Chemicals and Drugs Commons^™

Reversible Nonthrombocytopenic Palpable Purpura Associated With Metoclopramide, Jeffery A. Goad

Pharmacy Faculty Articles and Research

OBJECTIVE: To report a case of reversible nonthrombocytopenic palpable purpura associated with metoclopramide.

CASE SUMMARY: A 72-year-old white man was admitted for worsening palpable purpura over a two-day period. Two days prior to admission, metoclopramide 10 mg orally three times per day was started for a gastrointestinal condition. Upon admission, all drugs were continued except metoclopramide. Over the next two days, the purpura began to resolve. Platelet count was within normal limits on admission and the patient developed no serious consequences because of the purpura.

DISCUSSION: According to the literature, reversible nonthrombocytopenic palpable purpura has not been …

The Role Of Gap Junctions In Congenital Diseases Of The Heart, Scott Henry Britz-Cunningham

Loma Linda University Electronic Theses, Dissertations & Projects

Background. Gap junctions are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. Connexin43, the major protein of gap junctions in the heart, is targeted by several protein kinases that regulate myocardial cell-cell coupling. We hypothesized that mutations altering sites critical to this regulation would lead to functional or developmental abnormalities of the heart.

Methods. Connexin43 DNA from 25 normal subjects and 30 children with a variety of congenital heart diseases was amplified by the polymerase chain reaction and sequenced. Mutant DNA was expressed in cell culture and examined for its effect …

The Relationship Between Tamoxifen And Depressive Symptoms In Women With Breast Cancer, Terry Marie Lynn

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to determine whether women with breast cancer and the presence of the drug tamoxifen, are more severely depressed than women with breast cancer and the absence of tamoxifen. Average Beck Depression Inventory (BDI) scores did not differ between the two sub-groups; however, two significant group differences were found. First, 10 women in the tamoxifen group had scores of zero (versus 4 in the absence of prescribed tamoxifen group). Research has shown that scores of zero do not always reflect an absence of depression. Second, the most severely depressed women (BDI scores in the 25 …

Analysis Of Serotonin And Postural Instability In Parkinson’S Disease, Sandra Kuniyoshi

Loma Linda University Electronic Theses, Dissertations & Projects

Postural instability is one of the most debilitating symptoms of Parkinson’s disease and the best clinical prognostic indicator of progressive disease. Significant differences in neuropathology, neurochemistry, response to L-dopa therapy and stereotactic surgery as well as prognosis have been identified in subtypes when patients with predominant postural instability and gait difficulty (PIGD)/Type B were differentiated from those with predominant symptoms of tremor and rigidity/Type A. Postural instability is resistant to the therapeutic effects of L-dopa, despite its continued efficacy on other Parkinson’s symptomatology, implicating the nondopaminergic mechanism of postural instability in Parkinson’s disease. Patients with significant postural instability and gait …

Progestin Stimulation Of The Protooncogene C-̲M̲Y̲C In T47d Human Breast Cancer Cells, Kristy Ann Blankenship

Theses, Dissertations and Capstones

Moore and co-workers have previously demonstrated that progestins stimulate the growth of T47D human breast cancer cells. We now investigate the possibility that progestins might transactivate the protooncogcne c-myc as part of the mechanism for growth stimulation. Treatment of T47D cells with the synthetic progestin R5020 results in a rapid, dose-dependent increase in c-myc mRNA. This stimulation is evident as early as 5 minutes, increases up to 4-fold at 1 hour, and then returns toward basal levels. The optimal concentration of R5020 for induction of c-myc gene expression is 10 nM, which is within the physiologically relevant range of hormone …

In Vitro Anti-Hepatitis B Virus Activities Of 5’-O-Myristoyl Analogue Derivatives Of 3’-Fluoro-2’,3’-Dideoxythymidine (Flt) And 3’-Azido-2’,3’- Dideoxythymidine (Azt), Keykavous Parang, Leonard I. Wiebe, Edward E. Knaus, Jyy-Shiang Huang, David L. Tyrrell

