Pittsburgh, PA, United States
Pittsburgh, PA, United States

The University of Pittsburgh is a state-related research university located in Pittsburgh, Pennsylvania. It was founded on the edge of the American frontier as the Pittsburgh Academy in 1787, and evolved into the Western University of Pennsylvania by alteration of its charter in 1819. After surviving two devastating fires and various relocations within the area, the school moved to its current location in the Oakland neighborhood of the city and was renamed to the University of Pittsburgh in 1908. For most of its history Pitt was a private institution, until it became part of the Commonwealth System of Higher Education in 1966.The university is composed of 17 undergraduate and graduate schools and colleges located at its urban Pittsburgh campus, home to the university's central administration and 28,766 undergraduate, graduate, and professional students. The university also includes four additional undergraduate schools located at campuses within Western Pennsylvania: Bradford, Greensburg, Johnstown, and Titusville. The 132-acre Pittsburgh campus comprises multiple historic buildings of the Schenley Farms Historic District, most notably its 42-story gothic revival centerpiece, the Cathedral of Learning. The campus is situated adjacent to the flagship medical facilities of its closely affiliated University of Pittsburgh Medical Center , as well as the Carnegie Museums of Pittsburgh, Schenley Park, and Carnegie Mellon University.The university has an annual operating budget of approximately $2 billion that includes nearly $900 million in research and development expenditures. A member of the Association of American Universities, Pitt is the sixth largest recipient of federally sponsored research funding among U.S. universities in 2013 and is a major recipient of research funding from the National Institutes of Health. It is the second largest non-government employer in the Pittsburgh region behind UPMC. Pitt has been placed among the top public universities in the United States in both domestic and international rankings, and has been listed as a "best value" in higher education by multiple publications.Pitt students have access to various arts programs throughout the campus and city, and can participate in approximately 350 student organizations. Pitt's varsity athletic teams, collectively known as the Pittsburgh Panthers, compete in Division I of the NCAA, primarily as members of the Atlantic Coast Conference. Wikipedia.

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University of Pittsburgh | Date: 2016-10-18

The present invention relates to methods of treatment of clinical disorders associated with protein polymerization comprising administering, to a subject, an effective amount of carbamazepine, oxcarbazepine or another carbamazepine-like compound. It is based, at least in part, on the discovery that, in cells having a genetic defect in 1-antitrypsin, carbamazepine was able to decrease levels of the mutant protein. Furthermore, carbamazepine reduced the hepatic load of mutant 1-antitrypsin and the toxic effect of that mutant protein accumulation, hepatic fibrosis, in vivo using a mouse model of the disease. As patients having this defect in 1-antitrypsin exhibit toxic accumulations of the protein, treatment according to the invention may be used to ameliorate symptoms and signs of disease.

University of Pittsburgh | Date: 2014-12-29

The invention provides a method of modulating electrophysiological activity of an excitable cell. The method involves causing exogenous expression of a glycine receptor (GlyR) protein in an excitable cell of a subject. Thereafter, the excitable cell is exposed to an allosteric modulator of the GlyR protein. Modulation of the exogenous GlyR protein (an ion channel) in response to the allosteric modulator modulates the electrophy-stological activity of the excitable cell. The method can be used to control pain in a subject. The invention further provides a replication-defective HSV vector comprising an expression cassette encoding a GlyR protein, stocks and pharmaceutical compositions containing such vectors, and a transgenic animal.

University of Pittsburgh | Date: 2016-08-17

Disclosed herein are novel amine-functionalized porphyrin compounds, as wells as pharmaceutically acceptable salts or esters thereof. The disclosed compounds can be used to impart antioxidant, anti-inflammatory, anti-microbial, and/or cell-adhesion specificity to a surface or material in need thereof, such as a surface of an indwelling medical implant, or a marine surface.

University of Pittsburgh | Date: 2016-08-04

A cartridge device is provided for applying a fiber matrix to a tubular member such as a saphenous vein graft. The cartridge includes a housing, a tubular member holder, a rotational drive, and a polymer delivery assembly. The housing defines a chamber which surrounds the tubular member holder. The rotational drive rotates the tubular member during the fiber application process.

Provided herein are methods of fractionating extracellular matrix (ECM) materials, producing soluble and structural fractions having different immunological activities. Also provided are compositions and devices comprising the fractions. A method of immune modulation also is provided in which an amount of a soluble or structural ECM fraction prepared according to the methods provided herein is administered to a patient in an amount effective to modulate immune function, for example macrophage function.

