Pharmacy and Pharmaceutical Sciences Commons^™

Solubility Enhancement, Mechanical Properties And Taste Masking Of Poorly Water Soluble Compounds By Optimizing Hot Melt Extrusion Processing, Abdullah Saud Alshetaili

Electronic Theses and Dissertations

Pharmaceutical research includes investigation and development of a new drug and determination of the delivery route and delivery system, as well as the technology to create the delivery system. It can also consist of a combination of these steps. Researchers studying potential delivery routes have explored oral, nasal, dermal, transdermal, transmucosal, pulmonary, and injection routes for their ability to deliver large and small drug molecules. This research project focuses on the oral route, which is generally accepted as an effective delivery route for many drug products with a large market share, and studies the use of this route for the …

Stratification Of The Impact Of Inappropriate Empirical Antimicrobial Therapy For Gram-Negative Bloodstream Infections By Predicted Prognosis, Sarah E. Cain, Joseph Kohn, P. Brandon Bookstaver, Helmut Albrecht, Majdi N. Al-Hasan

Faculty Publications

The bloodstream infection mortality risk score (BSIMRS) predicts the outcome of patients with Gram-negative bloodstream infections (BSI) with high discrimination. This retrospective cohort study examined the impact of inappropriate antimicrobial therapy on mortality in adult patients with Gram-negative BSI admitted to Palmetto Health Hospitals in Columbia, SC, USA, from 1 January 2011 to 31 December 2012 after stratification by predicted prognosis at initial presentation using BSIMRS. A multivariate Cox regression model was used to identify independent risk factors for 28-day mortality overall and within each predefined BSIMRS category (<5, 5 to 9, and ≥10). Relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) were calculated from a predictive logistic regression model of mortality. Overall, 390 unique patients with first episodes of Gram-negative BSI were identified. The median age was 66 years, and 229 (59%) were women. There was significant association between inappropriate antimicrobial therapy and mortality in patients with BSIMRS of 5 to 9 (adjusted hazard ratio [aHR], 3.55; 95% confidence intervals [CI], 1.22 to 8.31; P = 0.02) and BSIMRS of ≥10 (aHR, 4.99; 95% CI, 1.09 to 22.87; P = 0.04) but not in those with BSIMRS of <5 (aHR, 3.34; 95% CI, 0.17 to 22.77; P = 0.34). RRR, ARR, and NNT were 0.25, 0.02, and 63 for BSIMRS of <5; 0.56, 0.32, and 3 for BSIMRS of 5 to 9; and 0.39, 0.39, and 3 for BSIMRS of ≥10, respectively. There is a significant benefit from appropriate antimicrobial therapy in patients with Gram-negative BSI with guarded (BSIMRS of 5 to 9) and poor (BSIMRS of ≥10) predicted prognosis. Survival difference remains unclear among those with good predicted prognosis (BSIMRS of <5) at initial presentation.

Dendritic And Langerhans Cells Respond To Aβ Peptides Differently: Implication For Ad Immunotherapy, Jiang Cheng, Xiaoyang Lin, David Morgan, Marcia Gordon, Xi Chen, Zhen-Hai Wang, Hai-Ning Li, Lan-Jie He, Shu-Feng Zhou, Chuanhai Cao

Molecular Pharmacology & Physiology Faculty Publications

Both wild-type and mutated beta-amyloid (Aβ) peptides can elicit an immune response when delivered subcutaneously. However, only mutated forms of Aβ can sensitize dendritic cells when administered intravenously or intraperitoneally. To understand the role of mutation and delivery routes in creating immune responses, and the function of dendritic cells as therapeutic agents, we used fluorescent-conjugated WT Aβ1-40 (WT40) and artificially mutated Aβ1-40 (22W40) peptides to treat dendritic and Langerhans cells from young and/or old mice at different time points. The cell types were analyzed by flow cytometry and confocal microscopy to identify differences in function and antigen presentation, and Luminex …

