Research Methods in Life Sciences Commons^™

Does Environmental Enrichment Promote Recovery From Stress In Rainbow Trout?, Kieran C. Pounder, Jennifer L. Mitchell, Jack S. Thomson, Tom G. Pottinger, Jonathan Buckley, Lynne U. Sneddon

Experimental Research and Animal Welfare Collection

The EU Directive on animal experimentation suggests that all protected animals should have enrichment to improve welfare yet relatively little research has been conducted on the impact of enrichment in fish. Studies employing enrichment in zebrafish have been contradictory and all fish species should be provided with species-specific enrichments relevant to their ecology. Salmonids are important experimental models in studies within aquaculture, toxicology and natural ecosystems. This study therefore sought to establish whether an enriched environment in an experimental aquarium may promote improved welfare in rainbow trout (Oncorhynchus mykiss) by enhancing their recovery from invasive procedures. Trout were …

Imparting Research Ethics In Emergency Medicine-A Perspective From The Developing World, Shahan Waheed, Muhammad Akbar Baig, Asad Mian

Department of Emergency Medicine

No abstract provided.

Use Of Non-Human Primates In Cocaine Research, Raija H. Bettauer

Experimentation Collection

No abstract provided.

Privatization Of Biomedical Research: A Short Term Answer With Long Term Consequences, Frederick Azalekor

Nebraska College Preparatory Academy: Senior Capstone Projects

Biomedical research owned by the government is now available to be owned by private institutions. This results in stagnant innovations because researchers have trouble with all the restrictions that are placed by private institutions. Privatization of biomedical research has short term positive effects but its negative effects are overarching and disastrous. One way to combat this, is for licenses to be deployed slowly with future consequences in mind.

• Privatization has short term benefits but long term disadvantages are disastrous. • To reduce damaging effect, privatization must be deployed slowly and carefully. • Patents or proprietary ownership must be given …

Epigenetic Modification Prevents Excessive Wound Healing And Scar Formation After Glaucoma Filtration Surgery, Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jason W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS).

METHODS. A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 lM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, a-smooth muscle …

Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan

Pharmacy Faculty Articles and Research

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading …

Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-β1, as well as matrix metalloproteinase (MMP) activity.

Methods—Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-β1 (5ng/ml) and SAHA (2.5μM) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and …

Assessment Of Celecoxib Poly(Lactic-Co-Glycolic) Acid Nanoformulation On Drug Pharmacodynamics And Pharmacokinetics In Rats, Sam Harirforoosh, Kelsi O. West, Derek E. Murrell, James W. Denham, Peter C. Panus, Greg A. Hanley

Pharmacy Faculty Articles and Research

OBJECTIVE: Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP).

MATERIALS AND METHODS: Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP). Plasma and urine (over 12 hrs) samples were collected prior to and post-treatment. The mean percent change from baseline of urine flow rate along with electrolyte concentrations in plasma …

Effect Of Prior Trauma Exposure On Alpha Amplitude, Heart Rate, And Self-Reported Negative Affect, Gina L. Denoble

All Master's Theses

This study was conducted to investigate whether the number of traumatic events an individual has previously experienced influences that individual’s physiological and psychological reactions when exposed to a negative affective stimulus followed by a mindfulness-based stress reduction (MBSR) intervention. Twenty-eight participants were placed into intact quasi-experimental groups based on their scores on the Traumatic Life Events Questionnaire (TLEQ). The negative affective stimulus consisted of a series of photos bearing negative affective valence. The photos were selected from the International Affective Picture System (IAPS), and paralleled the areas of trauma exposure evaluated by the TLEQ. All participants were exposed to the …

Predicting Human Drug Toxicity And Safety Via Animal Tests: Can Any One Species Predict Drug Toxicity In Any Other, And Do Monkeys Help?, Jarrod Bailey, Michelle Thew, Michael Balls

Laboratory Experiments Collection

Animals are still widely used in drug development and safety tests, despite evidence for their lack of predictive value. In this regard, we recently showed, by producing Likelihood Ratios (LRs) for an extensive data set of over 3,000 drugs with both animal and human data, that the absence of toxicity in animals provides little or virtually no evidential weight that adverse drug reactions will also be absent in humans. While our analyses suggest that the presence of toxicity in one species may sometimes add evidential weight for risk of toxicity in another, the LRs are extremely inconsistent, varying substantially for …

Beyond Pain—Controlling Suffering In Laboratory Animals, Bernard E. Rollin

Experimental Research and Animal Welfare Collection

No abstract provided.

Lessons From Toxicology: Developing A 21st‑Century Paradigm For Medical Research, Gill Langley, Christopher P. Austin, Anil K. Balapure, Linda S. Birnbaum, John R. Bucher, Julia Fentem, Suzanne C. Fitzpatrick, John R. Fowle Iii, Robert J. Kavlock, Hiroaki Kitano, Brett A. Lidbury, Alysson R. Muotri, Shuang-Qing Peng, Dmitry Sakharov, Troy Seidle, Thales Trez, Alexander Tonevitsky, Anja Van De Stolpe, Maurice Whelan, Catherine Willett

Experimentation Collection

Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translation. The full potential of advanced approaches may not be achieved within a 20th-century conceptual framework dominated by animal models. Novel technologies are being integrated into environmental health research and are also applicable to disease research, but these advances need a new medical research and drug discovery paradigm to gain maximal benefits. We suggest a new conceptual …

Arkansas Animal Science Department Report 2015, Paul Beck, Jason Apple, Beth Kegley, Charles Rosenkrans Jr.

