Medicine and Health Sciences Commons^™

Mixture Of Medium Chain Fatty Acids For Protein Precipitation In Purification Process Of Equine Anti-Rabies Immunoglobulin As F(Ab′)2, Sirisak Sathorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Besides the widely used caprylic acid (C8) as protein precipitating agent, capric acid (C10) and lauric acid (C12) were investigated as alternative medium chain fatty acids (MCFAs) for their capabilities on protein purification. The optimization process conducted with normal bovine plasma as a model antibody demonstrated the essential effect of temperature during filtration to significantly reduce the content of albumin, a contaminant marker, compared with filtration at room temperature (p<0.05). From SDS-PAGE analysis, the optimal concentrations of 3% C8 and 5% C10 increased IgG purity from 30.2% to 94.6% and 80.4%, respectively. Interestingly, precipitation by C10 provided the lowest turbidity of filtrates. Purification by C12 showed unsatisfied results that albumin content was minutely decreased when increasing C12 concentration. C8 and C10 were then variously combined into 2 levels of 3% and 5% binary mixture for plasma purification. The synergist effect of C8 and C10 mixtures was clearly demonstrated in albumin elimination that the purity of fractionates were increased to 95%. Moreover, binary mixtures with higher concentration of C10 improved the filtration velocity in plasma model. Selected C8:C10 mixtures were then applied for both ERIG-IgG and ERIG-F(ab′)2 purification. SDS-PAGE analysis confirmed the absence of albumin protein in all purified samples. For ERIG-IgG purification, C8:C10 mixture at ratio 1.5:3.5 demonstrated the best in homogeneity with high recovery rate of bioactive antibody, while the mixtures at 2.25:0.75 showed the best purification capabilities to obtain highly purified ERIG-F(ab′)2. Furthermore, the purification by C8:C10 mixtures displayed superior process characteristic than the commercially non-chromatographic technique for ERIGF(ab′)2 purification in terms of antibody recovery, purity and lower in aggregate formation. The novelty on beneficial use of MCFA mixture as protein precipitating agent for antibody purification has been demonstrated.

The Motivations And Perceived Benefits Of Student Participation In Dance Marathon, Emily Nettesheim

Undergraduate Honors Thesis Collection

The Children’s Miracle Network Dance Marathon movement has attracted over one million college students nationwide and fundraised over $38 million in 2017. The objective of this study was to determine student motivations and perceptions of the benefits of participation in Dance Marathon. This was a quantitative and qualitative cross-sectional study administered using an online survey software. Undergraduate students from three different Indiana programs were invited to participate. The survey consisted of 20 questions divided into four categories: demographics, what is Dance Marathon participation, motivations, and perceived benefits from DM involvement. There were 161 respondents out of 1492 recipients for an …

A New Consultation Service For Community Pharmacies? An Investigation Of Pharmacists' Perspective On Implementing A Weight Management Program, Shelby N. Strength

Honors Theses

Pharmacists are capable and interested in providing a targeted weight management intervention addressing the high rates, and associated risk, of obesity. A series of in-depth phone interviews with Mississippi community pharmacists were used to gain their perspective on a systematic approach for delivering a weight and obesity management service to patients. Using qualitative content analysis, three themes were identified and analyzed. These themes included: pharmacist’s perceptions of patient’s needs, program structural components, and pharmacist’s implementational needs. These findings can be used to expand the role of pharmacists, serve as a model for the development of other consultation services, improve health …

Development And Characterization Of Sustained-Release Formulations Via Novel Hot Melt Extrusion Techniques, Bjad Khalaf Almutairy

Electronic Theses and Dissertations

Hot melt extrusion (HME) is a leading technology that can be applied to many pharmaceutical preparations as solid dispersions. Part of this research project focus on injecting pressurized carbon dioxide (P-CO2) gas during the HME process. These combined techniques have an additional advantage of being adaptable and portable to a hot melt extruder instrument. The use of HME alongside with other techniques (P-CO2 or co extrusion process) for preparing an improved controlled/sustained release formulation is the main theme of this research project. Current research focusing on Active Pharmaceutical Ingredients (APIs) with good aqueous solubility requires novel approach to obtain tailored …

