Medical Toxicology Commons^™

Subconjunctivally Implantable Hydrogels With Degradable And Thermoresponsive Properties For Sustained Release Of Insulin To The Retina., Gauri P. Misra, Ravi S.J. Singh, Tomas S. Aleman, Samuel G. Jacobson, Thomas W. Gardner, Tao L. Lowe

College of Pharmacy Faculty Papers

The objective of this work is to develop subconjunctivally implantable, biodegradable hydrogels for sustained release of intact insulin to the retina to prevent and treat retinal neurovascular degeneration such as diabetic retinopathy. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide (NIPAAm) monomer and a dextran macromer containing multiple hydrolytically degradable oligolactate-(2-hydroxyetheyl methacrylate) units (Dex-lactateHEMA) in 25:75 (v:v) ethanol:water mixture solvent. Insulin is loaded into the hydrogels during the synthesis process with loading efficiency up to 98%. The hydrogels can release biologically active insulin in vitro for at least one week and the release kinetics can be modulated by varying …

Airway Smooth Muscle As An Immunomodulatory Cell., Gautam Damera, Omar Tliba, Reynold A. Panettieri, Jr.

College of Pharmacy Faculty Papers

Although pivotal in regulating bronchomotor tone in asthma, airway smooth muscle (ASM) also modulates airway inflammation in asthma. ASM myocytes secrete or express a wide array of immunomodulatory mediators in response to extracellular stimuli, and in chronic severe asthma, increases in ASM mass may also render the airway irreversibly obstructed. Although the mechanisms by which ASM secretes cytokines and chemokines are shared with those regulating immune cells, there exist unique ASM signaling pathways that may provide novel therapeutic targets. This review provides an overview of our current understanding of the proliferative as well as synthetic properties of ASM.

Transcriptional Regulation Of Cytokine Function In Airway Smooth Muscle Cells., Deborah Clarke, Gautam Damera, Maria B. Sukkar, Omar Tliba

College of Pharmacy Faculty Papers

The immuno-modulatory properties of airway smooth muscle have become of increasing importance in our understanding of the mechanisms underlying chronic inflammation and structural remodeling of the airway wall in asthma and chronic obstructive pulmonary disease (COPD). ASM cells respond to many cytokines, growth factors and lipid mediators to produce a wide array of immuno-modulatory molecules which may in turn orchestrate and perpetuate the disease process in asthma and COPD. Despite numerous studies of the cellular effects of cytokines on cultured ASM, few have identified intracellular signaling pathways by which cytokines modulate or induce these cellular responses. In this review we …

Jnk1 Activation Predicts The Prognostic Outcome Of The Human Hepatocellular Carcinoma, Qingshan Chang, Jianguo Chen, Kevin J. Beezhold, Vince Castranova, Xianglin Shi, Fei Chen

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with an extremely poor prognosis. The classification of HCC based on the molecular signature is not well-established.

RESULTS: In the present study, we reported HCC signature genes based on the JNK1 activation status in 31 HCC specimens relative to the matched distal noncancerous liver tissue from 31 patients. The HCCs with high JNK1 (H-JNK1) and low JNK1 (L-JNK1) were sub-grouped. Two different signature gene sets for both H-JNK1 and L-JNK1 HCC were identified through gene expression profiling. A striking overlap of signature genes was observed between the H-JNK1 …

Is Chaalia/Pan Masala Harmful For Health? Practices And Knowledge Of Children Of Schools In Mahmoodabad And Chanesar Goth, Karachi, Sameena Shah, Riaz Qureshi, Iqbal Azam Syed

Department of Family Medicine

OBJECTIVE: To determine the practices and knowledge of harmful effects regarding use of Chaalia and Pan Masala in three schools of Mahmoodabad and Chanesar Goth, Jamshed Town, Karachi, Pakistan.

METHODS: To achieve the objective a cross-sectional design was used in three government schools of Mahmoodabad and Chanesar Goth, Jamshed Town, Karachi. Students of either gender drawn from these schools fulfilling the inclusion and exclusion criteria were interviewed using a pre-coded structured questionnaire. Along with demographic data, questions regarding frequency of Chaalia and Pan Masala use, practices of this habit in friends and family and place of procurement of these substances, …

Didox Modulates Reactive Oxygen Species Production And Inflammatory Events Induced By Lipopolysaccharide (Lps) And Aryl Hydrocarbon Receptor (Ahr) Ligands In Raw 264.7 Murine Macrophages., Thabe Matsebatlela

All Dissertations

Aberrant activation of macrophages during inflammation results in oxidative burst release of reactive oxygen and reactive nitrogen species (ROS/RNS) which are widely accepted to participate in pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. It is demonstrated here that Didox (3,4-Dihydroxybenzohydroxamic acid) possesses antioxidative and anti-inflammatory properties that can protect against inflammation and oxidative stress induced by lipopolysaccharide (LPS) and aryl hydrocarbon receptor (AHR) ligands (PCB126, E804, and IO) in Raw 264.7 murine macrophages. In brief, it is demonstrated here that Didox inhibits LPS-induced oxidative stress, …

Title: Student Readiness For Interprofessional Learning: Baseline And Midpoint In The Jefferson Health Mentor Program, Elena M. Umland, Cynthia A. Sanoski, Jon Veloski, Kevin Lyons, Carolyn Giordano, Christine Arenson, Molly Rose

College of Pharmacy Faculty Papers

Objectives: To measure pharmacy student readiness for interprofessional education (IPE) and compare the results to medical, nursing, occupational therapy (OT), and physical therapy (PT) student peers using the Readiness for Interprofessional Learning Scale (RIPLS).

