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A Combination Of Generated Hydrogen Sulfide And Nitric Oxide Activity Has A Potentiated Protectant Effect Against Cisplatin Induced Nephrotoxicity, Faria Khurshid, Javeid Iqbal, Fiaz Ud Din Ahmad, Arslan Hussain Lodhi, Abdul Malik, Suhail Akhtar, Azmat Ali Khan, Marvi Imam Bux, Mohammed Younis

Biomedical Sciences Faculty Publications

Aim: Hydrogen sulfide and nitricoxide possess cytoprotective activity and in vivo, they are generated from exogenous sodium hydrosulfide and L-arginine respectively. Cisplatin is a major chemotherapeutic agent used to treat cancer and has a high incidence of nephrotoxicity as a side effect. The study aim was to explore the effects of NaHS and L-arginine or their combination on cisplatin induced nephrotoxicity in rats. Methods: Wistar Kyoto rats were given a single intraperitoneal dose of cisplatin (5 mg/kg) followed either by NaHS (56 μmol/kg, i. p.), L-arginine (1.25 g/L in drinking water) or their combination daily for 28-days. Post-mortem plasma, urine …

Nur77 Mitigates Endothelial Dysfunction Through Activation Of Both Nitric Oxide Production And Anti-Oxidant Pathways, Lin Lu, Soohwa Jang, Jiaqi Zhu, Qing Qin, Lijun Sun, Jianxin Sun

Center for Translational Medicine Faculty Papers

BACKGROUND: Nur77 belongs to the member of orphan nuclear receptor 4A family that plays critical roles in maintaining vascular homeostasis. This study aims to determine whether Nur77 plays a role in attenuating vascular dysfunction, and if so, to determine the molecular mechanisms involved.

METHODS: Both Nur77 knockout (Nur77 KO) and Nur77 endothelial specific transgenic mice (Nur77-Tg) were employed to examine the functional significance of Nur77 in vascular endothelium in vivo. Endothelium-dependent vasodilatation to acetylcholine (Ach) and reactive oxygen species (ROS) production was determined under inflammatory and high glucose conditions. Expression of genes was determined by real-time PCR and western blot …

Inhaled Epoprostenol Compared With Nitric Oxide For Right Ventricular Support After Major Cardiac Surgery, Kamrouz Ghadimi, Jhaymie L. Cappiello, Mary Cooter Wright, Jerrold H. Levy, Benjamin S. Bryner, Adam D. Devore, Jacob N. Schroder, Chetan B. Patel, Sudarshan Rajagopal, Svati H. Shah, Carmelo A. Milano, Inspire-Flo Investigators

Respiratory Therapy Faculty Publications and Presentations

Background: Right ventricular failure (RVF) is a leading driver of morbidity and death after major cardiac surgery for advanced heart failure, including orthotopic heart transplantation and left ventricular assist device implantation. Inhaled pulmonary-selective vasodilators, such as inhaled epoprostenol (iEPO) and nitric oxide (iNO), are essential therapeutics for the prevention and medical management of postoperative RVF. However, there is limited evidence from clinical trials to guide agent selection despite the significant cost considerations of iNO therapy.

Methods: In this double-blind trial, participants were stratified by assigned surgery and key preoperative prognostic features, then randomized to continuously receive either iEPO or iNO …

Hepatopulmonary Syndrome In A 22 Year Old Gentleman With Liver Cirrhosis, Blesset Alexander, Joseph Caporusso, Priyasha Suri

Research Symposium

Background: Hepatopulmonary syndrome is a severe complication of end-stage liver disease characterized by triad of liver disease, intrapulmonary vascular dilatation, and arterial hypoxemia. Although the pathogenesis is not completely understood, pulmonary vascular dilatation occurs due to imbalance between vasodilators and vasoconstrictors. Liver injury is thought to increase endothelin production and cause bacterial translocation, causing increased nitric oxide production, causing vasodilation of pulmonary vasculature. History and physical examination are important in leading the physician to the correct diagnosis as the majority of these patients present with non-specific clinical manifestations and imaging. Identification of specific physical exam findings is important in not …

