Skin and Connective Tissue Diseases Commons^™

Stevens-Johnson Syndrome From Combined Allopurinol And Angiotensin-Converting Enzyme Inhibitors: A Narrative Review, Isabella M. Fabian, Kirsten Maddox, Cameron Robicheaux, Rahib K. Islam, Ahmed Anwar, Bradley Dorius, Christopher L. Robinson, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Stevens-Johnson syndrome (SJS) is a severe and potentially debilitating skin reaction frequently related to medication use. Allopurinol and angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for prevalent health conditions worldwide, and their interaction associated with SJS warrants further investigation. A comprehensive literature search was performed to investigate cases as studies related to SJS occurring in patients with concomitant use of allopurinol and ACE inhibitors. We identified case reports and studies detailing hypersensitivity reactions, including SJS, attributed to a combination of allopurinol and ACE inhibitors. Despite the drug-drug interactions or lack thereof seen in patient populations, there is no definitive …

Characterization Of Epithelial Growth Factor Transcripts Identified In Crotalus Atrox Venom, Ivan Lopez, Ying Jia

Research Symposium

Epithelial Growth Factor (EGF) is the primary source in regeneration and stimulation of essential fibroblasts cells commonly found in epithelium. Studies have shown that snake venom components are becoming a growing factor in treating illnesses such as cancer, muscular dystrophy, chronic pain, blood pressure, blood clotting, etc. EGF in human cells contains a promising quaternary structure that can bind to snake venom metalloproteinases, proposing a means of activating biochemical responses through protein-protein interactions to regulate unwanted cellular functions. This supports promising research in achieving a greater understanding of regulation along cellular pathways through ligands, increasing the likelihood of targeting unwanted …

Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu

School of Medicine Faculty Publications

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …

Case Report: Nosocomial Digital Eczema From Surface Cleansing Bleach, James Espinosa, Umar Sannoh, Alan Lucerna

Rowan-Virtua Research Day

We report the case of a healthcare provider who developed hand eczema, predominantly on the first digit and thumb of the right hand, in association with contact with the surface of a desk and mouse pad at work. The eczema abated on days off and was exacerbated within hours of work. The diagnosis was made of hand eczema from surface cleaning bleach. It was noted that several other healthcare providers had developed similar symptoms. The patient's eczema was confirmed by a dermatologist and was successfully treated with topical triamcinolone and emollient cream to the affected areas. Prevention by adhesive strip …

Death Due To Drug Reaction With Eosinophilia And Systemic Symptoms (Dress) Syndrome: A Case Report, Samantha P. Sternad, Jane Pangburn, Chad Johnston, David Rowe

HCA Healthcare Journal of Medicine

Background

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening, multi-organ adverse drug reaction with an incidence of 1 in 1000 to 1 in 10 000 highrisk drug exposures.

Case Presentation

An elderly female presented to the hospital with progressive weakness and a diffuse erythematous macular rash covering most of her body that started 3 days prior. Over the next 3 days, the patient quickly deteriorated, developing disorientation with acute onset left-sided weakness, leukocytosis, thrombocytopenia, eosinophilia, liver and kidney failure, and hypoxia. Clinical and histological changes supported the diagnosis of DRESS syndrome caused by intravenous (IV) ampicillin …

Hereditary Angioedema: Diagnosis, Clinical Implications, And Pathophysiology, Evan S. Sinnathamby, Peter P. Issa, Logan Roberts, Haley Norwood, Kevin Malone, Harshitha Vemulapalli, Shahab Ahmadzadeh, Elyse M. Cornett, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a mutation in the C1 esterase inhibitor gene. HAE affects 1/50,000 people worldwide. Three main types of HAE exist: type I, type II, and type III. Type I is characterized by a deficiency in C1-INH. C1-INH is important in the coagulation complement, contact systems, and fibrinolysis. Most HAE cases are type I. Type I and II HAE result from a mutation in the SERPING1 gene, which encodes C1-INH. Formally known as type III HAE is typically an estrogen-dependent or hereditary angioedema with normal C1-INH activity. Current guidelines now recommend subdividing …

