Walter Manucha - Academia.edu (original) (raw)

Papers by Walter Manucha

Research paper thumbnail of Heat shock protein 70/nitric oxide effect on stretched tubular epithelial cells linked to WT-1 cytoprotection during neonatal obstructive nephropathy

International Urology and Nephrology, Jul 15, 2017

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Research paper thumbnail of A Gender Comparison of Postobstructive Injury in the Rat Kidney

Kidney & Blood Pressure Research, 2010

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Research paper thumbnail of Mediators and mechanisms of heat shock protein 70 based cytoprotection in obstructive nephropathy

Cell Stress & Chaperones, Jul 31, 2015

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Research paper thumbnail of El suplemento con altas dosis de vitaminaD podría representar una alternativa promisoria para prevenir o tratar la infección por COVID-19./ El suplemento con altas dosis de vitaminaD podría representar una alternativa promisoria para prevenir o tratar la infección por COVID-19./ Vitamin D high do...

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Research paper thumbnail of Gut Microbiota Dysbiosis in COVID-19: Modulation and Approaches for Prevention and Therapy

International Journal of Molecular Sciences

Inflammation and oxidative stress are critical underlying mechanisms associated with COVID-19 tha... more Inflammation and oxidative stress are critical underlying mechanisms associated with COVID-19 that contribute to the complications and clinical deterioration of patients. Additionally, COVID-19 has the potential to alter the composition of patients’ gut microbiota, characterized by a decreased abundance of bacteria with probiotic effects. Interestingly, certain strains of these bacteria produce metabolites that can target the S protein of other coronaviruses, thereby preventing their transmission and harmful effects. At the same time, the presence of gut dysbiosis can exacerbate inflammation and oxidative stress, creating a vicious cycle that perpetuates the disease. Furthermore, it is widely recognized that the gut microbiota can metabolize various foods and drugs, producing by-products that may have either beneficial or detrimental effects. In this regard, a decrease in short-chain fatty acid (SCFA), such as acetate, propionate, and butyrate, can influence the overall inflammatory...

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Research paper thumbnail of Mechanistic approaching study in COVID-19 patients treated with high doses of vitamin D

Exploration of Medicine

Aim: To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patient... more Aim: To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patients hospitalized with mild coronavirus disease 2019 (COVID-19) and contrast them with patients with identical clinical conditions but treated with high doses of vitamin D (vitD). Methods: From the 218 patients recruited (ClinicalTrials.gov NCT04411446), 16 participated in this sub-study and were randomized to a single oral dose of 500,000 IU vitD (n = 10) or placebo (n = 6). Plasmatic Ang II and Ang-(1-7) levels were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8, and 10 and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay before and after treatment. Parallel, serum 25-hydroxyvitamin D3 (25-OH vitD) concentrations as vitD status was measured by a chemiluminescence immunoassay. Results: A trend towards an increase in Ang-(1-7) and a decrease in Ang II levels were observed in placebo- and vitD-treated COVID-19 patients compared to baseline values. There...

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Research paper thumbnail of Metabolic Syndrome and Cardiac Remodeling Due to Mitochondrial Oxidative Stress Involving Gliflozins and Sirtuins

Current Hypertension Reports

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Research paper thumbnail of Nanomedicine and Addictive Disorders: A New Approach With Cannabinoids

Current Pharmaceutical Design

Background: Most cannabinoids usually present several limitations when evaluating their clinical ... more Background: Most cannabinoids usually present several limitations when evaluating their clinical use, mainly related to the side effects they may cause at the central nervous system and other levels. In this regard, nanotechnology applied to the development of pharmacotherapeutic nanoformulations has become an attractive tool that allows taking advantage of the beneficial properties of multiple drugs while minimizing or avoiding their undesirable side effects. Nanotechnology is a relatively recent scientific field that involves the study, manipulation, development, and characterization of drug delivery systems at the nanoscale (1 to 1000 nm; 1 nm= 1x10-9 m). Usually, the physicochemical properties of matter at the nanoscale are significantly different compared to the matter at the macroscale, which provides several advantages over conventional therapeutic alternative types of organic and inorganic drug delivery nanosystems. Posology, size, composition, surface properties, and differ...