Fret Detection Of Lymphocyte Function-Associated Antigen-1 Conformational Extension, Alexandre Chigaev, Yelena Smagley, Mark K. Haynes, Oleg Ursu, Cristian G. Bologa, Liliana Halip, Tudor Oprea, Anna Waller, Mark B. Carter, Yinan Zhang, Wei Wang, Tione Buranda, Larry A. Sklar

Pharmaceutical Sciences Faculty Publications

Lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18, αLβ2-integrin) and its ligands are essential for adhesion between T-cells and antigen-presenting cells, formation of the immunological synapse, and other immune cell interactions. LFA-1 function is regulated through conformational changes that include the modulation of ligand binding affinity and molecular extension. However, the relationship between molecular conformation and function is unclear. Here fluorescence resonance energy transfer (FRET) with new LFA-1-specific fluorescent probes showed that triggering of the pathway used for T-cell activation induced rapid unquenching of the FRET signal consistent with extension of the molecule. Analysis of the FRET quenching at rest revealed an …

Modeling, Optimization, And Sensitivity Analysis Of A Continuous Multi-Segment Crystallizer For Production Of Active Pharmaceutical Ingredients, Bradley James Ridder

Open Access Dissertations

We have investigated the simulation-based, steady-state optimization of a new type of crystallizer for the production of pharmaceuticals. The multi-segment, multi-addition plug-flow crystallizer (MSMA-PFC) offers better control over supersaturation in one dimension compared to a batch or stirred-tank crystallizer. Through use of a population balance framework, we have written the governing model equations of population balance and mass balance on the crystallizer segments. The solution of these equations was accomplished through either the method of moments or the finite volume method. The goal was to optimize the performance of the crystallizer with respect to certain quantities, such as maximizing the …

Expression Of The Nkcc2a Cotransporter In Mouse Central Nervous System, Katherine E. Fahy, James B. Lucot, Hayo Castrop, Mauricio Di Fulvio

Celebration of Undergraduate & Graduate Research, Scholarship, and Creative Activities Materials

Na-K-2Cl cotransporter 2A (NKCC2A), also known as the bumetanide-sensitive cotransporter 1 (BSC1), transports Na+, K+ and Cl- with a stoichiometry of 1:1:2. NKCC2A is considered a kidney specific cotransporter. It is abundantly expressed in apical membrane of the tubular cells in the thick ascending limb of the loop of Henle (TALH) and in the macula densa. However, NKCC2 has also been found at low levels in different cells, including insulin-secreting ones. This secondary active transporter uses the energy stored in the electrochemical gradients of Na and K maintained by the Na/K-ATPase located on the basolateral membrane of the TALH. The …

Analysis Of Humira, Electro-Acupuncture, And Pulsatile Dry Cupping On Reducing Joint Inflammation In Patients With Rheumatoid Arthritis, Natalie Noll

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Humira, an anti-TNF drug aimed at decreasing inflammation in Rheumatoid Arthritis patients, can cause skin diseases from rashes to skin cancer. Humira works by blocking the chemical receptor RANKL which inhibits the production of osteoclasts. Osteoclasts are cells that attack and eat bone and cartilage therefore an inhibitory mechanism would cause inflammation.. By analyzing Humira’s effect on the human body, Humira can be compared to other treatments such as electro-acupuncture and pulsatile dry cupping to determine the viability of these alternative treatment methods in regards to their abilities to decrease inflammation in Rheumatoid Arthritis patients through blocking RANKL. An analysis …

Nosh-Aspirin (Nbs-1120), A Dual Nitric Oxide And Hydrogen Sulfide-Releasing Hybrid, Reduces Inflammatory Pain, Miriam D. Fonseca, Fernando Q. Cunha, Khosrow Kashfi, Thiago M. Cunha

