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1.
Curr Neurol Neurosci Rep ; 21(6): 25, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825077

RESUMO

PURPOSE OF REVIEW: In the last few years, the attitude toward marijuana in many parts of the world has shifted from illicit to legalized for medical use and to decriminalized. In parallel, there has been a gradual increase in the consumption of this product in the general population, particularly among adolescents and young adults. Marijuana is generally perceived as a harmless drug. However, data obtained in observational studies and preclinical models have established associations between cannabis use and cardiovascular events. In addition, there is emerging evidence linking marijuana use to cerebrovascular complications. Here we provide a critical review of the literature with special emphasis on the association of cannabinoids with stroke and the possible pathogenic mechanisms involved. RECENT FINDINGS: Ischemic and hemorrhagic stroke have been described in association with cannabis use, particularly in young individuals. Cerebral infarction remains the most commonly reported stroke subtype seen in marijuana users. Several pathogenic mechanisms have been proposed to explain this association, including multifocal intracranial stenosis, reversible cerebral vasoconstriction syndrome, and coexisting vascular risk factors. Cannabis use is increasingly recognized in young individuals presenting with acute stroke. Our understanding of the pathogenic mechanisms associated with cannabis use and stroke is limited but rapidly evolving. Healthcare providers should educate patients about the potential cardiovascular and cerebrovascular complications related to marijuana or cannabinoids use.


Assuntos
Canabinoides , Cannabis , Fumar Maconha , Uso da Maconha , Acidente Vascular Cerebral , Adolescente , Cannabis/efeitos adversos , Humanos , Fumar Maconha/efeitos adversos , Fumar Maconha/epidemiologia , Uso da Maconha/efeitos adversos , Uso da Maconha/epidemiologia , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia , Adulto Jovem
2.
Tuberk Toraks ; 69(1): 65-73, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33853307

RESUMO

Introduction: The use of new oral anticoagulants (NOACs) for the treatment of thromboembolic diseases is becoming more widespread. The present study brings together the opinions and daily routine clinical practices of physicians regarding the use of NOACs in the geriatric age group for the treatment of venous thromboembolic diseases. Materials and Methods: The study accessed 274 physicians (197 attending, 70 resident and seven primary care physicians) with various specialties and academic positions through face-to-face interviews or e-mails, and asked them to complete a questionnaire form prepared for NOAC use on a voluntary basis between 1 May and 31 December 2019. Result: It was found that physicians preferred NOACs mostly for patients contraindicated for the regular use of low-molecular-weight heparins and warfarin (n: 264, 96%), and with an unbalanced INR level (n: 230, 87%). The use of NOACs was found to be higher in the geriatric age group than other anticoagulants due to the easy dose adjustment, the extended monitoring intervals and the low risk of bleeding. Among the physicians, neither the specialty nor a higher number of occupational working years affected the preference for NOACs or other anticoagulants. Conclusions: Our study has demonstrated that physicians consider NOACs to be a good treatment option in terms of efficacy and reliability for the treatment of thromboembolic diseases in the geriatric age group, who may have treatment compliance difficulties. It was found also that they plan treatment considering the benefit-to-harm ratio and the bleeding-ischemic event balance.


Assuntos
Anticoagulantes/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Idoso , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/tratamento farmacológico , Feminino , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Médicos , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Inquéritos e Questionários , Varfarina/uso terapêutico
3.
J Gen Intern Med ; 36(6): 1629-1637, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33754317

RESUMO

BACKGROUND: Anticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking. OBJECTIVE: Compare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people. DESIGN: Prospective cohort study. SETTING: Primary care (Australia and USA). PARTICIPANTS: 19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100. MEASUREMENTS: Baseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition. RESULTS: At baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1-2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications. LIMITATIONS: Residual confounding and reverse causality are possible. Assessment of dose or duration was not possible. CONCLUSIONS: High anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people.