University of Pittsburgh and Keio University | Date: 2015-04-29

Provided herein are methods or making and using whole or partial organ ECM structures comprising an anticoagulant. Also provided are organ structures prepared according to those methods.

University of Pittsburgh | Date: 2016-08-03

Provided herein are biodegradable poly(ester amide) elastomers, methods of making the elastomers, and methods of using the elastomers, for example for tissue engineering. The elastomers can be used for preparation of tissue prostheses, such as a heart valve leaflet, a heart valve, cartilage, myocardium, blood vessels, smooth muscle, skeletal muscle, or other tissues. Also provided herein are semiquantitative FTIR methods for determining structure of a poly(ester amide) elastomer.

University of Pittsburgh | Date: 2016-12-02

A material having a first non-zero elastic modulus capable of reversibly changing the first non-zero elastic modulus to a second non-zero elastic modulus in response to a redox reaction occurring in the material. A method of producing a material that is reversibly cyclable between a first non-zero elastic modulus and a second non-zero elastic modulus, comprising: preparing a polymer comprising both crosslinks that do not depend on metal binding and functional groups capable of having oxidation-state specific binding constants to a metal ion; and doping the polymer with a solution containing the metal ion.

Provided are novel biocompatible copolymers, compositions comprising the copolymers, and methods of using the copolymers. The copolymers are non-toxic and typically have an LCST below 37 C. Compositions comprising the copolymers can be used for wound treatment, as a cellular growth matrix or niche and for injection into cardiac tissue to repair and mechanically support damaged tissue. The copolymers comprise numerous ester linkages so that the copolymers are erodeable in situ. Degradation products of the copolymers are soluble and non-toxic. The copolymers can be amine-reactive so that they can conjugate with proteins, such as collagen. Active ingredients, such as drugs, can be incorporated into compositions comprising the copolymers.

University of Pittsburgh | Date: 2016-10-26

An implantable medical device including at least one double-walled microsphere containing an active agent, and a biodegradable polymer layer containing the at least one double-walled microsphere.

University of Pittsburgh | Date: 2015-03-04

Methods of decellularization of tissue, such as mammalian tissue, are provided, along with methods of making an extracellular matrix (ECM) preparation. Systems and apparatus useful in performing the methods are also provided.

University of Pittsburgh | Date: 2015-03-06

Methods are disclosed which combine electrospinning and a sacrificial template, such as with additive manufacturing (AM), to produce fibrous microvascular scaffolds which are biodegradable, porous, and easily handled. In one example, a process for fabricating a fibrous network construct is disclosed. The method includes electrospinning a first layer of fibrous material; printing a micropatterned sacrificial template; transferring the micropatterned sacrificial template onto the electrospun fibers; electrospinning a second layer of fibrous biomaterial onto the micropatterned sacrificial template thereby encapsulating the template and generating a construct with two layers; and removing the sacrificial template, producing a fibrous construct with channels or microstructures formed therein. Also disclosed are fibrous constructs and scaffolds produced by the provided methods.

University of Pittsburgh | Date: 2015-04-17

Methods are disclosed for producing pancreatic beta cells in a subject. The methods include administering to the subject a vector encoding heterologous Pancreas duodenal homeobox protein (Pdx) 1 and MafA, wherein the vector does not encode Neurogenin 3 (Ngn3) and wherein the subject is not administered any other nucleic acid encoding Ngn3. The vector is administered intraductally into a pancreatic duct of the subject. Compositions are disclosed that include a) a viral vector comprising a promoter operably linked to a nucleic acids encoding Pdx1 and a nucleic acid encoding MafA, wherein the vector does not encode Ngn3; b) a buffer; and c) a contrast dye for endoscopic retrograde cholangiopancreatography. These compositions are of use in any of the methods disclosed herein.

University of Pittsburgh | Date: 2016-07-07

The present invention provides a recombinant oncolytic Herpes Simplex Virus (oHSV) comprising a non-HSV ligand specific for a molecule (protein, lipid, or carbohydrate determinant) present on the surface of a cell (such as a cancer cell) and one or more copies of one or more microRNA target sequences inserted into one or more HSV gene loci, preferably one or more HSV gene(s) required for replication of HSV in normal (i.e., non-cancerous) cells. The invention further provides stocks and pharmaceutical compositions comprising the inventive oHSV and methods for killing tumor cells employing the inventive oHSV.

University of Pittsburgh and University of Washington | Date: 2016-10-17

The present invention relates to methods of inhibiting neurodegeneration in a subject suffering from or genetically at risk and/or destined to develop Huntingtons Disease comprising increasing, in neurons of the subject, the activity of the TIM23 mitochondrial protein import complex.

