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1.
Sci Total Environ ; 773: 145152, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33940720

RESUMEN

In the recent decades, the role of wastewater treatment plants has been entrenched for the dissemination of antibiotic resistant bacteria into the environment. The present study explores the dynamics of earthworms-microorganisms interactions involved in the high treatment efficacy of vermifiltration technology along with reduction of antibiotic resistant bacteria (ARB). This study is the first of its kind to investigate the performance efficacy of vermifilter (VF) for clinical laboratory wastewater treatment. The results of the study showed that earthworms and VF associated microbial community had a significant effect on Biochemical Oxygen Demand (BOD) and Chemical Oxygen Demand (COD) reduction (78-85%), coliforms and pathogen removal (>99.9%) and caused a significant shift in the prevalence pattern of ARB. Molecular profiling of resistance causing genes such as ESBL (blaSHV, blaTEM and blaCTX-M), MRSA (mec-A) and Colistin (mcr-1) confirmed the probable mechanisms behind the resistance pattern. The microbial community diversity in the influent, earthworm's coelomic fluid and gut and filter media layers associated with the VF assists in the formation of biofilm, which helps in the removal of pathogens from the wastewater. This biofilm formation further results in a paradigm shift in the resistance profile of ARB and ARG, specifically most effective against drugs, targeting cell wall and protein synthesis inhibition such as Ampicillin, Ticarcillin, Gentamicin and Chloramphenicol. These findings further validate vermifiltration technology as a sustainable and natural treatment technology for clinical laboratory wastewater, specifically for the removal of pathogens and antibiotic resistance.


Asunto(s)
Oligoquetos , Purificación del Agua , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Animales , Antibacterianos/farmacología , Bacterias/genética , Laboratorios , Oligoquetos/genética
2.
Cardiovasc Toxicol ; 21(6): 498-503, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33835386

RESUMEN

In March 2019 began the global pandemic COVID-19 caused by the new Coronavirus SARS-CoV-2. The first cases of SARS-CoV-2 infection occurred in November-19 in Wuhan, China. The preventive measures taken did not prevent the rapid spread of the virus to all countries around the world. To date, there are about 2.54 million deaths, effective vaccines are in clinical trials. SARS-CoV-2 uses the ACE-2 protein as an intracellular gateway. ACE-2 is a key component of the Renin Angiotensin (RAS) system, a key regulator of cardiovascular function. Considering the key role of ACE-2 in COVID-19 infection, both as an entry receptor and as a protective role, especially for the respiratory tract, and considering the variations of ACE-2 and ACE during the stages of viral infection, it is clear the important role that the pharmacological regulation of RAS and ACE-2 can assume. This biological knowledge suggests different pharmacological approaches to treat COVID-19 by modulating RAS, ACE-2 and the ACE/ACE2 balance that we describe in this article.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Antivirales/uso terapéutico , Pulmón/efectos de los fármacos , Receptores Virales/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , /efectos de los fármacos , /metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antivirales/efectos adversos , /virología , Interacciones Huésped-Patógeno , Humanos , Pulmón/enzimología , Pulmón/virología , Proteínas Recombinantes/uso terapéutico , /patogenicidad , Internalización del Virus
3.
Physiology (Bethesda) ; 36(3): 160-173, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33904788

RESUMEN

Beyond blood pressure control, angiotensin receptor blockers reduce common injury mechanisms, decreasing excessive inflammation and protecting endothelial and mitochondrial function, insulin sensitivity, the coagulation cascade, immune responses, cerebrovascular flow, and cognition, properties useful to treat inflammatory, age-related, neurodegenerative, and metabolic disorders of many organs including brain and lung.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antivirales/uso terapéutico , Sistema Renina-Angiotensina/efectos de los fármacos , /efectos de los fármacos , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Animales , Antiinflamatorios/uso terapéutico , Antihipertensivos/uso terapéutico , Antivirales/efectos adversos , /fisiopatología , Fibrinolíticos/uso terapéutico , Humanos , /patogenicidad
4.
Int J Mol Sci ; 22(6)2021 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-33799462