Assuntos
Demência , Acidente Vascular Cerebral , Idoso , Austrália , Antagonistas Colinérgicos/efeitos adversos , Estudos de Coortes , Demência/induzido quimicamente , Demência/epidemiologia , Humanos , Estudos Prospectivos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia
4.
Cochrane Database Syst Rev ; 3: CD013498, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33662147

RESUMO

BACKGROUND: People with type 1 diabetes mellitus (T1DM) need treatment with insulin for survival. Whether any particular type of (ultra-)long-acting insulin provides benefit especially regarding risk of diabetes complications and hypoglycaemia is unknown. OBJECTIVES: To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues to NPH insulin (neutral protamine Hagedorn) or another (ultra-)long-acting insulin analogue in people with type 1 diabetes mellitus. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform and the reference lists of systematic reviews, articles and health technology assessment reports. We explored the US Food and Drug Administration (FDA) and European Medical Agency (EMA) web pages. We asked pharmaceutical companies, EMA and investigators for additional data and clinical study reports (CSRs). The date of the last search of all databases was 24 August 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a duration of 24 weeks or more comparing one (ultra-)long-acting insulin to NPH insulin or another (ultra-)long-acting insulin in people with T1DM. DATA COLLECTION AND ANALYSIS: Two review authors assessed risk of bias using the new Cochrane 'Risk of bias' 2 (RoB 2) tool and extracted data. Our main outcomes were all-cause mortality, health-related quality of life (QoL), severe hypoglycaemia, non-fatal myocardial infarction/stroke (NFMI/NFS), severe nocturnal hypoglycaemia, serious adverse events (SAEs) and glycosylated haemoglobin A1c (HbA1c). We used a random-effects model to perform meta-analyses and calculated risk ratios (RRs) and odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) and 95% prediction intervals for effect estimates. We evaluated the certainty of the evidence applying the GRADE instrument. MAIN RESULTS: We included 26 RCTs. Two studies were unpublished. We obtained CSRs, clinical study synopses or both as well as medical reviews from regulatory agencies on 23 studies which contributed to better analysis of risk of bias and improved data extraction. A total of 8784 participants were randomised: 2428 participants were allocated to NPH insulin, 2889 participants to insulin detemir, 2095 participants to insulin glargine and 1372 participants to insulin degludec. Eight studies contributing 21% of all participants comprised children. The duration of the intervention varied from 24 weeks to 104 weeks. Insulin degludec versus NPH insulin: we identified no studies comparing insulin degludec with NPH insulin. Insulin detemir versus NPH insulin (9 RCTs): five deaths reported in two studies including adults occurred in the insulin detemir group (Peto OR 4.97, 95% CI 0.79 to 31.38; 9 studies, 3334 participants; moderate-certainty evidence). Three studies with 870 participants reported QoL showing no true beneficial or harmful effect for either intervention (low-certainty evidence). There was a reduction in severe hypoglycaemia in favour of insulin detemir: 171/2019 participants (8.5%) in the insulin detemir group compared with 138/1200 participants (11.5%) in the NPH insulin group experienced severe hypoglycaemia (RR 0.69, 95% CI 0.52 to 0.92; 8 studies, 3219 participants; moderate-certainty evidence). The 95% prediction interval ranged between 0.34 and 1.39. Only 1/331 participants in the insulin detemir group compared with 0/164 participants in the NPH insulin group experienced a NFMI (1 study, 495 participants; low-certainty evidence). No study reported NFS. A total of 165/2094 participants (7.9%) in the insulin detemir group compared with 102/1238 participants (8.2%) in the NPH insulin group experienced SAEs (RR 0.95, 95% CI 0.75 to 1.21; 9 studies, 3332 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 70/1823 participants (3.8%) in the insulin detemir group compared with 60/1102 participants (5.4%) in the NPH insulin group (RR 0.67, 95% CI 0.39 to 1.17; 7 studies, 2925 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin detemir with NPH insulin was 0.01%, 95% CI -0.1 to 0.1; 8 studies, 3122 participants; moderate-certainty evidence. Insulin glargine versus NPH insulin (9 RCTs): one adult died in the NPH insulin group (Peto OR 0.14, 95% CI 0.00 to 6.98; 8 studies, 2175 participants; moderate-certainty evidence). Four studies with 1013 participants reported QoL showing no true beneficial effect or harmful effect for either intervention (low-certainty evidence). Severe hypoglycaemia was observed in 122/1191 participants (10.2%) in the insulin glargine group compared with 145/1159 participants (12.5%) in the NPH insulin group (RR 0.84, 95% CI 0.67 to 1.04; 9 studies, 2350 participants; moderate-certainty evidence). No participant experienced a NFMI and one participant in the NPH insulin group experienced a NFS in the single study reporting this outcome (585 participants; low-certainty evidence). A total of 109/1131 participants (9.6%) in the insulin glargine group compared with 110/1098 participants (10.0%) in the NPH insulin group experienced SAEs (RR 1.08, 95% CI 0.63 to 1.84; 8 studies, 2229 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 69/938 participants (7.4%) in the insulin glargine group compared with 83/955 participants (8.7%) in the NPH insulin group (RR 0.83, 95% CI 0.62 to 1.12; 6 studies, 1893 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin glargine with NPH insulin was 0.02%, 95% CI -0.1 to 0.1; 9 studies, 2285 participants; moderate-certainty evidence. Insulin detemir versus insulin glargine (2 RCTs),insulin degludec versus insulin detemir (2 RCTs), insulin degludec versus insulin glargine (4 RCTs): there was no evidence of a clinically relevant difference for all main outcomes comparing (ultra-)long-acting insulin analogues with each other. For all outcomes none of the comparisons indicated differences in tests of interaction for children versus adults. AUTHORS' CONCLUSIONS: Comparing insulin detemir with NPH insulin for T1DM showed lower risk of severe hypoglycaemia in favour of insulin detemir (moderate-certainty evidence). However, the 95% prediction interval indicated inconsistency in this finding. Both insulin detemir and insulin glargine compared with NPH insulin did not show benefits or harms for severe nocturnal hypoglycaemia. For all other main outcomes with overall low risk of bias and comparing insulin analogues with each other, there was no true beneficial or harmful effect for any intervention. Data on patient-important outcomes such as QoL, macrovascular and microvascular diabetic complications were sparse or missing. No clinically relevant differences were found between children and adults.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Detemir/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina Isófana/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Adolescente , Adulto , Viés , Criança , Pré-Escolar , Intervalos de Confiança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/mortalidade , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/mortalidade , Hipoglicemiantes/efeitos adversos , Insulina Detemir/efeitos adversos , Insulina Glargina/efeitos adversos , Insulina Isófana/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/mortalidade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/mortalidade , Adulto Jovem
5.
Environ Health Prev Med ; 26(1): 15, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499804

