Digital Commons Network^™

Efficacy And Safety Of Mitomycin C As An Agent To Treat Corneal Scarring In Horses Using An In Vitro Model, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in-vitro model.

Procedure—An in-vitro model of equine corneal fibroblast (ECF) developed was used. The equine corneal fibroblast or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFβ1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion and MTT [(3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays …

"Transduction Efficiency Of Aav 2/6, 2/8 And 2/9 Vectors For Delivering Genes In Human Corneal Fibroblasts ", Ajay Sharma, Arkasubhra Ghosh, Eric T. Hansen, Jason M. Newman, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

In the present study, cellular tropism and relative transduction efficiency of AAV2/6, AAV2/8 and AAV2/9 vectors have been tested for the cornea using primary cultures of human corneal fibroblasts. The AAV6, AAV8 and AAV9 serotypes having AAV2 ITR plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Primary cultures of human corneal fibroblasts were exposed to AAV infectious particles at two different doses (1×105 and 2×105 MOI). Cytochemistry and enzyme assays were used to measure delivered transgene expression in samples collected at 4 and 30 hours after AAV infection …

Variable Number Of Tandem Repeat Polymorphisms (Vntrs) In The Acan Gene Associated With Pectus Excavatum, Michael W. Stacey, Serina Neumann, Ashley Dooley, Kara Segna, Robert Kelly, Donald Nuss, Anne Kuhn, Michael Goretsky, Annie Fecteau, Aimee Pastor, Virginia Proud

Bioelectrics Publications

No abstract provided.

Epigenetics: Blurring The Line Between Nature And Nurture, Elizabeth H. Rose

CMC Senior Theses

This long-standing nature versus nurture debate is cited in behavioral and physical expressions of disease dysfunctions, resiliencies, and recovery. Their purposes are noted both in scientific pursuits as well as literature. This discourse has been particularly intense in the fields of psychology, psychiatry, and biology where there is a long history of scientists’ attempts to disprove or discredit others’ intellectual and professional measures. Interestingly, recent advances in the neurosciences and genetic technologies have brought these fields closer together with a new focus – the interactional relationship between nature and nurture – epigenetics.

Vector Delivery Technique Affects Gene Transfer In The Cornea In Vivo, Rajiv R. Mohan, Ajay Sharma, Tyler C. Cebulko, Ashish Tandon

Pharmacy Faculty Articles and Research

Purpose: This study tested whether controlled drying of the cornea increases vector absorption in mouse and rabbit corneas in vivo and human cornea ex vivo, and studied the effects of corneal drying on gene transfer, structure and inflammatory reaction in the mouse cornea in vivo.

Methods: Female C57 black mice and New Zealand White rabbits were used for in vivo studies. Donor human corneas were used for ex vivo experiments. A hair dryer was used for drying the corneas after removing corneal epithelium by gentle scraping. The corneas received no, once, twice, thrice, or five times warm air for …

Is Oxidative Stress An Etiologic Factor In Idiopathic Male Infertility?, Ercan Yeni̇, Hali̇l Çi̇ftçi̇, Murat Savaş, Ayhan Veri̇t, Abdullah Taşkin

Turkish Journal of Medical Sciences

The total antioxidant capacity (TAC) and total peroxide (TP) levels in the blood and seminal plasma of idiopathic infertile patients were compared with those of fertile controls to determine the role of oxidative stress in the etiology of idiopathic male infertility. Material and methods: Thirty-two idiopathic infertile males and 30 healthy, married, age-matched control subjects were included in the study. TAC and TP levels were measured in the blood and seminal plasma, and sperm parameters were studied in both groups. Results: Sperm parameters were significantly impaired in the study group compared with the controls. Blood plasma TAC and TP levels …

The Effects Of Adding Methylprednisolone To Low-Potassium Dextran Solution On Preserved Ischemic Lungs, Ali̇ Yegi̇nsu, Makbule Ergi̇n, Hüseyi̇n Özyurt, Çi̇ğdem Elmas, Güleser Çağlar Göktaş

Turkish Journal of Medical Sciences

To investigate the effects of adding methylprednisolone to low-potassium dextran solution on cold-preserved ischemic lungs. Materials and methods: The study included 42 rat lung blocks that were divided into 7 groups (n = 6). Lung blocks were preserved in 40 mL of cold Perfadex solution, to which 5, 15, 30, 60, and 120 mg kg-1 (approximately 40, 120, 240, 480, and 960 mg L-1) of methylprednisolone were added. After a 24-h preservation period, the lungs were removed from the solution and examined. Results: As compared to the Perfadex only group, cell death and degeneration were significantly higher in the Perfadex …