Pharmacy Faculty Articles and Research

The objective of this study was to evaluate a dual action prodrug concept wherein an unnatural myristic acid analogue is coupled via an ester moiety to the 5’-position of FLT or AZT. Subsequent intracellular cleavage of the prodrug ester would simultaneously release FLT or AZT that could inhibit reverse transcriptase (RT), and the myristic acid analogue that could inhibit myristoyl- CoA:protein N-myristoyltransferase (NMT). Methods: Cytotoxicity (2.2.15 cell culture), and antihepatitis B activity of 5’-O-myristoyl analogue prodrug derivatives of FLT and AZT (2-8) were evaluated in vitro using human liver hepatitis B virus (HBV) producing 2.2.15 cell lines. Results: The 5’- …

Periodontal Repair In Dogs : Effect Of Recombinant Human Transforming Growth Factor Beta-1 On Guided Tissue Regeneration, Saghi Shayan Razi

Loma Linda University Electronic Theses, Dissertations & Projects

The objective of this study was to evaluate bone and cementum regeneration in the critical size, supraalveolar, periodontal defect model following surgical implantation of recombinant human transforming growth factor beta-1 (rhTGFß-1) in conjunction with guided tissue regeneration (GTR). Five male beagle dogs were used in a split-mouth design. Alternate jaw quadrants in consecutive animals received GTR with rhTGFß-1 in a resorbable calcium carbonate carrier. Contralateral jaw quadrants received GTR with carrier only (control). The healing interval was 4 weeks. Clinical healing was generally uneventful, however, minor membrane exposures were observed for both treatments with limited gingival inflammation. All defects with …

An Enzyme-Linked Immunosorbent Assay For The Detection Of Cardiac Myoglobin Using Monoclonal Antibodies, Deborah F. Kelly

Chemistry & Biochemistry Theses & Dissertations

The most prevalent life-threatening disease worldwide, secondary to coronary artery thrombosis is Acute Myocardial Infarction (AMI). Increases in three clinical markers have been explored as an early means of AMI detection: Cardiac myoglobin, and the two specific cardiac isoforms of Creatine Kinase, CK-MM and CK-MB. However, myoglobin levels have shown to give a more accurate correlation (R = 0.89) than does Creatine Kinase evaluation. Therefore, we have developed a two-site Enzyme-Linked Immunosorbent Assay (ELISA) using monoclonal antibodies against myoglobin isolated from human heart tissue. This assay is based on specific anti-genantibody interactions and is sensitive at the nanogram level. We …

Longitudinal Study Of Plasma And Erythrocyte Selenium Levels In Type I Diabetic Children During Development And Treatment Of Ketoacidosis, Pi-Hsia Fan

Chemistry & Biochemistry Theses & Dissertations

Most studies on the biological activity of selenium have focused on its role at the active site in the ubiquitous enzyme, glutathione peroxidase (GSH-Px) which catalyzes the removal of hydrogen peroxide and organic hydroperoxides (1). A connection between selenium deficiency and a wide range of diseases in animals and humans has been reviewed (2). Development of various forms of human cancer (3), failure of the immune system (4), as well as some cardiovascular diseases (5) have been reported or suspected to correlate with selenium deficiency. However, the physiological function of selenium in these different diseases is not fully understood, and …

Kinetic Characterization Of A Recombinant C-Terminal Mutant Of Reverse Transcriptase From The Human Immunodeficiency Virus, Thomas S. Heard

Chemistry & Biochemistry Theses & Dissertations

The human immunodeficiency virus (HIV) reverse transcriptase (RT) (EC 2.7.7.49) is the central replication enzyme for HIV. In general, the kinetic mechanism for this and all other polymerases involves the ordered binding of two substrates: a primer-template (PT) followed by a deoxyribonucleoside triphosphate (dNTP). Previous investigations prompted this research when it was discovered that the substrate dNTP, in absence of PT, could protect a recombinant c-terminal mutant HIV-1 RT from inhibition by pyridoxal-5'-monophosphate (PLP), an active-site dNTP inhibitor. In contrast, the non-mutant recombinant HIV-1 RT required both substrates for protection from PLP inhibition. This investigation sought to determine if this …

