Pharmacology Commons^™

Store-Operated Calcium Channels In The Function Of Intracardiac Neurons, Timetria Bonds

USF Tampa Graduate Theses and Dissertations

Proper autonomic regulation of mammalian cardiac function is dependent upon very complex and precise communication among the intracardiac ganglia and individual neurons within the ganglia. An array of neuromodulators is found within the ganglia that direct neuronal activity by modulating the movement of calcium. The current study determines that opioidergic agonists, which have been found to contribute to severe cardiac disease states and intracellular calcium mobilization, are also responsible for changes in the function of the intracardiac neuron via their effects on store-operated calcium channels (SOCs).

Previous studies suggest that phosphorylation plays a role in SOC regulation. Using Fura-2 calcium …

Formulation And Characterization Of Lipid-Based Drug Delivery System Of Raloxifene-Microemulsion And Self-Microemulsifying Drug Delivery System, Hetal Thakkar, Jitesh Nangesh, Mayur Parmar, Divyakant Patel

HPD Articles

BACKGROUND: Raloxifene, a second-generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. MATERIALS AND METHODS: In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS) formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM) and in vitro intestinal permeability. RESULTS: The results indicated that high …

Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah

Wayne State University Dissertations

The American Cancer Society estimated that 222,520 Americans were diagnosed with lung cancer and 157,300 died of lung cancer in 2010 (Jemal et al. 2009, 225-249;Jemal et al. 2011, 69-90). The clinical outcome of patients diagnosed with non-small cell lung cancer (NSCLC), the major lung cancer sub-types, is very poor, which calls for innovative research for finding novel therapeutic targets and agents for better treatment outcome.

Emerging evidences have suggested that a phenomenon called Epithelial-to-Mesenchymal Transition (EMT), which shares similar molecular characteristics with cancer stem-like cells, contributes to lung cancer treatment failure. In view of the fact that EMT process …

The Effects Of Protein Kinase C Inhibitors On Blood Nitric Oxide And Hydrogen Peroxide Release In Ischemia And Reperfusion Injury, Kyle D. Bartol

PCOM Biomedical Studies Student Scholarship

Vascular endothelial dysfunction is a key component initiating oxidative stress in ischemia/reperfusion (I/R). Endothelial dysfunction is characterized by an increase in hydrogen peroxide (H2O2) and a decrease in the bioavailability of nitric oxide (NO). Previous studies using protein kinase C (PKC) inhibitor Gö 6983 or PKC Beta (β) II inhibitor improved cardiac function in myocardial I/R, decreased leukocyte-endothelial interactions and leukocyte superoxide (SO) release and increased endothelial-derived NO release in vitro. This study examined the effects of Gö 6983 or PKC β II inhibitor on realtime H2O2 and NO release in femoral vein I/R in vivo. NO or H2O2 microsensors …

Pharmacotherapy Safety And Efficacy In Adolescent Smoking Cessation, Jennifer Lincoln

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: To determine whether or not pharmacotherapy is a safe and effective treatment option for smoking cessation in adolescents

Overuse Of Antibiotics In Children For Upper Respiratory Infections (Uris): A Dilemma, Malika Taufiq, Rukhsana Wamiq Zuberi

Department for Educational Development

No abstract provided.

Secreted Factors From Human Umbilical Cord Blood Cells Protect Oligodendrocytes From Ischemic Insult, Derrick Rowe

USF Tampa Graduate Theses and Dissertations

Oligodendrocytes (OL)s are the dominant cell type in the white matter and are integral for synaptic transmission essential for proper neuronal communication between brain areas. Previous studies have shown that intravenous administration of the mononuclear fraction of human umbilical cord blood (HUCB) cells in rat models of stroke reduced white matter injury, gray matter injury and behavioral deficits. Yet the mechanisms used by HUCB cells remain unknown in ischemic injury. These studies will investigate both in vitro and in vivo approaches to elucidate this mechanism in OLs. When mature primary OLs were coincubated with HUCB cells, HUCB cells secreted soluble …

Exhausted Or Unlicensed: Can Field-Of-Use Restrictions In Biotech License Agreements Still Prevent Off-Label Use Promotion After Quanta Computer?, Kristal M. Wicks

The University of New Hampshire Law Review

[Excerpt] “In the biotechnology (biotech) industry, companies must be increasingly aware of their intellectual property and how their licensing strategies can impact their rights. When licensing patented technology, it is common practice for biotech companies to include restricted field-of-use provisions in their license agreements. Such provisions permit a licensee to only use licensed technology in a defined field and restrict use or development in another field. This licensing strategy plays an important role within the biotech industry because it allows companies to more effectively control their intellectual property and to more efficiently research and develop pharmaceutical products.

