Chemicals and Drugs Commons^™

Templating Of Monomeric Alpha-Synuclein Results In Inflammation And Snpc Dopamine Neuron Death In A Genetic Mouse Model Of Induced Synucleinopathy, Matthew D. Byrne, Peyman Petramfar, Jae-Kyung Lee, Richard J. Smeyne

Department of Neuroscience Faculty Papers

While the etiology of most cases of Parkinson's disease (PD) are idiopathic, it has been estimated that 5-10% of PD arise from known genetic mutations. The first mutations described that leads to the development of an autosomal dominant form of PD are in the SNCA gene that codes for the protein alpha-synuclein (α-syn). α-syn is an abundant presynaptic protein that is natively disordered and whose function is still unclear. In PD, α-syn misfolds into multimeric b-pleated sheets that aggregate in neurons (Lewy Bodies/neurites) and spread throughout the neuraxis in a pattern that aligns with disease progression. Here, using IHC, HC, …

The Effect Of Tranexamic Acid On Blood Coagulation In Primary Total Hip Arthroplasty Using Rotational Thromboelastometry: A Randomized Controlled Trial, Uzung Yoon, David Beausang, Elia Elia, Marc Torjman, Jeffrey Mojica, James J. Purtill, David Nazarian, P. Maxwell Courtney, Yoogoo Kang

Department of Anesthesiology Faculty Papers

BACKGROUND: Tranexamic acid (TXA), is commonly administered prophylactically to reduce blood loss in patients undergoing total hip arthroplasty (THA). However, its effect has never been studied. We hypothesized that no difference exists in the degree of fibrinolysis and blood loss between patients receiving prophylactic TXA and placebo.

METHODS: This double-blinded randomized-controlled trial included 50 patients undergoing primary THA in 2021-2023. Clinicaltrials.gov (NCT03897621). Rotational-thromboelastometry (ROTEM) were performed to test blood coagulability using non citrated whole blood (NATEM) and blood treated with TXA (T-APTEM). The intervention group received TXA intravenously. The placebo group received 0.9% sodium chloride solution. The primary outcome measure …

Pembrolizumab And Lenvatinib In The Treatment Of Recurrent Ovarian Carcinoma: A Single Institution Experience, Helen Toma, Rebeca Kelly, Chelsea Katz, Hannah Hong, Hannah Diasti, David P Warshal, Lauren Krill

Kimmel Cancer Center Faculty Papers

BACKGROUND: Advanced stage ovarian carcinoma has a poor prognosis with recurrence rates of over 80%, 5-year survival of 36-45%, and limited response to standard therapy. Pembrolizumab and lenvatinib are FDA approved for treatment of microsatellite stable (MSS)/mismatch repair proficient (pMMR) endometrial and renal cell cancers. Early phase II studies have shown promising results in a variety of advanced solid tumors, including ovarian cancer. We report on the clinical outcome of recurrent MSS/pMMR ovarian cancer patients treated with this therapy.

METHODS: For this retrospective cohort study, patients with a diagnosis of ovarian cancer treated with pembrolizumab and lenvatinib from January 2020 …

Effect Of Margin Thickness And Cement Gap On The Fabrication And Fit Accuracy Of Additively Manufactured Crowns In Definitive Resins With Different Filler Content, Mustafa Borga Dönmez, Gülce Çakmak, Çiğdem Kahveci, Amir H. Nejat, Burak Yilmaz, Pinar Altinci

School of Dentistry Faculty Publications

PURPOSE: To evaluate how commercially available composite resins in varying filler content affect the fabrication and fit accuracy (trueness and precision) of additively manufactured (AM) definitive crowns with different margin thickness and cement gaps by comparing them to subtractively manufactured (SM) polymer-infiltrated ceramic crowns. MATERIALS AND METHODS: Two identical unprepared mandibular right first molars were prepared by an experienced prosthodontist for crowns with either 0.5 mm or 1.0 mm chamfer margins, verified using silicone indexes and a periodontal probe, and then digitized with an industrial-grade scanner. These scan files were used to design reference crowns with either 50-µm or 80-µm …

