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1.
Molecules ; 26(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805419

RESUMO

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.


Assuntos
Antivirais/farmacocinética , Reposicionamento de Medicamentos/métodos , Hipertensão Pulmonar/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/farmacocinética , Antivirais/sangue , Medicamentos Biossimilares , Bloqueadores dos Canais de Cálcio/farmacocinética , Simulação por Computador , Bases de Dados de Produtos Farmacêuticos , Desenvolvimento de Medicamentos/métodos , Humanos , Hipertensão Pulmonar/virologia , Distribuição Tecidual
2.
Circ Res ; 128(7): 1062-1079, 2021 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-33793331

RESUMO

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.


Assuntos
/tratamento farmacológico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Antagonistas de Receptores de Angiotensina/metabolismo , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , /metabolismo , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/metabolismo , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Humanos , Hipertensão/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Fatores de Risco
5.
Lancet Oncol ; 22(4): 558-570, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33794209

RESUMO

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.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Neoplasias/epidemiologia , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Neoplasias/induzido quimicamente , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
6.
Anticancer Res ; 41(4): 2093-2100, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813419

RESUMO

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.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Sinergismo Farmacológico , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Japão/epidemiologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
7.
Nat Commun ; 12(1): 1660, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712587

RESUMO

In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin-angiotensin-aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies.


Assuntos
/genética , /genética , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antivirais/farmacologia , /epidemiologia , Interações Medicamentosas , Feminino , Perfilação da Expressão Gênica , Genoma Viral , Antígenos HLA/genética , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Cidade de Nova Iorque/epidemiologia , Técnicas de Amplificação de Ácido Nucleico , Pandemias , RNA-Seq , /efeitos dos fármacos
8.
Diabetes Metab J ; 45(2): 251-259, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33752274

RESUMO

BACKGROUND: Dipeptidyl peptidase-4 inhibitor (DPP-4i) and renin-angiotensin system (RAS) blockade are reported to affect the clinical course of coronavirus disease 2019 (COVID-19) in patients with diabetes mellitus (DM). METHODS: As of May 2020, analysis was conducted on all subjects who could confirm their history of claims related to COVID-19 in the National Health Insurance Review and Assessment Service (HIRA) database in Korea. Using this dataset, we compared the short-term prognosis of COVID-19 infection according to the use of DPP-4i and RAS blockade. Additionally, we validated the results using the National Health Insurance Service (NHIS) of Korea dataset. RESULTS: Totally, data of 67,850 subjects were accessible in the HIRA dataset. Of these, 5,080 were confirmed COVID-19. Among these, 832 subjects with DM were selected for analysis in this study. Among the subjects, 263 (31.6%) and 327 (39.3%) were DPP4i and RAS blockade users, respectively. Thirty-four subjects (4.09%) received intensive care or died. The adjusted odds ratio for severe treatment among DPP-4i users was 0.362 (95% confidence interval [CI], 0.135 to 0.971), and that for RAS blockade users was 0.599 (95% CI, 0.251 to 1.431). These findings were consistent with the analysis based on the NHIS data using 704 final subjects. The adjusted odds ratio for severe treatment among DPP-4i users was 0.303 (95% CI, 0.135 to 0.682), and that for RAS blockade users was 0.811 (95% CI, 0.391 to 1.682). CONCLUSION: This study suggests that DPP-4i is significantly associated with a better clinical outcome of patients with COVID-19.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , /mortalidade , Bases de Dados Factuais , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Sistema Renina-Angiotensina/efeitos dos fármacos , República da Coreia , Resultado do Tratamento
10.
Curr Hypertens Rep ; 23(4): 17, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33768439

RESUMO

PURPOSE OF REVIEW: This review focuses on the associations between the renin-angiotensin system, hypertension, and severe acute respiratory syndrome (SARS-COV-2) infection. A brief prelude on the current state of affairs with COVID-19 is given. In addition to an overview of ACE2, Ang II, and Ang (1-7), this review presents a brief statement on hypertension, including the function of enzymes involved in the control of hypertension, cardiovascular disease, diabetes mellitus, and other malignancies. RECENT FINDINGS: There is currently no data in support of the concerns raised with the use of ACEIs/ARBs. Many researchers have voiced concerns that the use of ACEIs and ARBs may increase tissue ACE2 levels. These researchers therefore recommend that individuals on ACEIs/ARB's medications withhold such antihypertensive drugs, unless advised by their physicians to do so. SARS-CoV-2 uses ACE2 receptors as the port of entry to human hosts. ACE2 and ACE are different enzymes and ACE inhibitors do not inhibit ACE2. Therefore, the use of ARB's or ACEIs should not be discontinued if an individual is infected by SARS-CoV-2. Further studies are required to investigate the effect of ACEIs and ARBs on ACE2 expression and COVID-19.