RESUMO

BACKGROUND: Previous studies have suggested that exposure to air pollution may increase stroke risk, but the results remain inconsistent. Evidence of more recent studies is highly warranted, especially gas air pollutants. METHODS: We searched PubMed, Embase, and Web of Science to identify studies till February 2020 and conducted a meta-analysis on the association between air pollution (PM2.5, particulate matter with aerodynamic diameter less than 2.5 µm; PM10, particulate matter with aerodynamic diameter less than 10 µm; NO2, nitrogen dioxide; SO2, sulfur dioxide; CO, carbon monoxide; O3, ozone) and stroke (hospital admission, incidence, and mortality). Fixed- or random-effects model was used to calculate pooled odds ratios (OR)/hazard ratio (HR) and their 95% confidence intervals (CI) for a 10 µg/m3 increase in air pollutant concentration. RESULTS: A total of 68 studies conducted from more than 23 million participants were included in our meta-analysis. Meta-analyses showed significant associations of all six air pollutants and stroke hospital admission (e.g., PM2.5: OR = 1.008 (95% CI 1.005, 1.011); NO2: OR = 1.023 (95% CI 1.015, 1.030), per 10 µg/m3 increases in air pollutant concentration). Exposure to PM2.5, SO2, and NO2 was associated with increased risks of stroke incidence (PM2.5: HR = 1.048 (95% CI 1.020, 1.076); SO2: HR = 1.002 (95% CI 1.000, 1.003); NO2: HR = 1.002 (95% CI 1.000, 1.003), respectively). However, no significant differences were found in associations of PM10, CO, O3, and stroke incidence. Except for CO and O3, we found that higher level of air pollution (PM2.5, PM10, SO2, and NO2) exposure was associated with higher stroke mortality (e.g., PM10: OR = 1.006 (95% CI 1.003, 1.010), SO2: OR = 1.006 (95% CI 1.005, 1.008). CONCLUSIONS: Exposure to air pollution was positively associated with an increased risk of stroke hospital admission (PM2.5, PM10, SO2, NO2, CO, and O3), incidence (PM2.5, SO2, and NO2), and mortality (PM2.5, PM10, SO2, and NO2). Our study would provide a more comprehensive evidence of air pollution and stroke, especially SO2 and NO2.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Hospitalização/estatística & dados numéricos , Material Particulado/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Humanos , Incidência , Tamanho da Partícula , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/mortalidade
6.
Anticancer Res ; 41(2): 927-936, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517299

RESUMO

BACKGROUND/AIM: Limited published real-world data describe adverse events (AEs) among patients treated for mantle-cell lymphoma (MCL). The aim of this retrospective study was to describe treatment patterns, AEs, and associated healthcare costs. PATIENTS AND METHODS: Patients had two or more claims coded for MCL diagnosis, the first claim date (07/01/2012-05/31/2017) was the index date. Patients with pre-index MCL diagnosis or systemic treatment, or hematopoietic stem cell transplantation were excluded. Cohorts by regimen were followed for up to three lines of therapy. RESULTS: Patients (n=395; median age 72 years; 31% female) were observed over a total of 576 lines of therapy, the most common being bendamustine plus rituximab; rituximab monotherapy; R-CHOP; and ibrutinib. The most frequent AEs were hypertension (40.5%), anemia (37.7%), and infection (36.1%). However, hepatotoxicity ($19,645), stroke ($18,893), and renal failure ($9,037) were associated with the highest medical costs per patient per month. CONCLUSION: Among patients receiving common systemic treatments for MCL, AEs occurred frequently; some imposed substantial inpatient care costs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/economia , Linfoma de Célula do Manto/tratamento farmacológico , Insuficiência Renal/economia , Acidente Vascular Cerebral/economia , Adenina/efeitos adversos , Adenina/análogos & derivados , Adenina/economia , Adenina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/efeitos adversos , Cloridrato de Bendamustina/economia , Cloridrato de Bendamustina/uso terapêutico , Ciclofosfamida/efeitos adversos , Ciclofosfamida/economia , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/economia , Doxorrubicina/uso terapêutico , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Piperidinas/economia , Piperidinas/uso terapêutico , Prednisona/efeitos adversos , Prednisona/economia , Prednisona/uso terapêutico , Insuficiência Renal/induzido quimicamente , Estudos Retrospectivos , Rituximab/efeitos adversos , Rituximab/economia , Rituximab/uso terapêutico , Acidente Vascular Cerebral/induzido quimicamente , Vincristina/efeitos adversos , Vincristina/economia , Vincristina/uso terapêutico
7.
Eye (Lond) ; 35(2): 601-607, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32367002