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

The Flaws And Human Harms Of Animal Experimentation, Aysha Akhtar

Experimentation Collection

Nonhuman animal (“animal”) experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal …

The Flaws And Human Harms Of Animal Experimentation, Aysha Akhtar

Morality and Ethics of Animal Experimentation Collection

Nonhuman animal (“animal”) experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal …

The Multifactorial Role Of The 3rs In Shifting The Harm-Benefit Analysis In Animal Models Of Disease, Melanie L. Graham, Mark J. Prescott

Biomedical Research and Alternative Methods Collection

Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit …

Formulation And In Vivo Evaluation Of Aliskiren-Loaded Poly(Lactic-Co-Glycolic) Acid Nanoparticles, Derek E. Murrell, Jessica M. Coleman, Stacy D. Brown, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Aliskiren (ALS) is a direct renin inhibitor with low bioavailability and high drug cost. The goal of this study was to increase the bioavailability of ALS through nanoformulation. The optimized formulation was then evaluated in spontaneously hypertensive rats (SHRs). We developed an ALS poly(lactic-co-glycolic) acid nanoparticle (ALS-NP) through the emulsion–diffusion–evaporation method with various solvents, stabilizer concentrations, and centrifugation speeds. SHRs were orally dosed with 30 mg/kg ALS or dose equivalent ALS-NP. Several parameters were assayed in plasma and/or urine at baseline and 24 h post-dose, while pharmacokinetic analysis included serial sampling. The optimum formulation was found with ethyl acetate, a …

Low And Moderate Prenatal Ethanol Exposure Of Mice During Gastrulation Or Neurulation Delays Neurobehavioral Development, Uta B. Schambra, Jeff Goldsmith, Kevin Nunley, Yali Liu, Sam Harirforoosh, Heidi M. Schambra

Pharmacy Faculty Articles and Research

Human and animal studies show significant delays in neurobehavioral development in offspring after prolonged prenatal exposure to moderate and high ethanol doses resulting in high blood alcohol concentration (BECs). However, none have investigated the effects of lower ethanol doses given acutely during specific developmental time periods. Here, we sought to create a mouse model for modest and circumscribed human drinking during the 3rd and 4th weeks of pregnancy.

We acutely treated mice during embryo gastrulation on gestational day (GD) 7 or neurulation on GD8 with a low or moderate ethanol dose given via gavage that resulted in BECs of 107 …

Age-Dependent Breakdown Of The Blood Brain Barrier And Associated Changes In S100b Ko Mice, Eric V. Brown

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies play an important role in many autoimmune diseases. Recent research has shown that breakdown of the blood brain barrier (BBB) occurs concomitant to generation of brain reactive autoantibodies in many neurodegenerative diseases, which serve as biomarkers and drivers of pathology. SI00B, a calcium binding protein found most highly expressed in astrocytes which ensheathe the BBB, has many functions in neural development and signaling. Currently literature indicates that S100B KO mice develop normally, with no phenotypic abnormalities. Here, it is demonstrated that S100B KO mice seem to develop a chronic BBB breakdown similar to that seen in human neurodegenerative diseases. …

Human Animal Chimeras For Therapeutic Protocols, Bracha Sklar

The Science Journal of the Lander College of Arts and Sciences

Research on humans is limited, therefore human animal chimeras have been used to study human systems. A Human animal chimera is an animal containing animal and human cell lines. The primary goal of human animal chimera research is to establish an animal with human cellular characters, which can and should more realistically be able to imitate as closely as possible the in vivo situations in humans. This research is very important, because it allows scientists to study human systems in vivo using a humanized animal model. However ethical issues arise when experimenting with humans and animals being mixed together. Using …

2015 Oklahoma Research Day Full Program, Northeastern State University

Oklahoma Research Day Abstracts

This document contains all abstracts from the 2015 Oklahoma Research Day held at Northeastern State University.

Genome Engineering To Create Dominant Alleles In Caenorhabditis Elegans Using Crispr-Cas9 Technology, Abrar Sulaimani

Graduate School of Biomedical Sciences Theses and Dissertations

Many investigators have being using CRISPR-Cas9 as a method of genome engineering because it is easy, accurate and fast. This technique has been used to modify the genomes of a wide variety of organisms, including the nematode Caenorhabditis elegans (C. elegans). The short life cycle and ease of introducing exogenous plasmids make C. elegans an ideal system for advancing this technique. My thesis had two aims that focused on developing methods to create dominant alleles in C. elegans. Genetic modifications like precise deletion and insertions into a locus of chromosome are technically challenging. Additionally, although there are several ways of …

