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News Article | May 25, 2017
Site: www.sciencedaily.com

In the fight against super bacteria, University at Buffalo scientists are relying on strength in numbers to win the battle against drug resistance. A team of researchers found that combinations of three antibiotics -- that are each ineffective against superbugs when used alone -- are capable of eradicating two of the six ESKAPE pathogens when delivered together. ESKAPE pathogens are a group of antimicrobial-resistant bacteria that pose a grave threat, causing more than 2 million infections and nearly 23,000 deaths a year, according to the Centers for Disease Control and Prevention. The six super bacteria are also responsible for a substantial number of infections in hospitals. The new, triple combination treatments provide a new weapon in the evolutionary arms race between modern medicine and harmful bacteria. "These bacteria are extremely problematic and have become resistant to nearly all available antibiotics. We needed to think differently to attack this problem," says Brian Tsuji, PharmD, an author on two recent studies and associate professor in the Department of Pharmacy Practice in the UB School of Pharmacy and Pharmaceutical Sciences. One study, "Polymyxin-resistant, carbapenem-resistant Acinetobacter baumannii is eradicated by a triple combination of agents that lack individual activity," was published in the May issue of the Journal of Antimicrobial Chemotherapy, while another study, "Polymyxin B-Based Triple Combinations Wage War Against KPC-2-producing Klebsiella pneumoniae: New Dosing Strategies for Old Allies," was published in the April issue of Antimicrobial Agents and Chemotherapy. Non-traditional combinations of medication are frequently used to fight against superbug infections, however, questions remain over proper dosage and which combinations are most effective. The UB researchers tested combinations of the antibiotics polymyxin B, meropenem and ampicillin-sulbactam against the pathogen Acinetobacter baumannii. The bacterium Klebsiella pneumoniae was treated with polymyxin B, meropenem, and rifampin. "Each antibiotic was chosen to complement the other drugs' mechanisms of bacterial killing," says Justin Lenhard, PharmD, first author on the investigation of Acinetobacter baumannii and former postdoctoral researcher in Tsuji's lab. Lenhard is now an assistant professor at California Northstate University College of Pharmacy. "By combining antimicrobials that exert their bacterial killing in different ways, it is possible to outmaneuver the ESKAPE pathogens and completely overwhelm the bacteria's defensive countermeasures," he said. The medications were applied to the bacterial samples individually, in pairs and in triple combinations. Both the time needed for the antibiotics to kill the bacteria and the time it took for the pathogens to repopulate were measured. For the tests on Acinetobacter baumannii, none of the antibiotics were able to kill the bacteria when used alone. Of the pairs of antibiotics, only the grouping of polymyxin B and meropenem was able to effectively kill the pathogen, but the bacteria gradually regrew over three days. The triple combination achieved a similar kill rate to the pair of polymyxin B and meropenem, but the addition of ampicillin-sulbactam prevented regrowth of the pathogen. Within 96 hours, no viable bacteria cells were detected after exposure to all three antibiotics. The tests against Klebsiella pneumoniae were led by Zackery Bulman, PharmD, a postdoctoral researcher in Tsuji's lab. Individual antibiotics were unable to sustain the killing of bacteria over a 24-hour period. The most effective double combination was polymyxin B and rifampin, which killed bacteria for up to 30 hours before the population regrew to initial levels. The triple combination of polymyxin B, meropenem, and rifampin produced the highest kill rates and tripled the time it took for bacteria to regrow to 72 hours. Rifampin, the researchers suspect, temporarily suppresses the antibiotic resistance of Klebsiella pneumoniae, allowing the trio to destroy the bacteria. Additional research is required to validate the treatments against other clinically relevant strains of bacteria, but the results of both studies are promising. "These new antibiotic combinations may help to guide therapy in infections where no treatments appear to exist," says Tsuji.


