Pharmacy and Pharmaceutical Sciences Commons^™

Novel Function Of Phosphoinositide 3-Kinase In T Cell Ca2+ Signaling, Ao-Lin Hsu, Tsui-Ting Ching, Goutam Sen, Da-Sheng Wan, Subbarao Bondada, Kalwant S. Authi, Ching-Shih Chen

Pharmaceutical Sciences Faculty Publications

This study presents evidence that phosphoinositide (PI) 3-kinase is involved in T cell Ca²⁺ signaling via a phosphatidylinositol 3,4,5-trisphosphate PI(3,4,5)P₃-sensitive Ca²⁺entry pathway. First, exogenous PI(3,4,5)P₃ at concentrations close to its physiological levels induces Ca²⁺ influx in T cells, whereas PI(3,4)P₂, PI(4,5)P₂, and PI(3)P have no effect on [Ca²⁺]_i. This Ca²⁺ entry mechanism is cell type-specific as B cells and a number of cell lines examined do not respond to PI(3,4,5)P₃ stimulation. Second, inhibition of PI 3-kinase by wortmannin and by overexpression of the …

The Skn7 Response Regulator Of Saccharomyces Cerevisiae Interacts With Hsf1 In Vivo And Is Required For The Induction Of Heat Shock Genes By Oxidative Stress, Desmond C. Raitt, Anthony L. Johnson, Alexander M. Erkine, Kozo Makino, Brian Morgan, David S. Gross, Leland H. Johnston

Scholarship and Professional Work – COPHS

The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory trans-activators, Hsf1 and Skn7, share certain structural homologies, particularly in their DNA-binding domains and the presence of adjacent regions of coiled-coil structure, which are known to mediate protein–protein interactions. Here, we provide evidence that Hsf1 and Skn7 interact in vitro and …

Cell Cycle-Dependent Binding Of Yeast Heat Shock Factor To Nucleosomes, Christina Bourgeois Venturi, Alexander M. Erkine, David S. Gross

Scholarship and Professional Work – COPHS

In the nucleus, transcription factors must contend with the presence of chromatin in order to gain access to their cognate regulatory sequences. As most nuclear DNA is assembled into nucleosomes, activators must either invade a stable, preassembled nucleosome or preempt the formation of nucleosomes on newly replicated DNA, which is transiently free of histones. We have investigated the mechanism by which heat shock factor (HSF) binds to target nucleosomal heat shock elements (HSEs), using as our model a dinucleosomal heat shock promoter (hsp82-ΔHSE1). We find that activated HSF cannot bind a stable, sequence-positioned nucleosome in G₁-arrested …

Role Of KAtp Channels In Reduced Antinociceptive Effect Of Morphine In Streptozotocin-Induced Diabetic Mice, Vivek Sood, Ajay Sharma, Manjeet Singh

Pharmacy Faculty Articles and Research

The nociceptive effect was measured using withdrawal latency in tail flick test in mice rendered diabetic by administering streptozotocin (200 mg/kg, i.p.). The antinociceptive effect of morphine (4 and 8 mg/kg, s.c.) and cromakalim, a KATP channel opener, (0.3, 1 and 2 micrograms, i.c.v.) was significantly reduced in diabetic mice. Moreover, co-administration of cromakalim(0.3 microgram) did not alter the reduced antinociceptive effect of morphine(4 mg/kg) in diabetic mice. Spleenectomy in diabetic mice restored the decrease in antinociceptive effect of morphine and cromakalim. Multiple dose treatment with insulin to maintain euglycaemia for 3 days in diabetic mice prevented the decrease in …

Cellular Release Of And Response To Atp As Key Determinants Of The Set-Point Of Signal Transduction Pathways, Rennolds S. Ostrom, Caroline Gregorian, Paul A. Insel

Pharmacy Faculty Articles and Research

The determinants of “basal” activity of signaling pathways regulating cellular responses are poorly defined. One possibility is that cells release factors to establish the set-point of such pathways. Here we show that treatment of Madin-Darby canine kidney cells with the nucleotidase apyrase decreases basal arachidonic acid release and cAMP production 30–40% and that inhibitors of P2Y receptor action also affect basal and forskolin-stimulated cAMP accumulation. Changing medium prominently increases extracellular levels of ATP in Madin-Darby canine kidney, COS-7, and HEK-293 cells. Mechanical stimulation of ATP release likely occurs in virtually every experimental protocol with cultured cells, implicating such release and …

Effect Of Actinomycin D And Cycloheximide On Ischemic Preconditioning-Induced Delayed Cardioprotective Effect In Rats, Devinder Singh, Ajay Sharma, Manjeet Singh