RESUMO

OBJECTIVE: To evaluate the risk of stroke associated with intravitreal ranibizumab in age-related macular degeneration (AMD). METHODS: A nationwide retrospective case-crossover study was performed using data from the Korean National Health Insurance Service (KNHIS) database, which included patients with exudative AMD in South Korea (n = 41,860). The index date was the date of hospitalization for stroke. We defined the case period as 60 days and four control periods before the index date. A pharmacy prescription database was searched for ranibizumab use during the case and control periods. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with a conditional logistic regression model. RESULTS: A total of 865 patients with AMD and incident stroke were included. Of all the patients, 12.02% had been treated during the preceding 60-day case period, compared with 9.25-10.29% during control periods. The adjusted OR of stroke associated with intravitreal ranibizumab during the case period was 1.285 (95% CI 0.979-1.686) (p = 0.07). In the subgroup analysis, the risk of hemorrhagic stroke had an OR of 2.252 (95% CI 1.068-4.749, p = 0.033). Further analyses based on patient gender, age, and different risk periods of 15 and 30 days yielded no increase in the risk of stroke associated with intravitreal ranibizumab. CONCLUSIONS: This case-crossover analysis revealed no evidence of increased risk of hospitalization for stroke within 60 days of intravitreal ranibizumab injection in AMD patients. A secondary analysis indicated the possibility of an increased risk of hemorrhagic stroke, with borderline significance. Further research is needed regarding the underlying biological mechanisms and drug safety.


Assuntos
Degeneração Macular , Acidente Vascular Cerebral , Degeneração Macular Exsudativa , Inibidores da Angiogênese/efeitos adversos , Estudos Cross-Over , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Degeneração Macular/epidemiologia , Ranibizumab/efeitos adversos , República da Coreia/epidemiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/epidemiologia
8.
Clin Pharmacol Ther ; 109(2): 443-451, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32767756

RESUMO

Ticagrelor improves clinical outcomes in patients with acute myocardial infarction (AMI). This study aimed to compare the efficacy and safety of ticagrelor vs. clopidogrel in East Asian patients with AMI. Between July 2013 and December 2015, patients with AMI prescribed dual antiplatelet therapy were identified from the National Health Insurance Research Database of Taiwan. Using propensity score weighting, ticagrelor was compared with clopidogrel for the primary efficacy end point (a composite of all-cause death, myocardial infarction (MI), and stroke) and bleeding. A total of 32,442 patients with AMI (ticagrelor: 10,057; clopidogrel: 22,385) were eligible for analysis. After propensity score weighting, ticagrelor was comparable to clopidogrel in the incidence rate of the primary efficacy end point (23.6 vs. 22.76/100 patient-years; hazard ratio (HR) 0.97; 95% confidence interval (CI) 0.89-1.06; P = 0.513). Ticagrelor was associated with a lower risk of stroke (1.78 vs. 2.66/100 patient-years; HR 0.64; 95% CI 0.49-0.85; P = 0.002) and higher risks of overall (21.59 vs. 18.35/100 patient-years; HR 1.16; 95% CI 1.06-1.27; P = 0.002) and Bleeding Academic Research Consortium (BARC) type 2 bleeding (18.67 vs. 15.08/100 patient-years; HR 1.22; 95% CI 1.11-1.36; P < 0.001). The risks of death, MI, and BARC 3 or 5 bleeding were comparable between ticagrelor and clopidogrel. In the present study, ticagrelor was comparable to clopidogrel in the composite of death, MI, and stroke, but had an increased risk of BARC type 2 bleeding. Ticagrelor may be beneficial in preventing post-MI stroke in East Asian patients.


Assuntos
Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos de Coortes , Gerenciamento de Dados , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pontuação de Propensão , Acidente Vascular Cerebral/induzido quimicamente , Taiwan , Resultado do Tratamento
9.
J Neurochem ; 156(6): 917-928, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32750162

RESUMO

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by accumulated motor disability. However, whether remyelination promotes motor recovery following demyelinating injury remains unclear. Damage to the internal capsule (IC) is known to result in motor impairment in multiple sclerosis and stroke. Here, we induced focal IC demyelination in mice by lysophosphatidylcholine (LPC) injection, and examined its effect on motor behavior. We also compared the effect of LPC-induced IC damage to that produced by endothelin-1 (ET1), a potent vasoconstrictor used in experimental stroke lesions. We found that LPC or ET1 injections induced asymmetric motor deficit at 7 days post-lesion (dpl), and that both lesion types displayed increased microglia/macrophage density, myelin loss, and axonal dystrophy. The motor deficit and lesion pathology remained in ET1-injected mice at 28 dpl. In contrast, LPC-injected mice regained motor function by 28 dpl, with corresponding reduction in activated microglia/macrophage density, and recovery of myelin staining and axonal integrity in lesions. These results suggest that LPC-induced IC demyelination results in acute motor deficit and subsequent recovery through remyelination, and may be used to complement future drug screens to identify drugs for promoting remyelination.