Production And Characterization Of A Phage Endolysin With Putative Antimicrobial Activity Against Cutibacterium Acnes, Kathryn M. Collins

EWU Masters Thesis Collection

Acne vulgaris (acne) is the eighth most common skin disorder worldwide. Because of the heterogeneous pathology of acne and the increasing antibiotic resistance of the causal agent (Cutibacterium acnes), novel therapeutics need to be developed to treat acne. One option is endolysins, highly conserved enzymes from bacteriophages that disrupt the bacterial cell wall. Endolysins retain bactericidal and bacteriostatic activity when applied to bacteria in vitro and are safe for topical application. We hypothesize that the endolysin (ENDL) from the P100.1 C. acnes bacteriophage will exhibit bacteriostatic activity against C. acnes in vitro. This study aims to bioinformatically characterize the P100.1 …

Innovative Therapeutic Approach To Chemical Burns Produced By Vesicants; An Experimental Study, Cristina Anca Secara, Otilia Liudmila Cinteza, Diana Popescu, Claudia Valentina Popa, Camelia Andreea Hirjeu, Oana Cristina Voinea, Luiza Georgia Serbanescu, Andreea Marilena Pauna, Mihail Tudosie

Journal of Mind and Medical Sciences

Vesicants are compounds that cause severe toxic effects on various tissues. Such chemical action causes tissue necrosis, with clinical expression of skin lesions with a burning character and characteristic blisters. Clinical toxic effects of cutaneous vesicles are correlated with the absorbed dose and exposure time. The goals of the study are to evaluate in vitro the skin toxicity produced by the vesicant chemical compound 2-chloroethyl-ethyl sulfide (CEES), to develop a complex antidote formula, and to optimize the therapeutic efficacy by inclusion in controlled release systems. The experimental protocol aims at the in vitro evaluation of the cytotoxicity of the vesicant …

Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak

Undergraduate Student Research Internships Conference

Fibrosis is a progressive and typically irreversible disease process characterized by the excessive deposition of collagen in organs and in tissues of the musculoskeletal (MSK) system^1,2. This process, which causes loss of organ and tissue function, can be initiated by micro-traumas³, an excessive and/or prolonged immune response¹, the activation and proliferation of fibrosis-inducing progenitor cells⁴, and a pro-fibrotic extra-cellular microenvironment⁵. In parallel with the events that initiate fibrosis, genetic or environmental influences may cause cells and tissues to become predisposed to fibrosis development prior to initiation. This suggests that these …

A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang

Pharmacy Faculty Articles and Research

Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa …

The Role Of Age Ligand And Rap1a In Myofibroblast Signaling Cascade In Type 2 Diabetes Mellitus-Induced Cardiomyopathic Conditions, Camilla Puglia

Honors Theses

Diabetes is one of the leading causes of death in the United States, taking more than 90,000 lives annually. Type 2 diabetes mellitus-induced cardiac fibrosis is a common condition seen in diabetic patients. The AGE/RAGE signaling cascade has been strongly associated with this supposed cardiac fibrosis along with hyperactive myofibroblasts which excessively remodel extracellular matrix tissue, leading to damaged and enlarged heart muscle tissue. In diabetic patients, Advanced Glycation End Products (AGEs) are produced in abundance and accumulate in the extracellular matrix of heart tissue. To investigate the role of of the AGE ligand on fibroblast behavior, increasing amounts of …

Migratory Dermatographic Urticaria Following Covid-19 Vaccine Booster In Young Adult Male, Richard A. Maiella, Kelly Staples, Ashok Veldanda

Rowan-Virtua Research Day

With the recent approval of booster vaccinations in the United States for adults who already received their primary vaccinations, millions of adults have been administered the Pfizer-BioNTech or Moderna booster vaccines.

Adverse events related to these vaccines continue to be reported and are majority self-limited. In this case report, we present a young male who acquired chronic, migratory dermatographic urticaria two weeks after administration of the Moderna mRNA-1273 COVID-19 vaccine booster.