Publications and Research

The development of nitric oxide (NO)- and hydrogen sulfide (H2S)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) has generated more potent anti-inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H2S donors into aspirin (NOSH-aspirin) was recently developed. In the present study, the antinociceptive activity of this novel molecule was compared with aspirin in different models of inflammatory pain. It was found that NOSH-aspirin inhibits acetic acid-induced writhing response and carrageenan (Cg)-induced inflammatory hyperalgesia in a dosedependent (5–150 lmol/kg, v.o.) manner, which was superior to the effect of the same doses of aspirin. NOSH-aspirin’s antinociceptive effect was also …

A Randomized Prospective Study On Outcomes Of An Empathy Intervention Among Second-Year Student Pharmacists, Kajua B. Lor, Julie T. Truong, Eric J. Ip, Mitchell J. Barnett

Faculty Publications & Research of the TUC College of Pharmacy

Objective. To determine the impact of a single, 3-day intervention on empathy levels as measured by the validated Jefferson Scale of Empathy-Health Profession Students version (JSE-HPS).

Methods. Forty second-year student pharmacists were recruited to participate in a non-blinded prospective study. Subjects were randomized to an intervention group (n=20) or control group (n=20) and completed the JSE-HPS at baseline, 7 days postintervention, and 90 days postintervention. The intervention group consisted of a 3-day simulation, each day including a designated activity with loss of dominant hand usage, vision, and speech.

Results. The 3-day simulation increased empathy levels in the intervention group compared …

Pharmdigest Volume 2, Issue 2, Philadelphia College Of Osteopathic Medicine, School Of Pharmacy

PharmDigest

This issue of the Pharmacy Student Council newsletter includes the following articles:

• Journey to Pharmacy
• Live Your Why
• Daily Dose: Compounding
• Research Lab
• Let's Get Clinical

Scientific And Regulatory Policy Committee (Srpc) Review*: Interpretation And Use Of Cell Proliferation Data In Cancer Risk Assessment, Charles E. Wood, Renee R. Hukkanen, Radhakrisha Sura, David Jacobson-Kram, Thomas Nolte, Marielle Odin, Samuel M. Cohen

United States Food and Drug Administration: Publications

Increased cell proliferation is a central key event in the mode of action for many non-genotoxic carcinogens, and quantitative cell proliferation data play an important role in the cancer risk assessment of many pharmaceutical and environmental compounds. Currently, there is limited unified information on assay standards, reference values, targeted applications, study design issues, and quality control considerations for proliferation data. Here, we review issues in measuring cell proliferation indices, considerations for targeted studies, and applications within current risk assessment frameworks. As the regulatory environment moves toward more prospective evaluations based on quantitative pathway-based models, standardiza- tion of proliferation assays will …

Discovery Of Alternative Artemisinin Binding Sites In Plasmodium Falciparum Atpase-6, Shuneize Elizabeth Slater

Electronic Theses and Dissertations

Malaria is a fatal yet preventable and treatable disease. It is commonly spread through the bite of an infected Anopheles mosquito. Malaria parasites belong to the Plasmodium genus and can be caused by the falciparum, malariae, ovale, vivax, and knowlesi species. Artemisinin is an endoperoxide lactone extracted from qinghaosu (Artemisia annua L. or sweet wormwood). It and its derivatives possess uncharacteristically rapid action against Plasmodium falciparum. Artemisinin is unique in its effectiveness in deadly cerebral malaria. The endoperoxide bridge is crucial for its antimalarial activity; however, how it aids in killing the parasite is unknown. While there are multiple suggested …

Health Utility Assessment Among Caregivers Of Individuals With Multiple Sclerosis, Namita Joshi

Electronic Theses and Dissertations

OBJECTIVES The study objectives were to evaluate psychometric properties of the EuroQoL–five–dimensional questionnaire (EQ–5D–3L) among caregivers of individuals with multiple sclerosis (MS), assess caregiver utilities and determine predictors of utilities, and compare caregiver utilities obtained from the EQ–5D–3L and the SF–6D. METHODS A web–based survey was administered to MS caregivers via Qualtrics survey software using assistance from a MS patient registry– North American Research Committee on MS (NARCOMS). Measurement properties including convergent, discriminant, and known–groups validity, reliability, and ceiling and floors effects of the EQ–5D–3L were tested. Caregiver health utilities were estimated using the EQ–5D–3L and compared with population norms; …

Ehtnobotanical- And Chemometric-Guided Investigation Of Phytolacca Americana L., Michael Chan

Electronic Theses and Dissertations

No abstract provided.