Argininosuccinate Lyase Deficiency Causes Blood-Brain Barrier Disruption Via Nitric Oxide-Mediated Dysregulation Of Claudin Expression, Jordan Kho, Urszula Polak, Ming-Ming Jiang, John D Odom, Jill V Hunter, Saima M Ali, Lindsay C Burrage, Sandesh Cs Nagamani, Robia G Pautler, Hannah P Thompson, Akihiko Urayama, Zixue Jin, Brendan Lee

Journal Articles

Nitric oxide (NO) is a critical signaling molecule that has been implicated in the pathogenesis of neurocognitive diseases. Both excessive and insufficient NO production have been linked to pathology. Previously, we have shown that argininosuccinate lyase deficiency (ASLD) is a novel model system to investigate cell-autonomous, nitric oxide synthase-dependent NO deficiency. Humans with ASLD are at increased risk for developing hyperammonemia due to a block in ureagenesis. However, natural history studies have shown that individuals with ASLD have multisystem disease including neurocognitive deficits that can be independent of ammonia. Here, using ASLD as a model of NO deficiency, we investigated …

Diagnostic Role Of Fractional Exhaled Nitric Oxide In Pediatric Eosinophilic Esophagitis, Relationship With Gastric And Duodenal Eosinophils., Panamdeep Kaur, Rachel Chevalier, Craig A. Friesen, Jamie Ryan, Ashley K. Sherman, Stephanie Page

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Eosinophilic esophagitis (EoE) is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies. A non-invasive and cost-effective alternative for management of EoE is being researched. Previous studies assessing utility of fractional exhaled nitric oxide (FeNO) in EoE were low powered. None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.

AIM: To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.

METHODS: Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study. Patients on steroids …

Glucose 6-P Dehydrogenase Overexpression Improves Aging-Induced Endothelial Dysfunction In Aorta From Mice: Role Of Arginase Ii, Eva Serna, Maria D Mauricio, Teresa San-Miguel, Sol Guerra-Ojeda, David Verdú, Alicia Valls, Coralie Arc-Chagnaud, Adrián De La Rosa, José Viña

Journal Articles

The increase of vascular arginase activity during aging causes endothelial dysfunction. This enzyme competes with the endothelial nitric oxide synthase (eNOS) for L-arginine substrate. Our hypothesis is that glucose 6-P dehydrogenase (G6PD) overexpression could improve the endothelial function modulating the arginase pathway in aorta from mice. For this study, three groups of male mice were used: young wild type (WT) (6-9 months), old WT (21-22 months) and old G6PD-Tg (21-22 months) mice. Vascular reactivity results showed a reduced acetylcholine-dependent relaxation in the old WT but not old G6PD-Tg group. Endothelial dysfunction was reverted by nor-NOHA, an arginase inhibitor. Mice overexpressing …

Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer

School of Medicine Faculty Publications

BACKGROUND: Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a “2-hit” murine model. METHODS AND RESULTS: Nine-week-old male C57BL/6 N mice (n=15 per group) were treated concurrently with high-fat …

Inducible Nitric Oxide Synthase Embedded In Alginate/Polyethyleneimine Hydrogel As A New Platform To Explore No-Driven Modulation Of Biological Function, Shaimaa Maher, Lauren A. Smith, Celine A. El-Khoury, Haitham F. Kalil, Khalid Sossey-Alaoui, Mekki Bayachou

Chemistry Faculty Publications

Nitric oxide (NO), a small free radical molecule, turned out to be pervasive in biology and was shown to have a substantial influence on a range of biological activities, including cell growth and apoptosis. This molecule is involved in signaling and affects a number of physiologic functions. In recent decades, several processes related to cancer, such as angiogenesis, programmed cell death, infiltration, cell cycle progression, and metastasis, have been linked with nitric oxide. In addition, other parallel work showed that NO also has the potential to operate as an anti-cancer agent. As a result, it has gained attention in cancer-related …