Emerging Drug Targets And New Drugs In The Treatment Of Psoriatic Arthritis, Carmen Lariccia, Natalie Lennartz, Jessica Lewe, Jeffery Allison

Pharmacy and Wellness Review

Psoriasis is an autoimmune disease characterized by painful skin lesions. When joints and connective tissue also become involved, the condition is referred to as psoriatic arthritis (PsA). Current treatments for moderate to severe PsA include therapies used to treat rheumatoid arthritis (RA) despite differences in disease presentation which includes factors such as peripheral disease, sacroiliitis, stiffness, presence of rheumatoid factor and psoriasis. Treatment out-comes for PsA are measured by the American College of Rheumatology (ACR) Responder Index (ACR20) and the Dis-ease Activity Score for 28 joints (DAS28). First-line treatment includes disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, sulfasalazine or leflunomide …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Cyclosporine Shows Benefit As Compared To Methotrexate For Treatment Of Pediatric Atopic Dermatitis Refractory To Topical Medications When Rapidity Of Clinical Response Is Of Key Importance To The Patient, Connor R. Buechler, Steven Daveluy Md

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising El-Khalawany MA, Hassan H, Shaaban D, Ghonaim N, Eassa B. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. European Journal of Pediatrics. 2012;172(3):351-356. https://doi.org10.1007/s00431-012-1893-3 for a pediatric patient with severe atopic dermatitis.

Hailey-Hailey Disease Successfully Treated With Low-Dose Naltrexone, John Moesch, Richard Miller

West Florida Division Virtual Research Day 2020

Hailey-Hailey disease (HHD) is an uncommon autosomal dominant disorder resulting from a mutation in the ATP2C1 gene resulting in dysfunction of the Golgi apparatus calcium-associated ATPase, thus interfering with intercellular calcium signaling.

HHD presents clinically as flaccid blisters and erosions in intertriginous areas, especially the axillae and groin.

The major histologic finding is acantholysis throughout the spinous layer of the epidermis, commonly referred to as a “dilapidated brick wall” appearance.

The initial lesions and associated symptoms usually develop during the second or third decade of life.

Complications of HHD include infections (bacterial, fungal, and viral), and malignant transformation (cutaneous squamous …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

Does Enhancing Epidermal Barrier Function With Moisturizing Topical Products Improve Acne Vulgaris In Adult Patients Compared To Non-Moisturizing Products Or Non-Intervention?, Aziza Jadallah

Capstone Showcase

Introduction: Acne is a common skin disorder with multifactorial causes that can persist beyond adolescence or appear for the first time in adulthood. Treatments of varying potency exist, ranging from over-the-counter face washes and creams to prescription topical and oral treatments. Current treatment guidelines target sebum production, exfoliation of excess skin cells, and the bacteria Propionibacterium acnes. Research as early as 1995 suggests dysfunctions of the skin barrier, such as abnormal ceramide levels and increased water loss, play a role in the pathophysiology of acne and are not addressed by current treatments. This review analyzes the role of moisturizing …

Design And Biological Evaluation Of Colchicine-Cd44-Targeted Peptide Conjugate In An In Vitro Model Of Crystal Induced Inflammation, Khalid A. Zoghebi, Emira Bousoik, Keykavous Parang, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is an inflammatory arthritis due to the joint deposition of monosodium urate (MSU) crystals. Phagocytosis of MSU crystals by tissue macrophages results in the generation of reactive oxygen species (ROS) and production of inflammatory cytokines and chemokines. Colchicine use in gout is limited by severe toxicity. CD44 is a transmembrane glycoprotein that is highly expressed in tissue macrophages and may be involved in gout pathogenesis. The P6 peptide is a 20-amino acid residue peptide that binds to CD44. We hypothesized that the conjugation of colchicine to the P6 peptide would reduce its off-target cytotoxicity while preserving its anti-inflammatory effect. …

Biological Pathway Involvement In Melanoma Heterogeneity And Drug-Induced Resistance, Sarah V. Pack

STAR Program Research Presentations

Tumors develop resistance to numerous drug therapies, and this remains a major obstacle in treating many types of non-surgical cancers. Melanoma provides a good model system for studying drug resistance in cancer due to its high propensity to incur resistance after a significant initial response to a drug. Genes that are highly expressed in melanoma cancer cells have been studied, but in order to further understand the collective function of these highly expressed genes we must analyze gene sets, or pathways. A single gene’s function is rarely independent of other genes, and pathway analysis takes this into account.