Endangered Plant Species For Potential Drug Leads And Anticancer Prototypes For Treatment Of Breast And Pancreatic Cancers, Joonseok Oh

Electronic Theses and Dissertations

No abstract provided.

Influence Of Hot Melt Extrusion Processing Parameters On The Properties Of A Pharmaceutical Formulation, Saad M. Alshahrani

Electronic Theses and Dissertations

Hot melt extrusion (HME) is an old technology that has been recently adapted to be used in the pharmaceutical industry. HME is a continuous process that is widely used to produce a solid dispersion matrix. The aim of this dissertation is to evaluate different factors that will affect the pharmaceutical formulation properties that are produced using HME. For HME, there are different variables that will affect the product quality such as processing parameters, material selection, material ratio, and the presence of gas or moisture. One aim of this study is to find the most significant factor that affects the product …

Non-Invasive Drug Delivery To The Posterior Segment Of The Eye: Development Of Formulation Strategies And Evaluation Of Ocular Distribution And Pharmacological Activity, Goutham Reddy Adelli

Electronic Theses and Dissertations

Diseases of the posterior segment of the eye such as diabetic retinopathy, age related macular degeneration and glaucoma are the leading causes for blindness throughout the world. Topical eye drops is the most convenient formulation for daily application. The human eye, however, presents major physiological and dynamic barriers for the topically administered drug/molecule from reaching the retina. Similarly, the blood-retinal and blood-aqueous barriers restricts passage of drug from systemic circulation into the eye. Although intravitreal injections are the gold standards for the treatment of posterior segment ocular diseases, they are associated with pain, inflammation, endopthalmitis and infection. So there is …

Sodium Glucose Co-Transporter 2 Inhibitors In The Treatment Of Type 2 Diabetes Mellitus, Eden Miller, Jay H. Shubrook

Faculty Publications & Research of the TUC College of Osteopathic Medicine

Type 2 diabetes mellitus (T2DM) is a chronic, progressive disease, control of which typically requires multiple therapies. Current guidelines suggest that, in addition to improving glycemic control, antihyperglycemic therapy should be chosen on the basis of its effects on body weight and the risk of hypoglycemia. The newest class of oral antihyperglycemic agents, the sodium glucose cotransporter 2 (SGLT2) inhibitors, reduces renal glucose reabsorption and increases urinary glucose excretion via an insulin-independent mechanism of action. SGLT2 inhibitors have been shown to improve glycemic control and to reduce body weight and systolic blood pressure, and their use is associated with a …

Synthesis And Evaluation Of The Diarylthiourea Analogs As Novel Anti-Cancer Agents, Shengquan Liu, Maggie C. Louie, Vanishree Rajagopalan, Guangyan Zhou, Esmerelda Ponce, Tran Nguyen, Linda Green

Faculty Publications & Research of the TUC College of Osteopathic Medicine

No abstract provided.

Development Of A Multivalent Subunit Vaccine Against Tularemia Using Tobacco Mosaic Virus (Tmv) Based Delivery System, Sukalyani Banik, Ahd Ahmed Mansour, Ragavan Varadharajan Suresh, Sherri Wykoff-Clary, Meenakshi Malik, Alison A. Mccormick, Chandra Shekhar Bakshi

Faculty Publications & Research of the TUC College of Pharmacy

Francisella tularensisis a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV) based delivery platform. The multivalent subunit vaccine was formulated …