Intrapulmonary Inoculation Of Multicellular Tumor Spheroids To Construct An Orthotopic Lung Cancer Xenograft Model That Mimics Four Clinical Stages Of Non-Small Cell Lung Cancer, Yingbo Huang

University of the Pacific Theses and Dissertations

Lung cancer leads in mortality among all types of cancer in the US and Non-small cell lung cancer (NSCLC) is the major type of lung cancer. Immuno-compromised mice bearing xenografts of human lung cancer cells represent the most common animal models for studying lung cancer biology and for evaluating potential anticancer agents. However, orthotopic lung cancer models based on intrapulmonary injection of suspended cancer cells feature premature leakage of the cancer cells to both sides of the lung within five days, which generates a quick artifact of metastasis and thus belies the development and progression of lung cancer as seen …

Evaluating Ways To Reduce Errors In Medication Reconciliations Performed By Nurses In A Rural Hospital Setting, Kalen T. Freeman

MPA/MPP/MPFM Capstone Projects

Medication reconciliation, also known as “med recs”, are an important part of a patient’s care during their hospitalization. A med rec is when hospital personnel generate a list of the medications the patient takes at home. Med recs are vital in the hospital admission process because home medications need to be restarted at appropriate times to fully care for the patient. Also, mistakes in a home medication list can lead to serious consequences in the patient’s health. This study focuses on med recs being performed at Marcum and Wallace Hospital in Irvine, Kentucky. More specifically, the study explores the different …

Impact Of Area-Under-The-Curve Monitoring For Vancomycin On Incidence Of Acute Kidney Injury In Orthopedic Patients, Kelli R. Keats

MPA/MPP/MPFM Capstone Projects

Vancomycin is an antibiotic used regularly in hospitals across the world. The most concerning adverse effect of vancomycin is its documented effect on kidney function. This study examines the impact of two dosing strategies of vancomycin on patients’ kidney function at the University of Kentucky Albert B. Chandler Medical Center. It specifically focuses on patients on the orthopedic service because these patients traditionally receive higher doses of vancomycin for longer periods of time due to the severity of their infections, which puts them at an increased risk of vancomycin-induced nephrotoxicity compared to other patients.

This study will serve as a …

Xflow: An Algorithm For Extracting Ion Chromatograms, Mathew M. Gutierrez, Rob Smith

Graduate Student Theses, Dissertations, & Professional Papers

Abstract: Mass spectrometry is a fundamental tool for modern proteomics. The increasing availability of mass spectrometry data paired with the increasing sensitivity and fidelity of the instruments necessitates new and more potent analytical methods. To that end, we have created and present XFlow, a feature detection algorithm for extracting ion chromatograms from MS1 LC-MS data. XFlow is a parameter-free procedurally agnostic feature detection algorithm that utilizes the latent properties of ion chromatograms to resolve them from the surrounding noise present in MS1 data. XFlow is designed to function on either profile or centroided data across different resolutions and instruments. This …

Role Of Glial Glutamate Transporter In Animal Model Of Acute And Chronic Inflammatory Pain, Ghallab Alotaibi

Electronic Theses and Dissertations

No abstract provided.

Nanosuspension Based Electrolyte Sensitive In Situ Gel For Topical Ocular Delivery Of Natamycin, Poorva H. Joshi

Electronic Theses and Dissertations

Natamycin (NT) is a commercially available antifungal drug used for the treatment of fungal keratitis, an infection which affects the clear corneal surface and its associated layers. Currently, NT is available commercially as a 5% w/v ophthalmic suspension, to be administered topically. The main objective of the present investigation was to develop and evaluate the natamycin loaded nanosuspension (NT-NS), as well as it’s corresponding in-situ gel (NT-NS-GG), for the treatment of fungal keratitis. NT-NS was prepared using homogenization technique and optimized based on size, PDI, zeta potential (ZP), assay and process stability. Further, optimized NT-NS was modified into an in-situ …

Formulation Development Of Natamycin Loaded Nanoemulsion For Ocular Drug Delivery, Kanika Goel