Assuntos
Hipertensão , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina
11.
Heart Fail Clin ; 17(2): 255-262, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33673949

RESUMO

In recent decades, considerable advances have been made in the treatment of heart failure. The main target of heart failure therapy is the inhibition of the sympathetic nervous system and renin-angiotensin-aldosterone system. The angiotensin receptor blockers represent a breakthrough in the treatment of heart failure with a demonstrated effect on reduction of cardiovascular events. However, new perspectives derive from latest drugs developed for diabetes, iron deficiency, and hyperkalemia. New frontiers are also opened to the development of neurohormonal therapies, antagonists of inflammatory mediators, inotropic agents, and cell-based treatments.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Sistema Renina-Angiotensina/fisiologia , Insuficiência Cardíaca/metabolismo , Humanos
12.
Sci Total Environ ; 768: 144220, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33736325

RESUMO

Proper treatment is necessary to reduce antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in livestock manure before land application. Conventional stockpiling suffers unreliable removal efficiency, while composting can be complicated and expensive. The objective of this study was to test the feasibility of a novel heat-based technology, i.e., stockpiling manure on conductive concrete slabs, to inactivate ARB and ARGs in beef cattle manure. In this study, two independent bench-scale trials were conducted. In both trials, samples were taken from manure piles on conductive concrete slabs and regular slabs (i.e., heated and unheated piles). In the heated pile of the first trial, 25.9% and 83.5% of the pile volume met the EPA Class A and Class B biosolids standards, respectively. For the heated pile of the second trial, the two values were 43.9% and 74.2%. In both trials, nearly all forms of the total and resistant Escherichia coli and enterococci were significantly lower in the heated piles than in the unheated piles. Besides, significant reduction of ARGs in heated piles was observed in the first trial. Through this proof-of-concept study, the new technology based on conductive concrete slabs offers an alternative manure storage method to conventional stockpiling and composting with respect to reduce ARB and ARGs in manure.


Assuntos
Temperatura Alta , Esterco , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Animais , Antibacterianos , Bovinos , Resistência Microbiana a Medicamentos , Genes Bacterianos
13.
Int Heart J ; 62(2): 337-343, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33678794

RESUMO

It is unclear whether patients with hypertension are more likely to be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and whether there is a difference in the severity of coronavirus disease (COVID-19) pneumonia in patients who have taken ACEI/ARB drugs compared with those who have not.This observational study included data from all patients with clinically confirmed COVID-19 admitted to Hankou Hospital, Wuhan, China, between January 5 and March 8, 2020. Data were extracted from clinical and laboratory records. Follow-up was cut off on March 8, 2020.A total of 274 patients, 75 with hypertension and 199 without hypertension, were included in the analysis. Compared with patients without hypertension, patients with hypertension were older and were more likely to have preexisting comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. Moreover, patients with hypertension tended to have higher positive rate for SARS-CoV-2 PCR detection. Multivariate logistic regression analysis showed that age (P = 0.005) and gender (P = 0.019) were independent risk factors associated with the severity of pneumonia in patients on admission, whereas ACEI/ARB treatment (P = 0.184) was not.Patients with COVID-19 with hypertension were significantly older and were more likely to have underlying comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. ACEI/ARB drugs did not influence the severity of pneumonia in patients with SARS-CoV-2. In future studies, a larger sample size and multi-center clinical data would be needed to support these conclusions.