University of Pittsburgh | Date: 2016-09-14

A method of treating produced water from subterranean operations includes charging produced water into a container to create a mixture of the produced water and an aqueous medium including a source of sulfate ions within the container, removing an outflow via an outlet in the container; and charging barite particles into the container.

Astute Medical and University of Pittsburgh | Date: 2016-11-07

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more of hyaluronic acid (HA) as diagnostic and prognostic biomarker assays in renal injuries.

University of Pittsburgh | Date: 2016-10-28

The invention relates to biodegradable, metal alloy-containing compositions, methods for their preparation and applications for their use. The compositions include magnesium and other components, such as yttrium, calcium, silver, cerium, and zirconium; or zinc, silver, cerium, and zirconium; or aluminum, zinc, calcium, manganese, silver, yttrium; or strontium, calcium, zinc. The compositions are prepared by vacuum induction/crucible melting together the components and casting the melted mixture in a preheated mild steel/copper mold. In certain embodiments, the compositions of the invention are particularly useful for forming medical devices for implantation into a body of a patient.

University of Pittsburgh | Date: 2016-07-29

Provided herein are in silico methods of modeling hepatic inflammation, fibrosis/cirrhosis, and cancer. The models are computer-implemented agent-based models and are useful in determining patient prognoses in hepatic conditions, including viral infections, damage, inflammation, and cancer. The modeling system also is useful in modeling the effects of active agents on normal hepatic tissue or hepatic tissue perturbed by inflammation, infection, damage, fibrosis/cirrhosis, and cancer.

University of Pittsburgh | Date: 2017-03-01

Isolated monoclonal antibodies are disclosed herein that specifically bind endoplasmin. In some embodiments these antibodies are fully human. Recombinant nucleic acids encoding these antibodies, expression vectors including these nucleic acids, and host cells transformed with these expression vectors are also disclosed herein. In several embodiments the disclosed antibodies are of use for detecting and/or treating tumors that express endoplasmin, such as melanoma, breast cancer, head and neck squamous cell carcinoma, renal cancer, lung cancer, glioma, bladder cancer, ovarian cancer or pancreatic cancer. In one example, the tumor is a melanoma.

Jacobs R.L.,University of Pittsburgh | Montie J.E.,Taubman Center
CA Cancer Journal for Clinicians | Year: 2010

Bladder cancer is the fourth most common cancer and ranks eighth as a cause of death from cancer among men in the United States. Although guidelines assist in treatment, the art of managing bladder cancer, such as the decision to use neoadjuvant chemotherapy and the timing of cystectomy, is still variable. Bladder cancer has a propensity to recur, and with recurrence, a significant number of cases progress, which makes the early detection of high-risk patients imperative. Advances in detection, surveillance, and treatment of bladder cancer are reviewed in this article. © 2010 American Cancer Society, Inc.

Pekker D.,University of Pittsburgh | Varma C.M.,University of California at Riverside
Annual Review of Condensed Matter Physics | Year: 2015

The order parameter and its variations in space and time in many different states in condensed matter physics at low temperatures are described by the complex function ?(r, t). These states include erfluids, erconductors, and a subclass of antiferromagnets and charge density waves. The collective fluctuations in the ordered state may then be categorized as oscillations of phase and amplitude of ?(r, t). The phase oscillations are the Goldstone modes of the broken continuous symmetry. The amplitude modes, even at long wavelengths, are well defined and are decoupled from the phase oscillations only near particle-hole symmetry, where the equations of motion have an effective Lorentz symmetry, as in particle physics and if there are no significant avenues for decay into other excitations. They bear close correspondence with the so-called Higgs modes in particle physics, whose prediction and discovery are very important for the standard model of particle physics. In this review, we discuss the theory and the possible observation of the amplitude or Higgs modes in condensed matter physics - in erconductors, cold atoms in periodic lattices, and uniaxial antiferromagnets. We discuss the necessity for at least approximate particle-hole symmetry as well as the special conditions required to couple to such modes because, being scalars, they do not couple linearly to the usual condensed matter probes. © 2015 by Annual Reviews.