News Article | May 25, 2017
Site: www.eurekalert.org

Antibiotic combinations prove effective against two ESKAPE pathogens, a sextet of superbugs that cause the majority of US hospital infections BUFFALO, N.Y. - In the fight against super bacteria, University at Buffalo scientists are relying on strength in numbers to win the battle against drug resistance. A team of researchers found that combinations of three antibiotics - that are each ineffective against superbugs when used alone - are capable of eradicating two of the six ESKAPE pathogens when delivered together. ESKAPE pathogens are a group of antimicrobial-resistant bacteria that pose a grave threat, causing more than 2 million infections and nearly 23,000 deaths a year, according to the Centers for Disease Control and Prevention. The six super bacteria are also responsible for a substantial number of infections in hospitals. The new, triple combination treatments provide a new weapon in the evolutionary arms race between modern medicine and harmful bacteria. "These bacteria are extremely problematic and have become resistant to nearly all available antibiotics. We needed to think differently to attack this problem," says Brian Tsuji, PharmD, an author on two recent studies and associate professor in the Department of Pharmacy Practice in the UB School of Pharmacy and Pharmaceutical Sciences. One study, "Polymyxin-resistant, carbapenem-resistant Acinetobacter baumannii is eradicated by a triple combination of agents that lack individual activity," was published in the May issue of the Journal of Antimicrobial Chemotherapy, while another study, "Polymyxin B-Based Triple Combinations Wage War Against KPC-2-producing Klebsiella pneumoniae: New Dosing Strategies for Old Allies," was published in the April issue of Antimicrobial Agents and Chemotherapy. Non-traditional combinations of medication are frequently used to fight against superbug infections, however, questions remain over proper dosage and which combinations are most effective. The UB researchers tested combinations of the antibiotics polymyxin B, meropenem and ampicillin-sulbactam against the pathogen Acinetobacter baumannii. The bacterium Klebsiella pneumoniae was treated with polymyxin B, meropenem, and rifampin. "Each antibiotic was chosen to complement the other drugs' mechanisms of bacterial killing," says Justin Lenhard, PharmD, first author on the investigation of Acinetobacter baumannii and former postdoctoral researcher in Tsuji's lab. Lenhard is now an assistant professor at California Northstate University College of Pharmacy. "By combining antimicrobials that exert their bacterial killing in different ways, it is possible to outmaneuver the ESKAPE pathogens and completely overwhelm the bacteria's defensive countermeasures," he said. The medications were applied to the bacterial samples individually, in pairs and in triple combinations. Both the time needed for the antibiotics to kill the bacteria and the time it took for the pathogens to repopulate were measured. For the tests on Acinetobacter baumannii, none of the antibiotics were able to kill the bacteria when used alone. Of the pairs of antibiotics, only the grouping of polymyxin B and meropenem was able to effectively kill the pathogen, but the bacteria gradually regrew over three days. The triple combination achieved a similar kill rate to the pair of polymyxin B and meropenem, but the addition of ampicillin-sulbactam prevented regrowth of the pathogen. Within 96 hours, no viable bacteria cells were detected after exposure to all three antibiotics. The tests against Klebsiella pneumoniae were led by Zackery Bulman, PharmD, a postdoctoral researcher in Tsuji's lab. Individual antibiotics were unable to sustain the killing of bacteria over a 24-hour period. The most effective double combination was polymyxin B and rifampin, which killed bacteria for up to 30 hours before the population regrew to initial levels. The triple combination of polymyxin B, meropenem, and rifampin produced the highest kill rates and tripled the time it took for bacteria to regrow to 72 hours. Rifampin, the researchers suspect, temporarily suppresses the antibiotic resistance of Klebsiella pneumoniae, allowing the trio to destroy the bacteria. Additional research is required to validate the treatments against other clinically relevant strains of bacteria, but the results of both studies are promising. "These new antibiotic combinations may help to guide therapy in infections where no treatments appear to exist," says Tsuji. The research was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Investigators on the study, "Polymyxin B-Based Triple Combinations Wage War Against KPC-2-producing Klebsiella pneumoniae: New Dosing Strategies for Old Allies," include Bulman and Patricia N. Holden, UB School of Pharmacy and Pharmaceutical Sciences; Michael J. Satlin and Thomas J. Walsh, Weill Cornell Medical College in Cornell University; Liang Chen and Barry N. Kreiswirth, New Jersey Medical School in Rutgers University; Beom Soo Shin, Catholic University of Daegu; Alan Forrest, Eshelman School of Pharmacy in the University of North Carolina; and Roger L. Nation and Jian Li, Monash Institute of Pharmaceutical Sciences in Monash University. Additional researchers on the study, "Polymyxin-resistant, carbapenem-resistant Acinetobacter baumannii is eradicated by a triple combination of agents that lack individual activity," include Forrest; Shin; Nation; Li; Visanu Thamlikitkul, Department of Medicine in Mahidol University; Fernanda P. Silveira, University of Pittsburgh Medical Center; Samira M. Garonzik, UB School of Pharmacy and Pharmaceutical Sciences; Xun Tao and Jürgen B. Bulitta, College of Pharmacy in the University of Florida; and Keith S. Kaye, University of Michigan Medical School.


