Pharmacology Commons^™

Signaling Mechanisms For Muscarinic Receptor-Mediated Coronary Vasoconstriction In Isolated Rat Hearts, Yi Zhang

Electronic Theses and Dissertations

The signaling mechanisms for muscarinic receptor-mediated vasoconstriction in coronary resistance arteries were studied in KCl-arrested isolated rat hearts perfused at a constant flow rate. The cholinergic agonists acetylcholine and bethanechol were given by bolus injection or constant infusion. The coronary vascular resistance was monitored by measuring the changes in perfusion pressure. The selective muscarinic agonist bethanechol caused a similar vasoconstrictor response as ACh, but with less potency and efficacy. Bolus injection of bethanechol evoked a phasic vasoconstriction in a dose-dependent manner, while infusion of bethanechol evoked a tonic vasoconstriction without producing tachyphylaxis. Coronary vascular responses to bethanechol were further examined …

Comparison Of Beta-Adrenoceptor Coupled Camp Production In Cultured Human Mononuclear Leukocytes And Myometrial Cells, Yu-Li Liu

Electronic Theses and Dissertations

$\beta\sb2$-Adrenoceptor ($\beta\sb2$-AR) agonists, such as terbutaline, are used as tocolytic agents in the treatment of preterm labor. $\beta$-Adrenoceptor stimulation relaxes myometrium through specific receptors coupled through Gs to adenylyl cyclase (AC) that catalyzes the conversion of ATP to cAMP. The purpose of this study was to compare $\beta$-adrenoceptors and cAMP production in cultured human leukocytes and myometrial cells, and to determine the importance of $\beta$-adrenoceptors and cAMP production in isoproterenol-induced myometrial relaxation. $\sp{125}$I-iodopindolol was used to assess $\beta$-adrenoceptor affinity and number cAMP levels were analyzed before and after stimulation by isoproterenol, AlF$\sb4\sp-$, forskolin, and PGE$\sb1$. Isometric recording was used to …

Interleukin-2 Fusion Protein: An Investigational Therapy For Interleukin-2 Receptor Expressing Malignancies, Jean Nichols, Foss Francine, Kuzel Timothy, Lemaistre Charles Fred, Platanias Leonidas, Ratain Mark, Rook Alain, Mansoor Saleh, Schwartz Gary

Haematology and Oncology, East Africa

DAB3s91L-2 is an interleukin-2 receptor (IL-2R) specific fusion protein with a molecular weight of 58 kD containing the enzymatic and translocation domains of diphtheria toxin (DT) and human IL-2. This fusion protein is able to direct the cytocidal action of the DT enzymatic region only to cells which bear the IL-2R. The human IL-2R exists in three forms: low, intermediate and high affinity. The high-affinity form is believed to be the biologically relevant form on mature, activated T-lymphocytes, B-lymphocytes and monocytes. DAB3sgIL-2 is able to bind selectively to the high-affinity IL-2R in a concentration-dependent manner, and once bound is internalised …

503 Phase I Radioimmunotherapy (Rit) Study Of 90y-Cc49 Monoclonal Antibody (Mab) Therapy In Patients With Advanced Non-Small Cell Lung Cancer (Nsclc), Francisco Robert, Ruby Meredith, Michael Khazaeli, Charles Russell, William Grizzle, John Newsome, Mansoor Saleh

Haematology and Oncology, East Africa

503 Phase I radioimmunotherapy (RIT) study of 90Y-CC49 monoclonal antibody (MAb) therapy in patients with advanced non-small cell lung cancer (NSCLC) × Close The Infona portal uses cookies, ie strings of text saved by a browser on the user's device. The portal can access those files and use them to remember the user's data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms …

Phase Ia/Ib Trial Of Anti-Gd2 Chimeric Monoclonal Antibody 14.18 (Ch L4.18) And Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (Rhgm-Csf) In Metastatic Melanoma, James Murray, Eugenie Kleinerman, Shu-Fang Jia, Michael Rosenblum, Omar Eton, Antonio Buzaid, Sewa Legha, Merrick Ross, Lora Thompson, Mansoor Saleh

