Pharmaceutics and Drug Design Commons^™

In Vitro Metabolic Stability Study Of New Cyclen Based Antimalarial Drug Leads Using Rp-Hplc And Lc-Ms/Ms, Apoorva V. Rudraraju, Mohammad F. Hossain, Anjuli Shrestha, Prince N.A. Amoyaw, Babu L. Tekwani, M. O. Faruk Khan

Pharmaceutical Science and Research

Metabolic stability of the new antimalarial drug leads is determined using Human Liver Microsome (HLM) and specific cytochrome P450 enzyme (CYP2C8) taking the clinically used antimalarial drug chloroquine as a positive control. Experiment is done using standard methods. All the assays were conducted in 0.5 M phosphate buffer at pH 7.4. In general the metabolic reaction was initiated by adding 1 mM NADPH and 0.5 mg of enzyme. Incubations were done with time frequency of 0 hr, 1 hr, and 2 hrs at 37°C and the reactions were terminated by adding acetonitrile in the equal amounts of the assay mixture …

A Standardized Patient Counseling Rubric For A Pharmaceutical Care And Communications Course, Niambi Horton Pharmd, Kenna D. Payne Pharmd, Michelle Jernigan Pharmd, Jill Frost Pharmd, Stephen Wise Pharmd, Mary Klein Pharmd, Joel Epps Mba, H. Glenn Anderson Pharmd

Pharmaceutical Science and Research

Objective. To restructure a required pharmaceutical care and communications course to place greater emphasis on communication skills and include a high-stakes assessment.

Design. A standardized counseling rubric was developed for use throughout the pharmacy curriculum and the counseling laboratory practicals were changed to high-stakes assessments.

Assessment. An annual mid-semester and end-of-semester high-stakes patient-counseling objective structured clinical examination (OSCE) conducted prior to and after revision of the course and counseling rubric documented improvements in students’ scores. Performance on the post-course annual assessment patient counseling OSCE improved compared to that on the pre-course (p,0.001).

Conclusion. The 2010 course revision improved …

An Update On Braf Inhibitors And Other New Molecular Targets For The Treatment Of Malignant Melanoma Of The Skin, M. O. Faruk Khan, Carroll L. Ramos

Pharmaceutical Science and Research

Malignant melanoma of the skin originates from mutations in melanocytes and can be lethal if unrecognized or untreated in its earlier stages. Deaths from melanoma are increasing in the United States and around the world every year. The available treatments produce low rates of response with modest survival impact. Among potential molecular targets under investigation, which are mostly in the tyrosine kinase pathway, the BRAF (V-raf murine sarcoma viral oncogene homolog B1) gene is the best studied and most frequently reported mutation in melanoma. The molecular targets for melanoma treatment, promising drugs for future melanoma treatment as well as the …

The Fit-Hansa Demonstrates Reliability And Convergent Validity Of Functional Performance In Patients With Shoulder Disorders, Prajyot Kumta, Joy C. Macdermid, Saurabh Mehta, Paul W. Stratford

Physical Therapy Faculty Research

Study

DesignPsychometric study design.

Objectives

To assess the test-retest reliability and convergent validity of the Functional Impairment Test-Hand and Neck/Shoulder/Arm (FIT-HaNSA) in patients with shoulder disorders.

Background

Performance tests that assess functional ability of patients with shoulder disorders can provide useful information for making clinical or return-to-activity decisions. No performance-based shoulder test has yet demonstrated sufficient relevance or clinical measurement properties. The FIT-HaNSA examines upper extremity performance during repetitive tasks that emphasize shoulder reaching and static postures and, therefore, has greater relevance for assessing performance.

Methods

Thirty-six patients with shoulder disorders and 65 healthy controls were recruited for the study. …

Reactive Oxygen Species Modulation Of Na/K-Atpase Regulates Fibrosis And Renal Proximal Tubular Sodium Handling, Jiang Liu, David J. Kennedy, Yanling Yan, Joseph I. Shapiro Md

Pharmaceutical Science and Research

The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS)-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT) sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS) are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in the regulation of Na/K-ATPase …

Acetaminophen: Beyond Pain And Fever-Relieving, Eric R. Blough, Miaozong Wu

MIIR Faculty Research

Acetaminophen, also known as APAP or paracetamol, is one of the most widely used analgesics (pain reliever) and antipyretics (fever reducer). According to the U.S. Food and Drug Administration, currently there are 235 approved prescription and over-the-counter drug products containing acetaminophen as an active ingredient. When used as directed, acetaminophen is very safe and effective; however when taken in excess or ingested with alcohol hepatotoxicity and irreversible liver damage can arise. In addition to well known use pain relief and fever reduction, recent laboratory and pre-clinical studies have demonstrated that acetaminophen may also have beneficial effects on blood glucose levels, …

Why Patients Need Protection From The Sun, M. O. Faruk Khan, W. Steve Pray

Pharmaceutical Science and Research

Sunlight has been thought to be beneficial in recent decades, a time in which widespread tanning has become the norm. However, some patients’ quest for the perfect tan may lead them to permanent disfigurement and early death due to the damaging effects of ultraviolet (UV) radiation.

