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Adverse Effects of Nonsteroidal Antiinflammatory Drugs: An Update of Gastrointestinal, Cardiovascular and Renal ComplicationsHarirforoosh, Sam, Asghar, Waheed, Jamali, Fakhreddin 31 December 2013 (has links)
Non-steroidal anti-inflammatory drugs (NSAIDs) are used chronically to reduce pain and inflammation in patients with arthritic conditions, and also acutely as analgesics by many patients. Both therapeutic and adverse effects of NSAIDs are due to inhibition of cyclooxygenase (COX) enzyme. NSAIDs are classified as non-selective and COX-2-selective inhibitors (COXIBS) based on their extent of selectivity for COX inhibition. However, regardless of their COX selectivity, reports are still appearing on the GI side effect of NSAIDs particularly on the lower gastrointestinal (GI) tract and the harmful role of their controlled release formulations. In addition, previously unpublished data stored in the sponsor's files, question the GI sparing properties of rofecoxib, a COXIB that has been withdrawn due to cardiovascular (CV) side effects. Presently, the major side effects of NSAIDs are the GI complications, renal disturbances and CV events. There is a tendency to believe that all NSAIDs are associated with renal and CV side effects, a belief that is not supported by solid evidence. Indeed, lower but still therapeutics doses of some NSAIDs may be cardioprotective. In this review, we briefly discuss the GI toxicity of the NSAIDs and assess their renal and CV adverse effects in more detail.
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White Paper on Pharmacy Admissions: Developing a Diverse Work Force to Meet the Health-Care Needs of an Increasingly Diverse SocietyWall, Andrea L., Aljets, Alex, Ellis, Steve C., Hansen, Daniel J., Mark Moore, W., Petrelli, Heather M.W., Speedie, Marilyn K., TenHoeve, Tom, Watchmaker, Cynthia, Winnike, Janeen S., Wurth, Stephanie D. 01 January 2015 (has links)
No description available.
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Drug Development and Discovery: Challenges and OpportunitiesMoridani, Majid, Harirforoosh, Sam 01 January 2014 (has links)
No description available.
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Examining Flanking Sequence Specificity and Topological Specificity in the Binding of Various Molecular Types to DNAs Using Restriction Endonuclease Activity AssaysWinkle, S. A., Duran, E., Pulido, J., Santil, G., Talavera, M., Winkle, C., Sheardy, R. D., Ramsauer, V. 25 October 2011 (has links)
Observing alteration of restriction enzyme activity has been employed frequently to determine the sequence specificity of the binding of many types of molecules to DNAs. Generally, these studies employed restriction enzymes which cut the target DNA several times. The effects of binding to sequences flanking the restriction enzyme cleavage sites may have been obscured. In this study, we report on restriction enzyme activity assays of the binding of the intercalators actinomycin D, ametantrone and ethidium, the groove binder netropsin, and the covalent binding cisplatin to a mixture of supercoiled and relaxed phiX 174 RF DNA using restriction enzymes which cleave this DNA once or twice. Sequence selectivities and topological selectivities were observed for these ligands. In some cases restriction enzymes not containing the reported preferred binding sites had altered activities, suggesting binding to flanking sequences affects activity in neighboring DNA sequences.
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The Role of Cation-Chloride Transporters in Brain IschemiaSun, Dandan, Kintner, Douglas B., Pond, Brooks B. 01 December 2010 (has links)
This chapter presents the role of cation-chloride transporters in brain ischemia. Ischemic stroke is the inevitable consequence of transient or permanent reduction of regional cerebral blood flow to brain tissue. Because of the high energy demand of brain tissue, a reduction of blood flow below ∼50% will cause serious perturbations in tissue metabolism. The resulting tissue damage will depend on the severity and length of the brain perfusion deficit. The brain damage in the infarct core is considered to be irreversible in focal stroke. Within minutes, there is a complete collapse of energy production, dissipation of ion gradients, cessation of macromolecular synthesis and loss of cell structure. On the other hand, the penumbra, which surrounds the infarct core, retains residual blood flow and can remain viable for hours or even days. The penumbra tissue is the target for therapeutic intervention.