Our objective …

Towards Stable Electrochemical Sensing For Wearable Wound Monitoring, Sohini Roychoudhury

FIU Electronic Theses and Dissertations

Wearable biosensing has the tremendous advantage of providing point-of-care diagnosis and convenient therapy. In this research, methods to stabilize the electrochemical sensing response from detection of target biomolecules, Uric Acid (UA) and Xanthine, closely linked to wound healing, have been investigated. Different kinds of materials have been explored to address such detection from a wearable, healing platform. Electrochemical sensing modalities have been implemented in the detection of purine metabolites, UA and Xanthine, in the physiologically relevant ranges of the respective biomarkers. A correlation can be drawn between the concentrations of these bio-analytes and wound severity, thus offering probable quantitative insights …

In Vitro And Ex-Vivo Evaluation Of Topical Formulations Designed To Minimize Transdermal Absorption Of Vitamin K1, Ramina Nabiee, Barent Dubois, Laura Green, Ajay Sharma, Siu Fun Wong, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Topical application of Vitamin K1 has been demonstrated to effectively treat papulopustular skin rash, a serious and frequently encountered side effect of Epidermal Growth Factor Inhibitors (EGFRIs). Systemic absorption of vitamin K1 from skin and the resultant consequence of antagonizing EGFRIs anticancer effects jeopardizes the clinical acceptability of this rather effective treatment. The purpose of the present study was to rationally formulate and evaluate the release rate and transdermal absorption of a wide range of Vitamin K1 dermal preparations with a variety of physiochemical properties. A library of 33 formulations with were compounded and tested for Vitamin K1 permeation using …

Infections Not Fought: Antibiotic Resistance In Underserved Communities, Derek Lillestolen

Senior Honors Theses

In 1928, the profound effects of penicillin were discovered and antibiotic treatments became extremely popular. Broad-spectrum antibiotics, like tetracyclines, have been since branded as cure-all prescriptions and used profusely in the Western World and abroad. Due to ignorance of specific biochemical mechanisms and the misuse of antibiotics these drugs inadvertently allowed the rise in prevalence of antibiotic resistant strains of certain bacteria as the century progressed. Now, the specific genetic causes and mechanisms of antibiotic resistance are being understood, but the fight against antimicrobial resistance is far from over. In the United States, thousands of fatalities are caused annually by …

Stinging Nettle: The Bad, The Good, The Unknown, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Stinging nettle (Urtica dioica) is native to most of the United States. It has a characteristic description and distribution in the environment. Physical contact with numerous tiny needlelike hairs present on leaves and stems of this plant may result in a contact urticarial dermatitis due to chemical and mechanical irritation triggered by skin penetration of the hairs. The manifestations are self-limited in humans and may be treated by washing the skin, topical preparations and oral antihistamines. Explanation of the natural history of these encounters to the patient is helpful in reducing the sometimes significant anxiety. Preparations and extracts of stinging …

Stinging Nettle: The Bad, The Good, The Unknown, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Stinging nettle (Urtica dioica) is native to most of the United States. It has a characteristic description and distribution in the environment. Physical contact with numerous tiny needlelike hairs present on leaves and stems of this plant may result in a contact urticarial dermatitis due to chemical and mechanical irritation triggered by skin penetration of the hairs. The manifestations are self-limited in humans and may be treated by washing the skin, topical preparations and oral antihistamines. Explanation of the natural history of these encounters to the patient is helpful in reducing the sometimes significant anxiety. Preparations and extracts …