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Research paper thumbnail of Genomic or Non-Genomic? A Question about the Pleiotropic Roles of Vitamin D in Inflammatory-Based Diseases

Nutrients

Vitamin D (vit D) is widely known for its role in calcium metabolism and its importance for the b... more Vitamin D (vit D) is widely known for its role in calcium metabolism and its importance for the bone system. However, various studies have revealed a myriad of extra-skeletal functions, including cell differentiation and proliferation, antibacterial, antioxidant, immunomodulatory, and anti-inflammatory properties in various cells and tissues. Vit D mediates its function via regulation of gene expression by binding to its receptor (VDR) which is expressed in almost all cells within the body. This review summarizes the pleiotropic effects of vit D, emphasizing its anti-inflammatory effect on different organ systems. It also provides a comprehensive overview of the genetic and epigenetic effects of vit D and VDR on the expression of genes pertaining to immunity and anti-inflammation. We speculate that in the context of inflammation, vit D and its receptor VDR might fulfill their roles as gene regulators through not only direct gene regulation but also through epigenetic mechanisms.

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Research paper thumbnail of High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial

PLOS ONE

Background The role of oral vitamin D3 supplementation for hospitalized patients with COVID-19 re... more Background The role of oral vitamin D3 supplementation for hospitalized patients with COVID-19 remains to be determined. The study was aimed to evaluate whether vitamin D3 supplementation could prevent respiratory worsening among hospitalized patients with COVID-19. Methods and findings We designed a multicentre, randomized, double-blind, sequential, placebo-controlled clinical trial. The study was conducted in 17 second and third level hospitals, located in four provinces of Argentina, from 14 August 2020 to 22 June 2021. We enrolled 218 adult patients, hospitalized in general wards with SARS-CoV-2 confirmed infection, mild-to-moderate COVID-19 and risk factors for disease progression. Participants were randomized to a single oral dose of 500 000 IU of vitamin D3 or matching placebo. Randomization ratio was 1:1, with permuted blocks and stratified for study site, diabetes and age (≤60 vs >60 years). The primary outcome was the change in the respiratory Sepsis related Organ Failu...

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Research paper thumbnail of Epigenetic Mechanisms Involved in Inflammaging-Associated Hypertension

Current Hypertension Reports

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Research paper thumbnail of Desarrollo y valoración de una novedosa forma farmacéutica constituida por nanopartículas poliméricas portadoras de anandamida con potencial efecto terapéutico cardiovascular antihipertensivo

Introducción: El remodelado cardiovascular (RCV) se observa con frecuencia en sujetos hipertensos... more Introducción: El remodelado cardiovascular (RCV) se observa con frecuencia en sujetos hipertensos. Se sabe que anandamida (AEA), un cannabinoide endógeno, produce importantes efectos antihipertensivos. No obstante, poco se ha explorado sobre su papel cardioprotector debido a que presenta propiedades físico-químicas desfavorables y efectos psicoactivos tóxicos. En este contexto, la encapsulación de fármacos en nanotransportadores podría superar las limitaciones asociadas a la administración de AEA en forma libre.Objetivos: Desarrollar nanopartículas poliméricas de policaprolactona/Pluronic F127 portadoras de anandamida (AEA/PCL/PF127, NPs), caracterizar sus propiedades físico-químicas, determinar su biocompatibilidad, y evaluar su efecto sobre el RCV y conducta de ratas hipertensas tratadas con esta nanoformulación.Métodos: Se obtuvieron las NPs mediante técnica de electrospining. Posteriormente, se determinó potencial Z, hidrofilicidad, morfología, tamaño, propiedades térmicas y espectroscópicas de las NPs. Se calculó eficiencia de encapsulamiento y carga de AEA. Se determinó biocompatibilidad en cultivos de fibroblastos. Para los estudios sobre RCV, se emplearon ratas macho de 250-300 gr normotensas (WKY) e hipertensas (SHR), N=7 por grupo, tratadas o no con NPs (5 mg/Kg, IP) con una dosis semanal durante 1 mes. Se determinó AEA plasmática, parámetros hemodinámicos, estructurales, funcionales cardíacos, marcadores inflamatorios de interés, conducta asociada a la ansiedad y la exploración en todos los grupos.Resultados: Se obtuvieron partículas con propiedades físico-químicas óptimas y biocompatibles. En SHR, el tratamiento con NPs revirtió todos los parámetros hemodinámicos, estructurales y funcionales cardíacos, así también como marcadores inflamatorios alterados (P<0,05). El comportamiento anormal observado en ratas SHR desapareció luego del tratamiento con NPs. Conclusiones: A nivel cardiovascular, AEA nanoformulada demostró ser eficaz para el tratamiento de la hipertensión arterial y sus comorbilidades, especialmente el RCV demostrando propiedades físico-químicas mejoradas; además a nivel del sistema nervioso central, las NPs mejoraron la conducta y exhibieron ausencia de efectos perjudiciales o tóxicos.Fil: Gimenéz, Virna Martín. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Sanz, Raúl. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Mocayar Maron, Feres Jose. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Camargo, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Ramirez, Daniela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: García, Sebastián. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Yunes, Roberto Miguel Federico. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Kassuha, Diego Enrique. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Manucha, Walter Ariel Fernando. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaXXVI Congreso Argentino de Hipertensión ArterialMar del PlataArgentinaSociedad Argentina de Hipertensión ArterialInternational Americam Society of Hypertensio

