Medicinal and Pharmaceutical Chemistry Commons^™

Stribild: A Review Of Component Characteristics And Combination Drug Efficacy, Derek E. Murrell, Jonathan P. Moorman, Sam Harirforoosh

Pharmacy Faculty Articles and Research

BACKGROUND: Numerous methods have been devised to combat human immunodeficiency virus (HIV) replication and disease progression. Composed of an integrase strand transfer inhibitor, a pharmacoenhancer, and two reverse transcriptase inhibitors, Stribild is a relatively new combination HIV drug formulated for once-a-day dosing.

METHODS: Relevant information, original research articles and reviews, were gathered primarily through the use of the PubMed database. The search was conducted without date restrictions in order to collect both historical and recent information concerning HIV, individual drugs, and combinations for a thorough overview.

RESULTS: Stribild, when taken with food, provides therapeutic drug concentrations as …

Formulation And In Vitro Evaluation Of Niacin-Loaded Nanoparticles To Reduce Prostaglandin Mediated Vasodilatory Flushing, Dustin L. Cooper, Jennifer A. Carmical, Peter C. Panus, Sam Harirforoosh

Pharmacy Faculty Articles and Research

OBJECTIVE: Niacin, activating G-protein coupled receptor (GPR) 109A, stimulates release of vasodilatory prostaglandins (PGs) such as PGE2 which can elicit niacin-associated flushing side effects. Poly-lactic-co-glycolic acid (PLGA) and poly-lactic acid (PLA) are used in nanoparticle (NP) drug delivery to reduce adverse effects and modulate drug release. Our study evaluated the in vitro effects of niacin-loaded PLGA or PLA-NPs on PGE2 expression in whole human blood as a model for niacin-induced flushing.

MATERIALS AND METHODS: NPs were formulated using a solvent evaporation process and characterized by size, polydispersity, zeta potential, drug entrapment, morphology, and drug release. NP in vitro …

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 …

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 …

Effect Of Formulation Variables On Preparation Of Celecoxib Loaded Polylactide-Co-Glycolide Nanoparticles, Dustin L. Cooper, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib) reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v), drug amount (5, 10, 15, and 20 mg), and emulsifier (lecithin) on nanoparticle characterization were examined …

Nucleoside Reverse Transcriptase Inhibitors Possess Intrinsic Anti-Inflammatory Activity, Benjamin J. Fowler, Bradley D. Gelfand, Younghee Kim, Nagaraj Kerur, Valeria Tarallo, Yoshio Hirano, Shoba Amarnath, Daniel H. Fowler, Marta Radwan, Mark T. Young, Keir Pittman, Paul Kubes, Hitesh Agarwal, Keykavous Parang, David R. Hinton, Ana Bastos-Carvalho, Shengjian Li, Testuhiro Yasuma, Takeshi Mizutani, Reo Yasuma, Charles Wright, Jayakrishna Ambati

Pharmacy Faculty Articles and Research

Nucleoside reverse transcriptase inhibitors (NRTIs) are mainstay therapeutics for HIV that block retrovirus replication. Alu (an endogenous retroelement that also requires reverse transcriptase for its life cycle)–derived RNAs activate P2X7 and the NLRP3 inflammasome to cause cell death of the retinal pigment epithelium in geographic atrophy, a type of age-related macular degeneration. We found that NRTIs inhibit P2X7-mediated NLRP3 inflammasome activation independent of reverse transcriptase inhibition. Multiple approved and clinically relevant NRTIs prevented caspase-1 activation, the effector of the NLRP3 inflammasome, induced by Alu RNA. NRTIs were efficacious in mouse models of geographic atrophy, choroidal neovascularization, graft-versus-host disease, and sterile …

Ho-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, And Isoprostane Levels In Mice Fed High Fructose Diets, Zeid Khitan, Mohit Harsh, Komal Sodhi, Joseph I. Shapiro Md, Nader G. Abraham