Marazita M.L.,Center for Craniofacial and Dental Genetics | Marazita M.L.,University of Pittsburgh
Annual Review of Genomics and Human Genetics | Year: 2012

Orofacial clefts (OFCs)-primarily cleft lip and cleft palate-are among the most common birth defects in all populations worldwide, and have notable population, ethnicity, and gender differences in birth prevalence. Interest in these birth defects goes back centuries, as does formal scientific interest; scientists often used OFCs as examples or evidence during paradigm shifts in human genetics, and have also used virtually every new method of human genetic analysis to deepen our understanding of OFC. This review traces the evolution of human genetic investigations of OFC, highlights the specific insights gained about OFC through the years, and culminates in a review of recent key OFC genetic findings resulting from the powerful tools of the genomics era. Notably, OFC represents a major success for genome-wide approaches, and the field is poised for further breakthroughs in the near future. © 2012 by Annual Reviews. All rights reserved.

University of Oregon and University of Pittsburgh | Date: 2013-05-09

Disclosed herein are adeno associated viral plasmids and viral vectors. Also disclosed are methods of using adeno associated viral vectors.

University of Pittsburgh | Date: 2015-01-30

A wheelchair system includes a wheelchair including at least one adjustable seating function, a sensor system in operative connection with the wheelchair which includes at least one sensor to measure or sense a position of the at least one adjustable seating function, a processor system in operative connection with the sensor system, a memory system in operative connection with the processor system, and a communication system in operative connection with the processor system. The communication system is, for example, adapted to wirelessly communicate with one or more remote systems (that is, a system remote from the wheelchair; for example a remote system or server, which may include a database). The wheelchair system further includes a user interface system in operative connection with the processor system and at least one application stored on the memory system and executable by the processor system. The at least one application is executable to provide information via the user interface system to a user of the wheelchair related to data from the sensor system to assist the user to adjust the position of at least one adjustable seating in accordance with parameters stored in the memory system.

University of Pittsburgh | Date: 2014-12-09

A method for treating a respiratory injury or disease comprising: administering to a patient in need of treatment a pharmaceutical composition comprising a compound of general Formula I:

University of Pittsburgh | Date: 2014-05-09

Disclosed is a compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of: X^(1)-L-X^(2 ) wherein L is a linking moiety comprising an enone; and X^(1 )and X^(2 )are each independently an optionally-substituted N-heterocycle. Also disclosed are method for treating pulmonary conditions and other organ or system conditions with the compounds.

University of Pittsburgh | Date: 2016-04-25

A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:

University of Pittsburgh | Date: 2016-04-25

A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:

University of Pittsburgh | Date: 2013-03-13

A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:

University of Pittsburgh and U.S. Department Of Veterans Affairs | Date: 2013-09-18

A synthesized siRNA molecule having the sense strand with one or more uridine bases replaced by one or more respective nucleoside analogs, such as 5-fluoro-2-deoxyuridine (FdU).

University of Pittsburgh | Date: 2015-01-15

A pathway measurement system hereof includes a rigid frame and a mobility system attached to the frame. The mobility system includes at least one movable element which is adapted to contact a surface of a pathway via which the frame may be moved relative to the pathway. The pathway measurement system further includes at least one sensor adapted to measure at least one characteristic of a pathway. The pathway measurement system has a first mode of operation in which the mobility system moves the frame along the pathway to move the at least one sensor relative to the pathway. The at least one sensor is connected to the pathway system such that a distance between the at least one sensor and an axis of rotation of one of the moveable elements remains constant in the first mode of operation. In general, the at least one sensor is isolated from any compliance or suspension system.

University of Pittsburgh | Date: 2015-06-12

A system for evaluation of an operator of a vehicle including a steering system under observation of an evaluator within the vehicle includes a steering sensor system adapted to measure intervention of the evaluator in operating the steering system. A method for evaluating vehicle control of a driving entity of a vehicle under observation of an evaluator in the vehicle includes providing at least one sensor system adapted to measure intervention of the evaluator in operating the vehicle.

Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas, University of Chicago and University of Pittsburgh | Date: 2014-05-14

The present invention relates to the discovery that of a panel of serum or plasma markers may be used to diagnose Idiopathic Pulmonary Fibrosis (IPF) and distinguish this condition from other lung ailments. It further relates to the identification of markers associated with IPF disease progression.

McCrimmon R.J.,University of Dundee | Ryan C.M.,University of Pittsburgh | Frier B.M.,Royal Infirmary
The Lancet | Year: 2012

Cognitive dysfunction in type 1 and type 2 diabetes share many similarities, but important differences do exist. A primary distinguishing feature of type 2 diabetes is that people with this disorder often (but not invariably) do poorly on measures of learning and memory, whereas deficits in these domains are rarely seen in people with type 1 diabetes. Chronic hyperglycaemia and microvascular disease contribute to cognitive dysfunction in both type 1 and type 2 diabetes, and both disorders are associated with mental and motor slowing and decrements of similar magnitude on measures of attention and executive functioning. Additionally, both types are characterised by neural slowing, increased cortical atrophy, microstructural abnormalities in white matter tracts, and similar, but not identical, changes in concentrations of brain neurometabolites. Disconcertingly, the rapid rise in obesity and type 2 diabetes in all age groups might result in a substantial increase in prevalence of diabetes-related cognitive dysfunction.

