The world pandemic of vitamin D deficit culd possibly be explained by cellular inflammatory response activity induced by the renin angiotensin system

This review attempts to show that there may be a relationship between inflammatory processes induced by chronic overstimulation of the renin-angiotensin system (RAS) and the worldwide deficiency of vitamin D (VitD) and that both disorders are probably associated with environmental factors. Low VitD levels represent a risk factor for several apparently different diseases, such as infectious, autoimmune, neurodegenerative, and cardiovascular diseases, as well as diabetes, osteoporosis, and cancer. Moreover, VitD insufficiency seems to predispose to hypertension, metabolic syndrome, left ventricular hypertrophy, heart failure, and chronic vascular inflammation. On the other hand, inappropriate stimulation of the RAS has also been associated with the pathogenesis of hypertension, heart attack, stroke, and hypertrophy of the left ventricle and vascular smooth muscle cells. Because VitD receptors (VDRs) and RAS receptors are almost distributed in the same tissues, a possible link between VitD and the RAS is even more plausible. Furthermore, from an evolutionary point of view, both systems were developed simultaneously, actively participating in the regulation of inflammatory and immunological mechanisms. Changes in RAS activity and activation of the VDR seem to be inversely related; thus any changes in one of these systems would have a completely opposite effect on the other, making it possible to speculate that the two systems could have a feedback relationship. In fact, the pandemic of VitD deficiency could be the other face of increased RAS activity, which probably causes lower activity or lower levels of VitD. Finally, from a therapeutic point of view, the combination of RAS blockade and VDR stimulation appears to be more effective than either RAS blockade or VDR stimulation individually.Fil: Ferder, Marcelo. Universidad de Buenos Aires. Facultad de Medicina; Argentina;Fil: Inserra, Pablo Ignacio Felipe. Universidad Austral. Facultad de Cs.biomedicas; Argentina;Fil: Manucha, Walter Ariel Fernando. Universidad Nacional de Cuyo; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Ferder, León. Ponce School of Medicine and Health Sciences; Puerto Rico

Differences in RAAS/vitamin D linked to genetics and socioeconomic factors could explain the higher mortality rate in African Americans with COVID-19

COVID-19 is said to be a pandemic that does not distinguish between skin color or ethnic origin. However, data in many parts of the world, especially in the United States, begin to show that there is a sector of society suffering a more significant impact from this pandemic. The Black population is more vulnerable than the White population to infection and death by COVID-19, with hypertension and diabetes mellitus as probable predisposing factors. Over time, multiple disparities have been observed between the health of Black and White populations, associated mainly with socioeconomic inequalities. However, some mechanisms and pathophysiological susceptibilities begin to be elucidated that are related directly to the higher prevalence of multiple diseases in the Black population, including infection and death by COVID-19. Plasma vitamin D levels and evolutionary adaptations of the renin-angiotensin-aldosterone system (RAAS) in Black people differ considerably from those of other races. The role of these factors in the development and progression of hypertension and multiple lung diseases, among them SARS-CoV-2 infection, is well established. In this sense, the present review attempts to elucidate the link between vitamin D and RAAS ethnic disparities and susceptibility to infection and death by COVID-19 in Black people, and suggests possible mechanisms for this susceptibility.Fil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Ferder, León. Universidad de Maimónides; ArgentinaFil: Inserra, Felipe. Universidad de Maimónides; ArgentinaFil: García, Joxel. No especifíca;Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

The South American Plains Vizcacha, Lagostomus maximus, as a Valuable Animal Model for Reproductive Studies

The vast majority of our understanding of the mammalianreproductive biology comes from investigations mainlyperformed in mice, rats and humans. However, evidencegathered from non-conventional laboratory models, farm andwild animals strongly suggests that reproductive mechanismsshow a plethora of different strategies among species. Forinstance, studies developed in unconventional rodents suchas guinea pigs and hamsters, that share with humans someendocrine and reproductive characters, have contributed to abetter understanding of human physiology and disease [1,2]. Abetter knowledge on the variety of mechanisms that regulatereproduction could lead to improve early diagnosis, treatment,or novel strategies development to ameliorate fertility andguarantee a successful reproduction. In this letter, we brieflyintroduce Lagostomus maximus, an unconventional rodentwhose neuro-endocrinology and reproduction in general haveattracted significant interest in recent years in view of its unusualreproductive traits.Fil: Dorfman, Verónica Berta. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Inserra, Pablo Ignacio Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Leopardo, Noelia Paola. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Halperin, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Vitullo, Alfredo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentin

Vitamin D deficiency in African Americans is associated with a high risk of severe disease and mortality by SARS-CoV-2