Pharmaceutical Science and Research

Background. Fructose metabolism is an unregulated metabolic pathway and excessive fructose consumption is known to activate ROS.HO-1 is a potent antioxidant gene that plays a key role in decreasing ROS and isoprostanes.We examinedwhether the fructosemediated increase in adipocyte dysfunction involves an increase in isoprostanes and that pharmacological induction ofHO-1would decrease both isoprostane levels and adipogenesis. Methods and Results. We examined the effect of fructose, on adipogenesis in human MSCs in the presence and absence of CoPP, an inducer of HO-1. Fructose increased adipogenesis and the number of large lipid droplets while decreasing the number of small lipid droplets (𝑃 < 0.05). Levels of heme and isoprostane in fructose treated MSC-derived adipocytes were increased. CoPP reversed these effects andmarkedly increasedHO-1 and theWnt signaling pathway. Thehigh fructose diet increased heme levels in adipose tissue and increased circulating isoprostane levels (𝑃 < 0.05 versus control). Fructose diets decreasedHO-1 and adiponectin levels in adipose tissue. Induction ofHO-1 by CoPP decreased isoprostane synthesis (𝑃 < 0.05 versus fructose). Conclusion. Fructose treatment resulted in increased isoprostane production and adipocyte dysfunction, which was reversed by the increased expression of HO-1.

A Simple High Performance Liquid Chromatography Method For Determination Of Rebamipide In Rat Urine, Dustin L. Cooper, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Rebamipide is a mucoprotective agent commonly used to prevent nonsteriodal anti-inflammatory drug-induced gastrointenstinal side effects [1]. Human plasma and urine analysis of rebamipide utilizing high performance liquid chromatography (HPLC) have been reported [2]. Recently, we reported on the plasma levels of rebamipide in presense or absence of celecoxib or diclofenac in rats [3] using a modified HPLC method of detection developed by Jeoung et al. [4]. To tailor the method towards use in urinary rebamipide extraction and analysis, the following modifications were made:

• To compensate for high concentrations of rebamipide found in urine, a new rebamipide stock solution was prepared …

Structural Similarity Between Β3-Peptides Synthesized From Β3-Homo-Amino Acids Or L-Aspartic Acid Monomers, Sahar Ahmed, Tara Sprules, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Formation of stable secondary structures by oligomers that mimic natural peptides is a key asset for enhanced biological response. Here we show that oligomeric β³‐hexapeptides synthesized from l‐aspartic acid monomers (β³‐peptides 1, 5a, and 6) or homologated β³‐amino acids (β³‐peptide 2), fold into similar stable 14‐helical secondary structures in solution, except that the former form right‐handed 14‐helix and the later form left‐handed 14‐helix. β³‐Peptides from l‐Asp monomers contain an additional amide bond in the side chains that provides opportunities for more hydrogen bonding. However, based on the …

Exacerbation Of Celecoxib-Induced Renal Injury By Concomitant Administration Of Misoprostol In Rats, Dustin L. Cooper, Derek E. Murrell, Christopher M. Conder, Victoria E. Palau, Grace E. Campbell, Shaun P. Lynch, James W. Denham, Angela V. Hanley, Kenny W. Bullins, Peter C. Panus, Krishna Singh, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Nonsteroidal anti-inflammatory drugs (NSAIDs) can produce adverse effects by inhibiting prostaglandin (PG) synthesis. A PGE1 analogue, misoprostol, is often utilized to alleviate NSAID-related gastrointestinal side effects. This study examined the effect of misoprostol on celecoxib renal toxicity. Additionally, the effects of these drugs on cardiovascular parameters were evaluated. Four randomized rat groups were orally gavaged for 9 days, two groups receiving vehicle and two groups receiving misoprostol (100 µg/kg) twice daily. Celecoxib (40 mg/kg) was co-administered once daily to one vehicle and one misoprostol group from days 3 to 9. Urine and blood samples were collected and blood pressure parameters …

Design And Optimization Of Plga-Based Diclofenac Loaded Nanoparticles, Dustin L. Cooper, Sam Harirforoosh

Pharmacy Faculty Articles and Research

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 …

Adverse Effects Of Nonsteroidal Anti-Inflammatory Drugs: An Update Of Gastrointestinal, Cardiovascular, And Renal Complications, Sam Harirforoosh, Waheed Asghar, Fakhreddin Jamali

Pharmacy Faculty Articles and Research

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 …

Design, Synthesis And Evaluation Of Antimicrobial Activity Of N-Terminal Modified Leucocin A Analogues, Krishna Chaitanya Bodapati, Rania Soudy, Hashem Etayash, Michael Stiles, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Class IIa bacteriocins are potent antimicrobial peptides produced by lactic acid bacteria to destroy competing microorganisms. The N-terminal domain of these peptides consists of a conserved YGNGV sequence and a disulphide bond. The YGNGV motif is essential for activity, whereas, the two cysteines involved in the disulphide bond can be replaced with hydrophobic residues. The C-terminal region has variable sequences, and folds into a conserved amphipathic α-helical structure. To elucidate the structure–activity relationship in the N-terminal domain of these peptides, three analogues (1–3) of a class IIa bacteriocin, Leucocin A (LeuA), were designed and synthesized by …