Phosphorylation Of The Rex Protein Of Human T-Cell Leukemia Virus Type 1, Yoshifumi Adachi, Terry D. Copeland, Chiaki Takahashi, Tetsuya Nosaka, Aftab Ahmed, Stephen Oroszlan, Masakazu Hatanaka

Pharmacy Faculty Articles and Research

Rex protein, the posttranscriptional regulator of human T-cell leukemia virus type I (HTLV-I), is required for the control of viral structural protein expression and virus replication. Rex is a phosphoprotein found predominantly in the cell nucleolus, whose function is thought to be regulated by its nucleolar localization and phosphorylation. Therefore, we investigated the in vivo phosphorylation of Rex protein in more detail. Phosphorylation of Rex occurred in all HTLV-I-infected cell lines examined in vivo, primarily at serine residues and to a very small extent at threonine residues. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) led to significant but transient enhancement of …

Autonomic Nervous System And Cholesterol Transport, Yuan-Line Hung

Loma Linda University Electronic Theses, Dissertations & Projects

The effect of autonomic nervous system on cholesterol transport is of clinical interest because the relationship between lipoprotein metabolism and atherogenesis is expressed in coronary artery disease.

Generally speaking, beta blockers increase serum VLDL level but decrease both HDL and HDL₂ cholesterol levels without affecting the LDL in humans. We are unaware of reports concerning the effects of metoprolol on lipoprotein metabolism nor comparison of the effects of metoprolol and propranolol in the unhandled rat model. In part I we employed the unhandled rats to compared the effects of these 2 drugs administered with the drinking water in order …

Farmers' Estimations Of Sheep Weights To Calculate Drench Dose, R B. Besier, Diane Hopkins

Journal of the Department of Agriculture, Western Australia, Series 4

Undersosing with drenches is a mojor cause of anthelmintic (drench) resistance in worm parasites of sheep.

When farmers use a drench at less than the recommended dose rate, some worms may survive, and their ability to resist treatment with the chemical involved is passed to their offspring. Over a period of time, matings between worms with different degrees of resistance can produce individuals able to resist the drench at the recommended dose rate or even higher.

Farmers must use adequate dose rates so that worms do not have a chance to survive treatment.

Policy For Identifying And Assessing The Health Risks Of Toxic Substances, Maine Bureau Of Health

Maine Collection

Policy for Identifying and Assessing the Health Risks of Toxic Substances

by Norman T. Anderson, Environmental Toxicology Program, Division of Disease Control, Bureau of Health (February, 1988).

Contents: Section I: Introduction / Section II: Methods / Section III: Exposure Assessment / Section IV: Hazard Identification / Section V: Hazard Assessment / Section VI: Risk Characterization / List of Figures / List of Tables

Hemoglobin E B-Thalassemia In A Pakistani Family, Aftab Ahmed, Atiya Abbasi, Gerhard Braunitzer, Zafar H. Zaidi

Pharmacy Faculty Articles and Research

Hemoglobin E is a slow moving B chain variant of hemoglobin, first discovered by Itano¹. Characterized by Hunt et al² showed glutamic acid at B 26 to be replaced by lysine. It is a common variant of hemoglobin in the world and reported in high frequency from South-East Asia^3-6. Cases of Hb E, in combination with thalassemia have been reported on the basis of electrophoretic pattern only. In this communication a case of Hb E with B thalassemia is reported on the basis of amino acid sequencing of the abnormal peptide.

