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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.
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
5.
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
6.
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
8.
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
9.
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
10.
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
11.
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
12.
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
13.
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
14.
Clin Sci (Lond) ; 135(8): 1009-1014, 2021 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-33881142

RESUMEN

Angiotensin-converting enzyme 2 (ACE2) is the leading player of the protective renin-angiotensin system (RAS) pathway but also the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RAS inhibitors seemed to interfere with the ACE2 receptor, and their safety was addressed in COVID-19 patients. Pedrosa et al. (Clin. Sci. (Lond.) (2021), 135, 465-481) showed in rats that captopril and candesartan up-regulated ACE2 expression and the protective RAS pathway in lung tissue. In culture of pneumocytes, the captopril/candesartan-induced ACE2 up-regulation was associated with inhibition of ADAM17 activity, counterbalancing increased ACE2 expression, which was associated with reduced SARS-CoV-2 spike protein entry. If confirmed in humans, these results could become the pathophysiological background for justifying RAS inhibitors as cornerstone cardiovascular protectives even during COVID-19 pandemic.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Bencimidazoles , Compuestos de Bifenilo , Captopril/farmacología , Humanos , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Ratas , Sistema Renina-Angiotensina , Glicoproteína de la Espiga del Coronavirus , Tetrazoles
15.
Nat Commun ; 12(1): 2417, 2021 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-33893295

RESUMEN

SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.


Asunto(s)
/fisiopatología , Pulmón/fisiopatología , Sistema Renina-Angiotensina/fisiología , /aislamiento & purificación , Angiotensina II/administración & dosificación , Angiotensina II/metabolismo , Antagonistas de Receptores de Angiotensina/administración & dosificación , /metabolismo , Animales , /virología , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/virología , Imagen por Resonancia Magnética/métodos , Unión Proteica/efectos de los fármacos , Estudios Retrospectivos , /fisiología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Porcinos , Internalización del Virus/efectos de los fármacos
16.
Medicine (Baltimore) ; 100(16): e25532, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33879694

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread almost all regions of the world and caused great loss to the whole body of mankind. Thus, numerous clinical trials were conducted to find specific medicine for COVID-19 recently. However, it remains unanswered whether they are beneficial. OBJECTIVE: This study aimed to evaluate the efficiency and safety of the COVID-19 medicine. METHODS: Studies were determined through searching PubMed, Embase, Cochrane Library, and Medline. The studies of COVID-19 medicine were involved with eligible end points containing mortality, discharge rate, rate of clinical improvement, and rate of serious adverse events. RESULTS: A total of 33 studies involving 37,879 patients were included in our study, whose intervening measures contained three major types of COVID-19 medicine, ACEI/ARB, antiviral medicine, and chloroquine/hydroxychloroquine. Compared to control group, COVID-19 drugs have no distinct effect on mortality (RR, 0.93; 95% CI, 0.79-1.11, P = .43) and discharge rate (RR, 1.06; 95% CI, 0.98-1.14, P = .13). However, antiviral medicine presents the obvious advantage in clinical improvement (RR, 1.11; 95% CI, 1.01-1.23, P < .05). In addition, the serious adverse events rate (RR, 0.75; 95% CI, 0.63-0.88, P < .05) of COVID-19 medicine is lower than control group. CONCLUSION: The results indicated antiviral medicine was potential specific medicine for COVID-19 treatment by improving clinical symptoms, but it failed to increase the discharge rate and reduce mortality. Chloroquine/hydroxychloroquine and ACEI/ARB had no significant effect on treatment of COVID-19, thus they were not recommended for routine medication. Moreover, more trials are needed to find effective drugs to lower the mortality of COVID-19 patients.


Asunto(s)
Antivirales/efectos adversos , Antivirales/uso terapéutico , /tratamiento farmacológico , 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 , Cloroquina/efectos adversos , Cloroquina/uso terapéutico , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Resultado del Tratamiento
17.
Medicine (Baltimore) ; 100(16): e25621, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33879733

RESUMEN

ABSTRACT: This study aimed to investigate the effects of the basic treatment for heart failure and sequential treatment with rh-brain natriuretic peptide (rhBNP) alone or the combination of rhBNP and sacubitril/valsartan. Cardiac structure, pulmonary artery pressure, inflammation and oxidative stress in patients with acute heart failure were evaluated.Three hundred patients with acute heart failure were included. According to the random number table method, the patients were divided into 3 groups of 100 patients per group: the standard treatment group (treated with an angiotensin-converting enzyme inhibitor, ß receptor blocker, and corticosteroid antagonist), rhBNP group (basic treatment combined with rhBNP) and sequential treatment group (basic treatment for heart failure combined with rhBNP followed by sacubitril/valsartan). The changes in NT-probrain natriuretic peptide (BNP) levels, cardiac troponin T (cTnT) levels, cardiac structure, pulmonary artery pressure, and the levels inflammatory factors and oxidative stress factors were compared among the 3 groups at 1, 4, 12, and 36 weeks after treatment.The sequential treatment group displayed superior outcomes than the standard treatment group and the rhBNP group in terms of left atrium diameter, left ventricular end diastolic volume, left ventricular ejection fraction, pulmonary artery pressure, NT-proBNP levels, and cTnT levels, which respond to damage to the heart structure and myocardium. This result may be related to the decreased levels of inflammatory factors and the correction of oxidative stress imbalance.Sacubitril/valsartan significantly reduce the serum levels of inflammatory factors in patients with acute heart failure while decreasing the levels of oxidizing factors and increasing the levels of antioxidant factors. These changes may be one of the explanations for the better cardiac structure and better pulmonary artery pressure observed in the sequential treatment group.


