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Pharmacology, Toxicology and Environmental Health

Loma Linda University Electronic Theses, Dissertations & Projects

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Hypoxia And Fetal Programming Of Cardiovascular Dysfunction, Qin Xue Jun 2010

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 …


Impact Of Ambient Air Pollution On Survival Of Renal Transplant Recipients, Rhonda Kristine Hwang Sep 2009

Impact Of Ambient Air Pollution On Survival Of Renal Transplant Recipients, Rhonda Kristine Hwang

Loma Linda University Electronic Theses, Dissertations & Projects

There is increasing evidence that ambient air pollution is associated with coronary heart disease morbidity and mortality. This research has focused on the general public and less so on possible sensitive subgroups even though these may have even greater susceptibility to adverse effects of ambient air pollution. With highly prevalent traditional as well as nontraditional risk factors, renal transplant recipients may potentially be a sensitive subgroup. The purpose of this study was to evaluate the possible effect of between long-term exposure to air pollution on the risk of CHD mortality among renal transplant recipients. This cohort study includes 32,239 adult, …


Maturational Changes In Cerebrovascular Thick- And Thin-Filament Regulation, Renan Joel Sandoval May 2007

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 May 2007

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 …


Interaction Between Adrenergic And Nitric Oxide-Releasing Nerves In Cerebral Arteries, Emmanuel Ngu Mbaku Jun 2003

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 Mar 2002

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 Jun 2001

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 …


Cerebral Microcirculatory Effects Of Maturation, Scott R. Elliott Jun 1994

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 …


The Effects Of Maternal Administration Of Methadone On Beta-Endorphin Content In The Brain And Pituitary Of The Rat Progeny, Randall L. Braun Jun 1984

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 …


A Comparative In Vitro Metabolic Study Of Certain Pesticidal Phenyl N-Methyl-Carbamates, Larry A. Wheeler Apr 1970

A Comparative In Vitro Metabolic Study Of Certain Pesticidal Phenyl N-Methyl-Carbamates, Larry A. Wheeler

Loma Linda University Electronic Theses, Dissertations & Projects

Two critical parameters in the evaluation of the toxicological hazards of the use of carbamate pesticides are: (1) a rapid, sensitive, and precise analytical method of identification of the carbamate and its metabolites; and (2) their metabolism. A method in this study was developed whereby various carbamates and their metabolites could be chromatographed in the gaseous phase. Also, a comparative in vitro study of 15,000 g liver supernatants from human, rat, and dog was performed. Additional tissues investigated for metabolic activity toward the carbamates, Zectran and Mesurol, were kidney (from the dog only) and various blood fractions (red blood cells, …


Application Of Knowledge Of Medications By Senior Students In A Selected School Of Nursing, Patricia H. Okimi Jun 1961

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 Jun 1959

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 …