Medicine and Health Sciences Commons^™

Editorial Focus: An Ace Inhibitor Improves Vascular Outcomes In A Pkd Model, Surya M. Nauli

Pharmacy Faculty Articles and Research

Cardiovascular complications are the most common cause of death in patients with polycystic kidney disease (PKD). Within the context of clinical practice, two possible theories have been reviewed that could help describe the pathogenesis of vascular complications in PKD (7).

Calcium-Mediated Mechanisms Of Cystic Expansion, Shakila Abdul-Majeed, Surya M. Nauli

Pharmacy Faculty Articles and Research

In this review, we will discuss several well-accepted signaling pathways toward calcium-mediated mechanisms of cystic expansion. The second messenger calcium ion has contributed to a vast diversity of signal transduction pathways. We will dissect calcium signaling as a possible mechanism that contributes to renal cyst formation. Because cytosolic calcium also regulates an array of signaling pathways, we will first discuss cilia-induced calcium fluxes, followed by Wnt signaling that has attributed to much-discussed planar cell polarity. We will then look at the relationship between cytosolic calcium and cAMP as one of the most important aspects of cyst progression. The signaling of …

Neuroprotective Effects Of Bilobalide Are Accompanied By A Reduction Of Ischemia-Induced Glutamate Release In Vivo, Dorothee Lang, Cornelia Kiewert, Alexander Mdzinarishvili, Tina Maria Schwarzkopf, Rachita K. Sumbria, Joachim Hartmann, Jochen Klein

Pharmacy Faculty Articles and Research

Neuroprotective properties of bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24 h of middle cerebral artery occlusion (MCAO), bilobalide reduced infarct areas in the core region (striatum) by 40–50% when given at 10 mg/kg 1 h prior to MCAO. Neuroprotection was also observed at lower doses, or when the drug was given 1 h past stroke induction. Sensorimotor function in mice was improved by bilobalide as shown by corner and chimney tests. When brain metabolism in situ was monitored by microdialysis, MCAO caused a rapid disappearance of extracellular glucose in the …

Beta-Lysine Discrimination By Lysyl-Trna Synthetase, Marla S. Gilreath, Hervé Roy, Tammy J. Bullwinkle, Assaf Katz, Michael Ibba, William Wiley Navarre

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P is modified with (R)‐β‐lysine by the lysyl‐tRNA synthetase (LysRS) paralog PoxA. PoxA specificity is orthogonal to LysRS, despite their high similarity. To investigate α‐ and β‐lysine recognition by LysRS and PoxA, amino acid replacements were made in the LysRS active site guided by the PoxA structure. A233S LysRS behaved as wild type with α‐lysine, while the G469A and A233S/G469A variants decreased stable α‐lysyl‐adenylate formation. A233S LysRS recognized β‐lysine better than wildtype, suggesting a role for this residue in discriminating α‐ and β‐amino acids. Both enantiomers of β‐lysine were substrates for tRNA aminoacylation by LysRS, which, together with …

Spiking Patterns And Their Functional Implications In The Antennal Lobe Of The Tobacco Hornworm Manduca Sexta, Hong Lei, Carolina E. Reisenman, Caroline H. Wilson, Prasad Gabbur, John G. Hildebrand

Health Sciences and Kinesiology Faculty Articles

Bursting as well as tonic firing patterns have been described in various sensory systems. In the olfactory system, spontaneous bursts have been observed in neurons distributed across several synaptic levels, from the periphery, to the olfactory bulb (OB) and to the olfactory cortex. Several in vitro studies indicate that spontaneous firing patterns may be viewed as “fingerprints” of different types of neurons that exhibit distinct functions in the OB. It is still not known, however, if and how neuronal burstiness is correlated with the coding of natural olfactory stimuli. We thus conducted an in vivo study to probe this question …

The Trna Synthetase Paralog Poxa Modifies Elongation Factor-P With (R)-Β-Lysine, Hervé Roy, S. Betty Zou, Tammy J. Bullwinkle, Benjamin S. Wolfe, Marla S. Gilreath, Craig J. Forsyth, William Wiley Navarre, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The lysyl-tRNA synthetase paralog PoxA modifies elongation factor P (EF-P) with α-lysine at low efficiency. Cell-free extracts containing non–α-lysine substrates of PoxA modified EF-P with a change in mass consistent with addition of β-lysine, a substrate also predicted by genomic analyses. EF-P was efficiently functionally modified with (R)-β-lysine but not (S)-β-lysine or genetically encoded α-amino acids, indicating that PoxA has evolved an activity orthogonal to that of the canonical aminoacyl-tRNA synthetases.