Effect Of L-Carnitine On Diabetic Neuropathy And Ventricular Dispersion In Patients With Diabetes Mellitus, Hizir Ulvi̇, Recep Aygül, Recep Demi̇r

Turkish Journal of Medical Sciences

Diabetes is a common cause of polyneuropathy. Cardiac arrhythmias and markedly increased mortality rate have been demonstrated in patients with diabetic neuropathy and also demonstrated that abnormally prolonged QT dispersion interval (QTd) is associated with a higher risk of ventricular arrhythmias and sudden death. We investigated the efficacy and tolerability of L-carnitine (LC) in the treatment of diabetic neuropathy and ventricular dispersion, mainly by evaluating the effects of treatment on electrophysiological parameters. Materials and methods: We recruited 30 patients with type I or type II diabetes (mean age: 60 ± 9 years, range: 36-75; 18 males, 12 females) meeting clinical …

Effect Of Telmisartan On Vascular Endothelium In Hypertensive And Type 2 Diabetic Hypertensive Patients, Burcu Barutçuoğlu, Zuhal Parildar, M. Işil Mutaf, Di̇lek Özmen, Emi̇n Ali̇oğlu, Sara Habi̇f, Oya Bayindir

Turkish Journal of Medical Sciences

Hypertension and type 2 diabetes mellitus (DM) cause endothelial dysfunction and may result in cardiovascular disease. The aim of this study was to assess endothelial dysfunction in essential hypertensives, and normotensive and hypertensive type 2 diabetics and to evaluate the effect of telmisartan on endothelium in hypertensives. Materials and methods: Eighteen essential hypertensives (group 1), 16 type 2 diabetic hypertensives (group 2), 10 type 2 diabetic normotensives (group 3), and 10 control subjects (group 4) were included in this study. Groups 1 and 2 received 40 mg/day telmisartan for 12 weeks and were evaluated at the beginning and end. Groups …

Cervical Spine Movement During Intubation Using The Airtraq® And Direct Laryngoscopy, İ. Aydin Erden, A. Gülsün Pamuk, Şennur Uzun, Serdar Geyi̇k, Saruhan Çeki̇rge, Ülkü Aypar

Turkish Journal of Medical Sciences

To compare 2 endotracheal intubation techniques, namely direct laryngoscopy and Airtraq®, according to their influence on cervical spine movement and intubation time and success rates, complications, and hemodynamic responses. Materials and methods: Thirty three patients without cervical spine problems were enrolled in the study. Patients were randomized into direct laryngoscopy and Airtraq® groups. Assessment of movement of the cervical spine was made by taking 3 lateral cervical spine X-rays. First, when the cervical spine was in the neutral position, second during the greatest excursion of the cervical spine, and finally, after intubation. A reference line was drawn following the dorsal …

Endometrial Parameters In Ivf And Iui Administration On Elderly Women, Nafi̇ye Yilmaz, Sevtap Kiliç, Yusuf Madendağ, İlknur Madendağ, Ayli̇n Özgün, Gülnur Özakşi̇t, Sertaç Batioğlu

Turkish Journal of Medical Sciences

There are still controversial results about the role of endometrial thickness, pattern, volume, and vascularity in endometrial receptivity. We studied the predictivity of endometrial parameters in endometrial receptivity in over-aged, normogonadotrophic unexplained infertile women. Materials and methods: In this study, 150 women with an age range of 38-42 were included. The patients were divided into 4 groups: group 1 was applied recombinant FSH and intrauterine insemination, group 2 was applied clomiphene citrate and intrauterine insemination, group 3 was applied IVF, and group 4 (control group) was composed of fertile control patients. All patients in each study group had standard initiation …

Prevalence And Risk Factors Of Restless Leg Syndrome In A Single Hemodialysis Unit, Yasemi̇n Soyoral, Hayri̇ye Sayarlioğlu, Deni̇z Tuncel, Murat Şahi̇n, Ekrem Doğan, Reha Erkoç