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Pharmacokinetics of Synthetic Cathinones Found in Bath Salts in Mouse Brain and Plasma Using High-Pressure Liquid Chromatography–Tandem Mass SpectrometryGearlds, Courtney, Bouldin, Jessica B., McKinney, Mariah, Schreiner, Shannon, Brown, Stacy D., Pond, Brooks B. 01 January 2021 (has links)
Background and Objectives: Approximately 10 years ago, “bath salts” became popular as legal alternatives to the psychostimulants cocaine and the amphetamines. These products contained synthetic cathinones, including 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4-methylenedioxymethcathinone (methylone). Most preclinical investigations have only assessed the effects of these synthetic cathinones independently; however, case reports and Drug Enforcement Administration (DEA) studies indicate that bath salts contain mixtures of these substances. In this study, we examine the pharmacokinetic interactions of the drug combination. We hypothesized that combined exposure to MDPV, mephedrone, and methylone would result in increased drug concentrations and enhanced total drug concentrations when compared to individual administration. Methods: Adolescent male Swiss–Webster mice were injected intraperitoneally with either 10 mg/kg MDPV, 10 mg/kg mephedrone, 10 mg/kg methylone, or 10 mg/kg combined MDPV, mephedrone, and methylone. Following injection, brains and plasma were collected at 1, 10, 15, 30, 60, and 120 min. Drugs were extracted via solid-phase extraction, and concentrations were determined using a previously published high-pressure liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method. Results: All drugs crossed the blood–brain barrier quickly. For methylone, the maximal concentration (Cmax) and the total drug exposure [as represented by the area under the concentration-time curve (AUC)] were significantly higher when combined with mephedrone and MDPV in both matrices (2.89-fold increase for both Cmax and AUC with combined treatment). For mephedrone, the Cmax was unchanged, but the AUC in brain was increased when in combination by approximately 34%. Interestingly, for MDPV, the Cmax was unchanged, yet the AUC was higher when MDPV was administered individually (there was a 62% decrease in AUC with combined treatment). Conclusions: The pharmacokinetics of methylone, mepedrone, and MDPV are altered when the drugs are used in combination. These data provide insight into the consequences of co-exposure to synthetic cathinones in popular bath salt products.
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De-Conflating Religiosity/SpiritualityRoane, David S., Harirforoosh, Sam 01 January 2019 (has links)
No description available.
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A Simple and Sensitive High-Performance Liquid Chromatography–Electrochemical Detection Assay for the Quantitative Determination of Monoamines and Respective Metabolites in Six Discrete Brain Regions of MiceAllen, Serena A., Rednour, Stephanie, Shepard, Samantha, Pond, Brooks Barnes 01 November 2017 (has links)
A rapid, sensitive, and reproducible assay is described for the quantitative determination of the monoamine neurotransmitters dopamine, norepinephrine and serotonin, their metabolites, and the internal standard 3,4-dihydroxybenzlyamine hydro-bromide in mouse brain homogenate using high-performance liquid chromatography with electrochemical detection. The method was validated in the following brain areas: frontal cortex, striatum, nucleus accumbens, hippocampus, substantia nigra pars compacta and ventral tegmental area. Biogenic amines and relevant metabolites were extracted from discrete brain regions using a simple protein precipitation procedure, and the chromatography was achieved using a C18 column. The method was accurate over the linear range of 0.300–30 ng/mL (r = 0.999) for dopamine and 0.300–15 ng/mL (r = 0.999) for norepinephrine, 3,4-dihydroxybenzlyamine hydro-bromide, homovanillic acid and 5-hydroxyindolacetic acid, with detection limits of ~0.125 ng/mL (5 pg on column) for each of these analytes. Accuracy and linearity for serotonin were observed throughout the concentration range of 0.625–30 ng/mL (r = 0.998) with an analytical detection limit of ~0.300 ng/mL (12 pg on column). Relative recoveries for all analytes were approximately ≥90% and the analytical run time was <10 min. The described method utilized minimal sample preparation procedures and was optimized to provide the sensitivity limits required for simultaneous monoamine and metabolite analysis in small, discrete brain tissue samples.
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Misuses of Regression and ANCOVA in Educational ResearchKarpen, Samuel C. 01 January 2017 (has links)
No description available.
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Design and Optimization of PLGA-Based Diclofenac Loaded NanoparticlesCooper, Dustin L., Harirforoosh, Sam 28 January 2014 (has links)
Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug formulations. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Nonsteroidal anti-inflammatory drugs such as diclofenac block cyclooxygenase expression and reduce prostaglandin synthesis, which can lead to several side effects such as gastrointestinal bleeding and renal insufficiency. The aim of this study was to formulate and characterize diclofenac entrapped poly(lactide-co-glycolide) (PLGA) based nanoparticles. Nanoparticles were formulated using an emulsion-diffusion- evaporation technique with varying concentrations of poly vinyl alcohol (PVA) (0.1, 0.25, 0.5, or 1%) or didodecyldimethylammonium bromide (DMAB) (0.1, 0.25, 0.5, 0.75, or 1%) stabilizers centrifuged at 8,800 rpm or 12,000 rpm. The resultant nanoparticles were evaluated based on particle size, zeta potential, and entrapment efficacy. DMAB formulated NPs showed the lowest particle size (108±2.1 nm) and highest zeta potential (-27.71±0.6 mV) at 0.1 and 0.25% respectively, after centrifugation at 12,000 rpm. Results of the PVA based NP formulation showed the smallest particle size (92.4±7.6 nm) and highest zeta potential (-11.14±0.5 mV) at 0.25% and 1% w/v, respectively, after centrifugation at 12,000 rpm. Drug entrapment reached 77.3±3.5% and 80.2±1.2% efficiency with DMAB and PVA formulations, respectively. The results of our study indicate the use of DMAB for increased nanoparticle stability during formulation. Our study supports the effective utilization of PLGA based nanoparticle formulation for diclofenac.
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