Electronic Theses and Dissertations

Natamycin (NT), also known as Pimaricin, is predominantly used as an anti-fungal medication for the treatment of fungal infections around the eye. The goal of the present study was to formulate and optimize NT loaded nanoemulsion (NT-NE) and examine its potential application in ophthalmic drug delivery. Placebos were evaluated with respect to particle size, PDI and ZP to identify the aqueous phase and lipid phase concentrations to be carried forward with NT-NE development. NT-NE were prepared by hot homogenization and ultra-probe sonication method, using Castor oil (CO) and Miglyol 812 as liquid lipids, Tween®80 and Poloxomer 188 as surfactants. NT-NE …

Formulation Strategies To Address Physiological And Anatomical Constraints For Improved Topical Ocular Drug Delivery, Karthik Yadav Janga

Electronic Theses and Dissertations

Delivery of therapeutic molecules to the eye has been a complicated task owing to its anatomical and physiological barriers. This dissertation delineates several formulation strategies to circumvent dynamic and static constraints hampering the ocular drug delivery. Advanced vesicular systems, bilosomes and transfersomes, were prepared to improve the ocular pharmacotherapy of natamycin (NT). NT bilosomes and transfersomes were further loaded into in situ gel systems which transformed immediately to hydrogel, in the simulated tear fluid, with good viscoelastic and mucoadhesive properties.In vitro corneal transport studies confirmed the superior permeability characteristics of NT from the optimized bilosome and transfersome in situ gel …

Development Of Continuous Manufacturing Process Of Acyclovir Ointment Using Hot-Melt Extrusion, Rui Wang

Electronic Theses and Dissertations

Hot-melt extrusion is a viable technology in preparing the pharmaceutical delivery system and has been considered as an attractive alternative to conventional processing methods. The objective of this study was to utilize the advantage of continuous manufacturing in HME to design and evaluate a formulation of topical semisolid ointment. Melt fusion ointments containing 5% of acyclovir (ACV) in water-soluble base with PEG 400, PEG 1500, and PEG 3350 polymers at various ratio were prepared. A design of experiment using I-optimal design was conducted. This design was used to study the influence of polymer ratio on the physicochemical properties of the …

Development Of Topical Oil/Peg Creams Of Voriconazole, Abhishek Shivashankar Shettar

Electronic Theses and Dissertations

Voriconazole (VRC) was selected as a model drug for preparation of Oil/PEG cream consisting of PEG 2000, PEG 400 and propylene glycol after performing drug-excipient compatibility studies. Twin screw processor with a 10 mm co-rotating twin screw configuration was used for preparation of oil/PEG creams. Creams prepared using twin-screw processor were characterized for the following: Differential Scanning Calorimetry (DSC), pH, Solvent activity (as)), viscosity, drug content uniformity, in vitro drug release testing (IVRT) and in vitro permeation testing (IVPT) using human cadaver skin. Creams are heterogenous biphasic semi-solid preparations consisting of oil and aqueous phases, wherein one phase is dispersed …

Implementing Mass Spectrometry For The Structural And Compositional Analysis Of Proteins, Mohammad Riaz

Electronic Theses and Dissertations

Lectins are sugar-binding proteins that perform various biological functions such as cellular recognition attachments etc. Pulses the dried edible seeds of certain plants are great sources of lectins and a proteomics approach directed at lectins identification would bring substantial improvement in the lectin identification process. Lectins from nine different plant species were analyzed through SDS-PAGE and proteomics analysis. After LC-MS/MS analysis proteins were identified with protein database searches using Uniprot. Functionally uncharacterized proteins were identified with database searches were annotated with the Pfam and NCBI-CCD databases. In-vitro pharmacological screening will be carried out to assess the pharmacological effects of these …

Semisynthetic Aurones: A Family Of Newly Discovered Tubulin Inhibitors As Antineoplastic Agents, Yanqi Xie

Theses and Dissertations--Molecular and Cellular Biochemistry

Aurones belong to an uncommon class of plant flavonoids that provide the bright yellow coloration of some ornamental flowers and that possess a range of biological activities. Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the biologically active analogs developed in the course of this dissertation work were (Z …