A problem that …

Using Photoactive Vitamin Nanoparticles As Photodynamic Antimicrobial Chemotherapeutic (Pact) Agents To Treat Chronic Wounds, Rahul A. Khanke

All Capstone Projects

The objective of the proposed study is to develop new materials and methods to manage microbial growth in chronic wounds using phototherapy. Chronic wounds are considered as a worldwide health problem. The most common chronic wounds can be classified into three categories: venous ulcers, diabetic ulcers, and pressure ulcers. Venous ulcers, which usually occur in the legs, account for about 70% to 90% of chronic wounds and can become infected easily. Venous ulcers are sores that develop after veins in the legs have been damaged. These ulcers can penetrate deeply into the skin. Occasionally, if a venous ulcer persists for …

Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull

Dissertations and Theses (Open Access)

Chemotherapy is a common and effective method to treat many forms of cancer. However, treatment of cancer with chemotherapy has severe side effects which often limit the doses of therapy administered. Because some cancer chemotherapeutics target proliferating cells and tissues, all dividing cells, whether normal or tumor, are affected. Cell culture studies have demonstrated that UCN-01 is able to reversibly and selectively arrest normal dividing cells; tumor cells lines do not undergo this temporary arrest. Following UCN-01 treatment, normal cells displayed a 50-fold increase in IC50 for camptothecin; tumor cells showed no such increased tolerance.

We have examined the response …

Hypoxia And Fetal Programming Of Cardiovascular Dysfunction, Qin Xue

Loma Linda University Electronic Theses, Dissertations & Projects

Human epidemiological studies have shown a clear association of adverse intrauterine environment and an increased risk of ischemic heart disease in later adult life. Of all the stresses to which the fetus is subjected, perhaps the most important and clinically relevant is that of hypoxia. The goal of this project is to test the hypothesis that chronic hypoxia during gestation adversely affects fetal cardiovascular development and impairs cardiac function in offspring. In the first part of project, we tested the hypothesis that chronic hypoxia adversely regulates contractility of fetal pulmonary arteries and veins in sheep residing at high altitude (3,801 …

Studies Of Antioxidant And Angiotensin Converting Enzyme Inhibitory Activity Of Orthosiphon Stamineus (Misai Kucing)., Che Wan Imanina Che Wan Takwa

Student Works (2010-2019)

Abstract NA

Bioactivity And Chemical Investigations Of Pereskia Bleo And Pereskia Grandifollia., Sim Kae Shin

Student Works (2010-2019)

Ethnopharmacological data has been one of the common useful criteria in drug discovery. Pereskia bleo and Pereskia grandifolia (Cactaceae), commonly known as ‘Jarum Tujuh Bilah’ in Malay and ‘Cak Sing Cam’ in Chinese have long been used as natural remedies in Malaysia. The experimental approach in the present study was based on bioassay-guided fractionation. The crude methanol and fractionated extracts of both Pereskia spp. were initially investigated for their biological activities such as antioxidant, antimicrobial and cytotoxic effect against five human cancer cell lines, namely nasopharyngeal epidermoid carcinoma cell line (KB), cervical carcinoma cell line (CasKi), colon carcinoma cell line …

A Comparison Of Fluoroquinolones Versus Other Antibiotics For Treating Enteric Fever: Meta-Analysis, Durrane Thaver, Anita K. M. Zaidi, Julia Critchley, Asma Azmatullah, Syed Ali Madni, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Objectives: To review evidence supporting use of fluoroquinolones as first line agents over other antibiotics for treating typhoid and paratyphoid fever (enteric fever).
Design: Meta-analysis of randomised controlled trials. Data sources: Cochrane Infectious Diseases Group specialised register, CENTRAL (issue 4, 2007), Medline (1966-2007), Embase (1974-2007), LILACS (1982-2007), selected conferences, reference lists, and ongoing trial register (November 2007).
Review methods: Trials comparing fluoroquinolones with chloramphenicol, cephalosporins, or azithromycin in culture-proven enteric fever were included. Two reviewers extracted data and assessed methodological quality. Odds ratios with 95% confidence intervals were estimated. Trials recruiting over 60% children were analysed separately from trials on …