Detection Of Igg4-Specific Autoantibodies In Rheumatoid Arthritis Serum Samples, Azra Borogovac, Youmna Lahoud, Janice Weaver, Sheldon M. Cooper, Mercedes Rincon, Jonathan Kay, Ellen M. Gravallese

Ellen M. Gravallese

Background: Rheumatoid arthritis (RA) is a chronic multi-system autoimmune disease characterized by inflammatory synovitis. Autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) have been implicated in the pathogenesis of RA, and are currently important criteria for diagnosis within the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.1 Yet, many patients diagnosed with RA do not have measurable circulating ACPA or RF which may result in delayed diagnosis and treatment. After IgG1, IgG4 is the second most predominant isotype among ACPA and RF; however it is not detected in currently available diagnostic assays. Recent …

Detection Of Igg4-Specific Autoantibodies In Rheumatoid Arthritis Serum Samples, Azra Borogovac, Youmna Lahoud, Janice Weaver, Sheldon M. Cooper, Mercedes Rincon, Jonathan Kay, Ellen M. Gravallese

Jonathan Kay

Background: Rheumatoid arthritis (RA) is a chronic multi-system autoimmune disease characterized by inflammatory synovitis. Autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) have been implicated in the pathogenesis of RA, and are currently important criteria for diagnosis within the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.1 Yet, many patients diagnosed with RA do not have measurable circulating ACPA or RF which may result in delayed diagnosis and treatment. After IgG1, IgG4 is the second most predominant isotype among ACPA and RF; however it is not detected in currently available diagnostic assays. Recent …

Regulated Splicing Of The Alpha6 Integrin Cytoplasmic Domain Determines The Fate Of Breast Cancer Stem Cells, Hira Lal Goel, Tatiana Gritsko, Bryan Pursell, Cheng Chang, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Leslie M. Shaw, Arthur M. Mercurio

Arthur M. Mercurio

Although the alpha6beta1 integrin has been implicated in the function of breast and other cancer stem cells (CSCs), little is known about its regulation and relationship to mechanisms involved in the genesis of CSCs. We report that a CD44(high)/CD24(low) population, enriched for CSCs, is comprised of distinct epithelial and mesenchymal populations that differ in expression of the two alpha6 cytoplasmic domain splice variants: alpha6A and alpha6B. alpha6Bbeta1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by alpha6A integrins. The generation of alpha6Bbeta1 is tightly controlled and occurs as a consequence of …

The Mechanical Behavior Of Mutant K14-R125p Keratin Bundles And Networks In Neb-1 Keratinocytes, Daniel R. Beriault, Oualid Haddad, John V. Mccuaig, Zachary J. Robinson, David Russell, E. Birgitte Lane, Douglas S. Fudge

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Epidermolysis bullosa simplex (EBS) is an inherited skin-blistering disease that is caused by dominant mutations in the genes for keratin K5 or K14 proteins. While the link between keratin mutations and keratinocyte fragility in EBS patients is clear, the exact biophysical mechanisms underlying cell fragility are not known. In this study, we tested the hypotheses that mutant K14-R125P filaments and/or networks in human keratinocytes are mechanically defective in their response to large-scale deformations. We found that mutant filaments and networks exhibit no obvious defects when subjected to large uniaxial strains and have no negative effects on the ability of human …

Is Ceftobiprole A Safe And Effective Treatment For Skin And Skin Structure Infections?, Laura Thompson

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not ceftobiprole is a safe and effective treatment for complicated skin and skin structure infections

STUDY DESIGN: Review of all English language primary randomized controlled trials from 1996-2010

DATA SOURCES: Three randomized controlled trials were found using Pubmed and Cochrane databases

OUTCOMES MEASURES: Skin or skin-structure infection cure with ceftobiprole intervention and adverse effects of this new pharmaceutical. Cure or failure to cure skin infection was determined based on both clinical and microbiological assessment. Adverse events were measured based on patient reports, clinician reports, labs, and vital sign …