Developmental Expression Of Monocarboxylate Transporter 1 And 4 In Rat Liver, Michael Ng, Justin Louie, Jieyun Cao, Melanie A. Felmlee

School of Pharmacy Faculty Articles

PURPOSE: Monocarboxylate transporters (MCT) are proton-coupled integral membrane proteins that control the influx and efflux of endogenous monocarboxylates such as lactate, acetate and pyruvate. They also transport and mediate the clearance of drugs such as valproate and gamma-hydroxybutyrate. CD147 functions as ancillary protein that chaperones MCT1 and MCT4 to the cell membrane. There is limited data on the maturation of MCT and CD147 expression in tissues related to drug distribution and clearance. The objective of the present study was to quantify hepatic MCT1, MCT4, and CD147 mRNA, whole cell and membrane protein expression from birth to sexual maturity.

METHODS: Liver …

Hiv Viral Rebound Due To A Possible Drug-Drug Interaction Between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide And Calcium-Containing Products: Report Of 2 Cases, S. Lena Kang-Birken, Dena El-Sayed, John Prichard

School of Pharmacy Faculty Articles

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a potent fixed-dose, once-daily regimen for HIV-1 treatment and has rare emergence of drug resistance. We report a potential drug-drug interaction in 2 female patients both receiving treatment for HIV and cerebral toxoplasmosis: one case between E/C/F/TAF with calcium carbonate and a second case involving leucovorin as calcium salt. Both cases resulted in rise in HIV RNA levels and emergence of M184 V mutation and resistance to elvitegravir and raltegravir. To the best of our knowledge, these 2 cases are the first reports of rapid emergence of mutation from coadministration of E/C/F/TAF and calcium.

Responsible, Safe, And Effective Use Of Biologics In The Management Of Low Back Pain: American Society Of Interventional Pain Physicians (Asipp) Guidelines, Annu Navani, Laxmaiah Manchikanti, Sheri L. Albers, Richard E. Latchaw, Jaya Sanapati, Alan David Kaye, Sairam Atluri, Sheldon Jordan, Ashim Gupta, David Cedeno, Alejandro Vallejo, Bert Fellows, Nebojsa Nick Knezevic, Miguel Pappolla, Sudhir Diwan, Andrea M. Trescot, Amol Soin, Adam M. Kaye, Steve M. Aydin, Aaron K. Calodney, Kenneth D. Candido, Sanjay Bakshi, Ramsin M. Benyamin, Ricardo Vallejo, Art Watanabe, Douglas Beall, Todd P. Stitik, Patrick M. Foye, Erik M. Helander, Joshua A. Hirsch

School of Pharmacy Faculty Articles

BACKGROUND: Regenerative medicine is a medical subspecialty that seeks to recruit and enhance the body's own inherent healing armamentarium in the treatment of patient pathology. This therapy's intention is to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous or allogenic biologics. This field is rising like a Phoenix from the ashes of underperforming conventional therapy midst the hopes and high expectations of patients and medical personnel alike. But, because this is a relatively new area of medicine that has yet to substantiate its outcomes, care must be taken in its public …

Mechanisms Underlying Neuroprotection By The Nsaid Mefenamic Acid In An Experimental Model Of Stroke, Parto S. Khansari, Robert F. Halliwell

School of Pharmacy Faculty Articles

Stroke is a devastating neurological event with limited treatment opportunities. Recent advances in understanding the underlying pathogenesis of cerebral ischemia support the involvement of multiple biochemical pathways in the development of the ischemic damage. Fenamates are classical non-steroidal anti-inflammatory drugs but they are also highly subunit-selective modulators of GABAA receptors, activators of IKS potassium channels and antagonists of non-selective cation channels and the NLRP3 inflammosome. In the present study we investigated the effect of mefenamic acid (MFA) in a rodent model of ischemic stroke and then addressed the underlying pharmacological mechanisms in vitro for its actions in vivo. The efficacy …

Hiv With Opportunistic Neuroinfection, Rahul Vyas, Rajendra Prasad

Digital Journal of Clinical Medicine

No abstract provided.

