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

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

Key Aspects to Consider about Beneficial and Harmful Effects on the Central Nervous System by the Endocannabinoid Modulation Linked to New Cardiovascular Therapies

The endocannabinoid system (ECS) is closely related to the central nervous system (CNS) and exerts a promising therapeutic potential on the cardiovascular system, mainly through its neuromodulatory, neuroprotective, and neuroinflammatory effects. For this reason, when designing new treatments for different cardiovascular pathologies, it is necessary to consider the side effects that such therapies can cause at the neurological level. ObjectiveTo deepens the knowledge of each cannabinoid (CB) and the molecular mechanisms that can lead to undesired results to analyze its possible use in cardiovascular therapy.MethodsThe present review analyzes the psychoactive consequences of anandamide and other similar substances such as other endocannabinoids, phytocannabinoids, and synthetic cannabinoids, to assess their little-explored therapeutic potential in clinical investigations. Finally, the major behavioral tests most used until the moment to predict possible changes in the conduct of animals treated with various substances of cannabinoid nature are summarized. It has been observed that endocannabinoids have few adverse central nervous effects, unlike the phytocannabinoids, synthetic cannabinoids and antagonists of CB receptors. These molecules act on typical receptors due to a similar spatial configuration; however, their structure is not identical between them. For this reason, the competition and displacement of endogenous ligands of the ECS by exogenous cannabinoids provokes an alteration in the CNS normal functioning, leading to the associated side effects. An exhaustive analysis of each cannabinoid and the molecular mechanisms that can lead to undesired results is necessary at the time of proposing them as news cardiovascular therapeutic alternatives.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: Mocayar Maron, Feres Jose. 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: Ferder, Leon Fernando. Universidad de Miami; 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. Facultad de Ciencias Médicas; 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

The kidney in aging

Aging is a slow, inflammatory biological process that affects many organs of which the kidney is one of the main targets. Aging is associated with a decline in renal function coincident with a progressive loss of nephrons, with glomerular and tubulointerstitial scarring. These changes begin in the fourth decade of life and accelerate between the 5th and 6th decade, resulting in alterations in glomerular and tubular function, systemic hemodynamics and body homeostasis. While aging-related changes begin in mid-life, most of the discussion will revolve around the management of the older population, defined as > 65 years of age. It is important to realize that aging-associated renal disease may not be an inevitable consequence of life. Some subjects do not show age-related decline in GFR, and in some populations hypertension does not increase with aging, the latter occurring primarily in non-Westernized groups habitually on low sodium diets. This has led some to hypothesize that aging-associated renal disease may be an active process that is potentially preventable.Sociedad Argentina de Fisiologí

Pharmacological agents in the prophylaxis/treatment of organophosphorous pesticide intoxication

642-650 Organophosphorus pesticide poisoning causes tens of thousands of deaths each year across the world. Poisoning includes acute cholinergic crisis as a result of AChE inhibition, intermediate syndrome (IMS) due to neuromuscular necrosis and organophosphate-induced delayed neuropathy (OPIDN) due to inhibition of neuropathy target esterase (NTE). Standard treatment for acute poisoning involves administration of intravenous atropine, oxime 2-PAM to counter AChE inhibition and diazepam for CNS protection. However clinical trials showed ineffectiveness of the standard therapy regimen. Although new oximes that can reactivate both peripheral and cerebral AChE and other prophylactic agents such as human serum butyrylcholinesterase (Hu BChE), sodium bicarbonate, huperzine A (a reversible ChE inhibitor) with imidazenil (a GABAA receptor modulator) have been proved effective in animal models, systematic clinical trials in patients are warranted. For IMS which is non-responsive to standard therapy, supportive therapy specifically artificial respiration followed by recovery is indicated. For OPIDN which has a different target (NTE) than AChE, standard therapy is ineffective. However neuroprotective drugs such as corticosteroids proved partially effective. Pretreatment with protease inhibitor PMSF has been shown to protect the aging of NTE and prevent the development of delayed symptoms in hens. Since the biology of NTE is being explored, new pharmacological agents should be developed in future. OP pesticide poisoning is a serious condition that needs rapid diagnosis and treatment. Since respiratory failure is the major reason for mortality, artificial respiration, careful monitoring, appropriate treatment and early recognition of OP pesticide poisoning may decrease the mortality rate among these patients. </smarttagtype

Alcohol-induced hypertension: Mechanism and prevention.