Methods: First-year medical, nursing, OT, pharmacy, and PT students (n=544) participate in a 2-year longitudinal, interdisciplinary curriculum where they are assigned to a team including a Health Mentor (patient volunteer with chronic condition). Aims include understanding team roles and patient-centered care. All students complete the RIPLS at baseline and after completing years 1 and 2. RIPLS contains 3 subscales related to readiness for IPE: 1.)teamwork and …

An Evaluation Of Plastic Toys For Lead Contamination In Day Care Centers In The Las Vegas Valley, Joseph Alan Greenway

UNLV Theses, Dissertations, Professional Papers, and Capstones

The harmful effect of childhood exposure to environmental lead continues to be a major health concern. This study examined lead contamination within the plastic of children's toys. It was also hypothesized that the use of lead as a stabilizer would result in higher incidents of elevated lead (> 600 ppm) in polyvinyl chloride plastics (PVC) than non-PVC plastics. It was also hypothesized that, due to the use lead chromate, yellow toys would have higher incidents of elevated lead (> 600 ppm) than toys of other colors. Toy samples were limited to those found in day care centers in Las Vegas, …

Metallic Nickel Nano- And Fine Particles Induce Jb6 Cell Apoptosis Through A Caspase-8/Aif Mediated Cytochrome C-Independent Pathway, Jinshun Zhao, Linda Bowman, Xingdong Zhang, Xianglin Shi, Binghua Jiang, Vincent Castranova, Min Ding

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: Carcinogenicity of nickel compounds has been well documented. However, the carcinogenic effect of metallic nickel is still unclear. The present study investigates metallic nickel nano- and fine particle-induced apoptosis and the signal pathways involved in this process in JB6 cells. The data obtained from this study will be of benefit for elucidating the pathological and carcinogenic potential of metallic nickel particles.

RESULTS: Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we found that metallic nickel nanoparticles exhibited higher cytotoxicity than fine particles. Both metallic nickel nano- and fine particles induced JB6 cell apoptosis. Metallic nickel nanoparticles produced higher apoptotic induction than fine …

Dna Instability In Replicating Huntington's Disease Lymphoblasts, Milena Cannella, Vittorio Maglione, Tiziana Martino, Giuseppe Ragona, Luigi Frati, Guo-Min Li, Ferdinando Squitieri

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The expanded CAG repeat in the Huntington's disease (HD) gene may display tissue-specific variability (e.g. triplet mosaicism) in repeat length, the longest mutations involving mitotic (germ and glial cells) and postmitotic (neurons) cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths.

RESULTS: Although most lymphoblastoid cell lines …

Angiotensin Ii Induction Of Regional Effects In Murine Vasculature, Albert Phillip Owens Iii

University of Kentucky Doctoral Dissertations

The renin angiotensin system (RAS) exerts many diverse physiological functions throughout the body, mediated by its effector peptide, angiotensin II (AngII). AngII has been linked with a variety of different functions ranging from the initiation of severe vascular pathologies, such as atherosclerosis and abdominal aortic aneurysm (AAA), to mundane physiological processes of fluid homeostasis, vascular contraction, and regulation of blood pressure. To provide a potential link between these functions, an in-depth analysis of regional effects of AngII on aortic vasculature was performed.

The studies presented in this dissertation tested the overall hypothesis of whether regional changes exist in the vasculature …

Role Of Mel-18 In Regulating Protein Sumoylation And Identification Of A New Polymorphism In Bmi-1, Jie Zhang

University of Kentucky Doctoral Dissertations

Small ubiquitin-like modifier (SUMO) regulates numerous biological functions. In a previous study we found that sumoylation of HSF2 is involved in regulating HSF2 bookmarking function, but the mechanism that mediates this regulation was unknown. The results in my work support the intriguing hypothesis that polycomb protein, Mel-18, actually functions as an anti-SUMO E3 protein, interacting both with HSF2 and the SUMO E2 Ubc9, but acting to inhibit Ubc9 activity and thereby decrease sumoylation of the HSF2.

This study also suggested that Mel-18 negatively regulates the sumoylation of other cellular proteins, and we extend its targets to RanGAP1 protein. The results …

Role Of Oxidative Stress And T Cell Homing In The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jacqueline Perez-Rodriguez

University of Kentucky Doctoral Dissertations

Syngeneic graft-versus-host disease (SGVHD) is induced by reconstituting lethally irradiated mice with syngeneic BM cells followed by a 21 day treatment with the immunosuppressive agent cyclosporine A (CsA). Clinical symptoms of the disease appear 2-3 weeks following cessation of CsA therapy and disease-associated inflammation occurs primarily in the colon and liver.

The development of SGVHD is a complex process resulting from the cooperative interaction of multiple effector cell populations including NK cells, T cells and macrophages. T_H1 cytokines (IL-12, TNF-α, IFN- γ), produced by these effector cells, serve as inflammatory mediators contributing to the pathogenesis of SGVHD. The …

Saving Lives And Changing Family Histories: Appropriate Counseling Of Pregnant Women And Men And Women Of Reproductive Age, Concerning The Risk Of Radiation Exposures During And Before Pregnancy, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.