Nitric Oxide Does Not Improve Liver Mitochondrial Function 48 Hours After Cecal Ligation And Perforation In Experimental Sepsis, Pierre Eyenga, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

Nitric oxide (NO) has a dual effect on mitochondria. Incubating liver mitochondria with NO improves oxidative phosphorylation (OXPHOS) efficiency by decreasing state 4 respiration more than ATP synthesis and preventing mitochondrial permeability transition pore (mPTP) opening. We evaluated the effect of L-arginine (L-arg), an NO donor, on isolated liver mitochondrial respiration and mPTP in sepsis. Male mice were subjected to cecal ligation and perforation (CLP) with saline resuscitation or sham. After 8, 24, and 48 h, with and without L-arg, we measured isolated liver mitochondrial respiration and cytochrome c oxidase (COX) activity using polarographic methods and calcium retention capacity (CRC) …

Novel Piperidone And Bispidine Derivatives: A New Approach In Cancer Therapy, Lereen Khaled Youssry

Theses and Dissertations

Cancer remains the second leading cause of death worldwide. As a result, scientists have been trying to find novel therapeutic approaches that target specific metabolic pathways selective to tumor cells. In this study, two novel piperidone and bispidine derivatives, organic molecules that target polyamine metabolism, were synthesized, and their potential cytotoxic, antioxidant and anti-inflammatory effects were investigated. Polyamines are naturally occurring metabolites that were reported to be in excess at cancer cells and were accounted for tumor proliferation, invasion and metastasis. Accordingly, the novel piperidone and bispidine derivatives were expected to disrupt tumor growth and progression via up-regulation of key …

Prognostic Value Of Lipoprotein(A) For Cardiovascular Events After Lower Limb Revascularization In Diabetic Patients With Chronic Limb-Threatening Ischemia, Federico Biscetti, Maria Margherita Rando, Maria Anna Nicolazzi, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

BACKGROUND: Chronic limb-threatening ischemia (CLTI) presents a major clinical challenge in patients with Type 2 Diabetes Mellitus (T2DM), requiring lower extremity revascularization (LER) to mitigate adverse cardiovascular and limb outcomes. Lipoprotein(a) (Lp(a)) has been implicated in cardiovascular risk, but its role in patients with T2DM and CLTI undergoing revascularization remains unclear. Thus, this study aimed to investigate the prognostic value of Lp(a) levels in diabetic CLTI patients for major adverse cardiovascular events (MACE), major adverse limb events (MALE), or both after LER.

METHODS: In this prospective cohort study of 158 individuals with T2DM and CLTI undergoing LER, baseline clinical data …

Identification Of Serum Exosome Proteins In Systemic Sclerosis With Interstitial Lung Disease By Aptamer Proteomics, Sonsoles Piera-Velazquez, Simon T. Dillon, Xuesong Gu, Towia A. Libermann, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

OBJECTIVE: A major unmet need for Systemic Sclerosis (SSc) clinical management is the absence of well validated biomarkers for early diagnosis of SSc-associated interstitial lung disease (SSc-ILD). The objective of this study was to identify proteins contained within serum exosomes that may serve as potential biomarkers to differentiate patients with Diffuse SSc without SSc-ILD from patients with Diffuse SSc with SSc-ILD employing aptamer-based proteomics.

METHODS: Serum exosomes were isolated from two cohorts of patients. The first cohort included 15 patients with Diffuse SSc without SSc-ILD and 14 patients with Diffuse SSc with SSc-ILD and the second cohort included 12 patients …

First-In-Human Phase I Open-Label Study Of The Anti-Tim-3 Monoclonal Antibody Incagn02390 In Patients With Select Advanced Or Metastatic Solid Tumors, Martin E. Gutierrez, Shou Ching Tang, John D. Powderly, Ani S. Balmanoukian, Paul E. Hoyle, Zhiwan Dong, Lulu Cheng, Xiaohua Gong, John E. Janik, Nawel Bourayou, Omid Hamid