Dietary Nitrate Supplementation Enhances Performance And Speeds Muscle Deoxyhaemoglobin Kinetics During An End-Sprint After Prolonged Moderate-Intensity Exercise, Samantha N. Rowland, Mariasole Da Boit, Rachel Tan, George P. Robinson, Emma O’Donnell, Lewis J. James, Stephen J. Bailey

All Faculty Open Access Publications

Short-term dietary nitrate (NO3−) supplementation has the potential to enhance performance during submaximal endurance, and short-duration, maximal-intensity exercise. However, it has yet to be determined whether NO3− supplementation before and during submaximal endurance exercise can improve performance during a short-duration, maximal-intensity end-sprint. In a randomised, double-blind, crossover study, 9 recreationally active men ingested NO3−-rich (BR: 8 mmol NO3−/day) and NO3−-depleted (PL: 0.75 mmol NO3−/day) beetroot powder for 7 days. On day 7, participants completed 2 h of moderate-intensity cycling, which immediately transitioned into a 60 s maximal-intensity end-sprint, with supplements ingested 2 h before and 1 h into the moderate-intensity …

Dietary Nitrate Intake In Relation To The Risk Of Dementia And Imaging Markers Of Vascular Brain Health: A Population-Based Study, Tosca O.E. De Crom, Lauren Blekkenhorst, Meike W. Vernooij, M. Kamran Ikram, Trudy Voortman, M. Arfan Ikram

Research outputs 2022 to 2026

Background

Nitric oxide is a free radical that can be produced from dietary nitrate and positively affects cardiovascular health. With cardiovascular health playing an important role in the etiology of dementia, we hypothesized a link between dietary nitrate intake and the risk of dementia.

Objectives

This study aimed to find the association of total, vegetable, and nonvegetable dietary nitrate intake with the risk of dementia and imaging markers of vascular brain health, such as total brain volume, global cerebral perfusion, white matter hyperintensity volume, microbleeds, and lacunar infarcts.

Methods

Between 1990 and 2009, dietary intake was assessed using food-frequency …

Effects Of Co-Ingesting Dietary Nitrate And Vitamin C On Nitric Oxide Bioavailability, Blood Pressure, And Cardiovascular Reactivity In Hispanic Females, Joanna Powell, Katherine M. Price, Isabella G. Lincoln, Keonabelle P. Paniagua, Sean T. Karl, Julie Ahn, Noelle G. Seekamp-Hicks, Lauren Wideen, Joshua Park, Rachel Tan

International Journal of Exercise Science: Conference Proceedings

High blood pressure is a hallmark of chronic disease and is disproportionately prevalent in ethnic minorities. Dietary nitrate has been shown to lower blood pressure via increased nitric oxide (NO), but few studies have examined if combining nitrate with vitamin C (VITC) could have beneficial synergistic effects on blood pressure by augmenting NO, and limited data exist in females. PURPOSE: To investigate if combining nitrate-rich beetroot juice (BR) with VITC could further augment NO bioavailability and improve blood pressure in Hispanic females compared to BR and VITC ingested alone. METHODS: Eight sedentary Hispanic females participated in four conditions …

The Effects Of Acute Beetroot Juice Ingestion On Exercise And Cognitive Performance In Female Athletes, Isabella G. Lincoln, Courtney Merrill, Katherine M. Price, Sean T. Karl, Ryan T. Kenney, Alyssa A. Riley, Chandler F. Riley, Maya A. Hammer, Adam Pennell, Rachel Tan

International Journal of Exercise Science: Conference Proceedings

Nitrate-rich beetroot juice can enhance intense exercise performance which is attributed to enhanced skeletal muscle contractility. However, limited data exist in females and it is unknown whether dietary nitrate has an ergogenic effect in this population. PURPOSE: To investigate the potential effects of acute nitrate ingestion on a battery of exercise performance and cognitive tests before and after fatiguing intermittent running exercise. METHODS: Fifteen female team-sport athletes were assigned in a randomized, double-blind, crossover design to consume nitrate-rich beetroot juice (BR; 12 mmol of nitrate) and nitrate-depleted beetroot juice (PL; 0.10 mmol of nitrate) 2.5 h prior to …