Assuntos
Doenças Desmielinizantes/fisiopatologia , Cápsula Interna/fisiopatologia , Transtornos das Habilidades Motoras/fisiopatologia , Bainha de Mielina/patologia , Animais , Axônios/patologia , Doenças Desmielinizantes/induzido quimicamente , Endotelina-1 , Imuno-Histoquímica , Cápsula Interna/patologia , Lisofosfatidilcolinas , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/patologia , Transtornos das Habilidades Motoras/induzido quimicamente , Transtornos das Habilidades Motoras/patologia , Oligodendroglia/patologia , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/fisiopatologia
10.
J Intern Med ; 289(1): 42-52, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32602228

RESUMO

BACKGROUND: Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population. OBJECTIVES: This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin. METHODS: This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013-30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare each drug, 6 propensity score-matched (PSM) cohorts were created. Patient cohorts were pooled from 4 databases after PSM. Cox models were used to estimate hazard ratios (HR) of S/SE and MB. RESULTS: Amongst NVAF patients, 34% (N = 150 487) met frailty criteria. Apixaban and rivaroxaban were associated with a lower risk of S/SE vs warfarin (apixaban: HR: 0.61, 95% CI: 0.55-0.69; rivaroxaban: HR: 0.79, 95% CI: 0.72-0.87). For MB, apixaban (HR: 0.62, 95% CI: 0.57-0.66) and dabigatran (HR: 0.79, 95% CI: 0.70-0.89) were associated with a lower risk and rivaroxaban (HR: 1.14, 95% CI: 1.08-1.21) was associated with a higher risk vs warfarin. CONCLUSION: Amongst this cohort of frail NVAF patients, NOACs were associated with varying rates of stroke/SE and MB compared with warfarin. Due to the lack of real-world data regarding OAC treatment in frail patients, these results may inform clinical practice in the treatment of this patient population.


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Idoso Fragilizado , Hemorragia/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Administração Oral , Idoso , Anticoagulantes/uso terapêutico , Causas de Morte , Dabigatrana/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Pontuação de Propensão , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Estados Unidos/epidemiologia , Vitamina K/antagonistas & inibidores , Varfarina/efeitos adversos
11.
J Oncol Pharm Pract ; 27(4): 1016-1019, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32903144

RESUMO

INTRODUCTION: 5-Fluorouracil is an antineoplastic agent generally used to treat various types of solid tumors. The common adverse drug reaction associated with 5-fluorouracil are myelosuppression, mucositis, diarrhea, and hand-foot syndrome. Neurological side effects such as headache, dizziness, convulsion, encephalopathy, and acute cerebellar syndrome are rare in nature. CASE PRESENTATION: We report a case of 5-fluorouracil induced cerebrovascular accident (CVA) in a patient with no risk factors for CVA before chemotherapy. A 37 years old female patient diagnosed with carcinoma rectum underwent six cycles of chemotherapy with 5- fluorouracil- calcium leucovorin- irinotecan (FOLFIRI regimen). After completing the last cycle, she developed headache, vomiting, and facial deviation along with high blood pressure (260/160 mmHg). MRI brain was done, and it revealed acute non-hemorrhagic lacunar infarct in the left half of pons. 5-fluorouracil induced CVA was suspected and was managed with dual antiplatelet, statin, and antihypertensives. CONCLUSION: The clinicians and clinical pharmacists must be aware about the potential of 5-FU to induce rare side effects such as CVA even in low risk patients in order to avoid permanent harm to the patient.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Fluoruracila/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Feminino , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico
12.
Environ Res ; 193: 110538, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33285155