Apodaca G.,University of Pittsburgh | Gallo L.I.,University of Pittsburgh | Bryant D.M.,University of California at San Francisco
Nature Cell Biology | Year: 2012

Epithelial cells have an apical-basolateral axis of polarity, which is required for epithelial functions including barrier formation, vectorial ion transport and sensory perception. Here we review what is known about the sorting signals, machineries and pathways that maintain this asymmetry, and how polarity proteins interface with membrane-trafficking pathways to generate membrane domains de novo. It is becoming apparent that membrane traffic does not simply reinforce polarity, but is critical for the generation of cortical epithelial cell asymmetry. © 2012 Macmillan Publishers Limited. All rights reserved.

Wang M.-T.,University of Pittsburgh | Fredricks J.A.,Connecticut College
Child Development | Year: 2014

Drawing on the self-system model, this study conceptualized school engagement as a multidimensional construct, including behavioral, emotional, and cognitive engagement, and examined whether changes in the three types of school engagement related to changes in problem behaviors from 7th through 11th grades (approximately ages 12-17). In addition, a transactional model of reciprocal relations between school engagement and problem behaviors was tested to predict school dropout. Data were collected on 1,272 youth from an ethnically and economically diverse county (58% African American, 36% European American; 51% females). Results indicated that adolescents who had declines in behavioral and emotional engagement with school tended to have increased delinquency and substance use over time. There were bidirectional associations between behavioral and emotional engagement in school and youth problem behaviors over time. Finally, lower behavioral and emotional engagement and greater problem behaviors predicted greater likelihood of dropping out of school. © 2013 Society for Research in Child Development, Inc.

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 256.22K | Year: 2013

DESCRIPTION (provided by applicant): Controlled release formulations can improve patient adherence and drug safety or even enable new types of basic medical research. The key to realizing these benefits is the ability to design and produce these formulations in a cost-effectiv and timely manner. Thus far, strategies at improving this process have focused on the development of novel materials and production processes that tailored for experimentally tuning a formulation's performance. Recently, the University of Pittsburgh (Pitt) has discovered new in silico design techniques that may, for the first time, make it possible to transform an expensive and time consuming empirical development process into a rapid and cost effective process. ChroKnow's long-term objective is to bring speed and efficiency formulation design process, a crucial step toward the enabling widespread adoption of controlled release systems by pharmaceutical companies and even academic laboratories. We hypothesize that algorithms (developedat Pitt) can be used to predictively design and build a diverse set of controlled release formulations based on unmet needs pharmaceutical scientists or academic researchers over a period of time that is yet unprecedented in the field. This hypothesis is supported by in vitro data demonstrating that two representative formulations have successfully been designed and produced using ChroKnow's algorithms. Herein, we put forth three real-world challenges to complete this validation: Specific Aim 1: To design and build a formulation that delivers Genentech's ranibizumab for 3 months. Motivation: Dramatically improve adherence in patients with ARMD over the current once-monthly treatment. Specific Aim 2: To create a formulation that delivers Complexa's 10-NO2-octadeca-9-enoic acid for 2 weeks. Motivation: Replicate delivery performance of osmotic pump implants current used in preclinical testing Specific Aim 3: To create a formulation for an academic PI that delivers vasotocin antisense for 10 days. Motivation:Permit the first extended evaluation of this neuropeptide's action on animal behavior in the field. Each of the formulations specified above will be designed and built in collaboration between ChroKnow Inc. and the University of Pittsburgh. Completion ofeach aim will yield a formulation whose in vitro release kinetics are consistent with the performance predicted by the algorithms. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: This work has relevance to public health as it intends to bring speed and efficiency to the development of controlled release formulations. As prescription medications, these formulations address the leading causes of patient nonadherence, which is responsible for 10% of hospitalizations and over 100 billion in annualmedical expenses. As tools for research these formulations enable identifications of new drug targets and novel biomimetic treatments in fields ranging from immunology to neuroethology.