Effects Of Dietary Nitrate Supplementation On Performance And Muscle Oxygenation During Resistance Exercise In Men, Rachel Tan, Adam Pennell, Katherine M. Price, Sean T. Karl, Noelle G. Seekamp-Hicks, Keonabelle K. Paniagua, Grant D. Weiderman, Joanna P. Powell, Luka K. Sharabidze, Isabella G. Lincoln, Justin M. Kim, Madeleine F. Espinoza, Maya A. Hammer, Richie P. Goulding, Stephen J. Bailey

All Faculty Open Access Publications

The purpose of the current study was to assess the effects of acute and short-term nitrate (NO3−)-rich beetroot juice (BR) supplementation on performance outcomes and muscle oxygenation during bench press and back squat exercise. Fourteen recreationally active males were assigned in a randomized, double-blind, crossover design to supplement for 4 days in two conditions: (1) NO3−-depleted beetroot juice (PL; 0.10 mmol NO3− per day) and (2) BR (11.8 mmol NO3− per day). On days 1 and 4 of the supplementation periods, participants completed 2 sets of 2 × 70%1RM interspersed by 2 min of recovery, followed by one set of …

The Effects Of Acute Beetroot Juice Ingestion On Upper And Lower Body Muscular Power During Weightlifting Exercise In Men, Grant Weiderman, Chandler Riley, Joanna Powell, Katie Price, Lauren Wideen, Andrew Fest, Justin Kim, Maya Hammer, Sean Karl, Isabella Lincoln, Noelle Seekamp-Hicks, Joshua Leow, Maddy Espinoza, Adam Pennell, Rachel Tan

Seaver College Research And Scholarly Achievement Symposium

Nitrate-rich beetroot juice (BR) supplementation improves movements with high-velocity and high-power muscle contractions which may be due to enhanced blood flow, oxygenation and contractile function in type II muscle fibers. The literature has focused predominantly on the effects of BR supplementation running and cycling performance, but its efficacy in resistance exercise, a modality that relies on type II muscle fibers, has limited data. Furthermore, it is unknown how supplementation strategies impact the physiological and ergogenic effects of BR during exercise. Therefore, the purpose of this study is to assess whether single or multi-day nitrate ingestion will improve performance and muscle …

The Effect Of Co-Ingesting Beetroot Juice And Vitamin C On Blood Pressure In Hispanic Women: A Literature Review And A Proposal, Mikela De La Flor, Maya Hammer, Noelle Seekamp-Hicks, Rachel Tan

Seaver College Research And Scholarly Achievement Symposium

Dietary nitrate supplementation is known for improving blood pressure through vasodilation and may favorably alter oral microbial populations related to cardiovascular health. Co-ingestion with vitamin C (VITC) may further potentiate these benefits but this remains unexplored. Additionally, this field has yet to examine the influence of sex and ethnicity, which is important given that physiological differences exist between populations. The purpose of this study is to assess the effects of combining dietary nitrate, in the form of beetroot juice, and VITC on blood pressure and the oral microbiome in women of Hispanic, African American, and American descent across multiple institutions. …

Pomegranate Extract Supplementation On Neuromuscular Performance During Resistance Exercise, Katie Price, Joanna Powell, Matthew Joyner, Adam Pennell, Rachel Tan

Seaver College Research And Scholarly Achievement Symposium

Dietary nitrate supplementation has been shown to improve skeletal muscle function during high-velocity and high-power contractions due to its high nitrate levels; however, there is limited data examining its potential in exercise requiring these movements, such as resistance exercise. Nitrate supplementation has been studied extensively as beetroot juice, but its poor taste severely limits its application. Pomegranate extract (POM) may be an alternative nitrate source due to its superior taste, high nitrate content, and additional antioxidants but has yet to be explored. The purpose of the present study is two-fold: 1) to determine the nitrate concentration in POM; and 2) …

The Effects Of Acute Beetroot Juice Ingestion On Upper And Lower Body Muscular Power During Weightlifting Exercise In Men., Sean Karl, Isabella Lincoln, Joanna Powell, Grant Weiderman, Katie Price, Lauren Wideen, Andrew Fest, Justin Kim, Maya Hammer, Noelle Seekamp-Hicks, Joshua Leow, Maddy Espinoza, Adam Pennell, Rachel Tan