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Research paper thumbnail of Nanotecnología y enfermedad cardiovascular: Avances y aplicaciones

Fil: Martin Gimenez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de C... more Fil: Martin Gimenez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Cs. de la Alimentacion, Bioquimicas y Farmaceuticas. Instituto de Investigacion En Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina

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Research paper thumbnail of Vitamin D supplementation: An alternative to enhance the effectiveness of vaccines against SARS-CoV-2?

Vaccine, 2021

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Research paper thumbnail of Central nervous system, peripheral and hemodynamic effects of nanoformulated anandamide in hypertension

Advances in Medical Sciences, 2021

PURPOSE Hypertensive lesions induce alterations at hemodynamic, peripheral, and central levels. A... more PURPOSE Hypertensive lesions induce alterations at hemodynamic, peripheral, and central levels. Anandamide (N-arachidonoylethanolamine; AEA) protects neurons from inflammatory damage, but its free administration may cause central adverse effects. AEA controlled release by nanoformulations could reduce/eliminate its side effects. The present study aimed to evaluate the effects of nanoformulated AEA (nf-AEA) on systolic blood pressure (SBP), behavior, and central/peripheral inflammatory, oxidative, and apoptotic state in spontaneously hypertensive rats (SHR). MATERIALS/METHODS Male rats were used, both Wistar Kyoto (WKY) and SHR (n ​= ​10 per group), with/without treatment with nf-AEA (obtained by electrospraying) at a weekly dose of 5 ​mg/kg IP for 4 weeks. SBP was measured and behavioral tests were performed. Inflammatory/oxidative markers were quantified at the central (brain cortex) and peripheral (serum) level. RESULTS SHR showed hyperactivity, low anxiety, and high concentrations of central/peripheral inflammatory/oxidative markers, also higher apoptosis of brain cortical cells compared to WKY. As opposed to this group, treatment with nf-AEA in SHR significantly reduced SBP, peripheral/central inflammatory/oxidative makers, and central apoptosis. Nf-AEA also increased neuroprotective mechanisms mediated by intracellular heat shock protein 70 (Hsp70), which were attenuated in untreated SHR. Additionally, nf-AEA reversed the abnormal behaviors observed in SHR without producing central adverse effects. CONCLUSIONS Our results suggest protective properties of nf-AEA, both peripherally and centrally, through a signaling pathway that would involve the type I angiotensin II receptor, Wilms tumor transcription factor 1, Hsp70, and iNOS. Considering non-nf-AEA limitations, this nanoformulation could contribute to the development of new antihypertensive and behavioral disorder treatments associated with neuroinflammation.

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Research paper thumbnail of Vitamin D-RAAS Connection: An Integrative Standpoint into Cardiovascular and Neuroinflammatory Disorders

Current Protein & Peptide Science, 2020

Background: The neuroinflammatory process is associated with the pathogenesis of many cardiovascu... more Background: The neuroinflammatory process is associated with the pathogenesis of many cardiovascular disorders, particularly with hypertension. In this regard, the deficiency of vitamin D seems to increase the risk of cardiovascular pathologies related to neuroinflammation. Long-term lack of vitamin D leads to over-activation of the renin-angiotensin-aldosterone system (RAAS), one of the essential mechanisms of blood pressure regulation. Purpose of Review: This review summarizes the latest studies carried out to evaluate the primary mechanisms underlying the neuroprotective effect of vitamin D and its receptors (VDR) in the central nervous system. Besides, the present article condenses the evidence supporting the link between vitamin D and the RAAS in hypertension and neuroinflammation. Highlights Standpoints: Vitamin D deficiency is highly prevalent in the world, and the rising prevalence of neuroinflammatory diseases and associated pathologies such as hypertension around the world...

