addressable risk factors. Today’s market for anti-hypertensive agents is $35 billion and dyslipidemia treatments is $30 billion. While these therapies have been effective in the majority of patients in lowering blood pressure and LDL (low-density lipoprotein), they do not address other major cardiovascular risk factors such as obesity, liproprotein (a), HDL (high-density lipoprotein), and triglyceride levels. There is an unmet need for new agents that can be used alone or in combination with existing therapies to address these more elusive risk factors.   DESCRIPTION: Researchers at University of California San Francisco and Oregon Health Sciences University have discovered a new class of thyroid hormone metabolites. The most potent of these, 3-iodothyronamine, has been shown in animal studies to completely switch fuel utilization away from carbohydrates and toward lipids. In single dose hamster studies this lipid-burning effect was sustained for 24 hours, several hours after the compound had been excreted. Further studies showed both reduced LDL and significant weight loss that was selective for fat mass vs. lean mass. 3-iodothyronamine is known to be an endogenous chemical derivative of thyroid hormone, a key hormone in regulating basal metabolic rate, protein synthesis, bone growth, neuronal maturation, and metabolism of lipids and carbohydrates. (more...)

Background: Cigarette smoking is the single most preventable cause of premature death in the United States. Each year, one in every five deaths, (about 443,000 in total) is smoking related. The health risks associated with smoking translate into annual healthcare costs of more than $96 billion, with costs associated with second hand smoking averaging $10 billion. Interestingly, 70% of the 43.4 million U.S. adult smokers report that they want to quit completely and more than 40% try to quit each year. However, smoking cessation is extremely difficult; in fact, only about 4% - 7% of people are able to remain smoke free for six months on any given attempt. These success rates dramatically increase to between 14% - 27% if smokers use medicines or behavioral therapies, but such methods may be expensive for both the insurer and patient, inconvenient, or difficult to access. Therefore, it is imperative that a successful, convenient, and cost-effective smoking cessation aid be developed. Invention: Prominent University of California clinicians, Ricardo F. Muñoz, Ph.D. and Eliseo J. Pérez-Stable, M.D. have developed an extremely successful, web-based, smoking cessation program. The program takes eight weeks to complete and combines a smoking cessation guide with individually tailored advice, optional email reminders, and an optional mood management program. Since 2002, over 17,500 smokers from over 155 countries have participated in a series of randomized controlled smoking cessation trials using this program. The study boasts an impressive success rate, with 20% of the participants remaining smoke-free after one year. Significantly, this success rate is comparable to those seen for nicotine replacement therapies, or smoking cessation groups, yet the web program has the important advantages of reducing the cost per patient and increasing the ease of patient access. Furthermore, this fully developed stand alone program is available in both English and Spanish, making it accessible to virtually every American smoker. http://www.stopsmoking.ucsf.edu or http://www.dejardefumar.ucsf.edu (more...)

Targeted gene delivery to somatic tissues has importance in both genetic research and therapeutics. One of the most effective gene delivery vectors known is the recombinant human adenoviruses, which possess high infectivity with respect to a broad range of tissue types. The low selectivity (as to tissue type) is a disadvantage of these vectors limiting their usefulness as an in vivo therapeutic. Vectors which combine high infectivity with tissue- specific expression are needed. (more...)

The current treatment of heart failure is often heart transplantation. UCSD researchers have developed an alternative treatment for heart failure by regulating cytostolic calcium fluxes, in order to improve contractile function. Calcium regulation is achieved by enhancing the expression of a calcium binding protein in cardiac myocytes. In a diabetic mouse model for heart failure, overexpression of the calcium binding protein by adenoviral gene transfer dramatically rescued the abnormal contractile function in the diabetic heart. A specific application of the invention is the treatment of diabetic cardiomyopathy. (more...)

Oxidized phospholipids (OxPL) are present in vessel walls and have been shown to be pro-inflammatory and pro-atherogenic. When cholesterol is lowered by drugs or diet, the plasma levels of the OxPL increase, suggesting a movement or clearance of the phospholipids from the vessel wall into the circulation. This activity, then, is an important indicator that plaque stabilization and/or reduction is occurring. Currently, there are no plasma biomarkers that reflect the amount of plaque or determine the benefits of anti-atherosclerotic therapies. (more...)