Seaver College Research And Scholarly Achievement Symposium

Dietary nitrate supplementation, administered per beetroot juice (BR), has been shown to enhance performance while cycling and running. BR has enhanced skeletal muscle contraction and blood flow within type II fibers which are recruited during high-velocity and high-power contractions. However, it is unknown whether BR influences alternative forms of exercise, such as resistance exercise. The purpose of this study is to assess whether BR supplementation influences neuromuscular performance (muscle power and speed), and repetitions-to-failure in healthy, recreationally active men. In a double-blind, randomized crossover design, 14 males will be recruited to complete two 4-day supplementation periods in which they consume …

The Role Of Nitric Oxide And Cyclic Guanosine Monophosphate Signaling In Arteriovenous Fistula Maturation, Maheshika S. Somarathna

All ETDs from UAB

Vascular access is the single most important component of the hemodialysis procedure and the arteriovenous fistula (AVF) is the most preferred type. However, 60% of AVFs created fail to mature successfully for dialysis use (AVF maturation failure). AVF maturation failure is primarily the result of 1) intimal hyperplasia formation (IH) and 2) poor vascular outward remodeling. Currently, a major unmet clinical need in the field is the lack of effective therapies to treat/prevent AVF maturation failure due to the poor understanding of molecular mechanisms. This proposal is designed to: 1) elucidate the pathologic significance of nitric oxide (NO) and cyclic …

Soluble Guanylyl Cyclase: Molecular Basis For Ligand Selectivity And Action In Vitro And In Vivo, Gang Wu, Iraida Sharina, Emil Martin

Journal Articles

Nitric oxide (NO), carbon monoxide (CO), oxygen (O2), hydrogen sulfide (H2S) are gaseous molecules that play important roles in the physiology and pathophysiology of eukaryotes. Tissue concentrations of these physiologically relevant gases vary remarkable from nM range for NO to high μM range of O2. Various hemoproteins play a significant role in sensing and transducing cellular signals encoded by gaseous molecules or in transporting them. Soluble guanylyl cyclase (sGC) is a hemoprotein that plays vital roles in a wide range of physiological functions and combines the functions of gaseous sensor and signal transducer. sGC uniquely evolved to sense low non-toxic …

Associations Of Circulating Dimethylarginines With The Metabolic Syndrome In The Framingham Offspring Study, Ibrahim Musa Yola, Carlee Moser, Meredith S. Duncan, Edzard Schwedhelm, Dorothee Atzler, Renke Maas, Juliane Hannemann, Rainer H. Böger, Ramachandran S. Vasan, Vanessa Xanthakis

Biostatistics Faculty Publications

BACKGROUND: Circulating levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are positively associated with the prevalence of metabolic syndrome (MetS) in cross-sectional investigations. It is unclear if circulating ADMA and other methylarginines are associated with incident MetS prospectively.

METHODS: We related circulating ADMA, symmetric dimethylarginine (SDMA), L-arginine (ARG) concentrations (measured with a validated tandem mass spectrometry assay) and the ARG/ADMA ratio to MetS and its components in 2914 (cross-sectional analysis, logistic regression; mean age 58 years, 55% women) and 1656 (prospective analysis, Cox regression; mean age 56 years, 59% women) individuals from the Framingham Offspring Study …

Mediation Of The Uncoupled Enos Pathway Following Oxidative Stress Using Tetrahydrobiopterin And Nitric Oxide Donor Drugs To Restore Tetrahydrobiopterin Concentration, Brianna Munnich

Scholar Week 2016 - present

Presentation Location: Warming House, Olivet Nazarene University

Abstract

The eNOS pathway, found in the endothelium of blood vessels, is a key regulator of nitric oxide levels in the circulatory system. The pathway is controlled through several positive and negative feedback loops [2]. The cofactor tetrahydrobiopterin (BH4) is a major control point in this pathway and under conditions of stress can be reduced into the dihydrobiopterin (BH2) [2,6,7,8,9]. When the reduced form is predominant, the pathway produces reactive oxygen species (ROS) rather than nitric oxide, causing stress and damage to the vessels [6,7,8,9]. In this study, different treatments were studied …

