Pharmacology, Toxicology and Environmental Health Commons^™

Layer -By -Layer Self -Assembly Of Micro-Capsules For The Magnetic Activation Of Semi-Permeable Nano-Shells, Malcolm D. Prouty

Doctoral Dissertations

Layer-by-layer (LbL) self-assembly has demonstrated broad perspectives for encapsulating, and the controllable delivery, of drugs. The nano-scale polymer layers have the capability of material protection. Magnetic nanoparticles have great potential to be applied with LbL technology to achieve both "focusing" of the encapsulated drugs to a specific location followed by "switching" them on to release the encapsulated drugs. In this work, Phor21-βCG(ala), dextran, and dexamethasone were used as model drugs. Encapsulation of these drugs with layer-by-layer self-assembly formed biolnano robotic capsules for controlled delivery and drug release.

Silica nanoparticles coated with polyelectrolyte layers of sodium carboxymethyl cellulose (CMC) or gelatin …

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 …

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 …

Drug Loading And Release From Polypeptide Multilayer Nanofilms, Yang Zhong

Doctoral Dissertations

Polypeptides, linear macromolecules, are formed from amino acid residues by linkage of peptide bonds. Proteins are polypeptides too, with more complex conformations contributing to specific functionalities. Disulfide bonds are very important to maintain the structure and functions of proteins, which will form between two cysteine (Cys) residues under oxidizing circumstance.

Cys containing polypeptides are designed and synthesized by F-moc (9-Fluorenylmethyloxycarbonyl) chemistry. The number and position of Cys residues can be controlled by amino acid sequences design and following peptide synthesis, which is important to gain insights on the nature of polyelectrolyte multilayer film assembly and stability.

Both commercial and designed …

Patterns And Prevalence Of Metabolic Syndrome Among Persons Receiving Treatment With Antipsychotic Medications, Brittany Marie-Bach Harte

Dissertations, Theses, and Masters Projects

No abstract provided.

Xenobiotic Transporters In Lactating Mammary Epithelial Cells: Predictions For Drug Accumulation In Breast Milk, Philip Earle Empey

Theses and Dissertations--Pharmacy

Recent literature has established that breast cancer resistance protein (ABCG2) is upregulated during lactation and is responsible for the greater than predicted accumulation of many drugs in breast milk. The objectives of this project were (1) to investigate the role of this transporter in the reported apically-directed nitrofurantoin flux in the CIT3 cell culture model of lactation, (2) to develop a mathematical model for drug transfer into breast milk to relate initial flux rates, steady-state concentrations, efflux ratios, and in vivo milk to serum ratios (M/S) and (3) to identify xenobiotic transporters that are highly expressed, and therefore potentially important …

Neurodegeneration And Neuroinflammation In A Mouse Model Of Sarin Exposure, Molly Elizabeth Davidson

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Sarin is an organophosphorus (OP) ester chemical warfare agent (CWA) that has been used in past terrorist attacks. It remains a threat today because of its ease of manufacture and dispersal. Sarin acts by irreversibly inactivating acetylcholinesterase and interfering with neurotransmission by allowing acetylcholine to build up at neuro-effector junctions, where it continuously elicits a response. Symptoms of sarin toxicity include seizures, hypersecretions, respiratory distress and death in extreme cases. Previous studies on OP poisoning indicate that sarin exposure causes neurodegeneration and neuroinflammation in conjunction with seizure activity. In order to determine the mode of neuronal death and the extent …

Angiotensin At1 Receptor Blockade Protects The Brain From Ischemic Damage, Madhuri Penchikala

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Angiotensin (Ang) AT1 receptors are considered to play an important role in ischemic stroke via degenerative processes leading to cell death. Recent clinical and basic studies show that systemic blockade of Ang AT1 receptors reduces brain lesion in ischemic stroke. In this study we evaluated whether blockade of central Ang AT1 receptors protects the brain from ischemia and inflammation during ischemic stroke. Adult male C57BL/6 mice were divided into two groups for chronic intracerebroventricular (ICV) infusion of a selective Ang AT1 receptor antagonist, losartan (Los, n=18, 2 ug/hr) or isotonic saline (Con, n=20) using osmotic minipump. Twelve days post infusion, …

Role Of Angiotensin Converting Enzymes Ace And Ace2 In Diabetes Induced Cardiovascular Dysfunction, Keerthy Kanakamedala

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Cardiovascular disease is a long term complication of diabetes, which remains a leading cause of mortality and morbidity. There is recent evidence for activation of the Renin angiotensin system (RAS) in diabetic animals and humans. Emerging evidence shows that the vasoconstrictor actions of Ang II may be opposed by formation of the vasodilator, Ang (1-7). There is limited data on blood pressure in murine models of type 2 diabetes. The aim is to study the role of angiotensin converting enzymes ACE and ACE2 in diabetes induced cardiovascular dysfunction using type 2 diabetic murine mouse models (db/db mice). Both db/db mice …

Oral Ld50 Of Botulinum Toxin Serotype A In Guinea Pigs, Christina Marie Wilhelm

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As a disease, botulism is a neuroparalytic illness resulting from the action of a potent neurotoxin produced by C. Botulinum. Of the seven distinct C. Botulinum neurotoxin serotypes: A, B, C, D, E, F, and G, only serotypes A, B, E and F cause human disease. The duration of action of the seven toxin serotypes varies with serotype A having the most sustained action (i.e. months vs. days in serotype E). This study was performed due to recently identified critical gaps in our food safety procedures. The goal of this study was to assess whether fresh 2% milk provided protective …

The Processing Of Β-Endorphin In Morphine Treated Rats Using Seldi-Tof Mass Spectrometry, Jennifer Y. Edwards

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Endocrine glands secrete peptide hormones that bind to specific receptors, and elicit a response. In the pituitary, prohormone convertases (PC) PC1/3 and PC2 convert inactive prohormones into biologically active peptide hormones. Proopiomelanocortin (POMC) is a precursor molecule that proteolytically cleaves at paired basic residue sites, and produces smaller biologically active peptides, such as adrenocorticotropic hormone (ACTH), α-melanocyte stimulating hormone (α-MSH), and β-endorphin. β-endorphin is an endogenous opioid peptide hormone that plays a vital role in the body's physiological response to stress, fear, and anxiety. Morphine is an exogenous opioid, used for the treatment of moderate to severe pain and competes …