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Research paper thumbnail of La nanotecnología ofrece un enfoque terapéutico prometedor para el tratamiento de la hipertensión

Hipertensión y Riesgo Vascular, 2017

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Research paper thumbnail of Abstract 450: Cardiac Electrophysiological Changes Linked to Vitamin D Receptors Deficiency in Obstructive Nephropathy

Hypertension, 2013

Background: Chronic kidney disease is highly prevalent and is associated with cardiovascular dise... more Background: Chronic kidney disease is highly prevalent and is associated with cardiovascular disease. Paricalcitol protects individuals from some of the renal and cardiovascular complications associated with kidney disease. However, its electrophysiological effect during myocardial ischemia-reperfusion is currently unknown. Aims: Using an obstructive nephropathy (ON) model, we plan to investigate the potential, structural, and functional changes of the heart that are linked to vitamin D deficiency. Methods: The ureters of adult rats (n = 10) were unilaterally obstructed. An inductor of the vitamin D receptor (VDR) was administered for 15 days (30ng/Kg/day, ip). We evaluated histological, molecular, and biochemical parameters, as well, cardiac electrophysiological activity with ischemia-reperfusion protocol. Results: we found changes in the action potential duration (APD) at 90% (* P<0.05 vs. C, +P<0.05 vs. O). The analysis revealed arrhythmias, ventricular tachycardia (VT), an...

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Research paper thumbnail of Nanomedicine approaches for the diagnosis, treatment, and theragnosis of diabetes mellitus, hypertension, and their associated cardiovascular diseases

Diabetes and Cardiovascular Disease, 2021

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Research paper thumbnail of El factor de la trasncripción WT-1 y su relación con el desarrollo de la injuria renal inducida durante la nefropatía obstructiva

Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centr... more Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Mendoza. Instituto de Medicina y Biologia Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas; Argentina

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Research paper thumbnail of Heat shock protein 70/nitric oxide effect on stretched tubular epithelial cells linked to WT-1 cytoprotection during neonatal obstructive nephropathy

International Urology and Nephrology, Jul 15, 2017

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Research paper thumbnail of A Gender Comparison of Postobstructive Injury in the Rat Kidney

Kidney & Blood Pressure Research, 2010

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Research paper thumbnail of Mediators and mechanisms of heat shock protein 70 based cytoprotection in obstructive nephropathy

Cell Stress & Chaperones, Jul 31, 2015

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Research paper thumbnail of El suplemento con altas dosis de vitaminaD podría representar una alternativa promisoria para prevenir o tratar la infección por COVID-19./ El suplemento con altas dosis de vitaminaD podría representar una alternativa promisoria para prevenir o tratar la infección por COVID-19./ Vitamin D high do...

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Research paper thumbnail of Gut Microbiota Dysbiosis in COVID-19: Modulation and Approaches for Prevention and Therapy

International Journal of Molecular Sciences

Inflammation and oxidative stress are critical underlying mechanisms associated with COVID-19 tha... more Inflammation and oxidative stress are critical underlying mechanisms associated with COVID-19 that contribute to the complications and clinical deterioration of patients. Additionally, COVID-19 has the potential to alter the composition of patients’ gut microbiota, characterized by a decreased abundance of bacteria with probiotic effects. Interestingly, certain strains of these bacteria produce metabolites that can target the S protein of other coronaviruses, thereby preventing their transmission and harmful effects. At the same time, the presence of gut dysbiosis can exacerbate inflammation and oxidative stress, creating a vicious cycle that perpetuates the disease. Furthermore, it is widely recognized that the gut microbiota can metabolize various foods and drugs, producing by-products that may have either beneficial or detrimental effects. In this regard, a decrease in short-chain fatty acid (SCFA), such as acetate, propionate, and butyrate, can influence the overall inflammatory...

