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Full-Text Articles in Physiology

Effects Of Metal Protoporphyrins On Burn Wound Conversion, Katie Braun Dec 2008

Effects Of Metal Protoporphyrins On Burn Wound Conversion, Katie Braun

Theses and Dissertations

A murine model was utilized to test the influence of heavy metal protoporphyrins on burn conversion, heme oxygenase – 1 (HO-1) expression, and inflammation. Heavy metal protoporphyrins, such as cobalt protoporphyrin (Co PP) and tin protoporphyrin (Sn PP), were used to influence the heme oxygenase activity. The effects of these heavy metal protoporphyrins on burn wound conversion were examined using a burn comb model in rats. In addition to assessing the extent of conversion, HO-1 expression and parameters of inflammation were also examined in the area of injury (interspace region) subject to conversion. These studies demonstrate proof in principal that …


Effects Of Light Exposure On The Release Of Oxygen From Hemoglobin In A Red Blood Cell Suspension, Tanikka Toler Dec 2008

Effects Of Light Exposure On The Release Of Oxygen From Hemoglobin In A Red Blood Cell Suspension, Tanikka Toler

Theses and Dissertations

The main function of the cardiovascular system is to deliver a sufficient quantity of oxygenated blood to the tissues, cells, and organs of the body in order to provide the cells with essential nutrients for metabolism and for the removal of waste products. All cells require and utilize oxygen. Oxygen is transported to various cells and tissues via red blood cells flowing through the microcirculation of an organism. Measurement of oxygen transport in the microcirculation has shown that about ten times more oxygen appears to leave the blood of arterioles than can be accounted for by diffusion. One possibility to …


Co-Administration Of Sildenafil Potentiates Doxorubicin-Induced Apoptosis In Prostate Cancer: The Role Of Nf-Kappab, Sarah Hassanieh Dec 2008

Co-Administration Of Sildenafil Potentiates Doxorubicin-Induced Apoptosis In Prostate Cancer: The Role Of Nf-Kappab, Sarah Hassanieh

Theses and Dissertations

Our recent studies have shown that that erectile dysfunction (ED) drugs including Sildenafil (Viagra), Vardenafil (Levitra) and Tadalafil (Cialis) enhance killing of several types of cancer cells by anticancer drug, Doxorubicin (DOX). We observed increased cell death by apoptosis in response to the combined treatment with ED drugs and DOX. However, the mechanism of such enhancement of cell death by combined treatment of ED drugs and DOX is not fully understood. Nuclear factor-κB (NF-κB) is an oxidant-sensitive transcription factor that plays a critical role in the immediate-early activation of a multitude of genes that have been documented to play critical …


The Effects Of Excess Corticosterone On Lkb1 And Ampk Signaling In Skeletal Muscle Of Rats, Gary N. Nakken Dec 2008

The Effects Of Excess Corticosterone On Lkb1 And Ampk Signaling In Skeletal Muscle Of Rats, Gary N. Nakken

Theses and Dissertations

Cushing's syndrome and glucocorticoid therapy lead to central obesity, insulin resistance, and symptoms of altered energy regulation similar to those observed in the metabolic syndrome. We hypothesized that excess glucocorticoids alter energy sensing/signaling in skeletal muscle through mediation of the LKB1/AMPK signaling pathway. To test this hypothesis, three 100 mg pellets of corticosterone were implanted subcutaneously in each of nine rats for two weeks. Responses were compared with sham operated controls fed ad libitum or food restricted to produce the body weights similar to the treatment group rats. After the treatment period, animals were anesthetized and the right gastrocnemius-plantaris and …


Wnt5a Signaling Independently Of The Planar Cell Polarity Pathway Resulting In Convergent Extension And Neural Tube Closure During Vertebrate Development, Jared James Barrott Aug 2008

Wnt5a Signaling Independently Of The Planar Cell Polarity Pathway Resulting In Convergent Extension And Neural Tube Closure During Vertebrate Development, Jared James Barrott

Theses and Dissertations

Vertebrate development is regulated by cellular communication by mechanisms of cell fate and cell behavior. These crucial mechanisms are regulated by cellular signaling and in the case of cell fate, cellular signaling results in transcription of developmentally important genes. Communication between cells can also result in regulation of cell behavior by acting on cytoskeletal elements rather than nuclear factors. One of the cellular signals that regulate both cell fate and cell behavior is the family of Wnt signaling molecules. Wnt5a is one of 19 Wnt molecules and has been previously demonstrated to play critical roles in many important processes in …


Determining The Role Of Wnt5a Signaling In Embryonic Limb Outgrowth Via Clonal Analysis, Whitney Herrod Sowby Aug 2008