Haematology and Oncology, East Africa

We performed a phase Ia/Ib trial of chimeric anti-GD2 monoclonal antibody 14.18 (ch14.18) in combination with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to determine the maximum tolerated dose as well as immunologic and biologic responses to the regimen. Sixteen patients with metastatic malignant melanoma received escalating doses of ch14.18 (15-60 mg/m2) administered intravenously for 4 h on day 1. Twenty-four hours later, subcutaneous injections of rhGM-CSF were administered daily for a total of 14 days. Significant side effects were related to ch14.18 infusion and consisted of moderate to severe abdominal and/or extremity pain, blood pressure changes, headache, nausea, diarrhea, peripheral …

Persistent Oral Dyskinesias Induced By Long-Term Haloperidol Treatment Is Dissociated From Changes In Neostriatal B(Max) And Mrna Content For Dopamine D(2) Receptors, Nuoyu Huang

Electronic Theses and Dissertations

Due to the presumed associations of dopamine (DA) receptor supersensitivity phenomena in both long-term neuroleptic-treated tardive dyskinetic rats and neonatal 6-hydroxydopamine (n6-OHDA)-lesioned rats, we studied the influence of haloperidol on n6-OHDA-lesioned rats. At 3 days after birth rats received 6-OHDA-HBr (200 $\mu$g, bilateral intracerebroventricularly; desipramine pretreatment, 20 mg/kg, 1h) or vehicle. Two months later haloperidol (1.5/kg/day $\times$ 2 days/week for 4 weeks, then 1.5 mg/kg/day, every day for 10 months) was added to the drinking water. Spontaneous oral activity of intact and n6-OHDA-lesioned rats receiving haloperidol was reached and maintained at significantly higher levels after 15 weeks of haloperidol treatment. …

Indomethacin Reduces Splenic Red Pulp Macrophage Populations In Female New Zealand White Rabbits, Thane S. Thurmond

Electronic Theses and Dissertations

In an effort to elucidate the mechanism by which indomethacin (IN) attenuates the stimulatory effect of estradiol (E$\sb2$) on rabbit splenic red pulp macrophages (RPM), thirty-nine female New Zealand White rabbits were divided into 10 groups: ovariectomized (OVX), OVX/IN at 0.1 and 5.0 mg/kg body weight (bw)/day; sham OVX (SOVX), SOVX/IN at 0.1 and 5.0 mg/kg bw/day; OVX/25 mg E2, OVX/25 mg E$\sb2$/IN at 0.1 and 5.0 mg/kg bw/day; intact Control. Quantitative changes in RPM population in response to the treatments were measured using a 0 to 4 histologic grading scale. Estradiol treatment resulted in increased RPM grade when compared …

Altered Platelet Activating Factor Metabolism In Insulin Dependent Diabetes Mellitus, R A. Memon, S A. Saeed, A Jabbar, A Jafri, A H. Gilani, S Saleem, H Akbani

Department of Biological & Biomedical Sciences

Diabetes mellitus is associated with several abnormalities of platelet function. Recent studies have shown that the blood level of platelet activating factor (PAF), a potent inducer of platelet aggregation, is elevated in insulin dependent diabetes mellitus (IDDM) and remains unchanged in non-insulin dependent diabetes mellitus (NIDDM) patients. However, the mechanism of this increase in PAF levels has not been determined. In this study we have measured the activity of plasma PAF acetylhydrolase (an enzyme that regulates PAF levels) and lipoprotein levels in control subjects and diabetic patients. The data presented show that plasma PAF acetylhydrolase activity is significantly decreased in …

Phase Ii Trial Of Murine Monoclonal Antibody D612 Combined With Recombinant Human Monocyte Colony-Stimulating Factor (Rhm-Csf) In Patients With Metastatic Gastrointestinal Cancer, Mansoor Saleh, Michael Khazaeli, Richard Wheeler, Pat Bucy, Tiepe Liu, Michael Everson, David Mun, Jeff Schlom

Haematology and Oncology, East Africa

In a Phase II study, 14 patients with metastatic gastrointestinal cancer received the mAb D612 (40 mg/m2, days 4, 7, and 11) in combination with recombinant human monocyte colony-stimulating factor [(rhM-CSF) 80 ug/kg/days 1-14]. The combined treatment was well tolerated and resulted in characteristic biological activity associated with each of the agents. Thus, 10 of 14 patients experienced D612-associated secretory diarrhea, which responded to the prostaglandin inhibitor Indomethacin in 5 of 7 patients. rhM-CSF therapy was associated with peripheral mono- cytosis (peak absolute monocyte count, 1444 ±394/mm3) and thrombocytopenia (nadir count, 78 ±10/nim '). Monocyte surface marker analysis revealed a …