RESUMO

BACKGROUND: There is evidence that exposure to mercury (Hg) may be a risk factor for cardiovascular disease (CVD). OBJECTIVE: To conduct a systematic review of published studies and a meta-analysis of the results to examine the associations between chronic Hg exposure and CVD outcomes. METHODS: We searched PubMed, Embase, and TOXLINE using previously developed strategies. Studies were selected according to a priori-defined inclusion criteria, and their qualities were assessed. Study estimates were extracted, and subgroup analyses were conducted to explore potential sources of heterogeneity: 1) fatal vs. nonfatal events, 2) cohort study vs. non-cohort study, and 3) inorganic Hg vs. methyl mercury (MeHg). Dose-response meta-analyses were conducted for MeHg exposure and fatal/nonfatal ischemic heart disease (IHD), stroke, and all CVD. RESULTS: A total of 14 studies reporting results collected from more than 34,000 participants in 17 countries were included in the meta-analysis. Hg exposure was associated with an increase in nonfatal IHD (relative risk (RR): 1.21 (0.98, 1.50)), all-cause mortality (RR: 1.21 (0.90, 1.62)), CVD mortality (RR: 1.68 (1.15, 2.45)), and mortality due to other heart diseases (RR: 1.50 (1.07, 2.11)). No association was observed between Hg exposure and stroke. A heterogeneous relationship was found between studies reporting fatal and nonfatal outcomes and between cohort and non-cohort studies. However, these differences were mainly due to differences in Hg exposure level. Occupational inorganic Hg exposure was associated with similar increases in different mortality outcomes. A J-shaped relationship between Hg exposure and different fatal/nonfatal outcomes was observed, with turning points at hair Hg concentrations of 1 µg/g for IHD and 2 µg/g for stroke and all CVD. CONCLUSION: Chronic exposure to Hg was associated with an increased risk of all-cause mortality and fatal/nonfatal IHD. The risk of multiple cardiovascular endpoints starts to increase consistently at a hair Hg concentration of 2 µg/g.


Assuntos
Doenças Cardiovasculares , Mercúrio , Acidente Vascular Cerebral , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Humanos , Mercúrio/toxicidade , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia
13.
Am J Med ; 134(5): 614-620.e1, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33181103

RESUMO

BACKGROUND: Marijuana is the most commonly used psychoactive drug, while its effects on cardiovascular health are not well known and remain a subject of interest. METHODS: We used the pooled 2016-2018 data from the Behavioral Risk Factor Surveillance System to perform a cross-sectional analysis evaluating the association of marijuana and cardiovascular disease among US adults who never smoked cigarettes. RESULTS: Among US adults ages 18-74 years, when compared with nonusers, frequent marijuana use was associated with 88% higher odds of myocardial infarction or coronary artery disease (adjusted odds ratio [aOR] 1.88; 95% confidence interval [CI], 1.15-3.08), and 81% higher odds of stroke (aOR 1.81; 95% CI, 1.14-2.89). Among the premature cardiovascular disease group, frequent marijuana users had 2.3 times higher odds of myocardial infarction or coronary artery disease (aOR 2.27; 95% CI, 1.20-4.30), and 1.9 times higher odds of stroke (aOR 1.92; 95% CI, 1.07-3.43). In terms of the modality of marijuana use, frequent marijuana smoking had 2.1 times higher odds of myocardial infarction or coronary artery disease (aOR 2.07; 95% CI, 1.21-3.56), and 1.8 times higher odds of stroke (aOR 1.84; 95% CI, 1.09-3.10). A similar association was observed in the premature cardiovascular disease group who smoked marijuana (aOR [for myocardial infarction or coronary artery disease] 2.64; 95% CI, 1.37-5.09; aOR [for stroke] 2.00; 95% CI, 1.05-3.79). No association was observed between marijuana use in any form other than smoking and cardiovascular disease, across all age groups. CONCLUSION: Frequent marijuana smoking is associated with significantly higher odds of stroke and myocardial infarction or coronary artery disease, with a possible role in premature cardiovascular disease.


