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Nowak M.A.,California Northstate University | Nelson R.E.,ViroPharma | Breidenbach J.L.,Sanford Medical Center | Thompson P.A.,University of South Dakota | Carson P.J.,Sanford Medical Center
American Journal of Health-System Pharmacy | Year: 2012

Purpose. A pre-post analysis of an antimicrobial stewardship program (ASP) involving the use of data-mining software to prospectively identify cases for ASP intervention was conducted. Methods. The investigators evaluated clinical outcomes and cost metrics before and after implementation of the ASP, which entailed daily physician review of summary reports on all adult inpatients receiving antimicrobial therapy. The primary outcome measures were annual antimicrobial expenditures and rates of infections due to common nosocomial pathogens; secondary outcome measures included patient survival and length of stay (LOS) in cases involving the indicator diagnoses of pneumonia and abdominal sepsis. Results. Antimicrobial expenditures, which had increased by an average of 14.4% annually in the years preceding ASP implementation, decreased by 9.75% in the first year of the program and remained relatively stable in subsequent years, with overall cumulative cost savings estimated at $1.7 million. Rates of nosocomial infections involving Clostridium difficile, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci all decreased after ASP implementation. A pre-post comparison of survival and LOS in patients with pneumonia (n = 2186) or abdominal sepsis (n = 225) showed no significant differences in those outcomes in either patient group, possibly due to the hospital's initiation of other, concurrent infection-control programs during the study period. Conclusion. A prospective collaborative ASP employed automated reports to efficiently identify key data for ASP review. After ASP implementation, antimicrobial expenditures and rates of nosocomial infections caused by resistant pathogens dropped without significant changes in patient survival, LOS, and readmissions for the two studied illness categories. Copyright © 2012, American Society of Health-System Pharmacists, Inc. All rights reserved.

Arias H.R.,California Northstate University | Feuerbach D.,Novartis | Targowska-Duda K.M.,Medical University of Lublin | Aggarwal S.,Duquesne University | And 2 more authors.
Neurochemistry International | Year: 2012

The pharmacological properties of (±)-2-(N-tert-butylamino)- 3′-iodo-4′-azidopropiophenone [(±)-SADU-3-72], a photoreactive analog of bupropion (BP), were characterized at different muscle nicotinic acetylcholine receptors (AChRs) by functional and structural approaches. Ca2+ influx results indicate that (±)-SADU-3-72 is 17- and 6-fold more potent than BP in inhibiting human (h) embryonic (hα1β1γδ) and adult (hα1β1δ) muscle AChRs, respectively. (±)-SADU-3-72 binds with high affinity to the [ 3H]TCP site within the resting or desensitized Torpedo AChR ion channel, whereas BP has higher affinity for desensitized AChRs. Molecular docking results indicate that both SADU-3-72 enantiomers interact with the valine (position 13′) and serine (position 6′) rings. However, an additional domain, between the outer (position 20′) and valine rings, is observed in Torpedo AChR ion channels. Our results indicate that the azido group of (±)-SADU-3-72 may enhance its interaction with polar groups and the formation of hydrogen bonds at AChRs, thus supporting the observed higher potency and affinity of (±)-SADU-3-72 compared to BP. Collectively our results are consistent with a model where BP/SADU-3-72 and TCP bind to overlapping sites within the lumen of muscle AChR ion channels. Based on these results, we believe that (±)-SADU-3-72 is a promising photoprobe for mapping the BP binding site, especially within the resting AChR ion channel. © 2012 Elsevier Ltd. All rights reserved.