Menthol Binding And Inhibition Of A7-Nicotinic Acetylcholine Receptors, Abrar Ashoor, Jacob C. Nordman, Daniel Veltri, Keun-Hang Susan Yang, Lina T. Al Kury, Yaroslav M. Shuba, Mohamed Magoub, Frank Christopher Howarth, Bassem Sadek, Amarda Shehu, Nadine Kabbani, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh) receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca2+-dependent Cl− channels, since menthol inhibition remained unchanged by intracellular injection of the Ca2+ chelator BAPTA and perfusion with Ca2+-free bathing solution containing …

Development Of A Men’S Preference For Testosterone Replacement Therapy (P-Trt) Instrument, Sheryl L. Szeinbach, Enrique Seoane-Vazquez, Kent H. Summers

Pharmacy Faculty Articles and Research

Background: This study used a standard research approach to create a final conceptual model and the Preference for the Testosterone Replacement Therapy (P-TRT) instrument.

Methods: A discussion guide was developed from a literature review and expert opinion to direct one-on-one interviews with participants who used testosterone replacement therapy and consented to participate in the study. Data from telephone interviews were transcribed for theme analysis using NVivo 9 qualitative analysis software, analyzed descriptively from a saturation grid, and used to evaluate men’s P-TRT. Data from cognitive debriefing for five participants were used to evaluate the final conceptual model and …

Anti-Neoplastic Activity Of Two Flavone Isomers Derived From Gnaphalium Elegans And Achyrocline Bogotensis, Christan M. Thomas, Robert C. Wood Iii, Jarrett E. Wyatt, Morgan H. Pendleton, Ruben B. Torrenegra, Oscar E. Rodriguez, Sam Harirforoosh, Maria Ballester, Janet Lightner, Koyamangalath Krishnan, Victoria P. Ramsauer

Pharmacy Faculty Articles and Research

Over 4000 flavonoids have been identified so far and among these, many are known to have antitumor activities. The basis of the relationships between chemical structures, type and position of substituent groups and the effects these compounds exert specifically on cancer cells are not completely elucidated. Here we report the differential cytotoxic effects of two flavone isomers on human cancer cells from breast (MCF7, SK-BR-3), colon (Caco-2, HCT116), pancreas (MIA PaCa, Panc 28), and prostate (PC3, LNCaP) that vary in differentiation status and tumorigenic potential. These flavones are derived from plants of the family Asteraceae, genera Gnaphalium and Achyrocline reputed …

Pharmacokinetic/Pharmacodynamic (Pk/Pd) Modeling Of Anti-Neoplastic Agents, Daniel Lexcen, Ahmed H. Salem, Walid F. Elkhatib, Virginia Haynes, Ayman Noreddin

Pharmacy Faculty Books and Book Chapters

"Development of tumor resistance to chemotherapeutics is related to inherent tumor variations regarding sensitivity to chemotherapeutics and to sub-optimal dosing regimens, including variation in patient pharmacokinetics that result in suboptimal exposure of tumor cells to anti-neoplastic drugs [1, 2]. The rate and extent of drug efficacy depends on the extent of drug exposure at the tumor site and the time above the effective concentration [3]. In vitro models that incorporate these pharmacokinetic and pharmacodynamic (PK/PD) principles to optimize therapeutic response may be considered the method of choice for optimizing dosing schedules before translating data from static assays to animals and …

Pharmacists And Pharmacogenomics: An Evaluation Of Knowledge, Beliefs, Attitudes And Practices, Laressa Bethishou, Angela Chen, Chrissie Chew, Richard Dang, Courtney Greenber, Rebecca Ashlee Klevens, Vlada Treynker, Andrew Warnock, Melissa Durham, Jeffery A. Goad, Edith Mirzaian