The Future (Or Lack Of Future) Of Personalized Prescription In Psychiatry, Jose De Leon

Psychiatry Faculty Publications

Rapid technological advances in genetics have created conceptual chaos regarding the genetics of drug response. Terms for differing concepts are used interchangeably: pharmacogenetics with pharmacogenomics, personalized medicine with personalized prescription. Biomarker has many definitions. The author prefers the concept of personalized prescription and uses it with implications beyond pharmacogenetics by considering all scientific information valid for prescribing medication. Genetics may not be crucial for all drugs. In this comprehensive view, clinicians must consider genetic, environmental and personal variables when prescribing medication and incorporate some basic pharmacological principles: (1) safety and efficacy, (2) pharmacokinetics and pharmacodynamics, (3) therapeutic window and prescriber's …

Ros-Mediated Oxidative Stress Influence Anti-Apoptotic Genes And Cyt C Release In Hyperglycemic Mouse Kidneys To Initiate Late Nephropathic Complications, Krina Shah, Mayur S. Parmar, Sidhartha D. Ray

HPD Articles

Decades of intense research has shown that hyperglycemiainduced ROS production can lead to a redox-imbalance causing oxidative stress (OS) in a variety of target organs in vivo. In the absence of an efficient antioxidant counteracting system, massive OS often leads to activation of stress-responsive signaling pathways resulting in deregulated expression of pro-survival and/or pro-death genes. Persistent deregulation of such pathways eventually masterminds late complications of diabetes. Most studies hold hyperglycemia-induced OS as the ‘cause’, and premature onset of apoptosis as the ‘effect’. This ‘cause and effect’ axis ultimately initiates the development and progression of macro and microvascular complications including diabetic …

Insights Into Expression, Cellular Localization, And Regulation Of Supernatant Protein Factor, A Putative Regulator Of Cholesterol Biosynthesis, Elzbieta Ilona Stolarczyk

University of Kentucky Doctoral Dissertations

SPF (Supernatant Protein Factor) is a cytosolic protein that stimulates at least two enzymes in the cholesterol biosynthetic pathway: squalene monooxygenase and HMGCoA reductase. The mechanism of action has not been established but may be related to lipid transfer between intracellular membranes.

There are three human genes for SPF: SEC14L2 (SPF1), SEC14L3 (SPF2) and SEC14L4 (SPF3). The present study differentiates these closely related genes by evaluating their tissue-specific and relative expression levels. SPF1 mRNA was found to be most abundant in liver, mammary gland and stomach. SPF2 showed negligible expression in all tissues tested; SPF3 expression pattern was similar to …

Blood Pressure Lowering And Vasomodulator Effects Of Piperine, Syed Intasar Husain Taqvi, Abdul Jabbar Shah, Anwar Gilani

Department of Biological & Biomedical Sciences

This study was aimed to explore underlying mechanism(s) of cardiovascular effects of piperine. Intravenous administration of piperine caused a dose-dependent (1 to 10 mg/kg) decrease in mean arterial pressure (MAP) in normotensive anesthetized rats, the next higher dose (30 mg/kg) did not cause any further change in MAP. The fall in blood pressure (BP) was followed by small increase in MAP after each dose. In Langendorrf's rabbit heart preparation, piperine caused partial inhibition and verapamil caused complete inhibition of force and rate of ventricular contractions and coronary flow. In rabbit aortic rings, piperine inhibited high K(+) (80 mM) precontractions and …

Cannabinoids: A Novel Treatment Strategy For Retinal Neurodegenerative Disorders, Sandeep Samudre

Theses and Dissertations in Biomedical Sciences

Synthetic and naturally occurring cannabinoids are known to decrease intraocular pressure (IOP). Glaucomatous damage to the retina and optic nerve progresses even after therapy to maintain normal intraocular pressure (IOP). Topical application of cannabinoids decreases IOP while not affecting blood pressure or heart rate. Based upon their effects on other tissues, we hypothesize that these analogs reduce IOP and may also confer direct neuroprotective effects on the retina, possibly via CB1 and/or CB2 receptors. The purpose of this study is to determine if the newly synthesized CB agonists, lipid soluble O-1812 (CB 1), and water soluble O-2545 (CB 1