Turkish Journal of Medical Sciences

Restless legs syndrome (RLS) is characterized by symptoms of spontaneous, continuous leg movements associated with unpleasant paresthesias. RLS is common among dialysis patients, with a reported incidence of 6.6 to 6.8 percent. This study is an attempt to find out the prevalence of RLS in our hemodialysis patients. We compared several demographic and clinical characteristics of RLS patients identified by the International Restless Legs Syndrome Study Group (IRLSSG) criteria with those of individuals without RLS. Materials and methods: We studied 76 patients with end-stage renal disease (ESRD) on hemodialysis (34 females and 42 males, mean age: 52.28 ± 18.13, range: …

Serum Total Sialic Acid, Lipid Peroxidation, And Glutathione Reductase Levels In Patients With Rheumatoid Arthritis, Surapaneni Krishna Mohan, Vishnu Priya

Turkish Journal of Medical Sciences

The changes in the serum sialic acid levels, total lipid peroxidation products (MDA), and glutathione reductase activity were estimated in patients with rheumatoid arthritis. Serum Sialic acid is known as a parameter of inflammation. This work was undertaken to assess the potential role of sialic acid as well as oxidative stress and antioxidant status in patients with rheumatoid arthritis. Materials and methods: The levels of these parameters in serum were studied in 52 subjects with rheumatoid arthritis (study subjects) and 52 age and sex matched healthy subjects as controls. Serum total sialic acid levels were determined using the assay method …

Serum Lipid And Lipoprotein Levels, Dyslipidemia Prevalence, And The Factors That Influence These Parameters In A Turkish Population Living In The Province Of Tokat*, İlhan Çeti̇n, Beytullah Yildirim, Şemsetti̇n Şahi̇n, İdri̇s Şahi̇n, İlker Eti̇kan

Turkish Journal of Medical Sciences

To determine the mean total LDL and HDL cholesterol values and trigliseride levels as well as dyslipidemia and the factors that influence the parameters mentioned above in the population living in the province of Tokat located in the Middle Black Sea (Northeastern) region of Turkey. Materials and methods: The study was performed in 58 rural and 12 urban residential areas. The 58 rural regions were selected using a cluster sampling method. A total of 1095 subjects were selected through a random sampling method. Results: The total serum cholesterol level was 186 ± 42 mg/dL with 33.7% of the participants having …

Is The Tanner–Whitehouse (Tw3) Method Sufficiently Reliable For Forensic Age Determination Of Turkish Children?*, Bora Büken, Alp Alper Şafak, Erhan Büken, Burhan Yazici, Zerri̇n Erkol, Ömer Utku Erzengi̇n

Turkish Journal of Medical Sciences

The purpose of our study was to determine the accuracy of Tanner-Whitehouse 3 (TW3-RUS) bone age (BA) assessments for forensic age estimations of Turkish children. Materials and methods: Plain radiographs of left hands and wrists of 324 children were evaluated. Mean chronological age (CA) was compared with mean bone age (BA) according to the TW3 atlas for each sex, and differences by age group were determined. Pearson correlation coefficients and cubic regression were used to determine the differences and model the relationships between mean BA and CA. Statistical analyses were carried out using R-project. Results: The difference between the mean …

Prevalence Of Helicobacter Pylori Infection In Healthcare Workers, Maliheh Metanat, Batool Sharifi-Mood, Shahrokh Izadi

Turkish Journal of Medical Sciences

Helicobacter pylori (H. pylori) is a major factor in inflammatory and malignant diseases of the gastrointestinal tract. The epidemiologic pattern of this infection varies among developed and developing countries, and is related to the general standards of living in each region. In view of the importance of this infection and its different prevalence in different regions of Iran, as well as its long-term complications, this study was conducted to investigate the prevalence of H. pylori infection and its contributing factors in Zahedan. Materials and methods: Ninety-seven healthcare workers without digestive symptoms or a history of H. pylori eradication were randomly …

Fiber Modification Of Adenoviral Vectors For Cancer Gene Therapy, Miho Murakami

All ETDs from UAB

Cancer still remains a major public health concern despite improvements in primary prevention, early detection and advanced treatments. Cancer gene therapy using human adenovirus serotype 5 (HAdV-5) as a vector has been explored as a new therapeutic approach. HAdV-5 infection is initiated by binding to the coxsackie virus and adenovirus receptor (CAR), its primary cellular receptor. However, the levels and patterns of expression of CAR vary greatly in clinical tumor tissue samples, and the expression lev-els tend to decrease as the tumors progress. The low level expression of CAR in target cancer cells diminishes the utility of HAdV-5 as a …

