Juan Manuel Figueroa

Hospital de Clínicas "José de San Martín"

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Andrea Dugour

Consejo Nacional de Investigaciones Científicas y Técnicas

Doris Primrose

Hospital de Clínicas "José de San Martín"

Marcela Roque

Hospital de Clínicas "José de San Martín"

Magdalena Vocos

Hospital de Clínicas "José de San Martín"

F. Sánchez‐Sinencio

Center for Research and Advanced Studies of the National Polytechnic Institute

O. Zelaya

Instituto Politécnico Nacional

Anahí Kruger

Hospital de Clínicas "José de San Martín"

Gabriela Andrada

Hospital de Clínicas "José de San Martín"

Verónica Giubergia

Garrahan Hospital

ÁG

Ángel G. Valdivieso

Consejo Nacional de Investigaciones Científicas y Técnicas

Cooperative Institutions

Consejo Nacional de Investigaciones Científicas y Técnicas

University of Buenos Aires

Instituto Politécnico Nacional

Center for Research and Advanced Studies of the National Polytechnic Institute

Hospital de Clínicas "José de San Martín"

Fundación Ciencias Exactas y Naturales

Hospital de Clínicas

Pontificia Universidad Católica Argentina

Garrahan Hospital

Universidad Nacional Autónoma de México

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Estrechez relativa de las vías aéreas en niños con broncoespasmo inducido por el ejercicio

Archivos Argentinos de Pediatria (2004)

Juan Manuel Figueroa Liliana Gauna Marcela Roque Doris Primrose Ana Balanzat

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Citations (1)

Iota-carrageenan and Xylitol inhibit SARS-CoV-2 in cell culture

bioRxiv (Cold Spring Harbor Laboratory) (2020)

Shruti Bansal Colleen B. Jonsson Shannon L. Taylor Juan Manuel Figueroa Andrea Dugour

Abstract COVID-19 (coronavirus disease 2019) is a pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) infection affecting millions of persons around the world. There is an urgent unmet need to provide an easy-to-produce, affordable medicine to prevent transmission and provide early treatment for this disease. The nasal cavity and the rhinopharynx are the sites of initial replication of SARS-CoV-2. Therefore, a nasal spray may be a suitable dosage form for this purpose. The main objective of our study was to test the antiviral action of three candidate nasal spray formulations against SARS-CoV-2. We have found that iota-carrageenan in concentrations as low as 6 µg/ mL inhibits SARS-CoV-2 infection in Vero cell cultures. The concentrations found to be active in vitro against SARS-CoV-2 may be easily achieved by the application of nasal sprays already marketed in several countries. Xylitol at a concentration of 5 % m/V has proved to be viricidal on its own and the association with iota-carrageenan may be beneficial, as well.

Vero cell

Carrageenan

Coronavirus

2019-20 coronavirus outbreak

Nasal spray

10.1101/2020.08.19.225854

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Citations (32)

NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (CASP1) modulation by intracellular Cl^– concentration

Immunology (2021)

Mariángeles Clauzure Ángel G. Valdivieso Andrea Dugour Consuelo Mori María Macarena Massip-Copiz

The impairment of the cystic fibrosis transmembrane conductance regulator (CFTR) activity induces intracellular chloride (Cl

Pyrin domain

Nigericin

NALP3

10.1111/imm.13336

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Citations (13)

Kinetics of furfuryl alcohol polymerisation by iodine in methylene dichloride

European Polymer Journal (2002)

Regino González Jacques Rieumont Juan Manuel Figueroa Javier Siller Hilda González

Furfuryl alcohol

Cationic polymerization

Methylene

10.1016/s0014-3057(01)00091-x

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Citations (15)

Iota-carrageenan prevents the replication of SARS-CoV-2 on an in vitro respiratory epithelium model

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Augusto Varese Ana Ceballos Carlos Palacios Juan Manuel Figueroa Andrea Dugour

Abstract There are, except for remdesivir, no approved antivirals for the treatment or prevention of SARS-CoV-2 infections. Iota-carrageenan formulated into a nasal spray has already been proven safe and effective in viral respiratory infections. We explored this antiviral activity in Calu-3, a human respiratory model cell line. A formula of iota-carrageenan and sodium chloride, as a nasal spray, already approved for human use, effectively inhibited SARS-CoV-2 infection in vitro, providing a more substantial reference for further clinical studies or developments.

Carrageenan

Nasal spray

10.1101/2021.04.27.441512

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Citations (2)

N-acetyl cysteine reverts the proinflammatory state induced by cigarette smoke extract in lung Calu-3 cells

Redox Biology (2018)

Ángel G. Valdivieso Andrea Dugour Verónica Sotomayor Mariángeles Clauzure Juan Manuel Figueroa

Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are lethal pulmonary diseases. Cigarette consumption is the main cause for development of COPD, while CF is produced by mutations in the CFTR gene. Although these diseases have a different etiology, both share a CFTR activity impairment and proinflammatory state even under sterile conditions. The aim of this work was to study the extent of the protective effect of the antioxidant N-acetylcysteine (NAC) over the proinflammatory state (IL-6 and IL-8), oxidative stress (reactive oxygen species, ROS), and CFTR levels, caused by Cigarette Smoke Extract (CSE) in Calu-3 airway epithelial cells. CSE treatment (100 µg/ml during 24 h) decreased CFTR mRNA expression and activity, and increased the release of IL-6 and IL-8. The effect on these cytokines was inhibited by N-acetyl cysteine (NAC, 5 mM) or the NF-kB inhibitor, IKK-2 (10 µM). CSE treatment also increased cellular and mitochondrial ROS levels. The cellular ROS levels were normalized to control values by NAC treatment, although significant effects on mitochondrial ROS levels were observed only at short times (5´) and effects on CFTR levels were not observed. In addition, CSE reduced the mitochondrial NADH-cytochrome c oxidoreductase (mCx I-III) activity, an effect that was not reverted by NAC. The reduced CFTR expression and the mitochondrial damage induced by CSE could not be normalized by NAC treatment, evidencing the need for a more specific reagent. In conclusion, CSE causes a sterile proinflammatory state and mitochondrial damage in Calu-3 cells that was partially recovered by NAC treatment.

Proinflammatory cytokine

Mitochondrial ROS

10.1016/j.redox.2018.03.006

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Citations (33)

A Phase 2 Randomized, Double-Blind, Placebo–Controlled Study of the Safety and Efficacy of Talactoferrin in Patients With Severe Sepsis*

Critical Care Medicine (2013)

Alejandro C. Arroliga R.A. Balk Chad Cannon Nathan C. Dean Phillip Dellinger

Objectives: Lactoferrin is a glycoprotein with anti-infective and anti-inflammatory properties found in secretions and immune cells. Talactoferrin alfa, a recombinant form of human lactoferrin, has similar properties and plays an important role in maintaining the gastrointestinal mucosal barrier integrity. In experimental animal models, administration of talactoferrin reduces translocation of bacteria from the gut into the systemic circulation and mortality from sepsis. Our objective was to determine if talactoferrin could reduce 28-day all-cause mortality in patients with severe sepsis and to assess its safety. Design: Prospective, randomized, double-blind, placebo-controlled, multicenter phase 2 trial. Setting: Adult ICUs and emergency departments in the United States. Patients: One hundred ninety-four adults within 24 hrs of the onset of severe sepsis. Interventions: Enterally administered talactoferrin 1.5g or placebo every 8 hrs for up to 28 days or until discharge from the ICU. Measurements and Main Results: Modified intention-to-treat analysis was used to assess the primary (28-day all-cause mortality) and secondary endpoints. The all-cause mortality at 28 days was 26.9% in the placebo group and 14.4% in the talactoferrin group (two-sided p = 0.052), representing a 12.5% absolute and a 46.5% relative reduction in mortality, meeting the protocol-specified primary endpoint. Reduction in all cause mortality was sustained at 6 months (p = 0.039). These reductions in mortality were observed across a wide spectrum of subgroups. The drug was well tolerated with a safety profile similar to that of placebo. Conclusions: Enteral administration of talactoferrin reduced 28-day all-cause mortality in patients with severe sepsis. This reduction in mortality was sustained at 6 months. Talactoferrin was very well tolerated.

Clinical endpoint

Lactoferrin

Enteral administration

10.1097/ccm.0b013e3182741551

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Citations (70)

Development of a Carrier-Free Dry Powder Ofloxacin Formulation With Enhanced Aerosolization Properties

Journal of Pharmaceutical Sciences (2020)

Nazareth Eliana Ceschan Melany Denise Rosas Marı́a Eugenia Olivera Andrea Dugour Juan Manuel Figueroa

Aerosolization

Mucoadhesion

Pharmaceutics

10.1016/j.xphs.2020.05.027

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Citations (10)

Harmfull effects of cigarette smoke on a respiratory epithelium line (Calu 3): Prevention by N-acetylcisteine

European Respiratory Journal (2013)

Andrea Dugour Fernanda R. Elias Juan Manuel Figueroa

Background: Calu 3 is a respiratory epithelial cell line increasingly used in pharmacological and pathophysiological studies. Much of lung damage produced by cigarette smoke is based on oxidative stress. N-acetylciteine (NAC) has powerfull antioxidant activity. Objetives: to evaluate if N-acetylcisteine can modify the effects of mainstream cigarette smoke on Calu 3 cells. Methods: Calu 3 cells were cultured in monolayers in air-liquid interphase. In an experimental group NAC (5 mM) was added to the culture media; a second group stay as control. Smoke was generated placing successively 2 cigarettes at a tube connected to a vacuum pump; the generated smoke was expelled by another tube to a closer chamber where the two groups of cells remained for 10 minutes. Then the cells were kept without smoke for two hours and cell viability (colorimetric method) and apoptosis (acridine orange fluorescence) were evaluated. Results: in the control group cell viability decrease 40% after the contact with cigarette smoke, and this was associated with the appearance of apoptotic cells. In the group treated with NAC the viability do not decrease and apoptotic cells were not observed. Conclusions: incubation with NAC prevented cigarette smoke damage in Calu 3 cells.

Acridine orange

Viability assay

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Citations (2)

Asymptomatic carotideal atherosclerosis in type 2 diabetes, hyperlipemia, obesity and postmenopausea

Diabetes Research and Clinical Practice (2000)

Walter de la Torre Juan Manuel Figueroa Miriam Chicaiza

10.1016/s0168-8227(00)81678-2

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Citations (0)