Russell D.G.,Cornell University | Barry III C.E.,National Institute of Allergy and Infectious Diseases | Flynn J.L.,University of Pittsburgh
Science | Year: 2010

Mycobacterium tuberculosis has a penetrance of its host population that would be the envy of most human pathogens. About one-third of the human population would have a positive skin test for the infection and is thus thought to harbor the bacterium. Globally, 22 "high-burden" countries account for more than 80% of the active tuberculosis cases in the world, which shows the inequitable distribution of the disease. There is no effective vaccine against infection, and current drug therapies are fraught with problems, predominantly because of the protracted nature of the treatment and the increasing occurrence of drug resistance. Here we focus on the biology of the host-pathogen interaction and discuss new and evolving strategies for intervention.

Particle formulations are disclosed that include polymeric particles containing a small molecule drug and a high molecular weight therapeutic protein. Methods of making and using the particle formulations also are disclosed. These particle formulations are of use to treat an autoimmune disease, such as diabetes, or an inflammatory disease.

Veasey S.C.,University of Pennsylvania | Morgan B.J.,University of Wisconsin - Madison | O'Donnell C.P.,University of Pittsburgh
Physiological Reviews | Year: 2010

Sleep-induced apnea and disordered breathing refers to intermittent, cyclical cessations or reductions of airflow, with or without obstructions of the upper airway (OSA). In the presence of an anatomically compromised, collapsible airway, the sleep-induced loss of compensatory tonic input to the upper airway dilator muscle motor neurons leads to collapse of the pharyngeal airway. In turn, the ability of the sleeping subject to compensate for this airway obstruction will determine the degree of cycling of these events. Several of the classic neurotransmitters and a growing list of neuromodulators have now been identified that contribute to neurochemical regulation of pharyngeal motor neuron activity and airway patency. Limited progress has been made in developing pharmacotherapies with acceptable specificity for the treatment of sleep-induced airway obstruction. We review three types of major long-term sequelae to severe OSA that have been assessed in humans through use of continuous positive airway pressure (CPAP) treatment and in animal models via long-term intermittent hypoxemia (IH): 1) cardiovascular. The evidence is strongest to support daytime systemic hypertension as a consequence of severe OSA, with less conclusive effects on pulmonary hypertension, stroke, coronary artery disease, and cardiac arrhythmias. The underlying mechanisms mediating hypertension include enhanced chemoreceptor sensitivity causing excessive daytime sympathetic vasoconstrictor activity, combined with overproduction of superoxide ion and inflammatory effects on resistance vessels. 2) Insulin sensitivity and homeostasis of glucose regulation are negatively impacted by both intermittent hypoxemia and sleep disruption, but whether these influences of OSA are sufficient, independent of obesity, to contribute significantly to the "metabolic syndrome" remains unsettled. 3) Neurocognitive effects include daytime sleepiness and impaired memory and concentration. These effects reflect hypoxic-induced "neural injury." We discuss future research into understanding the pathophysiology of sleep apnea as a basis for uncovering newer forms of treatment of both the ventilatory disorder and its multiple sequelae. Copyright © 2010 the American Physiological Society.

Taylor W.D.,Vanderbilt University | Aizenstein H.J.,University of Pittsburgh | Alexopoulos G.S.,New York Medical College
Molecular Psychiatry | Year: 2013

The 'Vascular Depression' hypothesis posits that cerebrovascular disease may predispose, precipitate or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between LLD, vascular risk factors and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in LLD, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor, influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression, but also provide guidance on the potential repurposing of pharmacological agents that may improve LLD outcomes. © 2013 Macmillan Publishers Limited.

Yadav D.,University of Pittsburgh | Lowenfels A.B.,New York Medical College
Gastroenterology | Year: 2013

Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. © 2013 by the AGA Institute.

Brodsky J.L.,University of Pittsburgh | Skach W.R.,Oregon Health And Science University
Current Opinion in Cell Biology | Year: 2011

The evolution of eukaryotes was accompanied by an increased need for intracellular communication and cellular specialization. Thus, a more complex collection of secreted and membrane proteins had to be synthesized, modified, and folded. The endoplasmic reticulum (ER) thereby became equipped with devoted enzymes and associated factors that both catalyze the production of secreted proteins and remove damaged proteins. A means to modify ER function to accommodate and destroy misfolded proteins also evolved. Not surprisingly, a growing number of human diseases are linked to various facets of ER function. Each of these topics will be discussed in this article, with an emphasis on recent reports in the literature that employed diverse models. © 2011 Elsevier Ltd.