RESUMEN

In silico and in vitro methods were used to analyze ACE- and DPP-IV-inhibiting potential of Gouda cheese with a modified content of ß-casein. Firstly, the BIOPEP-UWM database was used to predict the presence of ACE and DPP-IV inhibitors in casein sequences. Then, the following Gouda cheeses were produced: with decreased, increased, and normative content of ß-casein after 1 and 60 days of ripening each (six variants in total). Finally, determination of the ACE/DPP-IV-inhibitory activity and the identification of peptides in respective Gouda-derived water-soluble extracts were carried out. The identification analyses were supported with in silico calculations, i.e., heatmaps and quantitative parameters. All Gouda variants exhibited comparable ACE inhibition, whereas DPP-IV inhibition was more diversified among the samples. The samples derived from Gouda with the increased content of ß-casein (both stages of ripening) had the highest DPP-IV-inhibiting potency compared to the same samples measured for ACE inhibition. Regardless of the results concerning ACE and DPP-IV inhibition among the cheese samples, the heatmap showed that the latter bioactivity was predominant in all Gouda variants, presumably because it was based on the qualitative approach (i.e., peptide presence in the sample). Our heatmap did not include the bioactivity of a single peptide as well as its quantity in the sample. In turn, the quantitative parameters showed that the best sources of ACE/DPP-IV inhibitors were all Gouda-derived extracts obtained after 60 days of the ripening. Although our protocol was efficient in showing some regularities among Gouda cheese variants, in vivo studies are recommended for more extensive investigations of this subject.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/aislamiento & purificación , Caseínas/química , Queso/análisis , Inhibidores de la Dipeptidil-Peptidasa IV/aislamiento & purificación , Inhibidores de la Enzima Convertidora de Angiotensina/química , Biología Computacional , Dipeptidil Peptidasa 4/química , Inhibidores de la Dipeptidil-Peptidasa IV/química , Humanos , Péptidos/química , Péptidos/aislamiento & purificación , Péptidos/farmacología , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/genética
5.
PLoS One ; 16(4): e0248080, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33891615

RESUMEN

BACKGROUND: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses. METHODS AND FINDINGS: In this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs. non-ARB/ACEI (excluding Veterans with compelling indications to reduce confounding by indication) and (B) ARB vs. ACEI among (1) SARS-CoV-2+ outpatients and (2) COVID-19 hospitalized inpatients. The primary outcome was all-cause hospitalization or mortality (outpatients) and all-cause mortality (inpatients). We estimated hazard ratios (HR) using propensity score-weighted Cox regression. Baseline characteristics were well-balanced between exposure groups after weighting. Among outpatients, there were 5.0 and 6.0 primary outcomes per 100 person-months for ARB/ACEI (n = 2,482) vs. non-ARB/ACEI (n = 2,487) users (HR 0.85, 95% confidence interval [CI] 0.73-0.99, median follow-up 87 days). Among outpatients who were ARB (n = 4,877) vs. ACEI (n = 8,704) users, there were 13.2 and 14.8 primary outcomes per 100 person-months (HR 0.91, 95%CI 0.86-0.97, median follow-up 85 days). Among inpatients who were ARB/ACEI (n = 210) vs. non-ARB/ACEI (n = 275) users, there were 3.4 and 2.0 all-cause deaths per 100 person months (HR 1.25, 95%CI 0.30-5.13, median follow-up 30 days). Among inpatients, ARB (n = 1,164) and ACEI (n = 2,014) users had 21.0 vs. 17.7 all-cause deaths, per 100 person-months (HR 1.13, 95%CI 0.93-1.38, median follow-up 30 days). CONCLUSIONS: This observational analysis supports continued ARB or ACEI use for patients already using these medications before SARS-CoV-2 infection. The novel beneficial association observed among outpatients between users of ARBs vs. ACEIs on hospitalization or mortality should be confirmed with randomized trials.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Hipertensión/tratamiento farmacológico , Anciano , /virología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Hipertensión/patología , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Veteranos
6.
PLoS One ; 16(4): e0250581, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33891663