The Development Of Humoral And Cellular Responses To Plasmodium Falciparum Malaria In The Hypoendemic Peruvian Amazon And Potential Clinical Protection, Eva Helen Clark

All ETDs from UAB

Each year 300-500 million cases of Plasmodium falciparum malaria occur, leading to more than 1 million deaths. In high malaria transmission regions, development of immunity from severe infection requires 2-10 years of persistent parasitemia. This delay has been attributed to difficulties in the development of protective humoral responses. Indeed, anti-malarial antibody responses tend to be short-lived, and immunologic memory seems to be dysfunctional in high-transmission regions. In contrast, in the low-transmission Peruvian Amazon >60% of infections are asymptomatic, suggesting that clinical immunity occurs despite low parasite exposure. To analyze more precisely the naturally-acquired humoral responses to malarial antigens and their …

Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley

All ETDs from UAB

Breast cancer remains a major health concern, despite efforts to develop improved therapeutics. Chemoprevention is a promising strategy for reducing breast cancer-related morbidity and mortality. However, with the exception of the selective estrogen receptor modulators (SERMs), which have limited efficacy and severe toxicities, no drugs have been approved for breast cancer chemoprevention. Studies demonstrate that certain nonsteroidal anti-inflammatory drugs (NSAIDs) display promising chemopreventive efficacy. Unfortunately, the depletion of physiologically important prostaglandins due to inhibition of the cyclooxygenase (COX) enzymes results in potentially fatal toxicities, which exclude the use of NSAIDs and COX-2 selective inhibitors for chemoprevention. Ample data, however, suggest …

Usp14: A Link Between The Proteasome And Synaptic Function, Brandon John Walters

All ETDs from UAB

The ubiquitin proteasome system (UPS) is a coordinated process by which the cell can control protein distribution and abundance. Proteins are marked for turnover by the construction of a polyubiquitin chain on the protein substrate. Once engaged by the proteasome, the ubiquitin side-chain is disassembled by proteasomal deubiquitinating enzymes (DUBs), preventing entry of ubiquitin into the proteasome and recycling it for use in future reactions. One of the DUBs that resides on the proteasome is Ubiquitin Specific Protease 14 (Usp14), which is mutated in the ataxia (axJ) mice. This mutation results in pronounced physical deficits and, unexpectedly, a deficit in …

Small Molecule Inhibitors Of Acid Sensing Ion Channel-1, Yawar J. Qadri

All ETDs from UAB

Acid Sensing Ion Channel 1 is one of the many proteins in the Epithelial Sodium Channel/Degenerin family. The proteins in this family interact to form cation channels with unique biophysical properties and can all be inhibited by the small molecule amiloride. Their expression in many different cell types underlies their involvement in a large variety of physiological and pathophysiological processes. ASIC-1 containing channels, specifically, are an important therapeutic target for ischemic stroke, nociception, the invasiveness of glioblastoma cells, and many other processes including anxiety and memory formation. Of the members of the ENaC/Deg family, chicken ASIC-1 is the only protein …

A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison

All ETDs from UAB

protein (CRP) and smoking, controlling for waist circumference (WC) and race, we find

Investigation Of Residues Of The Vesicular Stomatitis Virus Nucleocapsid Protein That Affect Transcription And Rna Replication, Djamila Harouaka

All ETDs from UAB

The template for transcription and RNA replication for vesicular stomatitis virus (VSV) and other negative-strand RNA viruses is a ribonucleoprotein (RNP) complex consisting of the viral RNA genome and associated nucleocapsid (N) protein. The structure of the RNP-like complex of VSV showed that the RNA is sequestered between two lobes of the N protein, and adjacent N monomers are linked by an extensive network of interactions. Long-range interactions mediated by the N-terminal arm and C-terminal loop of the N protein stabilize the side-to-side contacts between adjacent N monomers, and are required for RNA encapsidation. It is unclear how the polymerase …

O-Glcnac Transferase Modulates Jnk1 And Foxo4 Transcription Factor To Resist Acute Oxidative Stress, Shiuh-Rong Ho

All ETDs from UAB

O-GlcNAcylation is an abundant and dynamic post-translational modification on serine and threonine residues of nuclear and cytoplasmic proteins. O-GlcNAc Transferase (OGT) and Nuclear Cytoplasmic O-GlcNAcase and Acetyltransferase (NCOAT) are the only two enzymes and major regulators in this process. In the past two decades, many studies have demonstrated its important modulation roles in nutrient sensing, protein turnover, cell cycle progression, transcription, translation as well as stress resistance. Among these biological functions, the understanding of O-GlcNAcylation dependent oxidative stress is relatively unknown. This study aims to examine the effects of O-GlcNAcylation on JNK1 and FOXO4 transcription factors under acute oxidative stress …