Bellomo R.,Monash University | Kellum J.A.,University of Pittsburgh | Ronco C.,San Bortolo Hospital
The Lancet | Year: 2012

Acute kidney injury (formerly known as acute renal failure) is a syndrome characterised by the rapid loss of the kidney's excretory function and is typically diagnosed by the accumulation of end products of nitrogen metabolism (urea and creatinine) or decreased urine output, or both. It is the clinical manifestation of several disorders that affect the kidney acutely. Acute kidney injury is common in hospital patients and very common in critically ill patients. In these patients, it is most often secondary to extrarenal events. How such events cause acute kidney injury is controversial. No specific therapies have emerged that can attenuate acute kidney injury or expedite recovery; thus, treatment is supportive. New diagnostic techniques (eg, renal biomarkers) might help with early diagnosis. Patients are given renal replacement therapy if acute kidney injury is severe and biochemical or volume-related, or if uraemictoxaemia-related complications are of concern. If patients survive their illness and do not have premorbid chronic kidney disease, they typically recover to dialysis independence. However, evidence suggests that patients who have had acute kidney injury are at increased risk of subsequent chronic kidney disease.

Weaver C.T.,University of Alabama at Birmingham | Elson C.O.,University of Alabama at Birmingham | Kolls J.K.,University of Pittsburgh
Annual Review of Pathology: Mechanisms of Disease | Year: 2013

The recent discovery of a new CD4+ T cell subset, Th17, has transformed our understanding of the pathogenetic basis of an increasing number of chronic immune-mediated diseases. Particularly in tissues that interface with the microbial environment-such as the intestinal and respiratory tracts and the skin-where most of the Th17 cells in the body reside, dysregulated immunity to self (or the extended self, the diverse microbiota that normally colonize these tissues) can result in chronic inflammatory disease. In this review, we focus on recent advances in the biology of the Th17 pathway and on genome-wide association studies that implicate this immune pathway in human disease involving these tissues. © 2013 by Annual Reviews. All rights reserved.

Baxter International, Baxter Healthcare S.A. and University of Pittsburgh | Date: 2013-10-09

AS-oligonucleotides are delivered in microsphere form in order to induce dendritic cell tolerance, particularly in the non-obese-diabetic (NOD) mouse model. The microspheres incorporate antisense (AS) oligonucleotides. A process includes using an antisense approach to reverse an autoimmune diabetes condition in NOD mice in vivo. The oligonucleotides are targeted to bind to primary transcripts CD40, CD80, CD86 and their combinations.

Louisiana State University and University of Pittsburgh | Date: 2013-08-05

A vaccine is disclosed that promotes CD4+ T cell-independent host defense mechanisms to defend against infection by fungi such as Pneumocystis spp. The vaccine may be used to prevent or to treat fungal infections. The novel vaccine can provide protective immunity, even for immunocompromised individuals such as HIV patients having reduced levels of CD4+ T cells.

Baxter International, Baxter Healthcare SA and University of Pittsburgh | Date: 2016-02-10

A method is provided that includes using an antisense approach to reverse and/or delay an autoimmune diabetes condition in vivo. The oligonucleotides are targeted to bind to primary transcripts CD40, CD80, CD86 and their combinations.

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 225.00K | Year: 2015

DESCRIPTION provided by applicant This project entails the development of a novel dual component MRI contrast agent formulation for the detecting permeability in the luminal surface of the urinary bladder The purpose of having such a test is ultimately to allow clinicians in certain circumstances to differentially diagnose a chronic non infectious inflammation of the urinary bladder from a pelvic floor defect The two components of the formulation permit the simultaneous tracking of the bladder wall via one component that is composed of particles having a larger particle size as well as map the local permeability of the wall via the second component composed of particles having a much smaller particle size wherein each of the two components can be tracked independently The proposed project is segmented into two aims The first aim is an animal protocol where bladder wall permeability can be chemically influenced and the second aim is a pilot clinical protocol designed to assess the feasibility of a human diagnostic test For aim a mouse model that works well with the available bladder instillation and animal imaging equipment is proposed Protamine sulfate is the proposed drug for inducing bladder wall permeability not necessarily because it is the best model of bladder disease but because it provides the best controlled inflammatory effects in the time frames logistically available for the proposed imaging experiments Different levels of permeability induction as well as different levels of bladder distension are proposed as effectors to be tested Since the components used in the formulation are already FDA approved for parenteral route of administration IND approval to study true cystitis in human subjects will be available This proposal thus includes aim the test of clinical feasibility in six human subjects These six human sub jects are divided into three cohorts two healthy control subjects two subjects with interstitial cystitis bladder pain syndrome IC BPS and two IC BPS subjects also having Hunnerandapos s ulcer We anticipate that the results of the both aims of this proposed Phase study will provide the foundation for the development of a subse quent Phase proposal in which we would propose the further clinical development of the formulation and diagnostic method If successful this research could ultimately lead to a product that may be helpful in diagnosing inflammatory conditions of the urinary bladder such as IC BPS a diagnostic test which has been long sought after by the urology community PUBLIC HEALTH RELEVANCE Interstitial Cystitis Bladder Pain Syndrome IC BPS is an incurable chronic debilitating disease of the urinary bladder that involves urinary urgency frequency of urination and chronic pelvic pain Estimates of the prevalence of IC BPS in the U S range from to cases per persons Historically increased bladder permeability is suggested to be the key determinant of bladder pathology and IC BPS symptoms However there is a current lack of acceptable methods for direct measurement of bladder permeability in IC BPS patients and this proposal will develop a new objective MRI test for direct measurement of bladder permeability