A Role For Folk Psychology In Animal Cognition Research, Kristin Andrews

Experimentation Collection

If we consider that the field of animal cognition research began with Darwin’s stories about clever animals, we can see that over the 150 years of work done in this field, there has been a slow swing back and forth between two extreme positions. One extreme is the view that other animals are very much like us, that we can use introspection in order to understand why other animals act as they do, and that no huge interpretive leap is required to understand animal minds. On the other extreme we have the view that other animals are utterly different from …

Histopathology And Oxidative Stress Analysis Of Concomitant Misoprostol And Celecoxib Administration, Derek E. Murrell, James W. Denham, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Nonsteroidal anti-inflammatory drugs (NSAIDs), non-selective or selective inhibitors of cyclooxygenase (COX-1 and -2), reduce pain and inflammation associated with arthritic diseases. Celecoxib, a COX-2-selective inhibitor providing decreased gastric injury relative to on-selective NSAIDs, is commonly prescribed. Misoprostol, a prostaglandin analog, supplements NSAID-inhibited prostaglandin levels. As concomitant celecoxib and misoprostol administration has been shown to intensify renal adverse effects, this article examined the influence of concomitant administration on hepatic histopathology, oxidative stress, and celecoxib concentration. On days 1 and 2, rat groups (n = 6) were gavaged twice daily (two groups with vehicle and two groups with 100 μg/kg misoprostol). From …

Role Of 5'Tg3'-Interacting Factors (Tgifs) In Vorinostat (Hdac Inhibitor)-Mediated Corneal Fibrosis Inhibition, Ajay Sharma, Nishant R. Sinha, Saad Siddiqui, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: We have previously reported that vorinostat, an FDA-approved, clinically used histone deacetylase (HDAC) inhibitor, attenuates corneal fibrosis in vivo in rabbits by blocking transforming growth factor β (TGFβ). The 5′TG3′-interacting factors (TGIFs) are transcriptional repressors of TGFβ1 signaling via the Smad pathway. The present study was designed to explore the expression of TGIFs in human corneal fibroblasts and to investigate their role in mediating the antifibrotic effect of vorinostat.

Methods: Human corneal fibroblast cultures were generated from donor corneas. RNA isolation, cDNA preparation, and PCR were performed to detect the presence of TGIF1 and TGIF2 transcripts. The cultures were …

Female Breakfast Skippers Display A Disrupted Cortisol Rhythm And Levated Blood Pressure, Megan Witbracht, Nancy L. Keim, Shavawn Forester, Adrianne Widaman, Kevin D. Laugero

United States Department of Agriculture-Agricultural Research Service / University of Nebraska-Lincoln: Faculty Publications

Chronic stress and over-activity in the hypothalamic–pituitary–adrenal (HPA) axis may link breakfast skipping and poor cardiometabolic health. Missing the first major meal of the day in rodents prolongs elevated circulating corticosterone at a time when it's normally decreasing. To extend these findings to humans, we hypothesized that habitual breakfast skippers would display a similar pattern of circulating cortisol and alterations in meal and stress-induced cortisol reactions. Normal weight to obese women aged 18–45 years old who were strictly defined as either breakfast skippers (n = 30) or breakfast eaters (n = 35) were invited to participate in our …

Celecoxib Or Diclofenac Hepatic Status In The Presence Or Absence Of Rebamipide, Derek E. Murrell, Yuyun Rahmasari, James W. Denham, Peter C. Panus, Sam Harirforoosh

Pharmacy Faculty Articles and Research

OBJECTIVE: Utilization of nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, can produce gastrointestinal ulceration. Thus, cyclooxygenase-2-selective inhibitors, such as celecoxib, and protective agents (e.g. rebamipide) have been employed to alleviate harmful NSAID effects. This study sought to explore the influence of rebamipide on the hepatic outcomes following administration of two commonly prescribed NSAIDs.

MATERIALS AND METHODS: Rats were given either vehicle or rebamipide (30 mg/kg) orally twice daily for two days, then on the third day respective groups were dosed with either vehicle, celecoxib (40 mg/kg), or diclofenac (10 mg/kg) in addition to a respective dose of vehicle …

The Ethics Of Animal Research: A Survey Of Pediatric Health Care Workers, Ari Joffe, Meredith Bara, Natalie Anton, Nathan Nobis

Experimentation Collection

Introduction: Pediatric health care workers (HCW) often perform, promote, and advocate use of public funds for animal research (AR). We aim to determine whether HCW consider common arguments (and counterarguments) in support (or not) of AR convincing.

Design: After development and validation, an e-mail survey was sent to all pediatricians and pediatric intensive care unit nurses and respiratory therapists (RTs) affiliated with a Canadian University. We presented questions about demographics, support for AR, and common arguments (with their counterarguments) to justify the moral permissibility (or not) of AR. Responses are reported using standard tabulations. Responses of pediatricians and nurses/RTs were …

Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Laboratory Experiments Collection

Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90–93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer’s disease, Parkinson’s …

Arkansas Animal Science Department Report 2014, David L. Kreider, Paul Beck

Arkansas Agricultural Experiment Station Research Series

No abstract provided.