The …

Maturational Changes In Cerebrovascular Thick- And Thin-Filament Regulation, Renan Joel Sandoval

Loma Linda University Electronic Theses, Dissertations & Projects

The present study focused on the main hypothesis that age-related changes in myofilament Ca²⁺ sensitivity involve simultaneous changes in the relations between cytosolic Ca²⁺ transients, myosin phosphorylation, and force development. To define the effects of late fetal and early postnatal maturation, parallel experiments were carried out using cerebral arteries from both term lamb fetuses (140-141 days of gestation) and nonpregnant adult sheep. Fetal and adult cerebral arteries were stimulated by either mechanically, electromechanically, and/or pharmacomechanically-induced contractions, and the relations of cytosolic Ca²⁺, MLC phosphorylation, and contractile tensions were measured. These measurements allowed for stimulus and age-dependent …

Regulation Of Alpha-1-Adrenoceptor-Mediated Contractions Of The Uterine Artery By Pkc, Hongying Zhang

Loma Linda University Electronic Theses, Dissertations & Projects

Pregnancy is associated with a significant decrease in uterine vascular tone and a striking increase in uterine blood flow, which ensures normal fetal development. Multiple mechanisms are involved in the adaptation of uterine artery contractility during pregnancy. Both protein kinase C (PKC) and activation of ai-adrenoceptors play important roles in the regulation of uterine artery contractility. In addition, PKC mediates the pregnancyassociated decrease in myogenic tone of the uterine artery, and interacts with ajadrenoceptors leading to modulation of ai-adrenoceptor-mediated contractions of vascular smooth muscle. Yet, whether or to what extent PKC regulates ai-adrenoceptormediated contractions of the uterine artery and their …

Immunoadjuvanticity Of Chlorophyll, Jocelyn Helen Parks Ramos

All-Inclusive List of Electronic Theses and Dissertations

Background: Vaccines are formulations containing antigenic determinants (from non-self organic matters) and immuno-enhancers called adjuvants. Together, they evoke protective immune responses in hosts. Adjuvants are substances that further vaccines' capability to induce a robust immune response. Common side effects with conventional adjuvants used in most vaccines are toxicity, inflammation and granulomas. In this study we investigated the pigment chlorophyll (Chl) for immunoadjuvanticity. The selection of chlorophyll is based on the fact that it is a component in foods such as spinach, and that it contains an isoprenoid structure that is a feature of many conventional adjuvants, Pristane and Squalene. Chl …

Design, Synthesis, And Evaluation Of 10-N-Substituted Acridones As Novel Chemosensitizers In Plasmodium Falciparum, Jane X. Kelly, Martin J. Smilkstein, Roland A. Cooper, Kristin D. Lane, Robert A. Johnson, Aaron Janowsky, Rozalia A. Dodean, David J. Hinrichs, Rolf Winter, Michael Riscoe

Biological Sciences Faculty Publications

A series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for the ability to enhance the potency of quinoline drugs against multidrug-resistant (MDR) Plasmodium falciparum malaria parasites. A number of acridone derivatives, with side chains bridged three or more carbon atoms apart between the ring nitrogen and terminal nitrogen, demonstrated chloroquine (CQ)-chemosensitizing activity against the MDR strain of P. falciparum (Dd2). Isobolograrn analysis revealed that selected candidates demonstrated significant synergy with CQ in the CQ-resistant (CQR) parasite Dd2 but only additive (or indifferent) interaction in the CQ-sensitive …

Critical Evaluation Of The Claims Made By Pharmaceutical Companies In Drug Promotional Material In Pakistan, Dileep Kumar Rohra, Anwarul Hassan Gilani, Ismail Kamal Memon, Ghazala Perven, Muhammad Talha Khan, Hina Zafar, Rakesh Kumar