Prenatal Maternal Anxiety And Early Childhood Temperament, Megan M. Blair, Laura M. Glynn, Curt A. Sandman, Elysia Poggi Davis

Psychology Faculty Articles and Research

The consequences of exposure to prenatal maternal anxiety for the development of child temperament were examined in a sample of 120 healthy, 2-year-old children. Prenatal maternal state and pregnancy-specific anxiety (PSA) were measured five times during pregnancy, and maternal state anxiety was measured again at 2 years post partum. Child temperament was measured at 2 years using the Early Childhood Behavior Questionnaire. The relationship between the trajectory of maternal anxiety across gestation and negative affectivity was evaluated using hierarchical linear growth curve modeling. Higher maternal PSA between 13 and 17 weeks of gestation was associated with increased negative temperament …

Multiple Protein Kinases Determine The Phosphorylated State Of The Small Heat Shock Protein, Hsp27, In Sh-Sy5y Neuroblastoma Cells, Linda A. Dokas, Amy M. Malone, Frederick E. Williams, Surya M. Nauli, William S. Messer Jr.

Pharmacy Faculty Articles and Research

In SH-SY5Y human neuroblastoma cells, the cholinergic agonist, carbachol, stimulates phosphorylation of the small heat shock protein 27 (HSP27). Carbachol increases phosphorylation of both Ser-82 and Ser-78 while the phorbol ester, phorbol-12, 13-dibutyrate (PDB) affects only Ser-82. Muscarinic receptor activation by carbachol was confirmed by sensitivity of Ser-82 phosphorylation to hyoscyamine with no effect of nicotine or bradykinin. This response to carbachol is partially reduced by inhibition of protein kinase C (PKC) with GF 109203X and p38 mitogen-activated protein kinase (MAPK) with SB 203580. In contrast, phosphorylation produced by PDB is completely reversed by GF 109203X or CID 755673, an …

Antivirulence Potential Of Tr-700 And Clindamycin On Clinical Isolates Of Staphylococcus Aureus Producing Phenol-Soluble Modulins, Jason Yamaki, Timothy Synold, Annie Wong-Beringer

Pharmacy Faculty Articles and Research

Staphylococcus aureus strains (n = 50) causing complicated skin and skin structure infections produced various levels of phenol-soluble modulin alpha-type (PSMα) peptides; some produced more than twice that produced by the control strain (LAC USA300). TR-700 (oxazolidinone) and clindamycin strongly inhibited PSM production at one-half the MIC but exhibited weak to modest induction at one-fourth and one-eighth the MICs, primarily in low producers. Adequate dosing of these agents is emphasized to minimize the potential for paradoxical induction of virulence.

Patterns Of Fetal Heart Rate Response At ∼30 Weeks Gestation Predict Size At Birth, C. Sandman, C. J. Cordova, E. P. Davis, Laura M. Glynn, C. Buss

Psychology Faculty Articles and Research

There is evidence that fetal exposure to maternal stress is associated with adverse birth outcomes. Less is known about the association between fetal responses to a stressor and indicators of fetal maturity and developmental outcomes. The purpose of the present study was to determine whether fetal heart rate (FHR) patterns in response to a startling stimulus at ∼30 weeks of gestation were associated with gestational age at birth and birth weight. FHR was measured in 156 maternal–fetal dyads following a vibroacoustic stimulus. All pregnancies were singleton intrauterine pregnancies in English-speaking women who were primarily married, middle class, White and at …