Insulin And Glucagon Responses To Dietary Protein In Diabetic And Nondiabetic Men, Monica L. Blomstedt

Loma Linda University Electronic Theses, Dissertations & Projects

Five men with non-insulin-dependent diabetes mellitus and fourteen nondiabetic men, were given test meals with soy protein, casein or additional carbohydrate in place of protein. Blood levels of insulin, glucagon, glucose and lipids were measured at fasting, one-half hour and two hours postprandial. To all meals, the nondiabetic subjects responded with a quick rise of the insulin level which decreased at two hours. In contrast, the diabetics showed a significantly lower insulin response at one-half hour (p < 0.05), but a tendency to higher levels at two hours. The same pattern was observed in the insulin to glucagon ratio. No significant difference between the meals was found in regard to insulin or glucagon responses, suggests that a sustained, although delayed postprandial insulin response, may be a precursor to the higher cholesterol and increased risk for cardiovascular disease among diabetics.

Relationship Between Dietary Intake And Reproductive Hormones In Premenopausal Vegetarian And Nonvegetarian Seventh-Day Adventist Women, Joan M. Spuehler

Loma Linda University Electronic Theses, Dissertations & Projects

There is evidence that specific nutrients may modify hormonal balance and contribute to breast cancer etiology. To investigate the relationship between dietary nutrients and plasma reproductive hormones and to determine hormone-nutrient interrelationships, we measured plasma estrogens, androgens. progesterone and prolactin levels in 10 premenopausal Seventh-day Adventist (SDA) vegetarian and 10 premenopausal SDA nonvegetarian women. Over three days in each of three consecutive months. diet records and fasting midluteal blood samples were collected. The nonvegetarians consumed significantly more protein, total and saturated fats, oleic and linoleic acids, and cholesterol than did the vegetarians. Hormonal status of the two groups did not …

The Relationship Of Vitamins B-6 And B-12 To Plasma Homocysteine Levels In Men At Low- And High-Risk For Coronary Heart Disease, Marlene E. Swift

Loma Linda University Electronic Theses, Dissertations & Projects

There is evidence that homocysteine may be a factor in increasing the risk of coronary heart disease (CHD). To explore this relationship further, we assessed the interrelation of dietary vitamins B-6, B-12 and folate, and plasma pyridoxal-5'-phosphate and vitamin B-12 with plasma free and protein-bound homocysteine levels. Fasting blood and three-day dietary records were obtained from nine men low-risk (LR) and five at high-risk (HR) for CHD. The HR mean systolic blood pressure, total cholesterol (TC), and TC/cholesterol ratios were significantly higher than LR levels. Groups were comparable by age, weight, height, skinfolds, exercise, and smoking history. No significant difference …

A Quantitative Study Of The Distinctive Proteins Of The Eosinophil: A Comparison Of Normals And Eosinophilic Patients, James M. Olson

Honors Theses

Eosinophils have long been associated with parasitic and allergic diseases. Methods of procurement and purification of eosinophils in the last ten years have allowed intensive investigation into their components, properties, functions, and mechanisms (Gleich et al, 1982). The goals of this project are to separate eosinophils in blood samples taken from patients with eosinophilia and from normals based on density over distontinuous Metrizamide gradients; to determine quantitatively the levels of the three distinctive proteins of the eosinophil, specifically MBP, EDN, and ECP; and to compare the levels of these proteins found in eosinophils of patients with eosinophilia to the amounts …

The Effect Of Dietary Alpha - Linolenic Acid On Apparent Risk Factors Of Cardiovascular Disease, Kelvin D. Lindbeck

Loma Linda University Electronic Theses, Dissertations & Projects

Eight healthy male lacto-ovo-vegetarian subjects averaging 28.0 ± 3.6 years of age (22 to 53 years) were fed a diet rich in α-linolenic acid (18:3 ω 3) for four weeks. Arterial blood pressure and body weight were recorded each week. Plasma 6-keto-prostaglandin F_1α (6-keto- PGF_1α ), thromboxane B₂ (TXB₂), total cholesterol, triglyceride, and total phospholipid fatty acid composition were analyzed at 0, 2 and 4 weeks.