Determining The Role Of Wnt5a Signaling In Embryonic Limb Outgrowth Via Clonal Analysis, Whitney Herrod Sowby

Theses and Dissertations

The exact mechanisms that regulate limb outgrowth the mouse embryo are unknown. Although there are several models, we favor a hypothesis where cells become polarized by signals secreted from the AER which orient their cell migration and/or divisions causing limb outgrowth. Clonal analysis has provided a mechanism to study cell behavior. We have generated a targeting construct containing the Fgf8 inhibitor, Sprouty2, in order to generate mutant clones for behavioral analyses in the limb. In order to more effectively study clonal behavior we report the modification of a novel clonal analysis approach, exo-utero surgery. We have modified, enhanced and proven …


Cellular And Matrix Changes In Articular Cartilage Of The Disproportionate Micromelia Mouse Model Of Osteoarthritis, Crystal Noelle Smaldone Aug 2008

Cellular And Matrix Changes In Articular Cartilage Of The Disproportionate Micromelia Mouse Model Of Osteoarthritis, Crystal Noelle Smaldone

Theses and Dissertations

Osteoarthritis (OA) is a degenerative joint disease that affects more than 60% of Americans 65 and older. Because human subjects and samples are not readily available for research, animal models are an invaluable resource for the study of OA. Disproportionate micromelia (Dmm) is one such model that develops OA early in life due to a deletion in the c-propeptide of the Col2a1 gene. Light microscope analysis of the articular cartilage in Dmm has been completed, but is insufficient to show the cellular effects of the deletion mutation in Dmm in adequate detail. The present study explores the changes that occur …


Differential Expression And Functional Characterization Of Alpha3 Beta2 Neuronal Nicotinic Acetylcholine Receptors, John Hideo Mizukawa Jul 2008

Differential Expression And Functional Characterization Of Alpha3 Beta2 Neuronal Nicotinic Acetylcholine Receptors, John Hideo Mizukawa

Theses and Dissertations

Neuronal nicotinic acetylcholine receptors (nAChRs) are expressed in both the periperhal and central nervous systems, and are involved in pre-, post-, and non-synaptic control of neuronal activation. In the brain, these receptors play an important role in a variety of physiological processes such as cognition, development, learning, and memory formation. Malfunction of these receptors have been implicated in neurodegenerative diseases like Alzheimer's disease (AD), schizophrenia, and Parkinson's disease. To date, 17 different nAChR subunits, including α2-α7 and β2-β4, have been cloned that can form homo- and/or hetero-pentameric ionotropic receptors. The unique combinations of subunit pentamers manifest in distinct functional receptors. …


A Comparative Analysis Of Hydrolysis Kinetics By Spla2 Isoforms During Apoptosis In S49 Cells, Erin Dalene Olson Jul 2008

A Comparative Analysis Of Hydrolysis Kinetics By Spla2 Isoforms During Apoptosis In S49 Cells, Erin Dalene Olson

Theses and Dissertations

Secretory Phospholipase A2 (sPLA2) represents a diverse class of roughly 20 enzymes, 12 of which have been identified in humans. These isoforms can be distinguished based on their tissue distribution, structure, and regulation. These differences in structure between the isoforms lead to the question does the enzyme's ability to respond to physical changes in the membrane during apoptosis governed by structure. S49 cell apoptosis was initiated by treatment with either the glucocorticoid dexamethasone (6–48 h) or with the calcium ionophore, ionomycin. The rates of hydrolysis were compared with each treatment condition for various concentrations of snake venom and human groups …


Investigating And Modeling Possible Mechanisms By Which Healthy Cell Membranes Become Resistant To Hydrolysis By Secretory Phospholipase A2, Jennifer Nelson Jul 2008

Investigating And Modeling Possible Mechanisms By Which Healthy Cell Membranes Become Resistant To Hydrolysis By Secretory Phospholipase A2, Jennifer Nelson

Theses and Dissertations

Secretory phospholipase A2 (sPLA2) behaves differently toward the membranes of healthy cells compared to those of damaged or dying cells. The enzyme catalyzes rapid and sustained hydrolysis of compromised cells consistent with a simple catalytic mechanism. In contrast, when healthy cells are incubated with sPLA2, they become resistant to hydrolytic attack as manifest by three unusual observations: First, hydrolysis is transient and represents only a small fraction of the total membrane phospholipid content. Second, subsequent addition of sPLA2 fails to generate additional product. Third, the apparent potency of the enzyme to cause the membrane to be refractory is much greater …


The Role Of Microrna-155 And Microrna-146a As Putative Oncomirs In The Tumor Progression Of Prostate Cancer, Jennifer Hoyt Jul 2008