RESUMEN

BACKGROUNDS: Data on how lifestyle changes due to the coronavirus disease 2019 (COVID-19) pandemic have influenced the clinical features of kidney disease patients remain scarce. METHODS: This study retrospectively analyzed clinical variables in patients with stage G1-G4 chronic kidney disease (CKD) with complete or incomplete remission of proteinuria, who were managed in a nephrology outpatient clinic of a university hospital in Tokyo. The clinical variables during the COVID-19 pandemic (term 1, June-July 2020) were compared to those one year before the pandemic (term 0, June-July 2019). The urinary protein excretion (UPE) was used as the primary outcome measure. RESULTS: This study included 325 patients with stage G1-G4 CKD (mean age 58.5 years old, 37.5% female, 80.6% on renin-angiotensin aldosterone system inhibitors [RAASis], 12.0% on maintenance dose immunosuppression therapy) evaluated at term 0. The UPE at terms 0 and 1 was 247 (92-624) and 203 (84-508) mg/day [median (25th-75th percentile)], respectively; the value in term 1 was 18% lower than that in term 0 (p<0.001), with no marked difference in body weight, blood pressure, protein intake or urinary salt excretion. In multivariable analyses, incomplete remission of proteinuria in term 0 (odds ratio [OR] = 2.70, p = <0.001), RAASi use (OR = 2.09, p = 0.02) and decreased urinary salt excretion in term 1 vs. term 0 (OR = 1.94, p = 0.002) were identified as independent variables associated with reduced UPE in term 1 vs. term 0. No significant interactions between the variables were observed. CONCLUSION: In kidney disease patients receiving standard medical care from nephrologists, the UPE after the emergency declaration in relation to the COVID-19 pandemic was lower than before the declaration. The UPE reduction may be associated with reduced dietary salt intake during the pandemic in patients treated with RAASi for insufficient control of proteinuria. Our results support the current proposal to continue therapeutic approaches to these patients, which involve RAASi therapy along with optimizing dietary habits, even while dealing with the COVID-19 pandemic.


Asunto(s)
Proteinuria/patología , Insuficiencia Renal Crónica/patología , Adulto , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , /patología , Femenino , Humanos , Japón/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Proteinuria/complicaciones , Inducción de Remisión , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
7.
Clinics (Sao Paulo) ; 76: e2342, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33852652

RESUMEN

Among the multiple uncertainties surrounding the novel coronavirus disease (COVID-19) pandemic, a research letter published in The Lancet implicated drugs that antagonize the renin-angiotensin-aldosterone system (RAAS) in an unfavorable prognosis of COVID-19. This report prompted investigations to identify mechanisms by which blocking angiotensin-converting enzyme 2 (ACE2) could lead to serious consequences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The possible association between RAAS inhibitors use and unfavorable prognosis in this disease may have been biased by the presence of underlying cardiovascular diseases. As the number of COVID-19 cases has increased worldwide, it has now become possible to investigate the association between RAAS inhibitors and unfavorable prognosis in larger cohorts. Observational studies and one randomized clinical trial failed to identify any consistent association between the use of these drugs and unfavorable prognosis in COVID-19. In view of the accumulated clinical evidence, several scientific societies recommend that treatment with RAAS inhibitors should not be discontinued in patients diagnosed with COVID-19 (unless contraindicated). This recommendation should be followed by clinicians and patients.