Systolic blood pressure increased significantly between weeks 0 and 1 (106.5 ± 2.7 mmHg to 114.0 ± 3.7 mmHg; p < 0.003), but decreased to 107.3 t 2.6 mrHg (p < 0.02) at week 2. There was an insignificant increase in both systolic and diastolic blood pressures after four weeks. There was no significant change in either total cholesterol or triglyceride levels during the four weeks.

Plasma 6-keto-PGF_1α levels increased significantly from 60.13 ± …

Development Of A Procedure For Analysis Of High Density Lipoprotein Subclasses, Chan Chin

Chemistry & Biochemistry Theses & Dissertations

Human serum high density lipoprotein subclasses, HDL₂ and HDL₃ , were isolated by preparative salt density gradient ultracentrifugation and further analyzed by electrophoresis on a 4 to 15% concentration gradient polyacrylamide gel.

The separation of the major classes of serum lipoproteins was achieved after a single ultracentrifugation for 272,000 g at 15°c in a swinging bucket rotor. High resolution concentration gradient gel electrophoresis was found to be particularly suitable for the separation of lipoproteins. The isolation of HDL by precipitation methods, heparin-manganese and dextran-magnesium have also been evaluated in this study, and were found not to completely separate …

Radioprotection Of Oral Cavity Structures By S-2-(3-Aminopropylamino) Ethyl Phosphorothioate (Wr-2721), Ronald King

Masters Theses & Specialist Projects

Studies reporting a high concentration of WR-2721 in mouse salivary glands led to our studies of possible radioprotection of these glands by this drug from ionizing radiation. Oral effects of radiation in the presence of WR-2721 were studied in mice and dogs. Histological evaluation of mouse salivary glands irradiated with 1000 rads of ⁶⁰Co showed essentially no difference between control and experimental animals. Almost full regeneration of the serous salivary components occurred by 6 months in both groups and neither group had changes in the mucous glands. The use of higher doses of radiation in the mouse was prevented …

Antibiotics And The Wasting Disease In Neonatally Thymectomized Rats, Douglas M. Grignon

Loma Linda University Electronic Theses, Dissertations & Projects

The administration of the antibiotic, Chloramphenicol, to pregnant rats just prior to, and for four days after delivery, diminishes the incidence of the so-called "Wasting Disease" in neonatally thymectomized rats.

A total of 50 rats were divided into the following groups:

1. Thymectomy only---nonmedicated 17 rats
2. Thymectomy only---medicated 12 rats
3. Thymectomy-adrenalectomy---nonmedicated 5 rats
4. Thymectomy-adrenalectomy---medicated 8 rats
5. Controls---nonmedicated 4 rats
6. Controls---medicated 4 rats

Chloramphenicol was administered in the drinking water to the mothers of groups 2, 4 and 6 for about 2 days prior to delivery and 4 days after. On the day of birth or within three days after birth, the …

The Effect Of Adrenaline Injection On Glycogenolysis And Glycogenesis In Rat Livers, Virginia Mary Zingsheim

Bachelors’ Theses

Present day knowledge concerning the liver is derived from many sources and the accumulation of many methods of investigation. Sugar, which is needed by the body for energy, is stored in the liver as glycogen. Claude Bernard (26), an eminent physiologist, was the first to suspect that carbohydrates were stored in the liver. Faulty glycogen synthesis and hydrolysis results in one of our most widespread diseases, diabetes. Thus, many biochemists and physiologists have tried to find the mechanism of the process, and the primary and secondary facts which affect glycogenesis and glycogenolysis. Although the chemical secretions and hormones of such …

Insulin, Walter Zeit

Bachelors’ Theses

The objectives of this paper are: 1. A review of the discovery of insulin. 2. A discussion of the nature of insulin. 3. A discussion of the distribution of insulin. 4. A study of the development of the pancreas. 5. The presentation of a problem for further investigation.