The Role Of Microrna-155 And Microrna-146a As Putative Oncomirs In The Tumor Progression Of Prostate Cancer, Jennifer Hoyt

Theses and Dissertations

Prostate cancer is the most common cancer occurring in males. The identification of novel microRNAs (miRs) that contribute to tumor progression represents prospective treatment targets. miRs are small non-coding RNAs important in gene regulation with specific tissue expression patterns. Each miR is thought to affect the expression of hundreds of different RNA targets. Two putative oncomiRs, miR-155 and miR-146a, were shown to be differentially expressed in the human derived, prostate cell sublines M12 and F6. Quantification of endogenous miR expression showed high levels in the metastatic M12 cell line versus low in its weakly tumorigenic F6 variant. The restoration of …


Intravenous Administration Of Perfluorocarbon Emulsions As A Non-Recompression Therapy For Decompression Sickness, Cameron Smith Jun 2008

Intravenous Administration Of Perfluorocarbon Emulsions As A Non-Recompression Therapy For Decompression Sickness, Cameron Smith

Theses and Dissertations

Decompression sickness (DCS) results from a sudden decrease in ambient pressure leading to super-saturation of tissues with inert gas and subsequent bubble formation within both tissues and blood. Perfluorocarbons (PFC) are able to dissolve vast amounts of non-polar gases. The administration of intravenous (I.V.) PFC emulsions reduce both morbidity and mortality of DCS, but the mechanism of this protective effect has not yet been demonstrated. Juvenile Dorper cross sheep between 16 and 24 kg (n=31) were anaesthetized and instrumented for physiological monitoring, the administration of I.V. fluids and sampling of arterial and mixed venous blood. Animals were placed in a …


Effect Of Hemoglobin-Based Oxygen Carriers On Arterial Pressure And Vasoactivity In The Rat Mesentery, Michael Kim May 2008

Effect Of Hemoglobin-Based Oxygen Carriers On Arterial Pressure And Vasoactivity In The Rat Mesentery, Michael Kim

Theses and Dissertations

Hemoglobin-based oxygen carriers provide a promising future as an alternative to human blood transfusions. Hemoglobin-based oxygen carriers, HBOCs, provide a lowcost, easy to maintain, and safe solution. They require no refrigeration and are universally compatible, and the required transfusion volume is less than that of a normal transfusion. HBOCs have been known to have adverse side effects such as renal toxicity, gastrointestinal dismotility, and hypertension. Many of these problems stem from the lack of a membrane, which protects the hemoglobin from dissociating and extravasating into the blood vessel wall. Extracellular hemoglobin, like that found in HBOCs, has a greater affinity …


Effects Of Hemoglobin-Based Oxygen Carriers On The Vasoactivity Of The Spinotrapezius Muscle Of The Rat, Pete Meliagros Apr 2008

Effects Of Hemoglobin-Based Oxygen Carriers On The Vasoactivity Of The Spinotrapezius Muscle Of The Rat, Pete Meliagros

Theses and Dissertations

Hemoglobin-based oxygen carriers (HBOCs) offer a safe, more plentiful and long term alternate to blood banks. However, they have been found to increase blood pressure which can be attributed to an increase in total peripheral resistance (TPR). Lumenal nitric oxide (NO) scavenging by these HBOCs seems to be responsible for this hypertensive effect. In addition, it is believed that hemoglobin (Hb) tetramers and dimers may extravasate and consume additional nitric oxide in the perivascular and interstitial space. The purpose of the present study was to elucidate the role of NO scavenging and to confirm extravasation as a contributor to HBOC …


The Effects Of A Resveratrol Derivative On Regulatory Behaviors And Reproductive Health In Male And Female Long-Evans Rats, Kimberly Michelle Fabick Mar 2008

The Effects Of A Resveratrol Derivative On Regulatory Behaviors And Reproductive Health In Male And Female Long-Evans Rats, Kimberly Michelle Fabick

Theses and Dissertations

Phytoestrogens are chemicals produced by plants that act like estrogens and have the ability to bind to the mammalian estrogen receptor system. The purpose of this study is to evaluate a new phytoestrogen analog called 4-acetoxy Resveratrol. Resveratrol is a phytoestrogen that has been found in the skin of grapes. Resveratrol has been shown to be able to bind to the estrogen receptors and has a similar molecular structure as estradiol. Resveratrol has been shown to have many positive health benefits such as improving cardiovascular health, serving as a neuroprotective agent, acting as an anti-inflammatory agent, working as an anti-cancer …