Asunto(s)
Coronavirus , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Humanos , Peptidil-Dipeptidasa A/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Sistema Renina-Angiotensina
8.
Zhonghua Yi Xue Za Zhi ; 101(15): 1064-1070, 2021 Apr 20.
Artículo en Chino | MEDLINE | ID: mdl-33878833

RESUMEN

Objective: To investigate the application status of optimal medical therapy (OMT) in patients with coronary heart disease after percutaneous coronary intervention (PCI) and its influence on the 1-year prognosis of patients after surgery. Methods: Data of 3 812 patients diagnosed with coronary heart disease by coronary angiography and successfully completed PCI in the Department of Cardiology, TEDA International Cardiovascular Hospital from October 2016 to September 2017 were prospectively collected. The OMT status and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during the hospitalization and 1, 6, and 12 months after discharge were recorded. Patients were divided into OMT group (n=1 299) and non-OMT group (n=2 289) according to their adherence to OMT after PCI. Chi-square test was used to compare the differences of MACCE between groups, and to screen for significant differences and clinically significant variables between groups. Cox regression model was used to analyze the influencing factors of MACCE after PCI. Results: Among 3 588 patients (224 cases lost to follow-up), 58.8% (2 110/3 588) used OMT during hospitalization after PCI, and 36.0% (1 293/3 588) still adhered to OMT after 12 months of follow-up. The utilization rates of OMT showed a decreasing trend, among which till the 12th month, ß-blockers and ACEI/ARB showed the greatest decreasing degree, from 75.3%(2 701/3 588) and 75.1%(2 692/3 588) to 59.1%(2 122/3 588) and 53.0%(1 903/3 588). Pearson χ2 analysis showed that elderly patients, the number of amalgamative diseases, history of PCI, history of chronic myocardial infarction, history of chronic renal insufficiency, the lesion counts, lesion type, the Gensini score, adhere to the OMT and smoking during the follow-up were related to postoperative MACCE, the difference was statistically significant (P<0.05). Cox regression model showed that OMT adherence after PCI was an independent protective factor for postoperative MACCE events (HR=0.471,95%CI: 0.300-0.734, P=0.001). Conclusion: The application of OMT after PCI was suboptimal, and the application rate decreased with the lengthening of the discharge time, among which the use of ACEI/ARB and ß-blockers deserved more attention. Adherence to OMT after PCI was an independent protective factor, which could reduce the incidence of postoperative MACCE and improve the prognosis of patients.


Asunto(s)
Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Anciano , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Humanos , Pronóstico , Resultado del Tratamiento
9.
Einstein (Sao Paulo) ; 19: eRW5498, 2021.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-33852678

RESUMEN

Angioedema attacks are common causes of emergency care, and due to the potential for severity, it is important that professionals who work in these services know their causes and management. The mechanisms involved in angioedema without urticaria may be histamine- or bradykinin-mediated. The most common causes of histamine-mediated angioedema are foods, medications, insect sting and idiopathic. When the mediator is bradykinin, the triggers are angiotensin-converting enzyme inhibitors and factors related to acquired angioedema with deficiency of C1-inhibitor or hereditary angioedema, which are less common, but very important because of the possibility of fatal outcome. Hereditary angioedema is a rare disease characterized by attacks of edema that affect the subcutaneous tissue and mucous membranes of various organs, manifesting mainly by angioedema and abdominal pain. This type of angioedema does not respond to the usual treatment with epinephrine, antihistamines and corticosteroids. Thus, if not identified and treated appropriately, these patients have an estimated risk of mortality from laryngeal edema of 25% to 40%. Hereditary angioedema treatment has changed dramatically in recent years with the development of new and efficient drugs for attack management: plasma-derived C1 inhibitor, recombinant human C1-inhibitor, bradykinin B2 receptor antagonist (icatibant), and the kallikrein inhibitor (ecallantide). In Brazil, plasma-derived C1 inhibitor and icatibant have already been approved for use. Proper management of these patients in the emergency department avoids unnecessary surgery and, especially, fatal outcomes.