The paper, published 3 May and accessible via open access, explores the use of multimodal autofluorescence and light scattering to evaluate functional changes in the kidneys after ischemic injury. Conditions including accumulated arterial plaque or blood clots restrict the flow of oxygen and glucose to organs, and prolonged periods of such ischemia can compromise function. In "Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy," the authors report on their evaluation of various optical signatures to predict kidney viability and suggest a noncontact approach to provide clinically useful information in real time. While other current work in this area uses expensive multiphoton and laser-based techniques, the authors reduced expenses by switching to camera-based imaging. Currently, there is no real-time tool to measure the degree of ischemic injury incurred in tissue or to predict the return of its function. The inability to decisively determine tissue functional status runs two great risks: that dysfunctional tissue may be transplanted, increasing the morbidity and mortality of the patient; and that much-needed functional kidney tissue may be discarded. In their study, Rajesh Raman of Lawrence Livermore National Lab and co-authors Christopher Pivetti and Christoph Troppmann of the University of California Davis, Rajendra Ramsamooj of California Northstate University, and Stavros Demos of Lawrence Livermore acquired autofluorescence images of kidneys in vivo under 355, 325, and 266 nm illumination. Light-scattering images were collected at the excitation wavelengths while using a relatively narrow band light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. The recorded signals were then analyzed to obtain time constants, which were correlated to kidney dysfunction as determined by a subsequent survival study and histopathological analysis. Analysis of the light-scattering and autofluorescence images suggests that variations in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, combined with vascular response, contribute to the behavior of the recorded signals. These are used to obtain tissue functional information and enable the ability to predict post-transplant kidney function. This information can also be applied to the prediction of kidney failure when visual observation cannot, almost immediately following an injury. Reviewers of the study suggested other promising applications for future development, and envisioned this approach being used as a screening tool for assessing kidney viability prior to transplant. In particular, they said, these cost-effective screening methods could benefit healthcare in developing countries. Multimodal imaging also has provided insights into other physiological events that may occur during ischemia and reperfusion. "This work's exceptional value lies in the realization of a workable practical system that has excellent potential to be adopted in field situations," said journal associate editor Andreas Mandelis (University of Toronto). More information: Rajesh N. Raman et al, Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy, Journal of Biomedical Optics (2017). DOI: 10.1117/1.JBO.22.5.056001


News Article | May 5, 2017
Site: www.prweb.com

A new technique developed by researchers at Lawrence Livermore National Lab promises to improve accuracy and lower costs of real-time assessment of kidney function, reports an article published this week by SPIE, the international society for optics and photonics, in the Journal of Biomedical Optics. The paper, published 3 May and accessible via open access, explores the use of multimodal autofluorescence and light scattering to evaluate functional changes in the kidneys after ischemic injury. Conditions including accumulated arterial plaque or blood clots restrict the flow of oxygen and glucose to organs, and prolonged periods of such ischemia can compromise function. In “Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy,” the authors report on their evaluation of various optical signatures to predict kidney viability and suggest a noncontact approach to provide clinically useful information in real time. While other current work in this area uses expensive multiphoton and laser-based techniques, the authors reduced expenses by switching to camera-based imaging. Currently, there is no real-time tool to measure the degree of ischemic injury incurred in tissue or to predict the return of its function. The inability to decisively determine tissue functional status runs two great risks: that dysfunctional tissue may be transplanted, increasing the morbidity and mortality of the patient; and that much-needed functional kidney tissue may be discarded. In their study, Rajesh Raman of Lawrence Livermore National Lab and co-authors Christopher Pivetti and Christoph Troppmann of the University of California Davis, Rajendra Ramsamooj of California Northstate University, and Stavros Demos of Lawrence Livermore acquired autofluorescence images of kidneys in vivo under 355, 325, and 266 nm illumination. Light-scattering images were collected at the excitation wavelengths while using a relatively narrow band light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. The recorded signals were then analyzed to obtain time constants, which were correlated to kidney dysfunction as determined by a subsequent survival study and histopathological analysis. Analysis of the light-scattering and autofluorescence images suggests that variations in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, combined with vascular response, contribute to the behavior of the recorded signals. These are used to obtain tissue functional information and enable the ability to predict post-transplant kidney function. This information can also be applied to the prediction of kidney failure when visual observation cannot, almost immediately following an injury. Reviewers of the study suggested other promising applications for future development, and envisioned this approach being used as a screening tool for assessing kidney viability prior to transplant. In particular, they said, these cost-effective screening methods could benefit healthcare in developing countries. Multimodal imaging also has provided insights into other physiological events that may occur during ischemia and reperfusion. “This work's exceptional value lies in the realization of a workable practical system that has excellent potential to be adopted in field situations,” said journal associate editor Andreas Mandelis (University of Toronto). Lihong Wang, Bren Professor of Medical Engineering and Electrical Engineering at the California Institute of Technology, is editor-in-chief of the Journal of Biomedical Optics. The journal is published in print and digitally in the SPIE Digital Library, which contains more than 458,000 articles from SPIE journals, proceedings, and books, with approximately 18,000 new research papers added each year. SPIE is the international society for optics and photonics, an educational not-for-profit organization founded in 1955 to advance light-based science, engineering, and technology. The Society serves nearly 264,000 constituents from approximately 166 countries, offering conferences and their published proceedings, continuing education, books, journals, and the SPIE Digital Library. In 2016, SPIE provided $4 million in support of education and outreach programs. http://www.spie.org