Anti-Cancer Effects Of Renieramycin T On Human Non-Small Cell Lung Cancer Cells, Korrakod Petsri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Mcl-1 targeted therapy is promising strategy for lung cancer treatment since it is contributed to aggressive lung cancer and chemotherapeutic resistance. At present, many compounds targeting on Mcl-1 are currently under different clinical stages of development for cancer treatment. Herein, we report the Mcl-1 targeting activity of renieramycin T (RT), an alkaloid isolated from the blue sponge Xestospongia sp. RT was shown to target on Mcl-1 through ubiquitin-proteasomal degradation in lung cancer cells including chemotherapeutic resistant primary lung cancer cells. Additionally, RT also affects the activation of p53 and decrease of Bcl-2 which can lead to apoptosis of cancer cells. …

Developing A Rational Peptide Ligand Design Method Using Cd13 As A Prototype Target Receptor, Md Zahir Uddin

University of the Pacific Theses and Dissertations

Structure based computational peptide design methods have gained significant interest in recent years with the availability of structural insights of protein-protein interactions obtained from the crystal structures. Most of these approaches design new peptide ligands by connecting the crucial amino acid residues from the protein interface and are generally not based on any predicted receptor-ligand interaction. In this work, a peptide design method based on the Knob-Socket model was used to identify the specific ligand residues packing into the receptor interface. This method enables rational peptide ligand design by predicting amino acid residues that will fit best at the binding …

Fliposomes With A Ph-Sensitive Conformational Switch For Anticancer Drug Delivery Against Triple Negative Breast Cancer, Yifan Lu

University of the Pacific Theses and Dissertations

Cancer is the second leading cause of death in the US and worldwide, accounting for 16% of deaths worldwide in 2015. Of more than 100 types of cancers affecting humans, breast cancer is the most common cancer among women and is the second leading cause of death in women. Triple negative breast cancer (TNBC) is a subtype of breast carcinomas defined by the lack of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2 /neu). The prognosis and survival of TNBC patients remains the poor due to the lack of effective targeted therapy. …

Synthesis And Conformational Studies Of Various Amides, Marcos Beltran-Sanchez

University of the Pacific Theses and Dissertations

In the past, aminocyclohexanol rings have been successfully utilized as pH-triggered molecular switches in various trans-2-aminocyclohexanol derivatives. By changing the groups on the amine nitrogen, these models provided a wide pH range in which a switch can occur. The pH-induced switch of conformation was monitored by 1H-NMR spectroscopy. The models were also incorporated into the bilayer membrane of liposome structures and tested for their ability to disrupt their membrane upon their conformational flip induced by a decrease in pH.

In this work, the amide bond has been studied as a molecular switch and various amide derivatives have been tested for …

The Orphan Drug Act At 35: Observations And An Outlook For The Twenty-First Century, Nicholas Bagley, Benjamin Berger, Amitabh Chandra, Craig Garthwaite

Articles

On the thirty-fifth anniversary of the adoption of the Orphan Drug Act (ODA), we describe the enormous changes in the markets for therapies for rare diseases that have emerged over recent decades. The most prominent example is the fact that the profit-maximizing price of new orphan drugs appears to be greater today than it was in 1983. All else equal, this should reduce the threshold for research and development (R&D) investment in an economically viable product. Further, the small size of patient populations for orphan drugs, together with the increasing prevalence of biologics among orphan drugs, have created a set …

Sheehan Syndrome, Riya Jain, Shashidhara Kc, Savitha Savitha

Digital Journal of Clinical Medicine

No abstract provided.

Ectopia Lentis, Pratheek Prabhu

Digital Journal of Clinical Medicine

No abstract provided.

Cerebro-Vascular Accident, Mehak Gera, Rajendra Prasad, Suresh Babu, Manthappa M

Digital Journal of Clinical Medicine

No abstract provided.

Pulmonary Thromboembolism In A Case Of Alopecia Areata, Rakshith M

Digital Journal of Clinical Medicine

No abstract provided.