Pharmacy Faculty Articles and Research

"Pharmacogenomics is the term used to describe the rapidly advancing study on how genetic makeup can impact drug therapy. In specialized clinical situations, such as the use of irinotecan in colon cancer or abacavir in HIV infections, it is now possible to identify specific genotypes that correlate strongly with a patient's therapeutic outcome, with implications on both efficacy and side effects. On a broader scale, a systematic review published by the Journal of the American Medical Association on the top 27 adverse reaction-causing drugs found that a majority of the adverse effects have a genetic component, suggesting that an analysis …

Synthetic Peptides Derived From The Sequence Of A Lasso Peptide Microcin J25 Show Antibacterial Activity, Rania Soudy, Liru Wang, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Microcin J25 (MccJ25) is a plasmid-encoded, ribosomally synthesized antibacterial peptide with a unique lasso structure. The lasso structure, produced with the aid of two processing enzymes, provides exceptional stability to MccJ25. We report the synthesis of six peptides (1–6), derived from the MccJ25 sequence, that are designed to form folded conformation by disulfide bond formation and electrostatic or hydrophobic interactions. Two peptides (1 and 6) display good activity against Salmonella newport, and are the first synthetic derivatives of MccJ25 that are bactericidal. Peptide 1 displays potent activity against several Salmonella strains including two …

Differential Effects Of Pravastatin And Simvastatin On The Growth Of Tumor Cells From Different Organ Sites, David G. Menter, Victoria P. Ramsauer, Sam Harirforoosh, Kanishka Chakraborty, Peiying Yang, Linda His, Robert A. Newman, Koyamangalath Krishnan

Pharmacy Faculty Articles and Research

3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, commonly known as statins, may possess cancer preventive and therapeutic properties. Statins are effective suppressors of cholesterol synthesis with a well-established risk-benefit ratio in cardiovascular disease prevention. Mechanistically, targeting HMGCR activity primarily influences cholesterol biosynthesis and prenylation of signaling proteins. Pravastatin is a hydrophilic statin that is selectively taken up by a sodium-independent organic anion transporter protein-1B1 (OATP1B1) exclusively expressed in liver. Simvastatin is a hydrophobic statin that enters cells by other mechanisms. Poorly-differentiated and well-differentiated cancer cell lines were selected from various tissues and examined for their response to these two statins. Simvastatin …

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 …

The Use Of Spectroscopic Techniques In The Characterization Of Mycobacterial Metabolites, Engy Abdelhameed Mahrous

Theses and Dissertations (ETD)

The mycobacterial cell wall metabolites have always imposed great challenges to researchers due to their unusual complexity and structural diversity. A lot of research efforts have been directed towards the evaluation of these metabolites and the role they play in the pathogenesis and virulence of different serious human pathogens including Mycobacterium tuberculosis the causative agent of tuberculosis (TB). In the genomic era, it is crucial to develop new methodologies to analyze these components from a global perspective in a comprehensive and well-validated manner.

Towards this end, we developed a rapid NMR-based approach to produce metabolic profiles in the form of …

The Proteolytic Stability And Cytotoxicity Studies Of L‐Aspartic Acid And L‐Diaminopropionic Acid Derived Β‐Peptides And A Mixed Α/Β‐Peptide, Sahar Ahmed, Kamaljit Kaur

Pharmacy Faculty Articles and Research

The use of peptides as drugs in pharmaceutical applications is hindered by their susceptibility to proteolysis and therefore low bioavailability. β‐Peptides that contain an additional methylene group in the backbone, are gaining recognition from a pharmaceutical stand point as they are considerably more resilient to proteolysis and metabolism. Recently, we reported two new classes of β‐peptides, β³‐ and β²‐peptides derived from l‐aspartic acid and l‐diaminopropionic acid, respectively. Here, we report the proteolytic stability of these β‐peptidic compounds and a mixed α /β‐peptide against three enzymes (pronase, trypsin and elastase), as well as, human serum. The …

New Dosing Schedules Of Dasatinib For Cml And Adverse Event Management, Siu Fun Wong

Pharmacy Faculty Articles and Research

Resistance to imatinib in patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has emerged as a significant clinical issue. Dasatinib is a tyrosine kinase inhibitor that has 325-fold greater in vitro activity against native BCR-ABL (breakpoint cluster region-Abelson leukemia virus) compared with imatinib and can overcome primary (intrinsic) and secondary (acquired) imatinib resistance. Here, we review the clinical profile of dasatinib in imatinib-resistant and -intolerant patients and share clinical approaches for managing adverse events (AEs) to ensure maximum patient benefit. References were obtained through literature searches on PubMed as well as from the Proceedings …