Effect Of Standard Treatment Guidelines With Or Without Prescription Audit On Prescribing For Acute Respiratory Tract Infection (Ari) And Diarrhoea In Some Thana Health Complexes (Thcs) Of Bangladesh, M. O. Faruk Khan, A.K. Azad Chowdhury, M. A. Matin, K. Begum, M. A. Galib

Pharmaceutical Science and Research

Inappropriate prescribing for ARI and diarrhoea is a serious health problem in many developing countries including Bangladesh. A baseline retrospective prescribing survey for ARI and diarrhoea have been conducted in randomly selected 60 thana health complexes (THCs) of Dhaka division of Bangladesh. In the 38 of 60 THCs, the prescribers did not comply with the standard treatment guidelines (STG) for ARI. They are marked as 'unsatisfactory performers'. In these THCs unnecessary antibiotics were prescribed in more than 50% of the encounters. The study further revealed that in 26 THCs, comprising 41.6% of the 38 THCs, the situation was even worse …

Trypanothione Reductase: A Viable Chemotherapeutic Target For Antitrypanosomal And Antileishmanial Drug Design, M. O. Faruk Khan

Pharmaceutical Science and Research

Trypanosomiasis and leishmaniasis are two debilitating disease groups caused by parasites of Trypanosoma and Leishmania spp. and affecting millions of people worldwide. A brief outline of the potential targets for rational drug design against these diseases are presented, with an emphasis placed on the enzyme trypanothione reductase. Trypanothione reductase was identified as unique to parasites and proposed to be an effective target against trypanosomiasis and leishmaniasis. The biochemical basis of selecting this enzyme as a target, with reference to the simile and contrast to human analogous enzyme glutathione reductase, and the structural aspects of its active site are presented. The …

Antitrypanosomal, Antileishmanial, And Antimalarial Activities Of Quaternary Arylalkylammonium 2-Amino-4-Chlorophenyl Phenyl Sulfides, A New Class Of Trypanothione Reductase Inhibitor, And Of N-Acyl Derivatives Of 2-Amino-4-Chlorophenyl Phenyl Sulfide, Seheli Parveen, M. O. Faruk Khan, Susan E. Austin, Simon L. Croft, Vanessa Yardley, Peter Rock, Kenneth T. Douglas

Pharmaceutical Science and Research

Quaternization of the nitrogen atom of 2-amino-4-chlorophenyl phenyl sulfide analogues of chlorpromazine improved inhibition ∼40-fold (3′,4′-dichlorobenzyl-[5-chloro-2-phenylsulfan- ylphenylamino)-propyl]-dimethylammonium chloride inhibited trypanothione reductase from Trypanosoma cruzi with a linear competitive Ki value of 1.7 ( 0.2 µM). Molecular modelling explained docking orientations and energies by: (i) involvement of the Z-site hydrophobic pocket (roughly bounded by F396′, P398′, and L399′), (ii) ionic interactions for the cationic nitrogen with Glu-466′ or -467′. A series of N-acyl-2-amino-4-chlorophenyl sulfides showed mixed inhibition (Ki, Ki′ ) 11.3-42.8 µM). The quaternized analogues of the 2-chlorophenyl phenylsulfides had strong antitrypanosomal and antileishmanial activity in vitro against T. bruceirhodesiense STIB900, …

Probing Proteinase Active Sites Using Oriented Peptide Mixture Libraries – Adam-10, John L. Krstenansky, Jihong Wang, Gregg R. Chenail, Matthew R. Tiffany, Geoffrey M. Kuesters, Barbara C. Natke, John L. Nestor Jr.

Pharmaceutical Science and Research

Oriented Peptide Mixture Libraries can provide a full matrix of preferred and disfavored amino acids at each subsite of an optimal substrate for a new proteinase. This approach is rapid and convenient, requiring only two mixture libraries to complete the analysis. In this paper we demonstrate an extension of this type of analysis, using a focused library employing unnatural amino acids to probe the depth of the S1 position in the catalytic site of the alpha secretase ADAM-10. This analysis indicates that ADAM- 10 will accept amino acids with substantial length and hydrophobicity (e.g. 2- naphthylalanine), but suggests that the …