Multimodal Spectral Imaging Of Cells Using A Transmission Diffraction Grating On A Light Microscope, Dragan Isailovic, Yang Xu, Tyler Copus, Suraj Saraswat, Surya M. Nauli

Pharmacy Faculty Articles and Research

A multimodal methodology for spectral imaging of cells is presented. The spectral imaging setup uses a transmission diffraction grating on a light microscope to concurrently record spectral images of cells and cellular organelles by fluorescence, darkfield, brightfield, and differential interference contrast (DIC) spectral microscopy. Initially, the setup was applied for fluorescence spectral imaging of yeast and mammalian cells labeled with multiple fluorophores. Fluorescence signals originating from fluorescently labeled biomolecules in cells were collected through triple or single filter cubes, separated by the grating, and imaged using a charge-coupled device (CCD) camera. Cellular components such as nuclei, cytoskeleton, and mitochondria were …

Intermediate Filaments Regulate Tissue Size And Stiffness In The Murine Lens, Douglas S. Fudge, John V. Mccuaig, Shannon Van Stralen, John F. Hess, Huan Wang, Richard T. Mathias, Paul G. Fitzgerald

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

PURPOSE. To define the contributions of the beaded filament (BF), a lens-specific intermediate filament (IF), to lens morphology and biomechanics.

METHODS. Wild-type and congenic CP49 knockout (KO) mice were compared by using electrophysiological, biomechanical, and morphometric approaches, to determine changes that occurred because of the absence of this cytoskeletal structure.

RESULTS. Electrophysiological assessment established that the fiber cells lacking the lens-specific IFs were indistinguishable from wild-type fiber cells. The CP49 KO mice exhibited lower stiffness, and an unexpected higher resilience than the wildtype lenses. The absence of these filaments resulted in lenses that were smaller, and exhibited a higher ratio …

Pressure Distribution Over The Palm Region During Forward Falls On The Outstretched Hands, Woochol J. Choi, Stephen N. Robinovitch

Physical Therapy Faculty Articles and Research

Falls on the outstretched hands are the cause of over 90% of wrist fractures, yet little is known about bone loading during this event. We tested how the magnitude and distribution of pressure over the palm region during a forward fall is affected by foam padding (simulating a glove) and arm configuration, and by the faller’s body mass index (BMI) and thickness of soft tissues over the palm region.

Thirteen young women with high (n=7) or low (n=6) BMI participated in a “torso release experiment” that simulated falling on both outstretched hands with the arm inclined either at 20° or …

Unifying The Mathematical Modeling Of In Vivo And In Vitro Microdialysis, Peter M. Bungay, Rachita K. Sumbria, Ulrich Bickel

Pharmacy Faculty Articles and Research

A unifying approach is presented for developing mathematical models of microdialysis that are applicable to both in vitro and in vivo situations. Previous models for cylindrical probes have been limited by accommodating analyte diffusion through the surrounding medium in the radial direction only, i.e., perpendicular to the probe axis, or by incomplete incorporation of diffusion in the axial direction. Both radial and axial diffusion are included in the present work by employing two-dimensional finite element analysis. As in previous models, the nondimensional clearance modulus (Θ) represents the degree to which analyte clearance from the external medium influences diffusion through the …

Using Positive Deviance For Determining Successful Weight- Control Practices, Heather L. Stuckey, Jarol Boan, Jennifer L. Kraschnewski, Michelle Miller-Day, Erik B. Lehman, Christopher N. Sciamanna

Communication Faculty Articles and Research

Based on positive deviance (examining the practices of successful individuals), we identified five primary themes from 36 strategies that help to maintain long-term weight loss (weight control) in 61 people. We conducted in-depth interviews to determine what successful individuals did and/or thought about regularly to control their weight. The themes included weight-control practices related to (a) nutrition: increase water, fruit, and vegetable intake, and consistent meal timing and content; (b) physical activity: follow and track an exercise routine at least 3×/week; (c) restraint: practice restraint by limiting and/or avoiding unhealthy foods; (d) self-monitor: plan meals, and track calories/weight progress; and …