Cd16+ Monocytes In Patients With Cancer: Spontaneous Elevation And Pharmacologic Induction By Recombinant Human Macrophage Colony- Stimulating Factor, Mansoor Saleh, Goldman Samuel, Lobuglio Albert, Beall Arthur, Sabio Hernan, Mccord Melissa, Minasian Lori, Alpaugh Katherine, Weiner Louis, Munn David

Haematology and Oncology, East Africa

The small subset of circulating monocytes that express the maturation- associated CD16 antigen has recently been reported to be elevated in patients with bacterial sepsis. We now show that this novel CD16+ monocyte population is also spontaneously expanded in patients with cancer. We studied 14 patients with metastatic gastrointestinal carcinoma enrolled in a clinical trial of recombinant human macrophage colony-stimulating factor (rhMCSF) plus monoclonal antibody D612. We found that before any cytokine treatment, 12 of 14 patients constitutively displayed significant elevations in both the percentage and the absolute number of CD16+ monocytes, as compared with both normal subjects and ill …

Cerebral Microcirculatory Effects Of Maturation, Scott R. Elliott

Loma Linda University Electronic Theses, Dissertations & Projects

The present studies demonstrate that in the second (2B) and fourth (4B) branches of newborn and adult sheep middle cerebral arteries, 5-HT2 serotonergic receptors mediate contractile responses to serotonin and that alpha-1 adrenergic receptors mediate contractile responses to norepinephrine. In addition, tissue sensitivity to 5-HT and NE decreases significantly with maturation, but does not vary with branch order. These age-related changes were associated with a decrease in affinity and maximum response in 2B and 4B segments of 5-HT and NE contracted arteries, respectively. Norepinephrine and 5-HT occupancy at the pD₂ rose significantly in 2B segments, but did not change …

Denervation Supersensitivity Of The Rat Vas Deferens: A Role For Protein Kinase C, Sonny T. Abraham

Electronic Theses and Dissertations

A role for protein kinase C (PKC) in the denervation-induced supersensitivity of the rat vas deferens was investigated. Chronic, surgical denervation of the rat vas deferens (up to 8 days) resulted in tissues that produced enhanced contractile responses to norepinephrine (NE) in isolated organ baths. Single challenges of NE (10 $\mu$M) produced 0.6 $\pm$ 0.1 g of maximal tension in the control vas whereas in the paired, denervated tissue 2.2 $\pm$ 0.3 g of tension was recorded (n = 6). Cumulative concentration-effect curves to NE produced in the denervated vas deferens were shifted 18-fold to the left of the control …

Differential Role Of The Endothelium In Regulating Microvascular Blood Flow, Tao Tang

Electronic Theses and Dissertations

The vascular endothelial cell (EC) plays an important role in regulating vascular tone and local blood flow by sensing chemical and mechanical stimuli on the vascular wall and releasing a host of vasoactive substances upon activations of endogenous or exogenous vasoactive substances. The central hypothesis is that local control of blood now and autoregulatory behavior in the microcirculation is distinctive at different levels of the vasculature and is dependent on the cellular activities of the EC and its interaction with the local environment. The in vivo as well as the ex vivo, flow-controlled preparations of the hamster cheek pouch were …

Characterization Of The Vasoactivity Of Tachykinins In Isolated Rat Kidney: Functional Studies And In Vitro Receptor Autoradiography, Yuejin Chen

Electronic Theses and Dissertations

Although tachykinins have potent vascular actions, their effect on renal resistance blood vessels is currently unknown. The vasoactive properties of tachykinins and related analogs were assessed in isolated perfused rat kidney. At a basal perfusion pressure (PP) of 75 $\pm$ 6 mm Hg (n = 5), bolus injections of substance P (SP) had no significant vasoactive effect. Following a sustained increase in baseline PP (134 $\pm$ 10 mm Hg) produced by phenylephrine (1 $\mu$M), SP evoked a dose-dependent increase in PP. The largest dose of SP increased PP by 60 $\pm$ 5 mm Hg. The vasoconstrictor response to SP was …