An R.,University of Illinois at Urbana - Champaign | Lu L.,California Northstate University
Journal of Psychosomatic Research | Year: 2016

Objective: The upsurge in prevalence and long-term use of antidepressants among older adults might have profound health implications beyond depressive symptom management. This study examined the relationship between antidepressant use and functional limitation onset in U.S. older adults. Methods: Study sample came from 2006 and 2008 waves of the Health and Retirement Study, in combination with data from 2005 and 2007 Prescription Drug Study. Self-reported antidepressant use was identified based on the therapeutic classification of Cerner Multum's Lexicon. Functional limitations were classified into those pertaining to physical mobility, large muscle function, activities of daily living, gross motor function, fine motor function, and instrumental activities of daily living. Cox proportional hazard models were performed to assess the effects of antidepressant use on future functional limitation onset by limitation category, antidepressant type, and length of use, adjusted by depression status and other individual characteristics. Results: Antidepressant use for one year and longer was associated with an increase in the risk of functional limitation by 8% (95% confidence interval = 4%-12%), whereas the relationship between antidepressant use less than a year and function limitation was statistically nonsignificant. Antidepressant use was associated with an increase in the risk of functional limitation by 8% (3%-13%) among currently nondepressed participants but not currently depressed participants. Conclusion: Long-term antidepressant use in older adults should be prudently evaluated and regularly monitored to reduce the risk of functional limitation. Future research is warranted to examine the health consequences of extended and/or off-label antidepressant use in absence of depressive symptoms. © 2015 Elsevier Inc.

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.

Arias H.R.,California Northstate University | Lopez J.J.,University of Santiago de Chile | Feuerbach D.,Novartis | Fierro A.,University of Santiago de Chile | And 2 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2013

This work presents the design and synthesis of a series of novel 2-benzylquinuclidine derivatives, comprising 12 methiodide and 11 hydrochloride salts, and their structural and pharmacological characterization at the human (h) α7 and α4β2 nicotinic receptors (nAChRs). The antagonistic potency of these compounds was tested by Ca2+ influx assays on cells expressing the hα7 or hα4β2 nAChR subtype. To determine the inhibitory mechanisms, additional radioligand binding experiments were performed. The results indicate that the methiodides present the highest affinities for the hα7 nAChR agonist sites, while the same compounds bind preferably to the hα4β2 nAChR ion channel domain. These results indicate that the methiodides are competitive antagonists of the hα7 nAChR but noncompetitive antagonists of the hα4β2 subtype. Docking and molecular dynamics simulations showed that the methiodide derivative 8d binds to the hα7 orthosteric binding sites by forming stable cation-π interactions between the quaternized quinulinuim moiety and the aromatic box in the receptor, whereas compounds 7j and 8j block the hα4β2 AChR ion channel by interacting with a luminal domain formed between the serine (position 6′) and valine (position 13′) rings that overlaps the imipramine binding site. © 2013 Elsevier Ltd.

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.

Condren M.E.,University of Oklahoma | Desselle S.P.,California Northstate University
Journal of Patient Safety | Year: 2015

Objectives: The purpose of this study was to describe behaviors of community pharmacists related to pediatric prescriptions and examine the effect of demographic and situational factors on behaviors and confidence in performing recommended activities when dispensing medications for pediatric patients. Methods: The study employed a self-administered survey of community pharmacists in a regional chain. One intervention group attended a live continuing education session. A second intervention group received a dosing guide in the mail. One month after the intervention, both intervention groups and a control group completed the survey. Results: Sixty pharmacists participated, for a response rate of 61%. Obtaining a weight for a pediatric prescription was reported as difficult by participants, and 60% rarely obtained a weight if one was not provided. Only 32% of participants reported calculating a dose when the weight was available. The majority (92%) of participants stated they were confident in calculating a dose and detecting a dosing error for a child. Only the pharmacist's perception of the organizational culture correlated with their behaviors and level of confidence toward performing the activities surveyed (P < 0.005). Because of the small number of participants in the continuing education program, the impact of the intervention was unable to be measured. Conclusions: Pharmacists rarely check the accuracy of a weight-based dose for pediatric prescriptions, although they are confident in their ability to do so. Integrating this activity into the pharmacist's workflow and pharmacy culture is critical to reducing pediatric medication errors and promoting patient safety. © 2015 Wolters Kluwer Health, Inc.

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