Department of Biological & Biomedical Sciences

Background: In Pakistan, there is no mechanism to monitor the drug promotional campaign by pharmaceutical industry despite the fact that there is enough evidence that irrational pharmacotherapy is increasingly encountered even in the developed countries due to unethical practices of pharmaceutical promotion. Objectives. To audit the drug promotional claims made by the pharmaceutical companies in Pakistan.
Methods: Drug promotional pamphlets and brochures containing claims for the drugs, which were circulated by the pharmaceuticalrepresentatives were collected from 122 general practitioners (GPs) from Karachi and Larkana cities of the Sindh Province. The claims were critically analyzed and audited with the help of …

The Effects Of An Analgesic (Biofreeze®) On The Motoneuron Pool Excitability Of The Soleus Muscle, Desiree R. Barth

All-Inclusive List of Electronic Theses and Dissertations

Objective: The purpose of this study was to determine the effects on the Hoffman reflex and motor response with an analgesic (Biofreeze®). Design: The study was a 2X6 design. The independent variables in this study were treatment and time. The dependent variables were the H-reflex (volts) and the M response (volts). Treatment was randomly assigned to control for the effects of order. Setting: This study took place in the Exercise Physiology Laboratory located in the Health and Human Performance Building at Indiana State University. Subjects: 14 volunteers who were physically active and had no known neurological problems. Measurements: Skin and …

Hk-2 Cells As A Human Model Of Glucuronide Transport, Eliza E. Robertson

Theses, Dissertations and Capstones

Glucuronidation is primarily a pathway of detoxification in most species, but many glucuronide conjugates are associated with toxicity. Numerous drugs are excreted in the urine as glucuronide conjugates. Being organic anions, it is likely that glucuronides are secreted into the urine by organic anion transporters found in renal proximal tubule cells (PTCs). Some drugs that are metabolized by glucuronidation have been shown to cause renal toxicity, yet little is known about the renal handling of glucuronide conjugates. It is hypothesized that glucuronides are transported into renal PTCs by an organic anion transporter (OAT) on the basolateral membrane of the cell. …

Interaction Between Adrenergic And Nitric Oxide-Releasing Nerves In Cerebral Arteries, Emmanuel Ngu Mbaku

Loma Linda University Electronic Theses, Dissertations & Projects

Of all body tissues, the brain is the least tolerant of ischemia so much that interruption of cerebral blood flow by 5 sec can cause syncope, with irreversible tissue damage if the ischemia last a few minutes. In this respect, the body has an imperative duty of ensuring constant and adequate blood supply to the brain. It does so through a series of intrinsic and extrinsic control factors of which adrenergic and nitric oxide-releasing nerves are components. My research examined the interaction between these two nerve-types with emphasis on the mechanisms involved as well as on changes in their functions …

Modulatory Effects Of Citrus Flavonoids Towards The Metabolism And Mutagenicity Of Environmental Carcinogens, Wayne L. Bear

Loma Linda University Electronic Theses, Dissertations & Projects

The environmental carcinogens classified as heterocyclic amines (HCA’s) and the tobacco-specific nitrosamine NNK generally require internal enzymatic activation. This activation occurs via cytochrome P450 (CYP) enzymes and leads to metabolites that bind to human DNA which may in turn cause mutations which may then in turn lead to carcinogenesis. Certain nonnutritive plant compounds termed phytochemicals may protect against HCA and NNK-induced mutagenesis and carcinogenesis. We investigated the potential protective effects of five different phytochemicals of the flavonoid class which naturally occur in citrus. These flavonoids were diosmin, naringin. naringenin, rutin, and quercetin. Our results suggest that naringenin and quercetin were …

Age Related Changes In Contractile Sensitivity To Cyclic Gmp And Intracellular Calcium Compartmentalization In Ovine Arteries, Surya Margono Nauli

Loma Linda University Electronic Theses, Dissertations & Projects

The study examines the hypothesis that maturation changes the ability of cGMP to produce cerebral vasodilatation and alters the relative intracellular calcium pool sizes in ovine arteries. In ovine basilars taken from near-term fetal and young adult sheep, 8- pCPT-cGMP relaxed potassium- and serotonin-induced tone with pD2 values of 4.4±0.1 and 4.9±0.1 (fetal basilar) and 4.0±0.1 and 4.7±0.1 (adult basilar), respectively. In fura-2 loaded arteries, 8-pCPT-cGMP significantly lowered increases in cytosolic calcium concentration induced by serotonin but not potassium regardless of age. When calcium sensitivity was calculated in the same arteries as the slope of the relation between calcium concentration …

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 …