Co-Sensitization Of Dopamine And Serotonin Receptors Occurs In The Absence Of A Change In The Dopamine D1 Receptor Complex After A Neonatal 6-Ohda Lesion, Li Gong

Electronic Theses and Dissertations

To test whether SKF 38393 could ontogenetically sensitize dopamine (DA) D$\sb1$ receptors and whether this sensitization would be associated with biochemical changes, intact and neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats (200 $\mu$g i.c.v.) were treated daily from birth with SKF 38393 (3.0 mg/kg i.p. x 28 days) or its vehicle. In DA D$\sb1$ neonatally sensitized 6-OHDA rats, enhanced locomotor responses were observed with the first SKF 38393 challenge dose (3.0 mg/kg i.p.) at 6 weeks. This response increased further with weekly SKF 38393 treatments. Enhanced stereotyped behaviors were seen in both lesioned and sensitized rats at 8 weeks. There was no change …

Identification And Characterization Of Possible Multiple Binding Sites For ((3)H)8-Oh-Dpat In The Hippocampus, Dawna Lea Evans

Masters Theses

No abstract provided.

Fixed-Ratio Size As A Determinant Of The Development Of Tolerance To Morphine, Mark J. Nickel

Masters Theses

The acute and chronic effects of morphine were examined in pigeons exposed to a multiple schedule with fixed ratio 5, 25, and 125 components. Acute exposure to morphine (0.56-10.0 mg/kg) resulted in rate reductions under each component when the dose was 1 mg/kg or higher. With chronic exposure to 5.6 mg/kg, tolerance to the rate-reducing effects of morphine was evident under each fixed ratio component. The development of tolerance was determined to some extent by fixed-ratio size, a result similar to earlier findings with cocaine.

Pharmacokinetics, Immune Response, And Biodistribution Of Iodine-131-Labeled Chimeric Mouse/Human Igg1, K 17-1a Monoclonal Antibody, Ruby Meredith, Albert Lobuglio, Walter Plott, Roger Orr, Ivan Brezovich, Charles Russell, Elizabeth Harvey, Michael Yester, Mansoor Saleh

Haematology and Oncology, East Africa

Pharmacokinetics,immunogenicity,and biodistributionof a 131I-Iabeledmouse/human chimenc monoclonal antibody (C17-1A) was studiedin six metastaticcoloncancerpatients. Pharmacokinetics obtalned from serum radioactivity or chi mera concentration were identical after 5 mCi of 131I(>17-1A withmeanalphahalf-livesof 17.6±2.3 and19.7±2.9 and meanbeta half-livesof 100.9±16.1 and 106.4±14.1 hr, respectively. HPLC analysis documented the monomeric chi rneiic17-lA withoutevidenceof immunecomplexesorfree 1311 None of the patients developed antibody after ‘31I-chi merle17-1A exposure.Radiolocalizationoccurredin known areas of disease >4 cm in all patients. The half-life of total body radioactivity was 58 ±7 hr by whole-body counts and 64 ±13 hr by urine measurements. Whole-body and bone marrow dose estimates ranged from 0.75-1 .03 and …

A Phase Ii Trial Of Murine Monoclonal Antibody 17-1a And Interferon-Γ: Clinical And Immunological Data, Mansoor Saleh, Albert Lobuglio, Richard Wheeler, Kimberly Rogers, Amy Haynes, Jeannette Lee, M B. Khazaeli

Haematology and Oncology, East Africa

A group of 15 patients with metastatic colorectal adenocarcinoma received a combination of interferon γ (0.1 mg/m², days 1–15) and the murine monoclonal antibody 17-1A (400 mg, days 5, 7, 9 and 12). The treatment was tolerated with minimal toxicity. Of the 14 evaluable patients, 13 developed human antibody to murine 17-1A, with 11 patients demonstrating antibody to the variable region of 17-1A (anti-idiotype). Antibody to the variable region was inhibited by 17-1A but not by mouse immunoglobulin. Sera from patients with substantial anti-idiotype reactivity were capable of inhibiting the binding of murine 17-1A to antigen expressing LS174-T …