Asunto(s)
Angioedema , Angioedemas Hereditarios , Angioedema/diagnóstico , Angioedema/tratamiento farmacológico , Angioedemas Hereditarios/diagnóstico , Angioedemas Hereditarios/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Brasil , Servicio de Urgencia en Hospital , Humanos
10.
Pol Merkur Lekarski ; 49(290): 138-142, 2021 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-33895761

RESUMEN

Neurodegenerative processes with type 2 diabetes mellitus in particular aggravate the course of the disease, change the usual life rhythm, and are a considerable part of high disability and lethality rates. AIM: The aim of the study was to examine enalapril effect on protein peroxide oxidation, activity of proteolysis and fibrinolysis enzymes and morphological state of the cerebral cortex and hippocampus under conditions of neurodegeneration in case of experimental type 2 diabetes mellitus. MATERIALS AND METHODS: Changes in the content of protein peroxide oxidation products activity of proteolysis and fibrinolysis enzymes in the cerebral cortex and hippocampus are examined under enalapril effect (1 mg/kg) in nonlinear laboratory albino male rats with neurodegeneration under conditions of type 2 diabetes mellitus simulated by streptozotocin and high-fat diet. RESULTS: After introduction of enalapril during 14 days for rats with type 2 diabetes mellitus the content of proteins of a neutral and main character, activity of proteolysis and fibrinolysis enzymes in the cerebral cortex and hippocampus decreases, which is indicative of reduced protein peroxide oxidation, intensified under conditions of diabetic neurodegeneration. Morphological picture of the cerebral cortex and hippocampus is characterized by a decreased amount of cells with karyopyknosis and increased relative density of the tigroid substance staining of neurons and lack of denudation signs of the vessels, which is indicative of a positive rebuilding of the neuron structure. CONCLUSIONS: The conducted study demonstrates a protective effect of enalapril in case of central neurodegeneration caused by type 2 diabetes mellitus, one of the mechanisms of which is decrease of protein peroxide oxidation in the cerebral cortex and hippocampus inhibiting the processes of nerve cells destruction.


Asunto(s)
Diabetes Mellitus Tipo 2 , Enalapril , Inhibidores de la Enzima Convertidora de Angiotensina , Animales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Enalapril/farmacología , Enalapril/uso terapéutico , Estrés Oxidativo , Ratas , Estreptozocina
11.
Cells ; 10(3)2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33804069

RESUMEN

Evidence has arisen in recent years suggesting that a tissue renin-angiotensin system (tRAS) is involved in the progression of various human diseases. This system contains two regulatory pathways: a pathological pro-inflammatory pathway containing the Angiotensin Converting Enzyme (ACE)/Angiotensin II (AngII)/Angiotensin II receptor type 1 (AGTR1) axis and a protective anti-inflammatory pathway involving the Angiotensin II receptor type 2 (AGTR2)/ACE2/Ang1-7/MasReceptor axis. Numerous studies reported the positive effects of pathologic tRAS pathway inhibition and protective tRAS pathway stimulation on the treatment of cardiovascular, inflammatory, and autoimmune disease and the progression of neuropathic pain. Cell senescence and aging are known to be related to RAS pathways. Further, this system directly interacts with SARS-CoV 2 and seems to be an important target of interest in the COVID-19 pandemic. This review focuses on the involvement of tRAS in the progression of the mentioned diseases from an interdisciplinary clinical perspective and highlights therapeutic strategies that might be of major clinical importance in the future.


Asunto(s)
Antagonistas de Receptores de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Peptidil-Dipeptidasa A/metabolismo , Receptores de Angiotensina/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Autoinmunidad/efectos de los fármacos , Autoinmunidad/genética , /genética , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Humanos , Inflamación/tratamiento farmacológico , Inflamación/genética , Inflamación/metabolismo , Receptores de Angiotensina/genética , Regeneración/efectos de los fármacos , Regeneración/genética , Regeneración/fisiología , Sistema Renina-Angiotensina/genética , Sistema Renina-Angiotensina/fisiología , Vulvodinia/inmunología , Vulvodinia/fisiopatología
12.
Artículo en Inglés | MEDLINE | ID: mdl-33804606