Ucsd Researchers have previously identified a protein which they have named PHLPP (ph domain leucine rich repeat protein phosphatase) which was disclosed in Case No. SD2004-088.  The protein dephosphorylates Akt (protein kinase B) specifically at the hydrophobic motif and inactivates it.  In this disclosure, the inventors have shown that by inactivating PHLPP they could enhance Akt phosphorylation. Drugs or compounds that inhibit PHLPP, therefore, would be of therapeutic value in diseases such as diabetes or heart disease. Therefore, a potential drug would simply need to target PHLPP, thus inactivating it, for a therapeutic benefit to be observed. Preliminary experiments with others have shown that knock down of PHLPP increases glucose transport to the plasma mambrane suggesting a significant role in diabetes. Additional studies are being planned to look at PHLPP and its effect on the heart. Published paper in Molecular Cell, 4/1/05. http://health.ucsd.edu/news/2005/03_31_Newton.html (more...)

Catestatin is the most potent endogenous nicotinic cholinergic antagonist. The structure-function relationship of this peptide has been established and human studies indicate that catestatin is low, not only in hypertensive individuals, but also in individuals with a family history for hypertension. Naturally occurring human variants of catestatin and their effects on catecholamine secretion have been reported. Pre-treatment with catestatin lowers the high blood pressure in chromogranin A null mice to normal levels. It appears from recently published human data that the Gly364Ser variant of catestatin prevents humans from developing hypertension. (more...)

Cardiac arrhythmia is the leading cause of death in adults. Arrhythmic sites and triggers of arrhythmia can be precisely mapped by programmed electrical stimulation and intracardiac recordings. Arrhythmias occur preferentially in areas derived from developing cardiac conduction system (CCS) (which consists of the sinoatrial node, atrioventricular node, and His-Purkinje fibers). Abnormalities in CCS development have been postulated to predispose individuals to arrhythmias and sudden death. Therefore, an understanding of genes and signaling pathways underlying CCS development is of critical importance to gain molecular insights into human cardiac arrhythmogenesis and to develop effective interventive and regenerative therapies. Cellular automaticity and excitability in the CSS result from activities of a diversity of ion channels. The pacemaker current is encoded by a family of Hyperpolarization-activated, Cyclic Nucleotide gated (HCN) channels and plays a key role in the generation and autonomic regulation of sinus rhythm and rate. Four mammalian HCN isoforms (HCN1–4) have been identified, of which HCN4 is most abundantly expressed in the sinoatrial node. (more...)

Human blood is in short supply. Blood saving techniques and artificial blood are the two principal approaches to remedy shortfalls in the blood supply. Clinicians facing significant blood loss in patients with significant trauma or surgical intervention choose plasma expanders. In emergencies, the first priority is to re-establish a patient’s blood volume, which may be accomplished with a transfusion of plasma expanders. Once the blood volume is addressed, the next priority is to restore the oxygen carrying capacity of the blood, which requires a transfusion of blood. There are more than 200 million transfusions of plasma expanders in the U.S. annually and a novel plasma expander would be a valuable addition to the clinician's toolbox. (more...)

Although algorithms and chemistries for developing new therapeutic entities are constantly evolving, none can replicate the path and novelty of natural selection over eons of time. Inventors at the Scripps Institution of Oceanography have engaged their fleet of research ships to cull the oceans for marine organisms from which new compositions are isolated.  Using a variety of culture systems, selective fractionation and bioassays, two, distinct classes of compounds, isolated from actinomycetes, have demonstrated potent anti-tumor activity and considerable selectivity toward some cancers. One class of compounds, the ammosamides, are unique molecules that target a previously untargeted intracellular pathway. It is anticipated that proprietary methods and naturally evolved compositions may yield therapeutics that are significantly differentiated from those developed by limited iteration of pre-defined platforms. (more...)

This invention presents a novel cardiac imaging processing method, the tomography-based dynamic cardiac elastography (DCE) method for in vivo identification of the passive nonlinear viscoelastic properties and active contractility of myocardium of an individual heart. (more...)

Actinomycetes are well known soil bacteria that were once believed to occur in the ocean only when washed in from land. Today, it is clear that unique populations of marine actinomycetes reside in ocean sediments and that these bacteria are fundamentally different from those on land. Although terrestrial actinomycetes have been the source of many of today's more than 120 drugs, marine actinomycetes have only recently been incorporated into the discovery process. These bacteria are now proving to be a particularly rich source of unique natural products, many of which display potent biological activities. (more...)

Integrins are found throughout the animal kingdom where they play important roles in cell adhesion, migration, proliferation, and survival. In humans, integrins play critical roles in development. Aberrant activation is implicated in several disease states, including cancer and heart disease. Thus, drugs aimed at disrupting this specific interaction could lead to therapies for these conditions. (more...)