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Research paper thumbnail of Mechanistic approaching study in COVID-19 patients treated with high doses of vitamin D

Exploration of Medicine

Aim: To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patient... more Aim: To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patients hospitalized with mild coronavirus disease 2019 (COVID-19) and contrast them with patients with identical clinical conditions but treated with high doses of vitamin D (vitD). Methods: From the 218 patients recruited (ClinicalTrials.gov NCT04411446), 16 participated in this sub-study and were randomized to a single oral dose of 500,000 IU vitD (n = 10) or placebo (n = 6). Plasmatic Ang II and Ang-(1-7) levels were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8, and 10 and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay before and after treatment. Parallel, serum 25-hydroxyvitamin D3 (25-OH vitD) concentrations as vitD status was measured by a chemiluminescence immunoassay. Results: A trend towards an increase in Ang-(1-7) and a decrease in Ang II levels were observed in placebo- and vitD-treated COVID-19 patients compared to baseline values. There...

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Research paper thumbnail of Metabolic Syndrome and Cardiac Remodeling Due to Mitochondrial Oxidative Stress Involving Gliflozins and Sirtuins

Current Hypertension Reports

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Research paper thumbnail of Nanomedicine and Addictive Disorders: A New Approach With Cannabinoids

Current Pharmaceutical Design

Background: Most cannabinoids usually present several limitations when evaluating their clinical ... more Background: Most cannabinoids usually present several limitations when evaluating their clinical use, mainly related to the side effects they may cause at the central nervous system and other levels. In this regard, nanotechnology applied to the development of pharmacotherapeutic nanoformulations has become an attractive tool that allows taking advantage of the beneficial properties of multiple drugs while minimizing or avoiding their undesirable side effects. Nanotechnology is a relatively recent scientific field that involves the study, manipulation, development, and characterization of drug delivery systems at the nanoscale (1 to 1000 nm; 1 nm= 1x10-9 m). Usually, the physicochemical properties of matter at the nanoscale are significantly different compared to the matter at the macroscale, which provides several advantages over conventional therapeutic alternative types of organic and inorganic drug delivery nanosystems. Posology, size, composition, surface properties, and differ...

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Research paper thumbnail of Genomic or Non-Genomic? A Question about the Pleiotropic Roles of Vitamin D in Inflammatory-Based Diseases

Nutrients

Vitamin D (vit D) is widely known for its role in calcium metabolism and its importance for the b... more Vitamin D (vit D) is widely known for its role in calcium metabolism and its importance for the bone system. However, various studies have revealed a myriad of extra-skeletal functions, including cell differentiation and proliferation, antibacterial, antioxidant, immunomodulatory, and anti-inflammatory properties in various cells and tissues. Vit D mediates its function via regulation of gene expression by binding to its receptor (VDR) which is expressed in almost all cells within the body. This review summarizes the pleiotropic effects of vit D, emphasizing its anti-inflammatory effect on different organ systems. It also provides a comprehensive overview of the genetic and epigenetic effects of vit D and VDR on the expression of genes pertaining to immunity and anti-inflammation. We speculate that in the context of inflammation, vit D and its receptor VDR might fulfill their roles as gene regulators through not only direct gene regulation but also through epigenetic mechanisms.

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Research paper thumbnail of High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial

PLOS ONE

Background The role of oral vitamin D3 supplementation for hospitalized patients with COVID-19 re... more Background The role of oral vitamin D3 supplementation for hospitalized patients with COVID-19 remains to be determined. The study was aimed to evaluate whether vitamin D3 supplementation could prevent respiratory worsening among hospitalized patients with COVID-19. Methods and findings We designed a multicentre, randomized, double-blind, sequential, placebo-controlled clinical trial. The study was conducted in 17 second and third level hospitals, located in four provinces of Argentina, from 14 August 2020 to 22 June 2021. We enrolled 218 adult patients, hospitalized in general wards with SARS-CoV-2 confirmed infection, mild-to-moderate COVID-19 and risk factors for disease progression. Participants were randomized to a single oral dose of 500 000 IU of vitamin D3 or matching placebo. Randomization ratio was 1:1, with permuted blocks and stratified for study site, diabetes and age (≤60 vs >60 years). The primary outcome was the change in the respiratory Sepsis related Organ Failu...

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Research paper thumbnail of Epigenetic Mechanisms Involved in Inflammaging-Associated Hypertension

Current Hypertension Reports

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Research paper thumbnail of Desarrollo y valoración de una novedosa forma farmacéutica constituida por nanopartículas poliméricas portadoras de anandamida con potencial efecto terapéutico cardiovascular antihipertensivo

Introducción: El remodelado cardiovascular (RCV) se observa con frecuencia en sujetos hipertensos... more Introducción: El remodelado cardiovascular (RCV) se observa con frecuencia en sujetos hipertensos. Se sabe que anandamida (AEA), un cannabinoide endógeno, produce importantes efectos antihipertensivos. No obstante, poco se ha explorado sobre su papel cardioprotector debido a que presenta propiedades físico-químicas desfavorables y efectos psicoactivos tóxicos. En este contexto, la encapsulación de fármacos en nanotransportadores podría superar las limitaciones asociadas a la administración de AEA en forma libre.Objetivos: Desarrollar nanopartículas poliméricas de policaprolactona/Pluronic F127 portadoras de anandamida (AEA/PCL/PF127, NPs), caracterizar sus propiedades físico-químicas, determinar su biocompatibilidad, y evaluar su efecto sobre el RCV y conducta de ratas hipertensas tratadas con esta nanoformulación.Métodos: Se obtuvieron las NPs mediante técnica de electrospining. Posteriormente, se determinó potencial Z, hidrofilicidad, morfología, tamaño, propiedades térmicas y espectroscópicas de las NPs. Se calculó eficiencia de encapsulamiento y carga de AEA. Se determinó biocompatibilidad en cultivos de fibroblastos. Para los estudios sobre RCV, se emplearon ratas macho de 250-300 gr normotensas (WKY) e hipertensas (SHR), N=7 por grupo, tratadas o no con NPs (5 mg/Kg, IP) con una dosis semanal durante 1 mes. Se determinó AEA plasmática, parámetros hemodinámicos, estructurales, funcionales cardíacos, marcadores inflamatorios de interés, conducta asociada a la ansiedad y la exploración en todos los grupos.Resultados: Se obtuvieron partículas con propiedades físico-químicas óptimas y biocompatibles. En SHR, el tratamiento con NPs revirtió todos los parámetros hemodinámicos, estructurales y funcionales cardíacos, así también como marcadores inflamatorios alterados (P<0,05). El comportamiento anormal observado en ratas SHR desapareció luego del tratamiento con NPs. Conclusiones: A nivel cardiovascular, AEA nanoformulada demostró ser eficaz para el tratamiento de la hipertensión arterial y sus comorbilidades, especialmente el RCV demostrando propiedades físico-químicas mejoradas; además a nivel del sistema nervioso central, las NPs mejoraron la conducta y exhibieron ausencia de efectos perjudiciales o tóxicos.Fil: Gimenéz, Virna Martín. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Sanz, Raúl. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Mocayar Maron, Feres Jose. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Camargo, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Ramirez, Daniela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: García, Sebastián. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Yunes, Roberto Miguel Federico. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Kassuha, Diego Enrique. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Manucha, Walter Ariel Fernando. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaXXVI Congreso Argentino de Hipertensión ArterialMar del PlataArgentinaSociedad Argentina de Hipertensión ArterialInternational Americam Society of Hypertensio

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Research paper thumbnail of Nanotecnología y enfermedad cardiovascular: Avances y aplicaciones

Fil: Martin Gimenez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de C... more Fil: Martin Gimenez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Cs. de la Alimentacion, Bioquimicas y Farmaceuticas. Instituto de Investigacion En Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina

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Research paper thumbnail of Vitamin D supplementation: An alternative to enhance the effectiveness of vaccines against SARS-CoV-2?

Vaccine, 2021

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Research paper thumbnail of Central nervous system, peripheral and hemodynamic effects of nanoformulated anandamide in hypertension