Asunto(s)
Aminobutiratos/administración & dosificación , Antagonistas de Receptores de Angiotensina/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Péptido Natriurético Encefálico/administración & dosificación , Tetrazoles/administración & dosificación , Enfermedad Aguda , Antagonistas Adrenérgicos beta/administración & dosificación , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Presión Arterial/efectos de los fármacos , Biomarcadores/sangre , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Antagonistas de Hormonas/administración & dosificación , Humanos , Inflamación , Mediadores de Inflamación/sangre , Masculino , Persona de Mediana Edad , Miocardio/patología , Estrés Oxidativo/efectos de los fármacos , Arteria Pulmonar/fisiopatología , Volumen Sistólico/efectos de los fármacos , Resultado del Tratamiento , Troponina T/sangre
18.
J Zhejiang Univ Sci B ; 22(4): 330-340, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33835767

RESUMEN

Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at increased risk of acute lung injury. However, it is still not clear whether this increased risk is related to the usage of renin-angiotensin system (RAS) blockers. We collected medical records of coronavirus disease 2019 (COVID-19) patients from the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China), and evaluated the potential impact of an angiotensin II receptor blocker (ARB) on the clinical outcomes of COVID-19 patients with hypertension. A total of 30 hypertensive COVID-19 patients were enrolled, of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received. Compared with the non-ARB group, patients in the ARB group had a lower proportion of severe cases and intensive care unit (ICU) admission as well as shortened length of hospital stay, and manifested favorable results in most of the laboratory testing. Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course. No significant difference in the time of seroconversion or antibody levels was observed between the two groups. The median levels of soluble angiotensin-converting enzyme 2 (sACE2) in serum and urine samples were similar in both groups, and there were no significant correlations between serum sACE2 and biomarkers of disease severity. Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport, bicarbonate transport, and blood coagulation. Our results suggest that ARB usage is not associated with aggravation of COVID-19. These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Anticuerpos Antivirales/sangre , Hipertensión/tratamiento farmacológico , Carga Viral , Anciano , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Biomarcadores , China , Femenino , Humanos , Hipertensión/complicaciones , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Transcriptoma
19.
Anticancer Res ; 41(4): 2093-2100, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813419

RESUMEN

BACKGROUND/AIM: The Renin-Angiotensin system (RAS) induces immunosuppression in the tumor microenvironment, and RAS inhibitors (RASi) improve the tumor immune microenvironment. We evaluated the impact of RASi on the efficacy anti-programmed cell death-1/Ligand-1 (anti-PD-1/PD-L1) antibodies. PATIENTS AND METHODS: This retrospective study analyzed non-small cell lung cancer (NSCLC) patients who received anti-PD-1/PD-L1 antibodies monotherapy as second- or later-line treatment. We classified patients into those with or without use of RASi. RESULTS: A total of 256 NSCLC patients were included and 37 patients used RASi. The median PFS of patients treated with RASi was significantly longer than that of patients treated without (HR=0.59, 95%CI=0.40-0.88). The median OS of patients treated with RASi tended to be longer than that of patients treated without (HR=0.71, 95%CI=0.45-1.11). CONCLUSION: The use of RASi was associated with a significantly longer PFS in NSCLC patients treated with anti-PD-1/PD-L1 antibodies. RASi use may enhance the efficacy of anti-PD-1/PD-L1 antibodies.


Asunto(s)
Antagonistas de Receptores de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antihipertensivos/uso terapéutico , Antineoplásicos Inmunológicos/administración & dosificación , Antígeno B7-H1/inmunología , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Sinergismo Farmacológico , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Japón/epidemiología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Nivolumab/uso terapéutico , Sistema Renina-Angiotensina/efectos de los fármacos , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
20.
Water Res ; 197: 117075, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33819660

RESUMEN

Although photo-driven advanced oxidation processes (AOPs) have been developed to treat wastewater, few studies have investigated the feasibility of AOPs to simultaneously remove antibiotic resistant bacteria (ARB), antibiotic resistance genes (ARGs) and micropollutants (MPs). This study employed a modified photo-Fenton process using ethylenediamine-N,N'-disuccinic acid (EDDS) to chelate iron(III), thus maintaining the reaction pH in a neutral range. Simultaneous removal of ARB and associated extracellular (e-ARGs) and intracellular ARGs (i-ARGs), was assessed by bacterial cell culture, qPCR and atomic force microscopy. The removal of five MPs was also evaluated by liquid chromatography coupled with mass spectrometry. A low dose comprising 0.1 mM Fe(III), 0.2 mM EDDS, and 0.3 mM hydrogen peroxide (H2O2) was found to be effective for decreasing ARB by 6-log within 30 min, and e-ARGs by 6-log within 10 min. No ARB regrowth occurred after 48-h, suggesting that the proposed process is an effective disinfectant against ARB. Moreover, five recalcitrant MPs (carbamazepine, diclofenac, sulfamethoxazole, mecoprop and benzotriazole at an initial concentration of 10 µg/L each) were >99% removed after 30 min treatment in ultrapure water. The modified photo-Fenton process was also validated using synthetic wastewater and real secondary wastewater effluent as matrices, and results suggest the dosage should be doubled to ensure equivalent removal performance. Collectively, this study demonstrated that the modified process is an optimistic 'one-stop' solution to simultaneously mitigate both chemical and biological hazards.


Asunto(s)
Peróxido de Hidrógeno , Contaminantes Químicos del Agua , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Antibacterianos/farmacología , Bacterias , Farmacorresistencia Microbiana/genética , Compuestos Férricos , Oxidación-Reducción , Aguas Residuales , Contaminantes Químicos del Agua/análisis
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