Croteau D.L.,U.S. National Institute on Aging | Popuri V.,U.S. National Institute on Aging | Opresko P.L.,University of Pittsburgh | Bohr V.A.,U.S. National Institute on Aging
Annual Review of Biochemistry | Year: 2014

RecQ helicases are an important family of genome surveillance proteins conserved from bacteria to humans. Each of the five human RecQ helicases plays critical roles in genome maintenance and stability, and the RecQ protein family members are often referred to as guardians of the genome. The importance of these proteins in cellular homeostasis is underscored by the fact that defects in BLM, WRN, and RECQL4 are linked to distinct heritable human disease syndromes. Each human RecQ helicase has a unique set of protein-interacting partners, and these interactions dictate its specialized functions in genome maintenance, including DNA repair, recombination, replication, and transcription. Human RecQ helicases also interact with each other, and these interactions have significant impact on enzyme function. Future research goals in this field include a better understanding of the division of labor among the human RecQ helicases and learning how human RecQ helicases collaborate and cooperate to enhance genome stability. Copyright © 2014 by Annual Reviews.

Rutgers University and University of Pittsburgh | Date: 2013-11-13

Provided herein are methods for treating planktonic bacteria or a biofilm. The methods include contacting the planktonic bacteria or biofilm with an effective amount of an isolated Citrobacter freundii colicin A polypeptide, wherein the polypeptide has an antibacterial activity against the planktonic bacteria or the biofilm. Methods are also provided herein for treating a subject that has a bacterial infection, for example caused by a biofilm. The methods can be used to treat a biofilm on a living or non-living surface. Also provided herein are Citrobacter freundii colicin A polypeptides that have an antibacterial activity against planktonic bacteria or surface attached bacteria, and nucleic acid sequences encoding the polypeptides. Medical devices comprising a surface having an antimicrobial effective amount of a Citrobacter freundii colicin A polypeptide, or a nucleic acid molecule encoding the polypeptide, are also disclosed.

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 219.34K | Year: 2014

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is a devastating neurodegenerative disorder. One of the few drugs used to treat AD is memantine, which inhibits N-methyl-d-aspartate receptors (NMDARs), glutamate receptor subtypes found at nearly all vertebrate excitatory synapses. NMDARs are critically involved in many aspects of nervous system function, including learning and memory. Memantine inhibits NMDARs by blocking the ion channel created by NMDARs and occluding current flow through thechannel. It is surprising that inhibition of NMDARs slows the cognitive decline associated with AD, since NMDARs are required for memory acquisition. We have proposed that memantine's utility in treating AD derives from the preferential inhibition of specific NMDAR subtypes by memantine. These NMDAR subtypes are thought to be preferentially expressed by inhibitory neurons in the cortex; as a result, memantine reduces cortical inhibition, partially compensating for a reduction in cortical excitation caused b

University of Pittsburgh and Battelle | Date: 2013-10-18

Methods for producing a superhydrophobic anodized surface including anodizing a surface of a substrate in an anodization acid to form a plurality of pores, etching the surface with an etchant to widen an edge of each of the plurality of pores; repeatedly anodizing the surface in the anodization acid and etching the surface with the etchant until the edges of the plurality of pores overlap to form a plurality of nano-sharp ridges, and coating the surface with a hydrophobic polymer to render the surface superhydrophobic, such that the surface exhibits a contact angle of at least 150 degrees with a drop of water. Articles including a surface having a series of nano-sharp pore ridges defined by a series of pores and a sub-m thick layer of a hydrophobic polymer on said surface.

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