Helical Peptides Derived From Lactoferrin Bind Hepatitis C Virus Envelope Protein E2, Reem Beleid, Donna Douglas, Norman Kneteman, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Hepatitis C virus is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma infecting more than 170 million people. Hepatitis C virus envelope 2 glycoprotein (E2) binds several cell‐surface molecules that act as receptor candidates mediating hepatitis C virus entry into hepatocytes. Peptides derived from human lactoferrin have been shown to bind hepatitis C virus‐E2 protein thereby preventing hepatitis C virus entry in cultured hepatocytes. In this study, starting from a 33‐residue human lactoferrin‐derived peptide, a number of biotin‐linked α‐peptides were synthesized and investigated for their E2 protein binding activity. E2 protein from hepatitis C virus genotype 1b …

Composites Comprising Cholesterol And Carboxymethyl Cellulose, Vuk Uskoković

Pharmacy Faculty Articles and Research

Whereby cholesterol presents one of the major fatty substances in human body, carboxymethyl cellulose is a water-soluble derivative of cellulose, the most abundant dietary fiber. Whereas on one hand in vivo precipitation of cholesterol is the major cause of atherosclerosis, dietary fibers are on the other hand known for their ability to clean the fatty plaque deposited on intestinal pathways, and prevent its build-up in other critical areas within the organism. In this work, a method for the preparation of a composite material comprising cholesterol and carboxymethyl cellulose from 1-hexanol/water biphase mixtures is reported. Specificity of the interaction between the …

Right-Handed 14-Helix In Β3-Peptides From L-Aspartic Acid Monomers, Kamaljit Kaur, Tara Sprules, Wael Soliman, Reem Beleid, Sahar Ahmed

Pharmacy Faculty Articles and Research

β-Peptides made from L-aspartic acid monomers form a new class of β³-peptides. Here we report the first three-dimensional NMR solution structure of a β³-hexapeptide (1) from L-aspartic acid monomers in 2,2,2-trifluoroethanol (TFE). We show that 1 forms a right-handed 14-helical structure in TFE. α-peptides from naturally occurring L-amino acids adopt a right-handed α-helix whereas β³-peptides formed from β³-amino acids derived from naturally occurring L-amino acids form left-handed 14-helices. The right-handed 14-helical conformation of 1 is a better mimic of α-peptide conformations. Using the NMR structure of 1 in TFE, we …

Protein Adducts Of Iso[4]Levuglandin E2, A Product Of The Isoprostane Pathway, In Oxidized Low Density Lipoprotein, Robert G. Salomon, Wei Sha, Cynthia Brame, Kamaljit Kaur, Ganesamoorthy Subbanagounder, June O'Neil, Henry F. Hoff, L. Jackson Roberts Ii

Pharmacy Faculty Articles and Research

Levuglandin (LG) E₂, a cytotoxic seco prostanoic acid co-generated with prostaglandins by nonenzymatic rearrangements of the cyclooxygenase-derived endoperoxide, prostaglandin H₂, avidly binds to proteins. That LGE₂-protein adducts can also be generated nonenzymatically is demonstrated by their production during free radical-induced oxidation of low density lipoprotein (LDL). Like oxidized LDL, LGE₂-LDL, but not native LDL, undergoes receptor-mediated uptake and impaired processing by macrophage cells. Since radical-induced lipid oxidation produces isomers of prostaglandins, isoprostanes (isoPs), via endoperoxide intermediates, we postulated previously that a similar family of LG isomers, isoLGs, is cogenerated with isoPs. Now …

What Is The Risk Of Teratogenicity With The Use Of Selective Serotonin Reuptake Inhibitors During Pregnancy?, Michael Z. Wincor, Mary Gutierrez, Ann Nguyen

Pharmacy Faculty Articles and Research

"The lifetime prevalence of major depressive disorder in women is 10 to 25%, with an average age of onset in the mid-20s.1 Over the nine years that the selective serotonin reuptake inhibitors (SSRis) have been available, for many prescribers, they have become first-line agents in the treatment of depression. In addition, sorne of them are also being used in the treatment of obsessive- compulsive disorder and panic disorder. In light of these facts, itis not unlikely that women of childbearing age would be treated with one of the SSRis. In considering the risks of exposing a fetus to an SSRI, …