RESUMEN

The emergence of antibiotic-resistant pathogens due to worldwide antibiotic use is raising concern in several settings, including aquaculture. In this work, the selection of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) was evaluated after exposure of zebrafish to oxytetracycline (OTC) for two months, followed by a recovery period. The selection of ARB in water and fish was determined using selective media. The abundance of tetA genes was estimated through qPCR. Higher prevalence of ARB was measured in all samples exposed to the antibiotic when compared to control samples, although statistical significance was only achieved five days after exposure. Isolates recovered from samples exposed to the antibiotic were affiliated with Pseudomonas and Stenotrophomonas. Various antibiotic susceptibility profiles were detected and 37% of the isolates displayed multidrug resistance (MDR). The selection of the tetA gene was confirmed by qPCR at the highest OTC concentration tested. Two MDR isolates, tested using zebrafish embryos, caused significant mortality, indicating a potential impact on fish health and survival. Overall, our work highlights the potential impact of antibiotic contamination in the selection of potential pathogenic ARB and ARGS.


Asunto(s)
Genes Bacterianos , Pez Cebra , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Animales , Antibacterianos/toxicidad , Bacterias/genética , Agua
13.
Medicine (Baltimore) ; 100(15): e25537, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33847680

RESUMEN

BACKGROUND: Although there are many studies showing potential benefit in aortic stenosis (AS) patients taking angiotensin-converting enzyme inhibitors (ACEI), but these studies are subject to significant selection and other biases, making the results challenging to interpret. Furthermore, the evidence on the use of ACEI in AS patients has not been reviewed systematically; we thus conducted this protocol assess the clinical effectiveness and safety of ACEI for patients with AS. METHODS: The following search terms will be used in PUBMED, Scopus, EMBASE, and Cochrane Library databases on May, 2021, as the search algorithm: (angiotensin-converting enzyme inhibitors) OR (ACEI) AND (aortic stenosis) OR (AS). Two searchers will independently draft and carry out the search strategy, and the third member will further complete it. The studies on cohort study focusing on assessing the efficacy of ACEI on AS patients will be included in our meta-analysis. At least one of the following outcomes should have been measured: left ventricular mass, exercise tolerance, B-type natriuretic peptide, adverse event, functional outcomes, and aortic valve area. All outcomes are pooled on random-effect model. A P value of <.05 is considered to be statistically significant. RESULTS: The results of this research will be delivered in a peer-reviewed journal. CONCLUSION: Depending on the previous studies, we assumed that ACEI could possibly improve the clinical symptoms and outcomes of symptomatic AS. SYSTEMATIC REVIEW REGISTRATION NUMBER: 10.17605/OSF.IO/G9KPT.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Estenosis de la Válvula Aórtica/tratamiento farmacológico , Estudios de Cohortes , Humanos , Metaanálisis como Asunto , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
14.
Circ Res ; 128(7): 1062-1079, 2021 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-33793331

RESUMEN

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associates with a considerable high rate of mortality and represents currently the most important concern in global health. The risk of more severe clinical manifestation of COVID-19 is higher in males and steeply raised with age but also increased by the presence of chronic comorbidities. Among the latter, early reports suggested that arterial hypertension associates with higher susceptibility to SARS-CoV-2 infection, more severe course and increased COVID-19-related deaths. Furthermore, experimental studies suggested that key pathophysiological hypertension mechanisms, such as activation of the renin-angiotensin system (RAS), may play a role in COVID-19. In fact, ACE2 (angiotensin-converting-enzyme 2) is the pivotal receptor for SARS-CoV-2 to enter host cells and provides thus a link between COVID-19 and RAS. It was thus anticipated that drugs modulating the RAS including an upregulation of ACE2 may increase the risk for infection with SARS-CoV-2 and poorer outcomes in COVID-19. Since the use of RAS-blockers, ACE inhibitors or angiotensin receptor blockers, represents the backbone of recommended antihypertensive therapy and intense debate about their use in the COVID-19 pandemic has developed. Currently, a direct role of hypertension, independent of age and other comorbidities, as a risk factor for the SARS-COV-2 infection and COVID-19 outcome, particularly death, has not been established. Similarly, both current experimental and clinical studies do not support an unfavorable effect of RAS-blockers or other classes of first line blood pressure lowering drugs in COVID-19. Here, we review available data on the role of hypertension and its management on COVID-19. Conversely, some aspects as to how the COVID-19 affects hypertension management and impacts on future developments are also briefly discussed. COVID-19 has and continues to proof the critical importance of hypertension research to address questions that are important for global health.