Assuntos
/epidemiologia , Hospitalização , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , /diagnóstico , China , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
14.
BMC Infect Dis ; 21(1): 262, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722197

RESUMO

INTRODUCTION: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality. METHODS: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome. RESULTS: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality. CONCLUSION: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Sistema Renina-Angiotensina , Reino Unido , Adulto Jovem
15.
Can Fam Physician ; 67(3): 171-179, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33727376

RESUMO

OBJECTIVE: To keep health care providers, in response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, informed about the medications that have been proposed to treat the disease and the evidence supporting their use. QUALITY OF EVIDENCE: A narrative review of medications most widely used to treat COVID-19 was conducted, outlining the best available evidence for each pharmacologic treatment to date. Searches were performed in PubMed, EMBASE, and MEDLINE using key words COVID-19 and treatment, as well as related terms. Relevant research studies conducted in human populations and cases specific to patients with COVID-19 were included, as were relevant hand-searched papers and reviews. Only articles in English and Chinese were included. MAIN MESSAGE: While current management of patients with COVID-19 largely involves supportive care, without a widely available vaccine, practitioners have also resorted to repurposing medications used for other indications. This has caused considerable controversy, as many of these treatments have limited clinical evidence supporting their use and therefore pose implications for patient safety, drug access, and public health. For instance, medications such as hydroxychloroquine and chloroquine, lopinavir-ritonavir, nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers gained widespread media attention owing to hype, misinformation, or misinterpretation of research evidence. CONCLUSION: Given the severity of the pandemic and the potential broad effects of implementing safe and effective treatment, this article provides a narrative review of the current evidence behind the most widely used medications to treat COVID-19 in order to enable health care practitioners to make informed decisions in the care of patients with this life-threatening disease.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antivirais/uso terapêutico , Medicina Baseada em Evidências , Imunoglobulinas/uso terapêutico , Cloroquina/uso terapêutico , Quimioterapia Combinada , Humanos , Hidroxicloroquina/uso terapêutico
16.
Curr Opin Cardiol ; 36(3): 367-373, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33709980

RESUMO

PURPOSE OF REVIEW: Preventive cardiology has an important role to play in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The SARS-CoV-2 pandemic has been observed to have a greater mortality impact on subgroups of people in the population who are deemed to be at higher medical disease risk. Individuals with cardiovascular disorders are one such COVID-19-associated high-mortality risk group. RECENT FINDINGS: Evidence is accumulating that COVID-19 infection may worsen an individual's future cardiovascular health, and, preinfection/postinfection cardiovascular evaluation may be warranted to determine if progressive cardiovascular damage has occurred because of COVID-19 infection. In this study, we conducted a systematic review and meta-analysis, focusing on the association between COVID-19 severity and cardiac-specific biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin T (TnT)/troponin I (TnI), lactate dehydrogenase (LDH), creatine kinase, and creatine kinase isoenzyme (CK-MB). TnT had the highest odds ratio or OR (11.83) indicating the greatest association with COVID-19 severity, followed by NT-proBNP (7.57), TnI (6.32), LDH (4.79), D-dimer (4.10), creatine kinase (3.43), and CK-MB (3.35). All of the biomarkers studied were significantly correlated with COVID-19 severity including severe symptoms, ICU care, and mortality (P < 0.0001, except P < 0.01 for CK-MB). SUMMARY: COVID-19 infection results in short-term and long-term disease risk that may involve adverse cardiovascular health issues including heart failure. Cardiac-specific biomarkers appear to identify a subset of COVID-19 patients who have the highest risk of an adverse medical outcome. Preventive cardiology has an important role to play in the COVID-19 pandemic.The risk/benefit analysis of maintaining or eliminating the use of the angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitor (ACE-I) medications deserves further investigation.


Assuntos
Pandemias , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Biomarcadores , Humanos
17.
Bioresour Technol ; 330: 124970, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33735726

RESUMO

Currently, anaerobic sludge digestion (ASD) is considered not only for treating residual sewage sludge and energy recovery but also for the reduction of antibiotic resistance genes (ARGs). The current review highlights the reasons why antibiotic resistant bacteria (ARB) and ARGs exist in ASD and how ASD performs in the reduction of ARB and ARGs. ARGs and ARB have been detected in ASD with some reports indicating some of the ARGs can be completely removed during the ASD process, while other studies reported the enrichment of ARB and ARGs after ASD. This paper reviews the performance of ASD based on operational parameters as well as environmental chemistry. More studies are needed to improve the performance of ASD in reducing ARGs that are difficult to handle and also differentiate between extracellular (eARGs) and intracellular ARGs (iARGs) to achieve more accurate quantification of the ARGs.