News Article | May 5, 2017
Site: www.eurekalert.org

Journal of Biomedical Optics authors evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability BELLINGHAM, Washington, USA , and CARDIFF, UK -- A new technique developed by researchers at Lawrence Livermore National Lab promises to improve accuracy and lower costs of real-time assessment of kidney function, reports an article published this week by SPIE, the international society for optics and photonics, in the Journal of Biomedical Optics. The paper, published 3 May and accessible via open access, explores the use of multimodal autofluorescence and light scattering to evaluate functional changes in the kidneys after ischemic injury. Conditions including accumulated arterial plaque or blood clots restrict the flow of oxygen and glucose to organs, and prolonged periods of such ischemia can compromise function. In "Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy," the authors report on their evaluation of various optical signatures to predict kidney viability and suggest a noncontact approach to provide clinically useful information in real time. While other current work in this area uses expensive multiphoton and laser-based techniques, the authors reduced expenses by switching to camera-based imaging. Currently, there is no real-time tool to measure the degree of ischemic injury incurred in tissue or to predict the return of its function. The inability to decisively determine tissue functional status runs two great risks: that dysfunctional tissue may be transplanted, increasing the morbidity and mortality of the patient; and that much-needed functional kidney tissue may be discarded. In their study, Rajesh Raman of Lawrence Livermore National Lab and co-authors Christopher Pivetti and Christoph Troppmann of the University of California Davis, Rajendra Ramsamooj of California Northstate University, and Stavros Demos of Lawrence Livermore acquired autofluorescence images of kidneys in vivo under 355, 325, and 266 nm illumination. Light-scattering images were collected at the excitation wavelengths while using a relatively narrow band light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. The recorded signals were then analyzed to obtain time constants, which were correlated to kidney dysfunction as determined by a subsequent survival study and histopathological analysis. Analysis of the light-scattering and autofluorescence images suggests that variations in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, combined with vascular response, contribute to the behavior of the recorded signals. These are used to obtain tissue functional information and enable the ability to predict post-transplant kidney function. This information can also be applied to the prediction of kidney failure when visual observation cannot, almost immediately following an injury. Reviewers of the study suggested other promising applications for future development, and envisioned this approach being used as a screening tool for assessing kidney viability prior to transplant. In particular, they said, these cost-effective screening methods could benefit healthcare in developing countries. Multimodal imaging also has provided insights into other physiological events that may occur during ischemia and reperfusion. "This work's exceptional value lies in the realization of a workable practical system that has excellent potential to be adopted in field situations," said journal associate editor Andreas Mandelis (University of Toronto). Lihong Wang, Bren Professor of Medical Engineering and Electrical Engineering at the California Institute of Technology, is editor-in-chief of the Journal of Biomedical Optics. The journal is published in print and digitally in the SPIE Digital Library, which contains more than 458,000 articles from SPIE journals, proceedings, and books, with approximately 18,000 new research papers added each year. SPIE is the international society for optics and photonics, an educational not-for-profit organization founded in 1955 to advance light-based science, engineering, and technology. The Society serves nearly 264,000 constituents from approximately 166 countries, offering conferences and their published proceedings, continuing education, books, journals, and the SPIE Digital Library. In 2016, SPIE provided $4 million in support of education and outreach programs. http://www.


Feng X.,California Northstate University | Tonnesen M.G.,State University of New York at Stony Brook | Tonnesen M.G.,Veterans Affairs Medical Center | Mousa S.A.,Albany College of Pharmacy and Health Sciences | Clark R.A.F.,State University of New York at Stony Brook
International Journal of Cell Biology | Year: 2013

Angiogenesis is a highly regulated event involving complex, dynamic interactions between microvascular endothelial cells and extracellular matrix (ECM) proteins. Alteration of ECM composition and architecture is a hallmark feature of wound clot and tumor stroma. We previously reported that during angiogenesis, endothelial cell responses to growth factors are modulated by the compositional and mechanical properties of a surrounding three-dimensional (3D) extracellular matrix (ECM) that is dominated by either cross-linked fibrin or type I collagen. However, the role of 3D ECM in the regulation of angiogenesis associated with wound healing and tumor growth is not well defined. This study investigates the correlation of sprout angiogenesis and ECM microenvironment using in vivo and in vitro 3D angiogenesis models. It demonstrates that fibrin and type I collagen 3D matrices differentially but synergistically regulate sprout angiogenesis. Thus blocking both integrin alpha v beta 3 and integrin alpha 2 beta 1 might be a novel strategy to synergistically block sprout angiogenesis in solid tumors. © 2013 Xiaodong Feng et al.


Mandal A.,Northeast Ohio Medical University | Bishayee A.,California Northstate University
International Journal of Molecular Sciences | Year: 2015

Trianthema portulacastrum, a medicinal and dietary plant, has gained substantial importance due to its various pharmacological properties, including anti-inflammatory and anticarcinogenic activities. We have recently reported that a characterized T. portulacastrum extract (TPE) affords a considerable chemoprevention of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumorigenesis though the underlying mechanisms are not completely understood. The objective of this study was to investigate anti-inflammatory mechanisms of TPE during DMBA mammary carcinogenesis in rats by monitoring cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90), nuclear factor-kappaB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Mammary tumors were harvested from our previous study in which TPE (50-200 mg/kg) was found to inhibit mammary tumorigenesis in a dose-response manner. The expressions of intratumor COX-2, HSP90, NF-κB, inhibitory kappaB-alpha (IκBα) and Nrf2 were determined by immunohistochemistry. TPE downregulated the expression of COX-2 and HSP90, blocked the degradation of IκBα, hampered the translocation of NF-κB from cytosol to nucleus and upregulated the expression and nuclear translocation of Nrf2 during DMBA mammary carcinogenesis. These results in conjunction with our previous findings suggest that TPE prevents DMBA-induced breast neoplasia by anti-inflammatory mechanisms mediated through simultaneous and differential modulation of two interconnected molecular circuits, namely NF-κB and Nrf2 signaling pathways. © 2015 by the authors; licensee MDPI, Basel, Switzerland.


This review glances at the voltage-gated sodium (Na+) channel (NaV) from the skewed perspective of natural history and the history of ideas. Beginning with the earliest natural philosophers, the objective of biological science and physiology was to understand the basis of life and discover its intimate secrets. The idea that the living state of matter differs from inanimate matter by an incorporeal spirit or mystical force was central to vitalism, a doctrine based on ancient beliefs that persisted until the last century. Experimental electrophysiology played a major role in the abandonment of vitalism by elucidating physiochemical mechanisms that explained the electrical excitability of muscle and nerve. Indeed, as a principal biomolecule underlying membrane excitability, the NaV channel may be considered as the physical analog or surrogate for the vital spirit once presumed to animate higher forms of life. NaV also epitomizes the "other secret of life" and functions as a quantal transistor element of biological intelligence. Subplots of this incredible but true story run the gamut from electric fish to electromagnetism, invention of the battery, venomous animals, neurotoxins, channelopathies, arrhythmia, anesthesia, astrobiology, etc. © 2016 Elsevier Inc.


Ofstad W.,California Northstate University | Brunner L.J.,California Northstate University
American Journal of Pharmaceutical Education | Year: 2013

Instructors wanting to engage students in the classroom seek methods to augment the delivery of factual information and help students move from being passive recipients to active participants in their own learning. One such method that has gained interest is team-based learning. This method encourages students to be prepared before class and has students work in teams while in the classroom. Key benefits to this pedagogy are student engagement, improved communication skills, and enhanced critical-thinking abilities. In most cases, student satisfaction and academic performance are also noted. This paper reviews the fundamentals of team-based learning in pharmacy education and its implementation in the classroom. Literature reports from medical, nursing, and pharmacy programs are also discussed.


Khansari P.S.,California Northstate University | Sperlagh B.,Hungarian Academy of Sciences
Inflammopharmacology | Year: 2012

In recent years, compelling evidence suggests that inflammation plays a critical role in the pathology of a vast number of neurological diseases such as stroke, Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis as well as neuropsychiatric diseases such as major depression and schizophrenia. Despite emerging evidence in human and animal models alike, modulating inflammatory responses have yet to be proven as an effective treatment to prevent or delay the progression of these diseases. The primary focus of this special edition is to highlight some of our current findings on the complexities of targeting neuroinflammation as a novel therapy, and its role in neurological and psychiatric disorders. © 2011 CARS.

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