Asunto(s)
/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Antagonistas de Receptores de Angiotensina/metabolismo , Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , /metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/metabolismo , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Humanos , Hipertensión/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiología , Factores de Riesgo
15.
J Cardiovasc Med (Hagerstown) ; 22(5): 329-334, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33795584

RESUMEN

Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus first identified in Wuhan, China. The global number of confirmed cases of COVID-19 has surpassed 28,285,700 with mortality that appears higher than for seasonal influenza. About 20% of COVID-19 patients have experienced cardiac involvement and myocardial infarction in patients infected with SARS-CoV-2 had a worse prognosis. Furthermore, the widespread use of antiviral drugs can be linked to a worsening of heart function. Arrhythmias and hypertension have also been reported in patients with Covid-19. On the other hand, previous cardiac diseases are present in 30% of patients infected with SARS-CoV-2. There is uncertainty in the use of ace inhibitors and angiotensin II (Ang II) antagonists in the COVID-19 era. The mechanism of action of SARS-CoV-2 has been elucidated. It has been demonstrated that angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the new coronavirus SARS-CoV-2 and it is required for host cell entry and subsequent viral replication. The effect of the SARS-CoV-2 infection is the downregulation of ACE2 that may contribute to the severity of lung pathologies as well as the cardiac function. ACE2, a homolog of ACE, is a monocarboxypeptidase that converts Ang II into angiotensin 1-7 (Ang 1-7) that with its vasodilatory, antifibrotic, antihypertrophic effects counterbalances the negative effects of Ang II. On the other hand, angiotensin-converting enzyme inhibitors (ACEi) and AT1R blockers have been shown to upregulate the expression of ACE2. Based on the mechanism of action of SARS-CoV-2, the use of renin angiotensin system (RAS) inhibitors was questioned although all scientific societies did not recommend discontinuation when clinically recommended. The BRACE CORONA, a phase 4, randomized study tested two strategies: temporarily stopping the ACE inhibitor/angiotensin receptor blockers (ARB) for 30 days versus continuing ACE inhibitors/ARBs in patients who were taking these medications chronically and were hospitalized with a confirmed diagnosis of COVID-19 was also discussed. Therefore, the goal of this review is to summarize recent laboratory and clinical investigations concerning the use of ACEi and ARBs during the COVID-19 pandemic. The available data, based also on a randomized trial, suggest that ACEIs or ARBs, when clinically indicated, should be regularly used in the COVID-19 era.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , /terapia , /patogenicidad , Humanos
16.
Medwave ; 21(2): e8105, 2021 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-33830976

RESUMEN

Objective: This living systematic review aims to provide a timely, rigorous, and continuously updated summary of the evidence available on the role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in the treatment of patients with COVID-19. Data sources: We conducted searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralized repository in L·OVE (Living OVerview of Evidence), which retrieves articles from multiple sources such as PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, among other pre-print and protocols repositories. In response to the COVID-19 emergency, L·OVE (Living OVerview of Evidence) was adapted to expand the range of evidence and customized to group all COVID-19 evidence in one place on a daily search basis. The search covered a period of time up to July 31, 2020. Eligibility criteria for selecting studies and methods: We adapted an already published standard protocol for multiple parallel living systematic reviews to this question's specificities. We included randomized trials evaluating the effect of either suspension or indication of angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers as monotherapy, or in combination versus placebo or no treatment in patients with COVID-19. We searched for randomized trials evaluating the effect of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers versus placebo or no treatment in patients with COVID-19. Two reviewers independently screened each study for eligibility, extracted data, and assessed the risk of bias. We pooled the results using meta-analysis and applied the GRADE system to assess the certainty of the evidence for each outcome. We will resubmit results every time the conclusions change or whenever there are substantial updates. Results: We screened 772 records, but none was considered for eligibility. We identified 55 ongoing studies, including 41 randomized trials evaluating angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for patients with COVID-19. Conclusions: We did not find a randomized clinical trial meeting our inclusion criteria, and hence there is no evidence for supporting the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in the treatment of patients with COVID-19. A substantial number of ongoing studies would provide valuable evidence to inform researchers and decision-makers in the near future. PROSPERO registration number: CRD42020182495. Protocol preprint DOI: 10.31219/osf.io/vp9nj.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , /tratamiento farmacológico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación
17.
Lancet Oncol ; 22(4): 558-570, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33794209