Assuntos
Genes Bacterianos , Esgotos , Anaerobiose , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Antibacterianos/farmacologia , Bactérias/genética , Digestão , Resistência Microbiana a Medicamentos/genética , Águas Residuárias
18.
PLoS One ; 16(3): e0248652, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33735262

RESUMO

BACKGROUND: A number of studies have reported the association between the use of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) medications and the occurrence or severity of coronavirus disease 2019 (COVID-19). Published results are inconclusive, possibly due to differences in participant comorbidities and sociodemographic backgrounds. Since ACEI and ARB are frequently used anti-hypertension medications, we aim to determine whether the use of ACEI and ARB is associated with the occurrence and severity of COVID-19 in a large study of US Veterans with hypertension. METHODS: Data were collected from the Department of Veterans Affairs (VA) National Corporate Data Warehouse (VA-COVID-19 Shared Data Resource) between February 28, 2020 and August 18, 2020. Using data from 228,722 Veterans with a history of hypertension who received COVID-19 testing at the VA, we investigated whether the use of ACEI or ARB over the two years prior to the index date was associated with increased odds of (1) a positive COVID-19 test, and (2) a severe outcome (hospitalization, mortality, and use of intensive care unit (ICU) and/or mechanical ventilation) among COVID-19-positive patients. We used logistic regression with and without propensity score weighting (PSW) to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for the association between ACEI/ARB use and a positive COVID-19 test result. The association between medication use and COVID-19 outcome severity was examined using multinomial logistic regression comparing participants who were not hospitalized to participants who were hospitalized, were admitted to the ICU, used a mechanical ventilator, or died. All models were adjusted for relevant covariates, including demographics (age, sex, race, ethnicity), selected comorbidities, and the Charlson Comorbidity Index (CCI). RESULTS: The use of ACEI significantly decreased the odds of a positive COVID-19 test among Veterans with hypertension (OR = 0.917, (0.887, 0.948) and OR = 0.926, (0.894, 0.958) with PSW). The use of ACEI, but not of ARB, was also associated with significantly increased odds of using mechanical ventilators (OR = 1.265, (1.010, 1.584) and OR = 1.210, (1.053, 1.39) with PSW) among all COVID-19 inpatients compared to outpatients. CONCLUSIONS: In this study of Veterans with hypertension, ACEI was significantly associated with decreased odds of testing positive for COVID-19. With the exception of the association of ACEI with a small non-clinically-important increase in the odds of using mechanical ventilators, neither ACEI nor ARB was found to be associated with clinical severity or mortality among COVID-19-positive Veterans. The results of this study need further corroboration and validation in other cohort samples outside the VA.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , /epidemiologia , Hipertensão/complicações , Adulto , Idoso , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
19.
Nat Commun ; 12(1): 1521, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750801

RESUMO

Resistance to next-generation anti-androgen enzalutamide (ENZ) constitutes a major challenge for the treatment of castration-resistant prostate cancer (CRPC). By performing genome-wide ChIP-seq profiling in ENZ-resistant CRPC cells we identify a set of androgen receptor (AR) binding sites with increased AR binding intensity (ARBS-gained). While ARBS-gained loci lack the canonical androgen response elements (ARE) and pioneer factor FOXA1 binding motifs, they are highly enriched with CpG islands and the binding sites of unmethylated CpG dinucleotide-binding protein CXXC5 and the partner TET2. RNA-seq analysis reveals that both CXXC5 and its regulated genes including ID1 are upregulated in ENZ-resistant cell lines and these results are further confirmed in patient-derived xenografts (PDXs) and patient specimens. Consistent with the finding that ARBS-gained loci are highly enriched with H3K27ac modification, ENZ-resistant PCa cells, organoids, xenografts and PDXs are hyper-sensitive to NEO2734, a dual inhibitor of BET and CBP/p300 proteins. These results not only reveal a noncanonical AR function in acquisition of ENZ resistance, but also posit a treatment strategy to target this vulnerability in ENZ-resistant CRPC.


Assuntos
Feniltioidantoína/análogos & derivados , Feniltioidantoína/farmacologia , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Antagonistas de Androgênios/farmacologia , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Sítios de Ligação , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Humanos , Masculino , Camundongos , Camundongos SCID , Organoides , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
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