School of Medicine Faculty Publications

Background T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is an immune checkpoint receptor upregulated during anti-programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy for cancer. TIM-3 blockade may improve the antitumor activity of PD-1/PD-L1inhibition. This phase 1 study evaluated INCAGN02390, a novel, fully human Fc-engineered antibody against TIM-3. Methods INCAGN02390 was evaluated by dose escalation at 10-1600 mg infused in 14-day cycles (every 2 weeks [Q2W]) in pretreated patients with select advanced/metastatic immunogenic solid tumors. Objectives included evaluation of safety/tolerability and maximum tolerated dose (MTD) (primary), pharmacokinetics, preliminary antitumor activity, pharmacodynamics, and immunogenicity (secondary). Results Forty patients were enrolled and …

Modulation Of Redox-Sensitive Cardiac Ion Channels, Rawan S. Orfali, Al Hassan Gamal El-Din, Varnika Karthik, Elisanjer Lamis, Vanna Xiao, Alena Ramanishka, Abdullah Alwatban, Osama Alkhamees, Ali Alaseem, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate …

Systemic Carbonic Anhydrase Inhibitors In Common Ophthalmic Diseases: A Scoping Review From A Clinical Standpoint, Shahin Hallaj, Wesam S. Shalaby, Sapna Sinha, Jonathan S. Myers, Reza Razeghinejad

Wills Eye Hospital Papers

PURPOSE OF REVIEW: This paper provides a detailed overview of systemic carbonic anhydrase inhibitors (CAIs) and their application in managing ophthalmic conditions, including glaucoma, cystoid macular edema, and idiopathic intracranial hypertension. Despite their recognized clinical benefits, the potential for severe systemic adverse effects often discourages clinicians from prescribing these agents. By examining the pharmacology, pharmacokinetics, safety profile, and clinical indications of systemic CAIs, this review highlights strategies to mitigate treatment challenges, particularly in patients with comorbidities and complex medical backgrounds.

RECENT FINDINGS: New insights into the diverse roles and distribution of carbonic anhydrase (CA) isozymes have expanded our understanding of …

Kshv Vil6 Inhibits Functional B Cell Maturation During De Novo Infection, Wajd Zakir, Jessica M. Osborn, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Despite causative links to lymphoproliferative disorders, little is known about early events governing KSHV infection in B lymphocytes. IL-6 signaling plays a critical role in KSHV-mediated disease, with human IL-6 (hIL6) levels correlating with viral load and disease progression. This dynamic is even more complex due to the coexistence of hIL6 and KSHV-encoded viral IL-6 (vIL6) in these diseases. We hypothesize that hIL6 and vIL6 play critical, separable and collective roles in the early stages of KSHV infection in B cells. In this study, we use our ex vivo model of KSHV infection in human tonsil lymphocytes to investigate the …

An Integrative Genomics Approach For The Discovery Of Potential Clinically Actionable Diagnostic And Prognostic Biomarkers In Colorectal Cancer, Mark Fertel, Duaa Mohammad Alawad, Chindo Hicks

School of Graduate Studies Faculty Publications

Background: Despite remarkable progress in clinical management of patients and intensified screening, colorectal cancer remains the second most common cause of cancer-related death in the United States. The recent surge of next generation sequencing has enabled genomic analysis of colorectal cancer genomes. However, to date, there is little information about leveraging gene expression data and integrating it with somatic mutation information to discover potential biomarkers and therapeutic targets. Here, we integrated gene expression data with somatic mutation information to discover potential diagnostic and prognostic biomarkers and molecular drivers of colorectal cancer. Methods: We used publicly available gene expression and somatic …

Pharmacological Considerations For Healthcare Providers When Caring For Muslim Patients: A Practical Guide, Layla Abubshait, Nissa Tasnim, Taha Cangoz

Einstein Health Papers

Healthcare providers increasingly encounter Muslim patients with unique pharmacological considerations influenced by religious beliefs and practices. Islam, as the world's second-largest religion, includes specific guidelines affecting medication permissibility, particularly regarding alcohol and pork-derived ingredients. This educational guide examines the intersection of Islamic teachings with pharmacotherapy, providing examples of commonly prescribed medications containing alcohol or porcine-derived gelatin from our academic medical center's inpatient and outpatient formulary. We document alcohol content percentages in various medications and suggest possible alternatives as illustrative examples. Most importantly, we present a step-by-step practical framework for using National Drug Code (NDC) numbers and the DailyMed database, enabling …

New Onset Diabetic Retinopathy With Glucagon-Like Peptide-1 Receptor Agonists: A Case Report, Jennifer Ko, Yaseman Jahromi

Pharmacy Faculty Articles and Research

Background

Alfred Russel Wallace Notes 37. What About Wallace On Vaccination . . . ?, Charles H. Smith

Faculty/Staff Personal Papers

Best known for his natural history studies on evolution and biogeography, Alfred Russel Wallace (1823−1913) had a significant second career as a social critic. One of his most controversial stances was his position on (smallpox) vaccination. Anti-vaxxers of the present frequently bring up his name as a resource for their side, but the situation is not so easily reducible to that.

Reaction Control Mechanism In Deoxyuridine 5'-Triphosphate Nucleotidohydrolase, Aaron Delay

School of Biological Sciences: Dissertations, Theses, and Student Research

Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is an enzyme involved in the pyrimidine biosynthesis pathway, a key component of cellular DNA metabolism. It regulates intracellular uracil carrying triphosphate levels by hydrolyzing dUTP, thereby providing a substrate for thymidylate synthase (TS). The effective inhibition of dUTPase is expected to enhance TS-targeted chemotherapy by promoting thymine-less apoptosis.

Although the reaction mechanism of dUTPase has been studied, the human nuclear homotrimeric form remains complex, as all three subunits cooperatively form a single active site. As a result, the detailed molecular dynamics of its catalysis are still not fully understood. In this study, I investigated the …

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Systemic Exogenous Progestins With Or Without Estrogens Are Associated With Decreased Rates Of Venous Procedures For Varicose Veins, Paarth Jain, Adam M. Ostrovsky, Paul J Dimuzio, Luis H. Eraso, Michael Nooromid, Dawn Salvatore, Babak Abai

Department of Surgery Faculty Papers

OBJECTIVES: Risk factors for varicose veins (VVs) such as female sex, pregnancy, and obesity are high estrogen states, yet the role of systemic progestins with or without estrogens (SPEs) in VV management is not well characterized. This study investigates how SPE use affects rates of venous procedures for patients with VV.

METHODS: The TriNetX database was queried for subjects with International Classification of Diseases, 10th edition, diagnoses of asymptomatic VV, chronic venous insufficiency, and complicated VV (inflammation or ulceration). Patients were divided into a control cohort with no subsequent SPE use, a progestin-only cohort, and a combined estrogen-progestin (CEP) cohort. …

The Loss Of Opa1 Accelerates Intervertebral Disc Degeneration And Osteoarthritis In Aged Mice, Vedavathi Madhu, Miriam Hernandaz-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige Boneski, Hiromi Sesaki, Ruteja Barve, John Collins, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling and

Surface Keratin 1, A Tumor-Selective Peptide Target In Human Triple-Negative Breast Cancer, Shih-Jing Yao, Farideh Amirrad, Elmira Ziaei, Azam Saghaeidehkordi, Moom R. Roosan, Kiumars Shamloo, Ajay Sharma, Rachita K. Sumbria, Surya M. Nauli, Christopher G. Bunick, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Targeting drugs to cancer cells via overexpressed cell-surface receptors has emerged as an effective therapeutic strategy for several cancers. However, identifying cell-surface receptors that allow selective uptake of targeting ligands by cancer cells—while sparing normal cells—remains a challenge, especially for triple-negative breast cancer (TNBC), which lacks a well-defined receptor for targeted delivery. In this study, immunohistochemical (IHC) analysis revealed that human TNBC patient tissues have significantly higher levels of keratin 1 (K1) compared to normal breast tissues. Among TNBC tissues, grade 3 tumors showed significantly higher (threefold) K1 expression compared to grade 2 tumors. We analyzed human TNBC and normal …

Clearance Of Acute Bilateral Idiopathic Central Corneal Stromal Haze Likely Due To Topical Losartan, Karen Asfar, Jad F. Assaf, Jeremiah Gendy, Sadeer Hannush, Shady T. Awwad

Wills Eye Hospital Papers

To report the use of topical losartan as a potential treatment of acute bilateral central corneal stromal haze in a patient presenting with a syndrome resembling central toxic keratopathy (CTK).Patient and Clinical Findings:A 51-year-old man presented with clinically significant central corneal stromal haze bilaterally 6 days after a periorbital and facial contact dermatitis secondary to pesticide exposure. Uncorrected and corrected distance visual acuity (UDVA and CDVA) were 20/80 and 20/70 in the right eye, and 20/200- and 20/150+ in the left eye, respectively. After unsuccessful treatment with topical antivirals, antibiotics and corticosteroids, the patient started off-label treatment with topical losartan …

Ifi16 Mediates Deacetylation Of Kshv Chromatin Via Interaction With Nurd And Sin3a Co-Repressor Complexes, Anandita Ghosh, Bala Chandran, Arunava Roy

School of Medicine Faculty Publications

IFI16 is a well-characterized nuclear innate immune DNA sensor that detects foreign dsDNA, including herpesviral genomes, to activate the inflammasome and interferon pathways. Beyond immune signaling, IFI16 also functions as an antiviral restriction factor, promoting the silencing of invading viral genes through transcriptional and epigenetic mechanisms. We recently demonstrated another role of IFI16, in which it interacts with and recruits the class I histone deacetylases, HDAC1 and 2, to the KSHV latency protein LANA, modulating its acetylation and function. In this study, we asked whether these IFI16-HDAC1/2 interactions contribute to broader epigenetic regulation of the KSHV chromatin. Our findings reveal …

Engineering Cxcr2-Ligand-Based Fusion Proteins To Modulate Myeloid Cell Trafficking In Pancreatic Cancer, Benjamin N. Christopher

MUSC Theses and Dissertations

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates of all cancers, and limited treatment options exist. Immunotherapy is effective in some cancer types, but the immunosuppressive tumor microenvironment (TME) of PDAC is a barrier to effective immunotherapy. CXCR2+ myeloid-derived suppressor cells (MDSCs) are abundant in PDAC tumors in humans and in mouse models. MDSCs suppress effector cell function, making them attractive targets for restoring anti-tumor immunity. The studies outlined in this dissertation (1) link tumor-intrinsic oncogenic signaling to dysregulated myeloid activity in PDAC, (2) describe a rationally designed fusion protein and potent inhibitor of CXCR2+ myeloid …

Pharmaceutical Innovation Through Computational Drug Design: A Comprehensive Exploration, Manasa Chandramouli, Madhusudhan Heggadadevanakote Surendra

Makara Journal of Science

Chemical biology and computer-aided drug design (CADD) are crucial for identifying and optimizing lead molecules in drug development. Chemical biology is employed to determine the biological function of the target and the mode of action of a chemical modulator. At the same time, in CADD, promising candidate medications are identified based on the structure of the target or known bioactive ligands. Structure-based and ligand-based drug designs should be used in tandem, and their integration with experimental methods can considerably accelerate drug design. Furthermore, the use of CADD along with conventional experimental approaches increases the efficiency and accuracy of the discovery …

Utility Of Cenegermin For The Management Of Neurotrophic Keratopathy After Penetrating Keratoplasty, Alexandra R. Zaloga, Ashley Khalili, Brandon D. Ayres, Brenton D. Finklea, Beeran B. Meghpara, Christopher J. Rapuano, Zeba A. Syed

Wills Eye Hospital Papers

BACKGROUND: The study aimed to report the outcomes of patients treated with cenegermin 0.002% for neurotrophic keratopathy (NK) following penetrating keratoplasty (PK).

MATERIALS AND METHODS: This retrospective case series included patients evaluated at a tertiary care hospital who completed an 8-week course of cenegermin for NK within 12 months following PK. The primary outcome measure was NK stage, while secondary outcomes included complete epithelial healing, epithelial defect size, and best-corrected visual acuity (BCVA) at baseline and four time points during and following treatment. We also evaluated disease progression.

RESULTS: Fourteen eyes of 14 patients were included and demonstrated significant improvement …

Next-Generation Biomaterials For Load-Bearing Tissue Interfaces: Sensor-Integrated Scaffolds And Mechanoadaptive Constructs For Skeletal Regeneration, Rahul Kumar, Kyle Sporn, Pranay Prabhakar, Phani Paladugu, Akshay Khanna, Alex Ngo, Chirag Gowda, Ethan Waisberg, Ram Jagadeesan, Nasif Zaman, Alireza Tavakkoli

SKMC Student Presentations and Publications

Advancements in load-bearing tissue repair increasingly demand biomaterials that not only support structural integrity but also interact dynamically with the physiological environment. This review examines the latest progress in smart biomaterials designed for skeletal reconstruction, with emphasis on mechanoresponsive scaffolds, bioactive composites, and integrated microsensors for real-time monitoring. We explore material formulations that enhance osseointegration, resist micromotion-induced loosening, and modulate inflammatory responses at the bone-implant interface. Additionally, we assess novel fabrication methods-such as additive manufacturing and gradient-based material deposition-for tailoring stiffness, porosity, and degradation profiles to match host biomechanics. Special attention is given to sensor-augmented platforms capable of detecting mechanical …

Detecting Early Changes In Cartilage Collagen And Proteoglycans Distribution Gradients In Mice Harboring The R992c Collagen Ii Mutant Using 2d Correlation Infrared Spectroscopy, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Collagen II is a vital structural component in developing bones and mature cartilage. Muta- tions in this protein cause spondyloepiphyseal dysplasia, a disease characterized primarily by altered skeletal growth and manifesting with a range of phenotypes, from lethal to mild. This study examined transgenic mice harboring the R992C (p.R1124C) substitution in colla- gen II. Previous research demonstrated significant growth abnormalities and disorganized growth plate structure in these mice, and histological signs of osteoarthritic changes in the knee joints of 9-month-old mice with the R992C mutation. Our study focuses on detecting early structural changes in the articular cartilage that occur before …

Economic Value Of Intra-Articular Knee Oa Therapies: A U.S. Perspective, Vinod Dasa, Wilson Ngai, Kevin Steele, Ronald Preblick, Heather Watson, Kevin L. Ong

School of Medicine Faculty Publications

AIMS: This study compared the six-month medical/pharmacy costs and healthcare resource utilization (HCRU) for knee OA patients undergoing intra-articular therapy with different classes of hyaluronic acid (HA) (by molecular weight) or corticosteroid (ICS). MATERIALS AND METHODS: Patients across high molecular weight (HMW) HA, medium molecular weight (MMW) HA, low molecular weight (LMW) HA, and ICS therapy groups were matched from a U.S. claims database (Optum's de-identified Clinformatics Data Mart Database), with a final size of 6,234 patients per group. Adjusted six-month medical/prescription costs per patient per month (PPPM), and HCRU rates and costs, were determined. Secondary endpoints included complication rates …

Impact Of Stereochemical Replacement On Activity And Selectivity Of Membrane-Active Antibacterial And Antifungal Cyclic Peptides, Sandeep Lohan, Anastasia G. Konshina, Eman H. M. Mohammed, Naiera M. Helmy, Srishhti K. Jha, Rakesh Kumar Tiwari, Innokentiy Maslennikov, Roman G. Efremov, Keykavous Parang

Pharmacy Faculty Articles and Research

Herein, we report a library of 7-mer macrocyclic peptides designed by systematically replacing one, multiple, or all L-amino acids with their D-isomers in our previously identified hit compounds. Lead peptides, 15c and 16c, showed broad-spectrum activity against bacteria (Gram-positive minimum inhibitory activity (MIC 1.5–6.2 µg/mL and Gram-negative MIC 6.2–25 µg/mL) and fungi (MIC = 3.1–25 µg/mL). Additionally, peptides 15c and 16c showed rapid kill kinetics and biofilm degradation potential against both bacteria and fungi, while resistance development was not observed. The antimicrobial effect of these macrocyclic peptides was attributed to their membranolytic action, which was confirmed by calcein dye …