Evaluating Mediated Perception Of Narrative Health Messages: The Perception Of Narrative Performance Scale, Jeong Kyu Lee, Michael L. Hecht, Michelle Miller-Day, Elvira Elek

Communication Faculty Articles and Research

Narrative media health messages have proven effective in preventing adolescents’ substance use but as yet few measures exist to assess perceptions of them. Without such a measure it is difficult to evaluate the role these messages play in health promotion or to differentiate them from other message forms. In response to this need, a study was conducted to evaluate the Perception of Narrative Performance Scale that assesses perceptions of narrative health messages. A sample of 1185 fifth graders in public schools at Phoenix, Arizona completed a questionnaire rating of two videos presenting narrative substance use prevention messages. Confirmatory factor analyses …

Alcohol And Other Drug Resistance Strategies Employed By Rural Adolescents, Jonathan Pettigrew, Michelle Miller-Day, Janice L. Krieger, Michael L. Hecht

Communication Faculty Articles and Research

This study seeks to identify how rural adolescents make health decisions and utilize communication strategies to resist influence attempts in offers of alcohol, tobacco, and other drugs (ATOD). Semi-structured interviews were conducted with 113 adolescents from rural school districts to solicit information on ATOD norms, past ATOD experiences, and substance offer response episodes. Rural youths’ resistance strategies were similar to previous findings with urban adolescents – refuse, explain, avoid, and leave (the REAL typology) – while unique features of these strategies were identified including the importance of personal narratives, the articulation of a non-user identity, and being “accountable” to self …

Polycystic Diseases In Visceral Organs, Shakila Abdul-Majeed, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are nonmotile, microtubule-based, antenna-like organelles projecting from the apical surface of most mammalian cells. Elegant studies have established the importance of ciliary structure and function in signal transduction and the sensory roles of cilia in maintaining healthy cellular state. In particular, dysfunctional cilia have been implicated in a large number of diseases mainly characterized by the presence of fluid-filled cysts in various organs. Aside from polycystic kidney disease (PKD), however, the roles of cilia in polycystic liver disease (PLD), polycystic pancreas disease (PPD), and polycystic ovarian syndrome (PCOS) are still very vague. In addition, although gender and sex …

3-Substitued Indoles: One Pot Synthesis And Evaluation Of Anticancer And Src Kinase Inhibitory Activities, V. Kameshwara Rao, Bhupender S. Chhikara, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

An efficient and economical method was developed for the synthesis of 3-substituted indoles by one pot three-component coupling reaction of a substituted or unsubstituted benzaldehyde, N-methylaniline, and indole or N-methylindole using Yb(OTf)3-SiO2 as a catalyst. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. The 4-methylphenyl (4o and 4p) and 4-methoxyphenyl (4q) indole derivatives inhibited the cell proliferation of SK-OV-3 and HT-29 cells by 7077% at a concentration of 50 μM. The unsubstituted phenyl (4d) and 3-nitrophenyl (4l) derivatives showed the inhibition of c-Src kinase …

A Typology Of Coping In Couples Undergoing Fertility Treatment, Brennan Peterson, Matthew Pirritano, Lone Schmidt

Marriage and Family Therapy Faculty Presentations

Poster presentation about the use of cluster analysis to identify clinically meaningful groups of infertile couples, and how such profiles can be used by medical and mental health professionals.

Maternal Defense: Breastfeeding Heightens Aggression By Reducing Stress, Jennifer Hahn-Holbrook, Julianne Holt-Lunstad, Colin Holbrook, Sarah M. Coyne, E. Thomas Lawson

Psychology Faculty Articles and Research

Mothers in numerous species exhibit heightened aggression in defense of their young. This shift typically coincides with the duration of lactation in nonhuman mammals, which suggests that human mothers may display similarly accentuated aggressiveness while breast feeding. Here we report the first behavioral evidence for heightened aggression in lactating humans. Breast-feeding mothers inflicted louder and longer punitive sound bursts on unduly aggressive confederates than did formula-feeding mothers or women who had never been pregnant. Maternal aggression in other mammals is thought to be facilitated by the buffering effect of lactation on stress responses. Consistent with the animal literature, our results …