Role Of Epithelial Sodium Channel And Acid Sensing Ion Channel In Glioblastoma Multiforme, Niren Kapoor

All ETDs from UAB

Glioblastoma Multifrome is the most common and aggressive of the primary brain tumors. These tumors express multiple members of the Epithelial Sodium Channel (ENaC)/Degenerin (Deg) family, associated with a basally active amiloride sensitive cation current. We hypothesize that this glioma current is mediated by a hybrid channel composed of a mixture of Epithelial Sodium Channel (ENaC) and Acid Sensing Ion Channel (ASIC) subunits. To test this hypothesis we made dominant negative cDNAs for ASIC1, αENaC, and γENaC. D54-MG glioma cells transfected with the dominant negative constructs for ASIC1, αENaC, or γENaC showed reduced protein expression for each of the specific …

Mechanisms Of Major Outer Membrane Protein (Momp)-Vaccine Induced Protective Immunity Against Chlamydia Muridarum Genital Infection, Christina M. Farris

All ETDs from UAB

Urogenital infection with Chlamydia trachomatis is the most common bacterial sexually transmit-ted disease with an estimated 90 million new infections occurring each year worldwide. In women infection with C. trachomatis can result in serious complications including ectopic pregnancy, pelvic inflammatory disease and tubal factor infertility. Despite very effective antimicrobial chemotherapy, control of the infection will likely require an effective vaccine. We have assessed the protective effect of an outer membrane based vaccine using a murine model of chlamydial genital tract infection. Female mice were vaccinated with C. muridarum major outer membrane protein (MOMP) plus the immunostimulatory adjuvants CpG-1826 and Montanide …

The Mechanism Of Human Papillomavirus E7 Protein Mediated S-Phase Reentry In The Squamous Epithelium, Nicholas John Genovese

All ETDs from UAB

different heteroskedasticity consistent covariance matrix estimators (HCCM) under

Transcriptional Regulation Of The Human Heme Oxygenase-1 Via Chromatin Looping In Renal Cells, Junghyun Kim

All ETDs from UAB

Heme oxygenase-1 (HO-1) is a critical enzyme catalyzing the degradation of heme and generating carbon monoxide, iron, and biliverdin. In addition to heme degradation, HO-1 expression is known to protect against various cellular insults and disease states including acute kidney injury, atherosclerosis, vascular restenosis, and others. Human HO-1 gene expression is tightly regulated at the level of transcription. The main goal of this study is to explore the transcriptional regulation of the human HO-1 gene in renal epithelial cells. Chromosome Conformation Capture (3C) demonstrates that multiple regulatory regions within the HO-1 promoter and enhancer regions are physically interacting with each …

The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon

All ETDs from UAB

Glioma-associated oncogene homolog 1 (Gli1) is a well-known oncogene and a transcription factor that mediates several signaling pathways important for tumor progression, such as hedgehog, TGFß, Ras, and EGFR. Although Gli1 is known to play an important role in cancers of brain, skin, prostate, and the pancreas, the role of Gli1 in breast cancer was not previously well-defined. Therefore, this dissertation focuses on defining the role of Gli1 and the mechanism underlying Gli1-mediated transcription in breast cancer. Interestingly, the major findings of the dissertation clearly indicate that Gli1 promotes cell survival and is predictive of a poor outcome in Estrogen …

Role Of Heme Oxygenase-1 In Acute Kidney Injury, Subhashini Bolisetty

All ETDs from UAB

Acute kidney injury (AKI), defined as the rapid loss of kidney function, is often seen in the setting of multiple organ failure in critically ill patients. Lack of established therapeutic approaches to overcome AKI has lead to unacceptably high incidence of morbidity and mortality in these patients. The molecular mechanisms that lead to AKI often have oxidative stress as a common pathogenic event. The kidney responds by prompt induction of its own anti-oxidant machinery including the highly inducible, anti-inflammatory and anti-apoptotic gene-heme oxygenase-1 (HO-1). This microsomal enzyme degrades pro-oxidant heme, which is released from heme proteins. The cytoprotective properties of …