Pharmacy Faculty Articles and Research

The present study was designed to investigate the effect of actinomycin D, a transcription inhibitor, and cycloheximide, a translation inhibitor, on the delayed cardioprotective effect of ischemic preconditioning. Left thoracotomy was performed in anaesthetized rats at 4th/5th intercostal space and polypropylene suture (5-0) was employed to occlude left common coronary artery. Ischemic preconditioning was produced by four episodes of 5 min of coronary artery occlusion followed by 5 min of reperfusion and thoracic cavity was sutured. Left thoracotomy was performed again after 24 hr of ischemic preconditioning and left coronary artery was occluded for 30 min followed by reperfusion for …

Investigations Of The Absorption And Metabolismof Antioxidant Flavonols, Abdul Aziz Azlina

Student Works (2000-2009)

Flavonols are polyphenols, secondary plant metabolites commonly found in plants and foods of plant origin. They have widespread biological properties in the human body. The recent discovery of their potential antioxidant activities has prompted extensive research. Flavonols particularly quercetin are potent antioxidants with higher antioxidant properties than the well known antioxidant vitamins C and E. Several epidemiology studies have demonstrated a strong inverse association between flavonoid intake and risk of coronary heart disease. The association with cancer is less defined with only some studies showing an inverse association and others not. In view of their potential to act as antioxidants …

Modulation Of The Pharmacokinetics And Pharmacodynamics Of Proteins By Polyethylene Glycol Conjugation, Reza Mehvar

Pharmacy Faculty Articles and Research

With the rapid advances in the field of biotechnology during the last decade, many peptides and proteins have been produced and evaluated for therapy of various diseases, including cancer. However, rapid clearance and the possibility of immunogenicity after the in vivo administration of these biotechnology-driven products have impeded their marketing. To circumvent these problems, synthetic and natural polymers such as polyethylene glycol (PEG) and dextrans, respectively, have been covalently attached to proteins, and some of these protein-polymer conjugates have shown promising therapeutic results. The conjugation of proteins with polymers usually causes a reduction in the recognition of the protein by …

Cooperative Binding Of Heat Shock Factor To The Yeast Hsp82 Promoter In Vivo And In Vitro, Alexander M. Erkine, Serena F. Magrogan, Edward A. Sekinger, David S. Gross

Scholarship and Professional Work – COPHS

revious work has shown that heat shock factor (HSF) plays a central role in remodeling the chromatin structure of the yeastHSP82 promoter via constitutive interactions with its high-affinity binding site, heat shock element 1 (HSE1). The HSF-HSE1 interaction is also critical for stimulating both basal (noninduced) and induced transcription. By contrast, the function of the adjacent, inducibly occupied HSE2 and -3 is unknown. In this study, we examined the consequences of mutations in HSE1, HSE2, and HSE3 on HSF binding and transactivation. We provide evidence that in vivo, HSF binds to these three sites cooperatively. This cooperativity is seen …

Inhibition Of Cpla2-Mediated Arachidonic Acid Release By Cyclic Amp Defines A Negative Feedback Loop For P2y-Receptor Activation In Mdck-D1 Cells, Mingzhao Xing, Steven Post, Rennolds S. Ostrom, Michael Samardzija, Paul A. Insel

Pharmacy Faculty Articles and Research

In Madin-Darby canine kidney D1cells extracellular nucleotides activate P2Y receptors that couple to several signal transduction pathways, including stimulation of multiple phospholipases and adenylyl cyclase. For one class of P2Y receptors, P2Y2 receptors, this stimulation of adenylyl cyclase and increase in cAMP occurs via the conversion of phospholipase A2 (PLA2)-generated arachidonic acid (AA) to prostaglandins (e.g. PGE2). These prostaglandins then stimulate adenylyl cyclase activity, presumably via activation of prostanoid receptors. In the current study we show that agents that increase cellular cAMP levels (including PGE2, forskolin, and the β-adrenergic agonist isoproterenol) can inhibit P2Y receptor-promoted AA release. The protein kinase …

Alterations In Calcium Homeostasis And The Insulin-Like Growth Factor Signaling Pathway Induced By Carcinogenic Polycyclic And Halogenated Aromatic Hydrocarbons In Human Mammary Epithelial Cells, Stacey L. Tannheimer