Fairness-Trust-Loyalty Relationship Under Varying Conditions Of Supplier-Buyer Interdependence, Thani Jambulingam, Ravi Kathuria, John R. Nevin

Business Faculty Articles and Research

Relationship marketing plays a significant role in supply chain practice and academic studies. Using the resource advantage theory within the relationship marketing framework, we studied the mediating role of trust as a governance mechanism in the fairness-loyalty relationship under different types of interdependence structure between suppliers (wholesalers) and buyers (retailers). Our findings, based on data from retail pharmacies, demonstrate that only under conditions of symmetric independence, trust, as a governance mechanism, completely mediate the relationship between fairness and loyalty. Under conditions of both perceived independence (i.e., lack of interdependence) and asymmetric buyer dependence, however, trust does not mediate but fairness …

The Mechanosensory Role Of Primary Cilia In Vascular Hypertension, Surya M. Nauli, Xingjian Jin, Beerend P. Hierck

Pharmacy Faculty Articles and Research

Local regulation of vascular tone plays an important role in cardiovascular control of blood pressure. Aside from chemical or hormonal regulations, this local homeostasis is highly regulated by fluid-shear stress. It was previously unclear how vascular endothelial cells were able to sense fluid-shear stress. The cellular functions of mechanosensory cilia within vascular system have emerged recently. In particular, hypertension is insidious and remains a continuous problem that evolves during the course of polycystic kidney disease (PKD). The basic and clinical perspectives on primary cilia are discussed with regard to the pathogenesis of hypertension in PKD.

Endothelin, Yoshifumi Kawanabe, Surya M. Nauli

Pharmacy Faculty Articles and Research

Endothelin-1 is the most potent vasoconstrictor agent currently identified, and it was originally isolated and characterized from the culture media of aortic endothelial cells. Two other isoforms, termed endothelin-2 and endothelin-3, were subsequently identified, along with structural homologues isolated from the venom of Actractapis eng-addensis known as the sarafotoxins. In this review, we will discuss the basic science of endothelins, endothelin-converting enzymes, and endothelin receptors. Only concise background information pertinent to clinical physician is provided. Next we will describe the pathophysiological roles of endothelin-1 in pulmonary arterial hypertension, heart failure, systemic hypertension, and female malignancies, with emphasis on ovarian cancer. …

Substituted Coumarin Derivatives: Synthesis And Evaluation Of Antiproliferative And Src Kinase Inhibitory Activities, Abha Kathuria, Sarah Jalal, Rakesh Tiwari, Amir Nasrolahi Shirazi, Shilpi Gupta, Shiv Kumar, Keykavous Parang, Sunil K. Sharma

Pharmacy Faculty Articles and Research

Six classes of coumarin derivatives (i.e. 3-alkyl-4-methylcoumarins, pyranocoumarins, coumarin carboxamides, quaternary ammonium coumarins, 7-aminocoumarins, and 4-aminocoumarins) were synthesized and evaluated for inhibition of cell proliferation of colon adenocarcinoma (HT-29), breast carcinoma (MDA-MB-468 or MCF-7), and human ovarian adenocarcinoma (SK-OV-3) cells. C-3-Alkyl substituted analogs of 4-methylcoumarins and pyranocoumarins, 5 and 6, inhibited the cell proliferation of MDA-MB-468 and SK-OV-3 cells by 53-74%, while 3-decyl substituted pyranocoumarin 10 and triethyl substituted quaternary ammonium coumarin derivative 29 inhibited the cell proliferation of HT-29 and SK-OV-3 cells by 63-72% at a concentration of 50 μM. Among all the compounds studied, C-3 decyl substituted quaternary …