The Effects Of Prenatally Administered Phytoestrogens On The Reproductive And Behavioral Development Of Long-Evans Rats, Crystal Blake Mar 2008

The Effects Of Prenatally Administered Phytoestrogens On The Reproductive And Behavioral Development Of Long-Evans Rats, Crystal Blake

Theses and Dissertations

Equol is known to be a selective androgen modulator and has the ability to bind and inhibit 5-alpha dihydrotestosterone (5α-DHT). Equol is also a selective estrogen receptor modulator and is able to bind beta estrogen receptors with high affinity. As estrogen receptors are found in the hypothalamus, pituitary, and gonads, prenatally administered equol could affect the morphological and reproductive development of offspring. To test this hypothesis, during gestational days 14 to 20, forty-two pregnant Long-Evans rats were given one of six treatments: 1) no treatment, 2) injection with dimethyl sulfoxide (DMSO), 3) injection with 10 mg/kg equol, 4) injection with …


Mechanisms By Which Apoptotic Membranes Become Susceptible To Secretory Phospholipase A2, Rachel Williams Bailey Mar 2008

Mechanisms By Which Apoptotic Membranes Become Susceptible To Secretory Phospholipase A2, Rachel Williams Bailey

Theses and Dissertations

During apoptosis, changes occur in T-lymphocyte membranes that render them susceptible to hydrolysis by secretory phospholipase A2 (sPLA2). To study the relevant mechanisms, a simplified model of apoptosis using a calcium ionophore was first applied. Kinetic and flow cytometry experiments provided key observations regarding ionophore treatment: initial hydrolysis rate was elevated, total reaction product was increased four-fold, and adsorption of the enzyme to the membrane surface was unaltered. Analysis of these results suggested that susceptibility during calcium-induced apoptosis is limited by substrate availability rather than enzyme adsorption. Fluorescence experiments identified three membrane alterations that might affect substrate access to the …


Augmentation Of T Cell Expansion For Adoptive Immunotherapy By Alternate Gamma Chain Cytokines And By Gemcitabine Mediated Inhibition Of Myeloid Derived Suppressor Cells, Hanh Le Jan 2008

Augmentation Of T Cell Expansion For Adoptive Immunotherapy By Alternate Gamma Chain Cytokines And By Gemcitabine Mediated Inhibition Of Myeloid Derived Suppressor Cells, Hanh Le

Theses and Dissertations

Successful treatment of cancer with adoptive immunotherapy (AIT) is dependent on the ability to produce large numbers of tumor-specific, functional T cells. The purpose of this thesis is to explore ways in which T cell expansion could be augmented. We have focused on exploring alternate gamma chain cytokines as stimulators of T cell proliferation and differentiation in addition to investigating the potential usefulness of gemcitabine (GEM) in abrogating the immunosuppressive effects of myeloid derived suppressor cells (MDSCs). B16 melanoma sensitized draining lymph node cells that have been activated in vitro with bryostatin-1 and ionomycin (B/I) were expanded in either IL-7/15 …


Role Of Vegf-C In Proliferation And Migration In A Cancer Model, Emily Marie Benke Jan 2008

Role Of Vegf-C In Proliferation And Migration In A Cancer Model, Emily Marie Benke

Theses and Dissertations

Head and neck cancer ranks high among the most common cancers world wide. In addition, there is a high recurrence rate, as well as a high prevalence of loco-regional tumor spread. Among many factors contributing to metastasis is vascular endothelial cell growth factor C. VEGF-C is primarily an inducer of new lymph vessel formation, typically during embryogenesis; however, some advanced cancers show a significant increase in VEGF-C expression, suggesting a role in metastasis. In the current study, the effects of VEGF-C expression were tested in HN12 cells, which are highly metastatic and known to express high levels of the chemokine …


The Effect Of Cell Type On The Efficacy Of Cmv Antiviral Drugs, Benjamin Meza Jan 2008

The Effect Of Cell Type On The Efficacy Of Cmv Antiviral Drugs, Benjamin Meza

Theses and Dissertations

Until recently, all in vitro drug susceptibility assays of cytomegalovirus (CMV) were performed in clinically irrelevant fibroblast cells. This study sought to test if drug susceptibility was affected by cell type. MRC-5 embryonic lung fibroblasts and ARPE-19 retinal pigmented epithelial cells were infected with BADrUL131-Y4 epithelial/fibroblast tropic virus under serial concentrations of ganciclovir (GCV) or maribavir (MBV). Virus was quantified using plaque reduction, GFP fluorescence, and yield reduction. Both drugs performed less efficiently in ARPE-19 cells. A cell type effect was observed for both plaque reduction and yield reduction assays with implications for the treatment of CMV retinitis as well …