Pharmaceutical Sciences ETDs

Breast cancer is a major health concern for women, with only a small percent of the risk factors currently identified. It has been estimated that environmental factors may contribute to up to 80% of breast cancer cases. Many environmental carcinogens, such as polycyclic and halogenated aromatic hydrocarbons (PAHs and HAHs), are proven mammary carcinogens in animal models. Therefore, these studies were conducted to elucidate potential roles of PAHs and HAHs in alterations in known signaling pathways in human mammary epithelial cells (HMEC). Carcinogenic PAHs have previously been shown to produce sustained alterations in the calcium (Ca2') homeostasis of lymphocytes Therefore, …

Alterations In Human B Cell Calcium Homeostasis By Polycyclic Aromatic Hydrocarbons: Possible Associations With Cytochrome P450 Metabolism And Increased Tyrosine Phosphorylation, Barbara J. Mounho

Pharmaceutical Sciences ETDs

Polycyclic aromatic hydrocarbons (PAHs), are known immunotoxicants in animals, and are suspect toxins to the human immune system. The mechanism(s), however, by which PAHs exert immunosuppression have not been fully elucidated. Previous studies conducted in our laboratory have shown that PAHs, such as 7,12-dimethylbenz(a)- anthracene (DMB A) and benzo(a)pyrene (BaP) may exert their immunotoxic effects by altering intracellular calcium (Ca2+) homeostasis in lymphocytes. Intracellular Ca2+ is an important second messenger in the immune response, and the mobilization of Ca2+ is critical in the transduction of intracellular signals from the plasma membrane to the nucleus. The overall objective of this project …

Book Review Of Baruch A. Brody, Ethical Issues In Drug Testing, Approval, And Pricing, Annalee Abelson

RISK: Health, Safety & Environment (1990-2002)

Review of Baruch A. Brody, Ethical Issues in Drug Testing, Approval, and Pricing (Oxford University Press 1995). Conclusions, index, introduction, preface. LC 94-4479; ISBN 0-19-508831-X. [268 pp. Cloth $35.00. 200 Madison Avenue, New York NY 10016.]

Anion Induced Blue To Purple Transition In Bacteriorhodopsin, Mrunalini Pattarkine, Anil K. Singh

Faculty Works

Purple membrane (PM, λ" role="presentation">λmax" role="presentation">max 570 nm) of H. halobium on treatment with sulphuric acid changes its colour to blue (λ" role="presentation">λmax" role="presentation">max 608 nm). The purple chromophore can be regenerated from the blue chromophore by exogeneous addition of anions such as CI−" role="presentation">− and HPO42−" role="presentation">2−4. Chloride ion is found to be more effective than the dibasic phosphate ion in regenerating the purple chromophore. Nevertheless, one thing common to the anion regeneration is that both CI−" role="presentation">− and HPO42−" role="presentation">2−4 show marked pH effect. At pH 1.0 the efficiency of …

Heat Shock Factor Gains Access To The Yeast Hsc82 Promoter Independently Of Other Sequence-Specific Factors And Antagonizes Nucleosomal Repression Of Basal And Induced Transcription, Alexander M. Erkine, C. C. Adams, T. Diken, D. S. Gross

Scholarship and Professional Work – COPHS

Transcription in eukaryotic cells occurs in the context of chromatin. Binding of sequence-specific regulatory factors must contend with the presence of nucleosomes for establishment of a committed preinitiation complex. Here we demonstrate that the high-affinity binding site for heat shock transcription factor (HSF) is occupied independently of other cis-regulatory elements and is critically required for preventing nucleosomal assembly over the yeast HSC82 core promoter under both noninducing (basal) and inducing conditions. Chromosomal mutation of this sequence, termed HSE1, erases the HSF footprint and abolishes both transcription and in vivo occupancy of the TATA box. Moreover, it dramatically reduces promoter chromatin …

Outpatient Administration Of Paclitaxel, Siu Fun Wong

Pharmacy Faculty Articles and Research

Paclitaxel (Taxol®, Bristol-Meyers Squibb), anti neoplastic agent made from the bark of the Pacific yew tree, is undoubtedly one of the most exciting agents to be evaluated over the past decade. Paclitaxel has demonstrated significant promise against ovarian and metastatic breast cancer, and appears to be the most effective single agent to date for non-small-cell lung cancer in trials conducted by Eastern Cooperative Oncology Group (ECOG).

Pharmaceutical Risk And The Quality Of Life, Beat Hiltbrunner, Andreas Breitsprecher

RISK: Health, Safety & Environment (1990-2002)

Quality-of-life research is briefly described and said to be in its infancy. However, the authors observe that such studies may, e.g., make it possible to better match patients and therapies. They also predict that, as scientific difficulties are overcome, the pharmaceutical industry will become more active in planning, implementing and evaluating such research.