Obesity, an epidemic problem in the US population, has been linked to several major medical problems, including diabetes, stroke, heart disease, high blood pressure and even cancer. Determinants of obesity are complex and genetics account for approximately 25-40% of cases. Although there is great emphasis on discovering the underlying genetic basis for predisposition to obesity, much remains unknown. As a result, there does not yet exist a safe, effective and proven therapy for treatment of obesity.UCSF investigators have developed a new mouse model of obesity. They have generated a transgenic mouse with a hypomorphic allele of the receptor tyrosine kinase TrkB. TrkB is expressed throughout the brain, including the hypothalamus, the center known to control eating behavior. These transgenic mice express TrkB protein at 24% of normal levels in the hypothalamus, and display a maturity onset obesity syndrome. By 12 weeks of age the mutant mice exhibit significant weight gain compared to their wildtype littermates and display hyperphagia as well as significantly increased levels of insulin and leptin in the bloodstream. A similar phenotype has been observed in mice with only one functional allele of BDNF, a ligand of the TrkB receptor (Kernie et al., EMBO J., 2000, 19:1290-1300). These phenotypes parallel those observed in human obesity, indicating that the BDNF/TrkB interaction is a potential target for the development of treatments for obesity and that the TrkB transgenic mice represent a valuable model for studying the development of obesity. (more...)

Researchers at the University of California have developed a fiber-based spectroscopic technique that can be used to quantify optical properties in superficial layers of tissue. (more...)

Recently, activation of the P2Y12 G-protein coupled receptor (GPCRs) has been shown to be central to platelet aggregation. Drugs preventing platelet aggregation are being tested, but one that would be specific to the P2Y12 receptor would capture a large market share. Developing drugs for the P1Y12 receptor is difficult, because it is a receptor that is naturally activated by ADP. Since practically every cell expresses ADP-activatable receptors, developing a drug screening program directed specifically at the P2Y12 receptor has not been possible. (more...)

Sodium/potassium ATPases (Na+/K+-ATPases), a family of multi-subunit ion pumps, are the most important active transporters in animal cells. They are required for maintaining the electrochemical gradient responsible for resting membrane potentials in neuronal cells and for the function of other transport proteins in a variety of cell types. The important regulatory activities of Na+/K+-ATPases make them an attractive therapeutic target for the treatment of neurodegenerative, cardiac, and other diseases. To date, there are unmet medical needs for the treatment of these diseases, and it is desirable to discover and develop novel therapeutic agents aimed at treating ion pump related disorders. (more...)

  Replacement heart valves are surgically implanted in over 60,000 patients a year.  While often life-saving, there can be complications to these heart prosthesis, such as calcification in bio-prosthetic valves, and thrombosis in mechanical heart valves.  If these complications are not detected early, the result is often death of the patient.  Ongoing monitoring would provide the opportunity to sharply decrease the morbidity and mortality associated with artificial heart valves, and would make the advantages of the procedure available to a broader range of patients.   University of California investigators have develop a system which allows the wireless monitoring of heart valve pressure gradients.  This is accomplished through the use of MEMS LC resonant circuits attached to the suture ring of a prosthetic aortic valve.  The non-invasive, passive quality of the monitoring has great advantages over prior monitoring methods.  A wireless hand held unit with antennas tuned to the resonate frequency of each sensor relays aortic valve pressure gradient to the physician.    The system measures the direct pressure on the aortic side and left ventricular side of the aortic valve.   (more...)

Measuring system used to measure swollen limbs of Lymphedema patients (more...)

Technology for engineering antibodies to bind irreversibly to their receptor has been developed by UC Davis researchers. This technology, enabling the formation of permanent antibody-antigen complexes has a number of potential applications in chemistry and biology, including: targeted medical imaging targeted medical therapies (e.g., cancer therapeutics) synthetic tag to replace avidin-biotin no competition from endogenous ligands no dissociation after capture humanized format Furthermore, UC Davis researchers have constructed a bispecific fusion protein that has tumor targeting properties and irreversibly captures a metal chelate. This combines irreversible metal chelate binding with tumor targeting activity for the first time in a highly homogenous genetic construction that can be expressed at high yields. In addition, this allows the substitution of other targeting sequences allowing for a wide range of cellular targets. The irreversible nature of the chelate binding has not been previously achieved in a single expressed protein fused to a tumor targeting functional segment. (more...)

Targeted Delivery of Nanoparticles to the Heart Endothelium with Large Pay-Load Potential, Applicable to Drug/Gene Delivery (more...)