The Effects Of Xanthine Analogs On Neonatal Rat And Adult Mouse Respiration, Susan M. Reynolds

Masters Theses

Apnea, a prolonged cessation of breathing, is commonly seen in premature infants. This condition, in its severest form, can be lethal and is a suspected cause of sudden infant death syndrome (SIDS). Sometimes referred to as apnea of prematurity, recurrent apnea is presently being treated with respiratory stimulants known as methylxanthines (MX) such as theophylline and caffeine. The benefits of MXs are accompanied by central nervous system stimulation and cardiostimulation which may be detrimental to a premature infant. Theophylline (1,3-diMX) has been shown to produce some of its effects by antagonizing endogenous adenosine. Another xanthine, enprofylline (3-propylxanthine), is presently being …

Acute Effects Of Phenytoin And Thioridazine, Alone And Combination, Upon Water Intake And Body Weight Changes In Rats, Miriana Witzig-Krstic

Masters Theses

Concommitant medication of anticonvulsants and psychotropics appears to be predominant among mentally retarded, geriatric, and psychiatric in- and out-patient populations. Despite suggested interaction and toxicity resulting from such combination treatment, substantial data remains unavailable. This study was designed to explore effects of dual treatment of thioridazine

The Effects Of Maternal Administration Of Methadone On Beta-Endorphin Content In The Brain And Pituitary Of The Rat Progeny, Randall L. Braun

Loma Linda University Electronic Theses, Dissertations & Projects

Methadone is often used in the maintenance and detoxification of opioid-dependent pregnant women. This use of methadone during pregnancy is known to be associated with teratogenic effects observed in the progeny. The present study is an attempt to gain insight into possible pathophysiologic mechanism(s) responsible for these teratogenic effects: specifically, a relationship between maternal methadone administration and the content of the endogenous opioid peptide, beta-endorphin, in the brain and pituitary of the rat progeny.

In brief, nulliparous mature female Sprague-Dawley rats received daily injections (5 mg./kg.) of methadone hydrochloride (methadone-treated) or a similar volume of physiological saline (controls), treatment started …

Sulfatides As Opiate Receptors: An Evaluation Of The Opiate Binding Potential Of Sulfogalactosylgylcerolipid, Darby Geoghegan Hand

Chemistry & Biochemistry Theses & Dissertations

Cerebroside sulfate (CS) has recently been shown to bind opiate drugs in a pharmacologically relevent manner and therefore satisfy the structural requirements of an opiate receptor. Seminolipid (SGG), a novel sulfated galactosyl. glycerolipid that has been isolated from the testes of a variety of mammals, may be viewed as a structural analog of CS. In view of this structural similarity, it is reasonable to presume that SGG may also bind opiate drugs. The isolation of SGG from boar testes was accomplished using silica gel dry column chromotography with a chloroform: methanol water solvent system. The structure and purity of the …

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 …

Application Of Knowledge Of Medications By Senior Students In A Selected School Of Nursing, Patricia H. Okimi

Loma Linda University Electronic Theses, Dissertations & Projects

The problem arose from the need to study the present method of pharmacology instruction in a selected school of nursing. "How much knowledge of medications do selected senior students have, and how do they apply their knowledge in the administration of medications?"

For this study, the normative survey approach was used as the method of research. Eleven senior students of nursing engaged in the administration of medications, as team leaders, were observed and questioned on two different occasions during one quarter of their school year. The tool of research used to collect data was an observation code sheet developed for …

Pharmacological Studies Of Antidiabetic Chinese Herbs, Mun Fa Lee

Loma Linda University Electronic Theses, Dissertations & Projects

Rehmannia glutinosa, Atractylus ovata, and Polygonatum chinense have all been employed by the Chinese as oral antidiabetic agents and reported by Min (1928), Kin (1931), and Li et al. (1936) to possess hypoglycemic activity. This prompted the pharmacological studies of these herbs.

Materials and methods. Their pharmacognosy was condensed from all available Chinese and scientific literature. Preliminary chemical and physical analyses included determinations for moisture, ash, crude fat, carbohydrates, protein, phosphorus, pH, alkaloids, melting point, and spectroscopy. Employing the Somogyi-Nelson method, their glycemic activity was studied in rats, rabbits, and dogs. Stress reactions were minimized. The effect …