Myeloperoxidase: A Versatile Mediator Of Endothelial Dysfunction And Therapeutic Target During Cardiovascular Disease, Sophie L. Maiocchi, Jacqueline Ku, Thuan Thai, Enoch Chan, Martin D. Rees, Shane R. Thomas

Education Papers and Journal Articles

Myeloperoxidase (MPO) is a prominent mammalian heme peroxidase and a fundamental component of the innate immune response against microbial pathogens. In recent times, MPO has received considerable attention as a key oxidative enzyme capable of impairing the bioactivity of nitric oxide (NO) and promoting endothelial dysfunction; a clinically relevant event that manifests throughout the development of inflammatory cardiovascular disease. Increasing evidence indicates that during cardiovascular disease, MPO is released intravascularly by activated leukocytes resulting in its transport and sequestration within the vascular endothelium. At this site, MPO catalyzes various oxidative reactions that are capable of promoting vascular inflammation and impairing …

Vegetable Nitrate Intake, Blood Pressure And Incident Cardiovascular Disease: Danish Diet, Cancer, And Health Study, Catherine P. Bondonno, Frederik Dalgaard, Lauren C. Blekkenhorst, Kevin Murray, Joshua R. Lewis, Kevin D. Croft, Cecilie Kyrø, Christian Torp-Pedersen, Gunnar Gislason, Anne Tjønneland, Kim Overvad, Nicola P. Bondonno, Jonathan M. Hodgson

Research outputs 2014 to 2021

Whether the vascular effects of inorganic nitrate, observed in clinical trials, translate to a reduction in cardiovascular disease (CVD) with habitual dietary nitrate intake in prospective studies warrants investigation. We aimed to determine if vegetable nitrate, the major dietary nitrate source, is associated with lower blood pressure (BP) and lower risk of incident CVD. Among 53,150 participants of the Danish Diet, Cancer, and Health Study, without CVD at baseline, vegetable nitrate intake was assessed using a comprehensive vegetable nitrate database. Hazard ratios (HRs) were calculated using restricted cubic splines based on multivariable-adjusted Cox proportional hazards models. During 23 years of …

Chronic Nitrite Treatment Activates Adenosine Monophosphate-Activated Protein Kinase-Endothelial Nitric Oxide Synthase Pathway In Human Aortic Endothelial Cells, Yang Liu, Kevin D. Croft, Jonathan M. Hodgson, Trevor Mori, Natalie C. Ward

Research outputs 2014 to 2021

Endothelial dysfunction, with impaired bioavailability and/or bioactivity of the vasoprotective molecule, nitric oxide, appears to be a vital step in the initiation of atherosclerosis. Several studies have shown that dietary nitrate/nitrite can have significant benefits on human cardiovascular homeostasis. Although serum nitrite concentrations can reach micromolar levels, the physiological significance of nitrate/nitrite in normal tissues has not been fully elucidated. We investigated in vitro the chronic effects of nitrate/nitrite on endothelial nitric oxide synthase (eNOS) to determine the potential vasoprotective effects of nitrate/nitrite and the underlying molecular mechanisms. Our results demonstrate the expression of phosphorylated eNOS at Ser1177 and phosphorylated …

Protective Effects Of Anandamide Against Cisplatin-Induced Peripheral Neuropathy Inrats, Çi̇ğdem Çengelli̇ Ünel, Başak Ayaz, Şule Aydin, Emel Ulupinar, Orhan Özati̇k, Bi̇lgi̇n Kaygisiz, Engi̇n Yildirim, Kevser Erol