COVID-19 is said to be a pandemic that does not distinguish skin color or ethnic origin, but data in many parts of the world, especially in the United States, begins to show that there is a sector of society that is suffering a more significant impact from this pandemic. The black population is being more vulnerable than the white population to infection and death by COVID-19, and hypertension and diabetes mellitus seems to predispose to this vulnerability. Over time, multiple disparities have been observed between the health of blacks and whites, mainly associated with inequalities in the socio-economic scope. However, little by little, some mechanisms and pathophysiological susceptibilities that are directly related to the higher prevalence of multiple diseases in the black population, including infection and death by COVID-19, begin to be elucidated.Plasma vitamin D levels and evolutionary adaptations of the renin-angiotensin-aldosterone system in black people are considerably different between this and other races, and it is well established their role in the development and progression of hypertension and multiple lung diseases, among them, COVID-19 infection.This letter to discuss and proposes whether or not vitamin D and renin-angiotensin-aldosterone system ethnical disparities influence susceptibility to infection and death by COVID-19 in black people and suggests possible mechanisms for this susceptibility.Fil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Inserra, Felipe. Universidad Maimónides; ArgentinaFil: Ferder, Leon Fernando. Universidad Maimónides; ArgentinaFil: García, Joxel. Ambitious Solutions for Health Cures; Estados UnidosFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Unexpected low genetic variation in the South American hystricognath rodent Lagostomus maximus (Rodentia: Chinchillidae)

The South American plains vizcacha, Lagostomus maximus inhabits primarily the Pampean and adjoining Espinal, Monte and Chaquenean regions of Argentina. In order to study the population genetic structure of L. maximus, a fragment of 560 bp of the mitochondrial DNA hypervariable region 1from 90 individuals collected from the 3 subspecies and 8 groups along Argentina was amplified and analyzed. We found 9 haplotypes. The haplotype network did not show an apparent phylogeographical signal. Although low levels of genetic variation were found in all the subspecies and groups analyzed, a radiation of L. maximus would have occurred from the North and Center of the Pampean region toward the rest of its geographic range in Argentina. Low levels of genetic diversity, the existence of a single genetically distinct population in Argentina and changes of its effective size indicate that metapopulation processes and changes in human population dynamics during the late-Holocene were important factors shaping the population genetic structure of L. maximus in Argentina.Fil: Gariboldi, María Constanza. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Inserra, Pablo Ignacio Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Lucero, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Failla, Mauricio. No especifíca;Fil: Perez, Sergio Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Antropología; ArgentinaFil: Vitullo, Alfredo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentin

COVID-19 pandemic and vitamin D deficiency: a different approach with an analysis of the findings and a complimentary proposal

Vitamin D is an essential immune-modulator with receptors widely distributed throughout the body, and its serum levels fluctuate significantly among individuals between winter and summer months (from 30 to 50%). This study examines the association between low vitamin D status and prevalence of COVID-19 cases around the world and proposes a relationship between the seasonal character of the human immune system strength rather than to the seasonal infectivity of viruses. Also, this review suggests the observed geographical disparities in COVID-19 infections were due to differences in vitamin D levels. On the international scale, serum vitamin D levels are reportedly lowest in China, the Middle East, and South Europe; these populations also had the largest outbreaks of COVID-19 cases. In addition to the geographical differences in vitamin D status, there are known risk groups (ethnic, age-related, pregnancies). On the contrary, some countries including Canada, Finland, and North Europe incorporate increased amounts of vitamin D through fortified foods, vitamin D supplements, and sunbathing. These countries show the lowest morbidity and mortality rates by COVID-19 infection and demonstrate that lower ambient temperatures do not contribute to a higher number of COVID-19 cases. COVID-19 has spread around the globe almost simultaneously in both warm and cold areas. Given this information, vitamin D measurement should become an essential component of public health monitoring as a biomarker of immunity status. Clinical trials should be conducted to confirm this hypothesis. COVID-19 tests should be performed together with vitamin D status tests to verify this proposed relationship.Fil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo. Facultad de Ciencias Quimicas y Tecnologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bergam, Ivana. Croatia Osiguranje Pension Company; CroaciaFil: Inserra, Felipe. Universidad Maimónides; ArgentinaFil: Ferder, Leon Fernando. Universidad Maimónides; ArgentinaFil: Reiter, Russel. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio; Estados UnidosFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; Argentin

Prolactin is a strong candidate for the regulation of luteal steroidogenesis in vizcachas (Lagostomus maximus)