Epidemiological, preclinical and clinical studies established the association between high alcohol consumption and hypertension. However the mechanism through which alcohol raises blood pressure remains elusive. Several possible mechanisms have been proposed such as an imbalance of the central nervous system, impairment of the baroreceptors, enhanced sympathetic activity, stimulation of the renin-angiotensin-aldosterone system, increased cortisol levels, increased vascular reactivity due to increase in intracellular calcium levels, stimulation of the endothelium to release vasoconstrictors and loss of relaxation due to inflammation and oxidative injury of the endothelium leading to inhibition of endothelium-dependent nitric oxide production. Loss of relaxation due to inflammation and oxidative injury of the endothelium by angiotensin II leading to inhibition of endothelium-dependent nitric oxide production is the major contributors of the alcohol-induced hypertension. For the prevention of alcohol-induced hypertension is to reduce the amount of alcohol intake. Physical conditioning/exercise training is one of the most important strategies to prevent/treat chronic alcohol-induced hypertension on physiological basis. The efficacious pharmacologic treatment includes the angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARBs) which have antioxidant activity and calcium channel blockers. The most effective prevention and treatment of alcohol-induced hypertension is physical exercise and the use of ACE inhibitors or ARBs in the clinic

Inflammation, oxidative stress and renin angiotensin system in atherosclerosis.

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin II (Ang II) and a decrease in nitric oxide. The renin-angiotensin system (RAS), and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors (angiotensin-converting enzyme inhibitors)], Ang II receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in ApoE-deficient atherosclerotic mice

Therapeutic Intervention of Human Pancreatic Cancer

Pancreatic cancer is one of the most lethal malignancies in the world. The incidence of pancreatic cancer keeps on increasing without a significant decrease in mortality. Current therapeutic options are surgical resections, radiation, and chemo, biologic, immune and palliative therapy. Surgical therapies are associated with acceptable outcomes but resected patients suffer from tumor recurrence. The role of post-operative radiotherapy reported increased survival. Currently four chemotherapy drugs approved by the United States Food and Drug Administration (US FDA) for the treatment of pancreatic cancer: ABRAXANE (albumin-bound paclitaxel), gemcitabine, 5-fluorouracil (5- FU) and ONIVYDE (irinotecan liposome injection). Among the conventional chemotherapies the combination of abraxane (nab-paclitaxel) with gemcitabine and FOLFIRINOX (5-FU/leucovorin, irinotecan, oxaliplatin) in metastatic pancreatic cancer patients are promising. Among the targeted therapies the combination of gemcitabine, erlotinib and capecitabine are likely to form the base for future treatment. Under biologic or immunotherapy antibodies against programmed death-1 receptor (PD-1), its ligand PD-L1, cytotoxic T lymphocyte associated antigen-4 (CTLA-4), KRAStargeting vaccines, mucin-1 (MUC1) vaccine, telomerase-targeting vaccine (GV1001), gastrinbased vaccine, dendritic cell (DC)-based vaccine alone or combined with Lymphokine Activated Killer (LAK) cells and allogeneic GM-CSF-secreting vaccine (GVAX) are new therapeutic option for pancreatic cancer. Current and future clinical trials using natural compounds such as deltatocotrienol, Huang-Qin-Tang (HQT) and its botanical formulation (PHY906) and curcumin in combination with other agents are ongoing to discover more effective ways of treating pancreatic cancer patients