Turkish Journal of Medical Sciences

Background/aim: Cisplatin (CIS) is an effective antineoplastic agent used in the treatment of several cancer types. Peripheral neuropathy is a major dose-limiting side-effect in CIS therapy. Cannabinoids may alleviate this painful side effect. This study investigated the analgesic effects of anandamide (AN) on CIS-induced peripheral neuropathy, in vitro effects of AN in CIS neurotoxicity, and the contribution of nitric oxide (NO) in this effect. Materials and methods: This is an experimental animal study. Primary dorsal root ganglion (DRG) cultures were prepared from oneday-old rats for in vitro investigations. DRG cells were incubated with CIS (100-300 μM), and AN (10, 50, …

Connexin Hemichannel Activation By S-Nitrosoglutathione Synergizes Strongly With Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing, Chiara Nardin, Chiara Peres, Sabrina Putti, Tiziana Orsini, Claudia Colussi, Flavia Mazzarda, Marcello Raspa, Ferdinando Scavizzi, Anna Maria Salvatore, Francesco Chiani, Abraham Tettey-Matey, Yuanyuan Kuang, Guang Yang, Mauricio A. Retamal, Fabio Mammano

Bioelectrics Publications

In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs). Intercellular calcium (Ca²⁺) waves propagated from irradiated to bystander cells promoting intracellular Ca²⁺ transfer from the endoplasmic reticulum (ER) to mitochondria and rapid activation of …

The Effect Of Dietary Nitrate And Vitamin C On Endothelial Function, Oxidative Stress And Blood Lipids In Untreated Hypercholesterolemic Subjects: A Randomized Double-Blind Crossover Study, Reem Basaqr, Michealia Skleres, Rani Jayswal, D. Travis Thomas

Athletic Training and Clinical Nutrition Faculty Publications

BACKGROUND: Vitamin C may enhance nitric oxide (NO) production through stepwise reduction of dietary nitrate (NO₃) to nitrite (NO₂) to NO. The combined effect of vitamin C and NO₃ supplementation is relatively unexplored in untreated hypercholesterolemia.

AIMS: We aimed to examine whether co-administration of vitamin C and nitrate for 4-weeks would improve endothelial function (primary outcome), plasma NO metabolites, oxidative stress, and blood lipids (secondary outcomes).

METHODS: Subjects 50–70 years of age with low density lipoprotein (LDL) > 130 mg/dL and RHI ≤ 2 were enrolled in this randomized double-blind crossover study. Subjects were assigned to …

Hdac6 Mediates Macrophage Inos Expression And Excessive Nitric Oxide Production In The Blood During Endotoxemia, Yan Wang, Ke Wang, Jian Fu

Toxicology and Cancer Biology Faculty Publications

Excessive nitric oxide (NO) production and NO-mediated nitrative stress contribute to vascular dysfunction, inflammation, and tissue injury in septic shock. New therapeutic targets are urgently needed to provide better control of NO level during septic shock. In the present study, we investigated the role of HDAC6 in the regulation of NO production and nitrative stress in a mouse model of endotoxin-induced septic shock. HDAC6 deficient mice and a specific HDAC6 inhibitor were utilized in our studies. Our data clearly indicate that HDAC6 is an important mediator of NO production in macrophages. HDAC6 mediates NO production through the regulation of iNOS …

Insufficient Sun Exposure Has Become A Real Public Health Problem, Lars Alfredsson, Bruce K Armstrong, D. Allan Butterfield, Rajiv Chowdhury, Frank R. De Gruijl, Martin Feelisch, Cedric F. Garland, Prue H. Hart, David G. Hoel, Ramune Jacobsen, Pelle G. Lindqvist, David J. Llewellyn, Henning Tiemeier, Richard B. Weller, Antony R. Young

Chemistry Faculty Publications

This article aims to alert the medical community and public health authorities to accumulating evidence on health benefits from sun exposure, which suggests that insufficient sun exposure is a significant public health problem. Studies in the past decade indicate that insufficient sun exposure may be responsible for 340,000 deaths in the United States and 480,000 deaths in Europe per year, and an increased incidence of breast cancer, colorectal cancer, hypertension, cardiovascular disease, metabolic syndrome, multiple sclerosis, Alzheimer's disease, autism, asthma, type 1 diabetes and myopia. Vitamin D has long been considered the principal mediator of beneficial effects of sun exposure. …