Advances in Medical Sciences, 2021

PURPOSE Hypertensive lesions induce alterations at hemodynamic, peripheral, and central levels. A... more PURPOSE Hypertensive lesions induce alterations at hemodynamic, peripheral, and central levels. Anandamide (N-arachidonoylethanolamine; AEA) protects neurons from inflammatory damage, but its free administration may cause central adverse effects. AEA controlled release by nanoformulations could reduce/eliminate its side effects. The present study aimed to evaluate the effects of nanoformulated AEA (nf-AEA) on systolic blood pressure (SBP), behavior, and central/peripheral inflammatory, oxidative, and apoptotic state in spontaneously hypertensive rats (SHR). MATERIALS/METHODS Male rats were used, both Wistar Kyoto (WKY) and SHR (n ​= ​10 per group), with/without treatment with nf-AEA (obtained by electrospraying) at a weekly dose of 5 ​mg/kg IP for 4 weeks. SBP was measured and behavioral tests were performed. Inflammatory/oxidative markers were quantified at the central (brain cortex) and peripheral (serum) level. RESULTS SHR showed hyperactivity, low anxiety, and high concentrations of central/peripheral inflammatory/oxidative markers, also higher apoptosis of brain cortical cells compared to WKY. As opposed to this group, treatment with nf-AEA in SHR significantly reduced SBP, peripheral/central inflammatory/oxidative makers, and central apoptosis. Nf-AEA also increased neuroprotective mechanisms mediated by intracellular heat shock protein 70 (Hsp70), which were attenuated in untreated SHR. Additionally, nf-AEA reversed the abnormal behaviors observed in SHR without producing central adverse effects. CONCLUSIONS Our results suggest protective properties of nf-AEA, both peripherally and centrally, through a signaling pathway that would involve the type I angiotensin II receptor, Wilms tumor transcription factor 1, Hsp70, and iNOS. Considering non-nf-AEA limitations, this nanoformulation could contribute to the development of new antihypertensive and behavioral disorder treatments associated with neuroinflammation.

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Research paper thumbnail of Vitamin D-RAAS Connection: An Integrative Standpoint into Cardiovascular and Neuroinflammatory Disorders

Current Protein & Peptide Science, 2020

Background: The neuroinflammatory process is associated with the pathogenesis of many cardiovascu... more Background: The neuroinflammatory process is associated with the pathogenesis of many cardiovascular disorders, particularly with hypertension. In this regard, the deficiency of vitamin D seems to increase the risk of cardiovascular pathologies related to neuroinflammation. Long-term lack of vitamin D leads to over-activation of the renin-angiotensin-aldosterone system (RAAS), one of the essential mechanisms of blood pressure regulation. Purpose of Review: This review summarizes the latest studies carried out to evaluate the primary mechanisms underlying the neuroprotective effect of vitamin D and its receptors (VDR) in the central nervous system. Besides, the present article condenses the evidence supporting the link between vitamin D and the RAAS in hypertension and neuroinflammation. Highlights Standpoints: Vitamin D deficiency is highly prevalent in the world, and the rising prevalence of neuroinflammatory diseases and associated pathologies such as hypertension around the world...

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Research paper thumbnail of La nanotecnología ofrece un enfoque terapéutico prometedor para el tratamiento de la hipertensión

Hipertensión y Riesgo Vascular, 2017

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Research paper thumbnail of Abstract 450: Cardiac Electrophysiological Changes Linked to Vitamin D Receptors Deficiency in Obstructive Nephropathy

Hypertension, 2013

Background: Chronic kidney disease is highly prevalent and is associated with cardiovascular dise... more Background: Chronic kidney disease is highly prevalent and is associated with cardiovascular disease. Paricalcitol protects individuals from some of the renal and cardiovascular complications associated with kidney disease. However, its electrophysiological effect during myocardial ischemia-reperfusion is currently unknown. Aims: Using an obstructive nephropathy (ON) model, we plan to investigate the potential, structural, and functional changes of the heart that are linked to vitamin D deficiency. Methods: The ureters of adult rats (n = 10) were unilaterally obstructed. An inductor of the vitamin D receptor (VDR) was administered for 15 days (30ng/Kg/day, ip). We evaluated histological, molecular, and biochemical parameters, as well, cardiac electrophysiological activity with ischemia-reperfusion protocol. Results: we found changes in the action potential duration (APD) at 90% (* P<0.05 vs. C, +P<0.05 vs. O). The analysis revealed arrhythmias, ventricular tachycardia (VT), an...

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Research paper thumbnail of Nanomedicine approaches for the diagnosis, treatment, and theragnosis of diabetes mellitus, hypertension, and their associated cardiovascular diseases

Diabetes and Cardiovascular Disease, 2021

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Research paper thumbnail of El factor de la trasncripción WT-1 y su relación con el desarrollo de la injuria renal inducida durante la nefropatía obstructiva

Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centr... more Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Mendoza. Instituto de Medicina y Biologia Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas; Argentina

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