Prolactin (PRL) is essential for the maintenance of the corpora lutea and the production of progesterone (P4) during gestation of mice and rats, which makes it a key factor for their successful reproduction. Unlike these rodents and the vast majority of mammals, female vizcachas (Lagostomus maximus) have a peculiar reproductive biology characterized by an ovulatory event during pregnancy that generates secondary corpora lutea with a consequent increment of the circulating P4. We found that, although the expression of pituitary PRL increased steadily during pregnancy, its ovarian receptor (PRLR) reached its maximum in midpregnancy and drastically decreased at term pregnancy. The luteinizing hormone receptor (LHR) exhibited a similar profile than PRLR. Maximum P4 and LH blood levels were recorded at midpregnancy as well. Remarkably, the P4-sinthesizing enzyme 3β-HSD accompanied the expression pattern of PRLR/LHR throughout gestation. Instead, the luteolytic enzyme 20α-HSD showed low expression at early and midpregnancy, but reached its maximum at the end of gestation, when PRLR/LHR/3ß-HSD expressions and circulating P4 were minimal. In conclusion, both the PRLR and LHR expressions in the ovary would define the success of gestation in vizcachas by modulating the levels of 20α-HSD and 3ß-HSD, which ultimately determine the level of serum P4 throughout gestation.Fil: Proietto, Sofia. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico. Departamento de Estudios Biomédicos y Biotecnológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cortasa, Santiago Andrés. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico. Departamento de Estudios Biomédicos y Biotecnológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Corso, María Clara. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico. Departamento de Estudios Biomédicos y Biotecnológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Inserra, Pablo Ignacio Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico. Departamento de Estudios Biomédicos y Biotecnológicos; ArgentinaFil: Charif, Santiago Elías. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico. Departamento de Estudios Biomédicos y Biotecnológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schmidt, Alan Raul. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico. Departamento de Estudios Biomédicos y Biotecnológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Di Giorgio, Noelia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lux Lantos, V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vitullo, Alfredo Daniel. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico. Departamento de Estudios Biomédicos y Biotecnológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dorfman, Verónica Berta. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico. Departamento de Estudios Biomédicos y Biotecnológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Halperin, Julia. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico. Departamento de Estudios Biomédicos y Biotecnológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Nutritional deficiency and placenta calcification underlie constitutive, selective embryo loss in pregnant South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha)

Plains vizcacha females are able to ovulate up to 800 oocytes per estrus cycle. However, just 10–12 embryos are implanted and only two of them, those located nearest the cervix, are gestated to term. Between 26 and 70 days post-coitum, a constitutive resorption occurs from the embryos located proximal to the ovary, extending progressively toward those distally implanted. Our previous studies on the dynamics of gestation in L. maximus, led us to hypothesize some kind of placental and nutritional insufficiency as the basis for the resorption process. We analyzed histology and arterial architecture of the reproductive tract in pregnant and non-pregnant females. Uterine horns are irrigated through the uterine artery, a branch of the internal iliac artery, in an ascending way from the cervix; segmental arteries irrigating the embryo vesicles become thinner as they approach the ovary. Contrast solution administered during angiographies accumulated in the placenta of embryos closest to cervix. Thus, blood stream favors the embryos nearest the cervix, indicating a gradual nutritional deficiency of those closest to the ovary. Besides, placenta becomes calcified early, at mid-gestation, during the resorption process. Finally, the detection of specialized endothelial venules and inflammatory cells suggest the concurrent participation of immunological processes in embryo vesicles undergoing resorption.Fil: Giacchino, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Claver, Juan Alberto. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Histología y Embriologías; ArgentinaFil: Inserra, Pablo Ignacio Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Lange, Fernando D.. Universidad Maimónides; ArgentinaFil: Gariboldi, María Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Ferraris, Sergio Raúl. Universidad Maimónides; ArgentinaFil: Vitullo, Alfredo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentin

Early detection of chronic kidney disease: multidisciplinary document

El aumento de la prevalencia de pacientes con Enfermedad Renal Crónica (ERC), la ha convertido en un problema de Salud Pública mundial, no sólo por el requerimiento de tratamiento sustitutivo renal, sino porque el desarrollo de enfermedad cardiovascular constituye la primera causa de muerte en estos pacientes. La creatinina plasmática (Crp) no siempre resulta un marcador precoz, pues su valor en sangre se eleva por encima del límite superior del intervalo de referencia cuando el Índice de Filtrado Glomerular (IFG) disminuye a la mitad. La medición del IFG con marcadores exógenos es el mejor indicador para evaluar la función renal (FR), aunque su uso en la práctica clínica se reserva para situaciones especiales. El Índice de depuración de creatinina (IDC) puede presentar errores por causa de una mala recolección de orina. Además, sobreestima el IFG debido a que la creatinina, además de ser excretada, se secreta a nivel tubular. La utilización de fórmulas asociadas a Crp está recomendada por la mayoría de las sociedades científicas. La ecuación MDRD-4 se adoptó por consenso "IFGe (mL/min/1,73 m2)= 186 x (Crp) -1.154 x (edad) -0.203 x (0,742 mujer) x (1,212 raza negra)". El factor inicial es 175 cuando el resultado de Crp es trazable a Espectrometría de Masa con Dilución Isotópica (EM-DI). Esta fórmula no es aplicable en casos de embarazadas, hospitalizados, menores de 18 o mayores de 70 años, amputados, etc. Dado que la medición de Crp es la mayor fuente de error para el cálculo de IFGe, el laboratorio debe validar su procedimiento analítico para determinar creatinina. El Error Total no debe superar el 8% para que no produzca un aumento mayor del 10% en la estimación del IFG. Para la detección de ERC se recomienda: 1) Estimar la VFG utilizando la ecuación MDRD-4 asociada a Crp (fuerza de recomendación C). 2) Informar valores de más de 60 mL/min/1,73 m2 sólo como "mayor de 60" y los valores menores de 60, como el número exacto obtenido; 3) Excluir en sistemas con cálculos automáticos las situaciones que limitan el uso de la ecuación.The increase in prevalence of patients with Chronic Kidney Disease (CKD) has turned it a worldwide public health problem not only due to its requirement of a kidney replaceable treatment, but also because cardiovascular disease is now the main cause of death among these patients. Plasma Creatinine (Crp) is not always an early marker, due to the fact that its blood levels exceed the highest limit of the reference range when the Glomerular Filtration Rate (GFR) decreases to a half. GFR measurement with exogenous markers is the best indicator to test renal function (RF), although its use in the clinical practice is only restricted to special situations. Creatinine Clearance (CC) may have errors caused by an inadequate urine collection. Moreover, it overestimates the GFR considering that creatinine is not only excreted but also secreted at the tubular level. The utilization of formulas associated to Crp is recommended by most of the Scientific Societies. The MDRD-4 equation has been adopted by consensus "eGFR (mL/min/1.73 m2)= 186 x (Crp) -1.154 x (age) -0.203 x (0.742 woman) x (1.212 black people)". When the creatinine results are traceable to isotope Dilution/Mass Spectrometry reference method, the initial factor is 175. This formula does not apply to pregnant women, hospitalized patients, people under 18 or older than 70 years old, amputees, etc. Given that the measurement of Crp is the biggest cause of error for the calculation of eGFR, the lab should validate the analytical procedure to determine creatinine. The Total Error should not exceed 8% in order not to yield an increase over 10% of GFR estimation. For CKD detection, it is recommended as follows: 1) Estimate the GFR using MDRD-4´s equation associated to Crp. (Strength of Recommendation C); 2) Report values over 60 mL/min/1.73 m2 only as "over 60" and values under 60 as the exact number obtained; 3) Exclude from automatic calculation systems, situations that limit the use of the equation.Fil: Alles, Alberto. Sociedad Argentina de Nefrología; ArgentinaFil: Fraga, Adriana Raquel. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Sociedad Argentina de Nefrología; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: García, Roberto Daniel. Fundación Bioquímica Argentina; ArgentinaFil: Gómez, Alejandra. Asociación Bioquímica Argentina; ArgentinaFil: Greloni, Gustavo. Sociedad Argentina de Nefrología; ArgentinaFil: Inserra, Pablo Ignacio Felipe. Sociedad Argentina de Nefrología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mazziotta, Daniel. Fundación Bioquímica Argentina; ArgentinaFil: Torres, María Lía. Fundación Bioquímica Argentina; ArgentinaFil: Villagra, Alberto. Asociación Bioquímica Argentina; Argentin

Lungs as Target of COVID-19 Infection: Protective Common Molecular Mechanisms of Vitamin D and Melatonin as a New Potential Synergistic Treatment

COVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level. Until now, there is not a specific and definitive treatment for this pathology that worries the world population, especially the older adults who constitute the main risk group. In this context, it results in a particular interest in the evaluation of the efficacy of existing pharmacological agents that may be used for overcoming or attenuating the severity of this pulmonary complication that has ended the lives of many people worldwide. Vitamin D and melatonin could be good options for achieving this aim, taking into account that they have many shared underlying mechanisms that are able to modulate and control the immune adequately and oxidative response against COVID-19 infection, possibly even through a synergistic interaction. The renin-angiotensin system exaltation with consequent inflammatory response has a leading role in the physiopathology of COVID-19 infection; and it may be down-regulated by vitamin D and melatonin in many organs. Therefore, it is also essential to analyze this potential therapeutic association and their relation with RAS as part of this new approach.Fil: Martín Giménez, Virna Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Catolica de Cuyo. Facultad de Ciencias Quimicas y Tecnologicas; ArgentinaFil: Inserra, Pablo Ignacio Felipe. Universidad de Maimónides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tajer, Carlos Daniel. Hospital El Cruce Néstor Kirchner; ArgentinaFil: Mariani, Javier. Hospital El Cruce Néstor Kirchner; ArgentinaFil: Ferder, Leon Fernando. Universidad de Maimónides; ArgentinaFil: Reiter, Russel. University Of Texas At San Antonio.; Estados UnidosFil: Manucha, Walter Ariel Fernando. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin