Matching Items (11)
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- All Subjects: Diabetes
- Creators: Caplan, Michael
Description
The effects of specific histone deacetylase inhibitors (HDACi) on transgene expression in combination with a novel polymer as a delivery vehicle are investigated in this research. Polymer vectors, although safer than viruses, are notorious for low levels of gene expression. In this investigation, the use of an emerging chemotherapeutic anti-cancer drug molecule, HDACi, was used to enhance the polymer-mediated gene expression. HDACi are capable of inhibiting deacetylation activities of histones and other non-histone proteins in the cytoplasm and nucleus, as well as increase transcriptional activities necessary for gene expression. In a prior study, a parallel synthesis and screening of polymers yielded a lead cationic polymer with high DNA-binding properties, and even more attractive, high transgene expressions. Previous studies showed the use of this polymer in conjunction with cytoplasmic HDACi significantly enhanced gene expression in PC3-PSMA prostate cancer cells. This led to the basis for the investigation presented in this thesis, but to use nuclear HDACi to potentially achieve similar results. The HDACi, HDACi_A, was a previously discovered lead drug that had potential to significantly enhance luciferase expression in PC3-PSMA cells. The results of this study found that the 20:1 polymer:plasmid DNA weight ratio was effective with 1 uM and 2 uM HDACI_A concentrations, showing up to a 9-fold enhancement. This enhancement suggested that HDACi_A was effectively aiding transfection. While not an astounding enhancement, it is still interesting enough to investigate further. Cell viabilities need to be determined to supplement the results.
ContributorsLehrman, Jennifer (Author) / Rege, Kaushal (Thesis advisor) / Caplan, Michael (Committee member) / Pizziconi, Vincent (Committee member) / Arizona State University (Publisher)
Created2012
Description
Ather Arop is bilingual. He is also fluent in Spanish and speaks some French. “Lost Boys Found” is an ongoing, interdisciplinary project that is collecting, recording and archiving the oral histories of the Lost Boys/Girls of Sudan. The collection is a work-in-progress, seeking to record the oral history of as many Lost Boys/Girls as are willing, and will be used in a future book.
ContributorsArop, Ather (Interviewee) / Amparano, Julie (Director) / Garcia, James (Interviewer) / MacNeill, MacNeill (Editor)
Created2017-10-14
Description
There has been an alarming rise in the prevalence of obesity which has been attributed to the paralleled rise in consumption of high-fat foods. It’s commonly accepted that high-fat diets can lead to increased weight gain, however not all fats have the same physiological action. This study primarily focuses on the effect of canola oil, a monounsaturated fat, on energy homeostasis and body composition when it’s given as a supplement to a high-fat diet composed of saturated fatty acid. Rodent models were divided into three dietary groups: 1) low-fat diet (LFD), 2) high-fat diet (HFD) and 3) canola oils supplemented HFD (HF+CAN). After 4 weeks of dietary intervention, samples of epididymal fat, perinephric fat, and liver were analyzed across the three groups to see if the changes in energy homeostasis could be explained by the cellular behavior and composition of these tissues. Interestingly, the supplement of canola oil appeared to reverse the deleterious effects of a saturated fat diet, reverting energy intake, body weight gain and adipose tissue sizes to that (if not lower than that) of the LFD group. The only exception to this effect was the liver: the livers remained larger and fattier than those of the HFD. This occurrence is possibly due to a decrease in free fatty acid uptake in the adipose tissues—resulting in smaller adipose tissue sizes—and increased fatty acid uptake in the liver. The mechanism by which this occurs has yet to be elucidated and will be the primary focus of upcoming studies on the effect of monounsaturated fat on other diets.
ContributorsZuo, Connie Wanda (Author) / Washo-Krupps, Delon (Thesis director) / Deviche, Pierre (Committee member) / Herman, Richard (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Sickle cell disease is a genetic disorder that can cause substantial helath problems. It is the result of a mutation in the DNA coding for hemoglobin. As a result of changes in two important amino acids, a person suffering from sickle cell disease will have erythrocytes that do not maintain the typical biconcave shape and instead for a crescent shape. Individuals with sickle cell disease may have many health problems tied to their irregular hemoglobin. The unusual shape of the erythrocytes leads to a much shorter cell life, which means that even though bone marrow remains active long past childhood to try to keep up with the loss of erythrocytes, the body is still unable to accommodate the rapid death of erythrocytes. The malformed erythrocytes can also cause vascular occlusion, blocking blood vessels and slowing blood flow. While sickle cell disease has the potential to spread worldwide, it is particularly common in Africa. This may be because people with the sickle cell trait have a high resistance to malaria, making them more likely to survive that ubiquitous disease and pass on their traits to their offspring. However, the mortality rate in young children with sickle cell disease is very high, in part because the spleen, already stressed by filtering out dead erythrocytes, has difficulties filtering out bacteria. One of the keys to stopping the spread of the disease is neonatal screening, but this requires specialized equipment that is fairly uncommon in rural areas, as can be seen in Kenya. Therefore, it would be highly beneficial to develop a more cost-effective and widely available method for testing for sickle cell disease.
ContributorsWold, John (Author) / Caplan, Michael (Thesis director) / LaBelle, Jeffrey (Committee member) / Snyder, Jan (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
Description
Sickle Cell Disease (SCD) is a prevalent genetic disease in Africa, and specifically in Kenya. The lack of available relevant disease education and screening mean that most don't understand the importance of getting testing and many children die before they can get prophylactic care. This project was designed to address the lack of knowledge with supplemental educational materials to be partnered with an engineering capstone project that provides a low cost diagnostic test.
ContributorsShawver, Jamie Christine (Author) / Caplan, Michael (Thesis director) / Snyder, Jan (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
The pathogenesis of type 1 diabetes (T1D) is still not fully understood in the scientific community. Evidence has shown that viral infections are one of the important environmental factors associated with the disease development. Seven of the top T1D related viruses were selected to study the prevalence of viral humoral response in T1D patients using our innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA). In this study, each viral gene was individually captured using various PCR based techniques, cloned into a protein expression vector, and assembled as the first version of T1D viral protein array. Humoral responses of IgG, IgA, and IgM were examined. Although each class of immunoglobulin generated a wide-range of reactivity, responses to various viral proteins from different proteins were observed. In summary, we captured most of the T1D related viral genes, established viral protein expression on the protein array, and displayed the serum response on the viral protein array. The successful progress will help to fulfill the long term goal of testing the viral infection hypothesis in T1D development.
ContributorsDavis, Amy Darlene (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Desi, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-05
Description
Diabetes is a growing epidemic in developing countries, specifically in rural Kenya. In addition to the high cost of glucose testing, many diabetics in Kenya do not understand the importance of testing their blood glucose, let alone the nature of the disease. This project addresses the insufficiency of educational materials regarding diabetes in rural Kenya. The resulting documents can easily be adjusted for use in other developing countries.
ContributorsBuchak, Jacqueline (Author) / Caplan, Michael (Thesis director) / Snyder, Jan (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
The purpose of this study, which was done in conjunction with the Arizona Heart Foundation, was to evaluate whether pyridoxine accelerates ulcer wound healing in diabetic patients with ulcers in the lower extremities. In this study, 100 mg of pyridoxine per day was given to patients in the experimental group (while they receive normal wound treatment) while patients in the control group received normal treatment of wounds without the pyridoxine. Over time, wound healing was evaluated by photographing and then measuring the size of patients' ulcer wounds on the photographs. Results from the experimental group were compared with those of the control group to evaluate the efficacy of the pyridoxine treatment. In addition, comparisons of the healing rates were made with respect to whether the patients smoked, had hypertension or hypotension, and the patients' body mass indexes. It has been found that there was no statistically significant difference in the mean healing rates between the control groups and experimental groups. In addition, it has been found that smoking, BMI and blood pressure did not have a statistically appreciable effect on the difference in mean healing rates between the control and experimental groups. This is evidence that pyridoxine did not have a statistically significant effect on wound healing rates.
ContributorsHaupt, Shawn Anthony (Author) / Caplan, Michael (Thesis director) / Pauken, Christine (Committee member) / Pagan, Pedro (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
Description
Type II diabetes is a serious, chronic metabolic disease that has serious impacts on both the health and quality of life in patients diagnosed with the disease. Type II diabetes is also a very prevalent disease both in the United States and around the world. There is still a lot that is unknown about Type II diabetes, and this study will aim to answer some of these questions. The question posed in this study is whether insulin resistance changes as a function of time after the start of a high fat diet. We hypothesized that peripheral insulin resistance would be observed in animals placed on a high fat diet; and peripheral insulin resistance would have a positive correlation with time. In order to test the hypotheses, four Sprague-Dawley male rats were placed on a high fat diet for 8 weeks, during which time they were subjected to three intraperitonal insulin tolerance tests ((NovoLogTM 1 U/kg). These three tests were conducted at baseline (week 1), week 4, and week 8 of the high fat diet. The test consisted of serially determining plasma glucose levels via a pin prick methodology, and exposing a droplet of blood to the test strip of a glucometer (ACCUCHEKTM, Roche Diagnostics). Two plasma glucose baselines were taken, and then every 15 minutes following insulin injection for one hour. Glucose disposal rates were then calculated by simply dividing the glucose levels at each time point by the baseline value, and multiplying by 100. Area under the curve data was calculated via definite integral. The area under the curve data was then subjected to a single analysis of variance (ANOVA), with a statistical significance threshold of p<0.05. The results of the study did not indicate the development of peripheral insulin resistance in the animals placed on a high fat diet. Insulin-mediated glucose disposal was about 50% at 30 minutes in all four animals, during all three testing periods. Furthermore, the ANOVA resulted in p=0.92, meaning that the data was not statistically significant. In conclusion, peripheral insulin resistance was not observed in the animals, meaning no determination could be made on the relation between time and insulin resistance.
ContributorsBrown, Kellen Andrew (Author) / Caplan, Michael (Thesis director) / Herman, Richard (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Monitoring complex diseases and their comorbidities requires accurate and convenient measurements of multiple biomarkers. However, many state-of-the-art bioassays not only require complicated and time-consuming procedures, but also measure only one biomarker at a time. This noncomprehensive single-biomarker monitoring, as well as the cost and complexity of these bioassays advocate for a simple, rapid multi-marker sensing platform suitable for point-of-care or self-monitoring settings. To address this need, diabetes mellitus was selected as the example complex disease, with dry eye disease and cardiovascular disease as the example comorbidities. Seven vital biomarkers from these diseases were selected to investigate the platform technology: lactoferrin (Lfn), immunoglobulin E (IgE), insulin, glucose, lactate, low density lipoprotein (LDL), and high density lipoprotein (HDL). Using electrochemical techniques such as amperometry and electrochemical impedance spectroscopy (EIS), various single- and dual-marker sensing prototypes were studied. First, by focusing on the imaginary impedance of EIS, an analytical algorithm for the determination of optimal frequency and signal deconvolution was first developed. This algorithm helped overcome the challenge of signal overlapping in EIS multi-marker sensors, while providing a means to study the optimal frequency of a biomarker. The algorithm was then applied to develop various single- and dual-marker prototypes by exploring different kinds of molecular recognition elements (MRE) while studying the optimal frequencies of various biomarkers with respect to their biological properties. Throughout the exploration, 5 single-marker biosensors (glucose, lactate, insulin, IgE, and Lfn) and one dual-marker (LDL and HDL) biosensor were successfully developed. With the aid of nanoparticles and the engineering design of experiments, the zeta potential, conductivity, and molecular weight of a biomarker were found to be three example factors that contribute to a biomarker’s optimal frequency. The study platforms used in the study did not achieve dual-enzymatic marker biosensors (glucose and lactate) due to signal contamination from localized accumulation of reduced electron mediators on self-assembled monolayer. However, amperometric biosensors for glucose and lactate with disposable test strips and integrated samplers were successfully developed as a back-up solution to the multi-marker sensing platform. This work has resulted in twelve publications, five patents, and one submitted manuscripts at the time of submission.
ContributorsLin, Chi En (Author) / La Belle, Jeffrey T (Thesis advisor) / Caplan, Michael (Committee member) / Cook, Curtiss B (Committee member) / Stabenfeldt, Sarah (Committee member) / Spano, Mark (Committee member) / Arizona State University (Publisher)
Created2018