Effect Of Dietary Aluminum Sulfate On Calcium And Phosphorus Metabolism Of Broiler Chicks, Akmed S. Hussein, Austin H. Cantor, Thomas H. Johnson, Robert A. Yokel

Animal and Food Sciences Faculty Publications

The effect of dietary aluminum sulfate on Ca and P metabolism was studied using 1-day-oldmale broiler chicks. In Experiment 1, practical diets providing .90% Ca plus .45% available P (P_av), .90% Ca plus .78% P_av, 1.80% Ca plus .45% P_av, or 1.80% Ca plus .90% P_av were fed with 0 or .392% Al as aluminum sulfate for 21 days. The control diet (.90% Caplus .45% P_av) without added A1 was fed to all chicks during Days 22 to 49. In general, Al significantly (Pi), tibia breaking strength, tibia weight, percentage of …

Relationship Of Dietary Aluminum, Phosphorus, And Calcium To Phosphorus And Calcium Metabolism And Growth Performance Of Broiler Chicks, Akmed S. Hussein, Austin H. Cantor, Thomas H. Johnson, Robert A. Yokel

Animal and Food Sciences Faculty Publications

Dietary treatments providing three levels of added Al (0, .196, or .392%) as aluminum sulfate and of available phosphorus (P_av) (.45, .68, or .78%) in a factorial arrangement were administered to day-old chicks in Experiment 1. Plasma inorganic phosphorus (P_i) was significantly (P < .05) elevated by increasing P_av and was decreased by Al. Body weight gain, feed intake, and the gain:feed ratio at Day 21 were significantly decreased by increased concentrations of Al, but were unaffected by the P_av concentrations. Decreases of 39 and 73% in weight gain and of 34 and 66% in feed intake resulted from feeding …

The Partial Purification And Characterization Of A Soluble Activator For The Sodium Adenosinetriphosphatase From Rat Cerebral Cortex And The Effect Of Cholinergic Agents, Thibaldo Javier Manrique Blanco

University of the Pacific Theses and Dissertations

In order for organisms to co-exist with nonliving matter, envelop to protect their delicate internal functions must be present. There are other reasons for this boundary to exist, e.g. to limit the volume occupied by the organism and to compartmentalize the contents of the organism so that certain critical concentrations may be easily maintained. Such envelopes are, of course, the cellular membranes. Membranes differ greatly between species, as well as within species. Given the complexity to which organisms have evolved, membranes have developed with a myriad of functions and components. It is easy to see differences between plant cellular membranes …

Computerized Formulation And Optimization Of Medicated Chewing Gum, Daniel J. Berky

University of the Pacific Theses and Dissertations

Sixty Four caffeinated chewing gum preparations were formulated by varying the amounts of (i) cinnamaldhyde, (0-0.75%), (ii) docusate (0-0.5%) and (iii) sucrose (40-60%). The gum base consisted of 33.33% yellow beeswax and 66.66% polyisobutylene MH, and was added, adjusting for a final weight of 2 grams per gum. The amount of caffeine was maintained at 100mg. The preparations were subjected to an in vivo release study as well as a hedonic survey with a panel of student volunteers.

Data were analyzed by using multiple linear regression on a mainframe computer. The resulting mathematical model was used to predict a theoretically …

Pharmacognosy Of The Saururaceae : Microscopy Of Powdered Drugs, Prakash Vaman Mallya

University of the Pacific Theses and Dissertations

Plants of the family Sauruaceae are used in folk medicine in various parts of the world. Chemistry of some plants of this family and their chemotaxonomy has been investigated in our laboratory (12).

It is very difficult to establish identity and authenticity of commercially available crude drugs and powders of the Saururaceae because a detailed, collective study of microscopic features of these plants is not available. Original papers establishing plants of this family (see later) do not include microscopic features; they describe only gross morphologic and other classical features required for systematics. They are not useful for a pharmacologist in …

The Synthesis Of Various Substituted 3-Amino-7-Hydroxy-2,2-Dimethyltetralins And Their Opioid-Related Activities, David Alan Lippman

University of the Pacific Theses and Dissertations

A series of aminotetralones and aminotetralins were synthesized from the common intermediate F, 3-amino-2,2-dimethyl-7-methoxy- 1-tetralone. The final compounds derived from F were simple substituted and/or reduced analogues. The products would allow a progressive structure activity relationship to be drawn based on pharmacological testing.