RESUMEN

BACKGROUND: Some studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials. METHODS: We searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from Jan 1, 1966, to Sept 1, 2019, to identify potentially eligible randomised controlled trials. Eligible studies were randomised controlled trials comparing one blood pressure lowering drug class with a placebo, inactive control, or other blood pressure lowering drug. We also required that trials had at least 1000 participant years of follow-up in each treatment group. Trials without cancer event information were excluded. We requested individual participant data from the authors of eligible trials. We pooled individual participant-level data from eligible trials and assessed the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), ß blockers, calcium channel blockers, and thiazide diuretics on cancer risk in one-stage individual participant data and network meta-analyses. Cause-specific fixed-effects Cox regression models, stratified by trial, were used to calculate hazard ratios (HRs). The primary outcome was any cancer event, defined as the first occurrence of any cancer diagnosed after randomisation. This study is registered with PROSPERO (CRD42018099283). FINDINGS: 33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4·2 years (IQR 3·0-5·0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0·99 [95% CI 0·95-1·04] for ACEIs; 0·96 [0·92-1·01] for ARBs; 0·98 [0·89-1·07] for ß blockers; 1·01 [0·95-1·07] for thiazides), with the exception of calcium channel blockers (1·06 [1·01-1·11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1·00 [95% CI 0·93-1·09] for ACEIs; 0·99 [0·92-1·06] for ARBs; 0·99 [0·89-1·11] for ß blockers; 1·04 [0·96-1·13] for calcium channel blockers; 1·00 [0·90-1·10] for thiazides). INTERPRETATION: We found no consistent evidence that antihypertensive medication use had any effect on cancer risk. Although such findings are reassuring, evidence for some comparisons was insufficient to entirely rule out excess risk, in particular for calcium channel blockers. FUNDING: British Heart Foundation, National Institute for Health Research, Oxford Martin School.


Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Neoplasias/epidemiología , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Neoplasias/inducido químicamente , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo
18.
Molecules ; 26(7)2021 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-33805419

RESUMEN

The COVID-19 pandemic has reached over 100 million worldwide. Due to the multi-targeted nature of the virus, it is clear that drugs providing anti-COVID-19 effects need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Among several targets and pathways that are under investigation, the renin-angiotensin system (RAS) and specifically angiotensin-converting enzyme (ACE), and Ca2+-mediated SARS-CoV-2 cellular entry and replication are noteworthy. A combination of ACE inhibitors and calcium channel blockers (CCBs), a critical line of therapy for pulmonary hypertension, has shown therapeutic relevance in COVID-19 when investigated independently. To that end, we conducted in silico modeling using BIOiSIM, an AI-integrated mechanistic modeling platform by utilizing known preclinical in vitro and in vivo datasets to accurately simulate systemic therapy disposition and site-of-action penetration of the CCBs and ACEi compounds to tissues implicated in COVID-19 pathogenesis.


Asunto(s)
Antivirales/farmacocinética , Reposicionamiento de Medicamentos/métodos , Hipertensión Pulmonar/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Antivirales/sangre , Biosimilares Farmacéuticos , Bloqueadores de los Canales de Calcio/farmacocinética , Simulación por Computador , Bases de Datos Farmacéuticas , Desarrollo de Medicamentos/métodos , Humanos , Hipertensión Pulmonar/virología , Distribución Tisular
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