Fatty Acyl Amide Dderivatives Of Doxorubicin: Synthesis And In Vitro Anticancer Activities, Bhupender S. Chhikara, Nicole St. Jean, Deendayal Mandal, Anil Kumar, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin is an anticancer drug extensively used in anticancer therapy. Doxorubicin is highly hydrophilic, has short half-life, and its use is associated with severe side effects at high doses. Fatty acyl amide derivatives of doxorubicin were synthesized with the expectation to improve the lipophilicity and anticancer activity of the drug. The lipophilicity was enhanced with the increase in chain length of fatty acyl moiety. Conjugation of 4-amino group with fatty acids through an amide bond reduced the anticancer activity in leukemia, breast, ovarian, and colon cancer cell lines, suggesting that the presence of free amino group is required for anticancer …

Synthesis Of 3-Phenylpyrazolopyrimidine-1,2,3-Triazole Conjugates And Evaluation Of Their Src Kinase Inhibitory And Anticancer Activities, Anil Kumar, Israr Ahmad, Bhupender S. Chhikara, Rakesh Tiwari, Deendayal Mandal, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of two classes of 3-phenylpyrazolopyrimidine-1,2,3-triazole conjugates were synthesized using click chemistry approach. All compounds were evaluated for inhibition of Src kinase and human ovarian adenocarcinoma (SK-Ov-3), breast carcinoma (MDA-MB-361), and colon adenocarcinoma (HT-29). Hexyl triazolyl-substituted 3-phenylpyrazolopyrimidine exhibited inhibition of Src kinase with an IC50 value of 5.6 µM. 4-Methoxyphenyl triazolyl-substituted 3-phenylpyrazolopyrimidine inhibited the cell proliferation of HT-29 and SK-Ov-3 by 73% and 58%, respectively, at a concentration of 50 µM.

Altered Self-Assembly And Apatite Binding Of Amelogenin Induced By N-Terminal Proline Mutation, Li Zhu, Vuk Uskoković, Thuan Le, Pamela Denbesten, Yulei Huang, Stefan Habelitz, Wu Li

Pharmacy Faculty Articles and Research

Objective—A single Pro-70 to Thr (p.P70T) mutation of amelogenin is known to result in hypomineralized amelogenesis imperfecta (AI). This study aims to test the hypothesis that the given mutation affects the self-assembly of amelogenin molecules and impairs their ability to conduct the growth of apatite crystals.

Design—Recombinant human full-length wild-type (rh174) and p.P70T mutated amelogenins were analyzed using dynamic light scattering (DLS), protein quantification assay and atomic force microscopy (AFM) before and after the binding of amelogenins to hydroxyapatite crystals. The crystal growth modulated by both amelogenins in a dynamic titration system was observed using AFM.

Results—As …

A Prospective Study Of Positive Psychological Well-Being And Coronary Heart Disease, Julia K. Boehm, Christopher Peterson, Mika Kivimaki, Laura D. Kubzansky

Psychology Faculty Articles and Research

Objective: Research suggests that positive psychological well-being is associated with cardiovascular health. However, much of this research uses elderly samples and has not determined the pathways by which psychological well-being influences cardiovascular disease or whether effects are similar for men and women. This study investigates the association between two aspects of well-being (emotional vitality and optimism) and coronary heart disease (CHD) in a sample of middle-aged men and women, and considers potential mediating factors.

Method: Between 1991 and 1994, well-being and coronary risk factors were assessed among 7,942 individuals without a prior cardiovascular event from the Whitehall II …

Development Of A Positive Psychology Intervention For Patients With Acute Cardiovascular Disease, Jeff C. Huffman, Carol A. Mastromauro, Julia K. Boehm, Rita Seabrook, Gregory L. Fricchione, John W. Denninger, Sonja Lyubomirsky

Psychology Faculty Articles and Research

The management of depression and other negative psychological states in cardiac patients has been a focus of multiple treatment trials, though such trials have not led to substantial improvements in cardiac outcomes. In contrast, there has been minimal focus on interventions to increase positive psychological states in cardiac patients, despite the fact that optimism and other positive states have been associated with superior cardiovascular outcomes. Our objective was to develop an 8-week, phone-based positive psychology intervention for patients hospitalized with acute cardiac disease (acute coronary syndrome or decompensated heart failure). Such an intervention would consist of positive psychology exercises adapted …