The common intermediate F was synthesized utilizing a six step procedure starting with p-methoxyphenylacetic acid. The overall yield from the precursor to the F:HC1 was 25%. Compound F was either O-demethylated to form 3-amino-2,2-dimethyl-7-hydroxy-l-tetralone (I) or was dimethylated on the amine and subsequently O-demethylated to yield the 3-dimethylamino-7-hydroxy-2,2-dimethyl-l-tetralone (J). The last major modification was the reduction of …

The Biochemistry Of Vascular Smooth Muscle In The Spontaneously Hypertensive Rat, John Edward Taylor

University of the Pacific Theses and Dissertations

Cyclic adenosine 3’,5’-monophosphate (cAMP) was first described as the mediator of the glycogenolytic effect of epinephrine and glucagon in the liver almost two decades ago. It has since been found that cAMP may mediate the effects of a number of hormones and neurohormones, and this observation has led to the development of the second messenger hypothesis of hormone action. According to the second messenger theory, the hormone or first messenger brings information to the cell, whereas, the second messenger (cAMP) transfers this information into intracellular events. More recent evidence has described the existence of an additional second messenger, cyclic guanosine …

Anticoagulant Half-Life Of Heparin In Human Subjects With Normal And Impaired Renal Function., Paul James Perry

University of the Pacific Theses and Dissertations

Numerous investigators have noted that individuals vary widely in their response to the anticoagulant, heparin. Animal model3 have suggested that patients with depressed renal function would be expected to clear heparin from the blood at a slower rate than patients with normal renal function.

Utilizing the Activated Coagulation Time clotting test, a method was developed to determine the anticoagulant half-life of heparin. The study calculated the half-life of heparin in a group of individuals with normal renal function and a population of patients in chronic renal failure. Intravenous heparin doses of 0,3 units/ml and 0.6 units/ml of blood were administered …

A Pharmacologic Investigation Of The Antiinflammatory Activity Of Cryogenine, Donald Saadia Kosersky

University of the Pacific Theses and Dissertations

This study was conducted in an attempt to define the anti inflammatory efficacy of cryogenine, the major alkaloid of Heimia salicifolia Link and Otto. The anti inflammatory effects produced by cryogenine, phenylbutazone, indomethacin, mefenamic acid, paramethasone, hydrocortisone and 6-mercaptopurine were compared considering the sequential changes in various motameters during the course of adjuvant-induced polyarthritis in rats. Polyarthritis was induced by the subplantar injection of a suspension of heat-killed Mycobacterium butyricus in mineral oil into the right hind paw of Sprague-Dawley rats. The manifestations of the diseases were monitored in terms of hind paw swelling, subjective appearance of secondary lesions, impairment …

The Pharmacology Of Rodenticides, S. A. Peoples

Vertebrate Pest Conference Proceedings: 4th (1970)

The compounds used as rodenticides are tremendously varied in their chemical structure and mechanism of action. With a few exceptions, these agents are generally poisonous to all animals, including man, and a great deal of study has been directed to their toxicity in animals other than rodents. However, the development of new compounds as Norbormide and certain antifertility drugs which are highly selective in their action may justify the hope that the ideal rodenticide free of secondary toxic hazards will soon be available. Until this happy announcement is made, a review of the pharmacology of the older compounds is in …

Anxiety And Its Pharmacologic Control, Robert R. Schopbach

Henry Ford Hospital Medical Journal

No abstract provided.

The Alkaloids, Felix F. Barre

Electronic Theses and Dissertations

This thesis, presented for the degree of Bachelor of Science, provides a systematic chemical study of the alkaloids, a class of complex nitrogenous plant substances possessing basic properties. Barre opens by defining the alkaloids and surveying the various systems used to classify them, whether by natural versus artificial origin, chemical nucleus (pyridine, quinoline, or isoquinoline), volatility, or botanical family of origin, and outlines their general physical and chemical properties, including solubility, optical activity, and characteristic reactions with precipitating and color-test reagents.

The thesis details standard laboratory methods for the extraction and separation of alkaloids from plant material, including a step-by-step …

Certain Cultural Characteristics Of Digitalis Pupurea, (Linne) With A Proposed Chemical Assay, Clark W, Eidsmoe

Electronic Theses and Dissertations

Since its introduction into modern medicine digitalis has occupied a very important position in our material medica. Its widespread use as a remedy in conditions of failing heart, and its effectiveness as a diuretic in certain dropsical conditions have gained for it a reputation which is equaled by few other drugs. The opinion of pharmacologiate and physicians as to its mode of action and its field of clinical usefulness has been revised a number of times, and there is much diversity of teaching as to its use in special ailments. Among some workers there is a tendency to restrict its …