Assuntos
Doenças Cardiovasculares/induzido quimicamente , Fumar Maconha/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Sistema de Vigilância de Fator de Risco Comportamental , Doenças Cardiovasculares/epidemiologia , Doença da Artéria Coronariana/induzido quimicamente , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/epidemiologia , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
14.
Aesthet Surg J ; 41(6): NP602-NP608, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33351073

RESUMO

Vascular compromise and blindness are reported but rare complications of facial soft tissue filler injections. Stroke is an even rarer complication resulting from intraarterial injection of fillers. We present a case of a patient suffering all 3 complications following hyaluronic acid filler injection: forehead skin vascular compromise, unilateral blindness, and ipsilateral subclinical strokes. Were it not for a stroke workup protocol, the incidental strokes may have otherwise gone undetected, suggesting the incidence of stroke from intraarterial injection may be higher than reported. Further, we review the literature and recommendations for prevention and management of threatened tissue ischemia and vision loss from facial filler injection.


Assuntos
Técnicas Cosméticas , Preenchedores Dérmicos , Acidente Vascular Cerebral , Cegueira/induzido quimicamente , Cegueira/diagnóstico , Técnicas Cosméticas/efeitos adversos , Preenchedores Dérmicos/efeitos adversos , Humanos , Ácido Hialurônico/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/diagnóstico
15.
PLoS One ; 15(12): e0242558, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33259522

RESUMO

Tobacco is well known as a risk factor for early morbidity and mortality worldwide. However, the relative risk of mortality and the effects of smoking vary among the countries. Indonesia, as one of the world's largest market for smoking tobacco, is significantly affected by tobacco-related illness. Previous research has shown that smoking causes several diseases, including stroke, neoplasm and coronary heart disease. There has to date been no research on the hazard risk of smoking for all-cause mortality in Indonesia. This study aimed to identify the association between smoking and all-cause mortality rates in Indonesia. Information from a total of 3,353 respondents aged 40 years and older was collected in this study. The data were taken from the Indonesian Family Life Survey (IFLS) Wave 4 (2007) to collect personal information and determine smoking status and from Wave 5 (2015) to collect information about deaths. Current smokers make up 40.3% of Indonesia's population. Current smokers were more likely to have a higher risk of all-cause death (hazard ratio = 1.48, 95% confidence interval = 1.11 to 1.98) than non-current smokers. The number of smokers in Indonesia remains high and is expected to increase gradually every year. A firm government policy is needed to reduce the number of smokers in Indonesia which would automatically reduce the health problem of smoking-related illness in the future.


Assuntos
Doença das Coronárias/mortalidade , Neoplasias/mortalidade , Acidente Vascular Cerebral/mortalidade , Fumar Tabaco/efeitos adversos , Adulto , Idoso , Causas de Morte , Doença das Coronárias/induzido quimicamente , Feminino , Humanos , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Morbidade , Neoplasias/induzido quimicamente , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente
16.
Epidemiology ; 31(6): 880-888, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33003152

RESUMO

BACKGROUND: Observational healthcare data can be used for drug safety and effectiveness research. The use of inverse probability of treatment weights (IPW) reduces measured confounding under the assumption of accurate measurement of the outcome variable; however, many datasets suffer from systematic outcome misclassification. METHODS: We introduced a modification to IPW to correct for the presence of outcome misclassification. To demonstrate the utility of these modified weights in realistic settings, we investigated postmyocardial infarction statin use and the 1-year risk of stroke in the Clinical Practice Research Datalink. RESULTS: We computed an IPW-adjusted odds ratio (OR = 0.67; 95% confidence interval (CI) = 0.48, 0.93). We employed a technique to modify IPW for the presence of outcome misclassification using linked hospital records for outcome validation (modified IPW adjusted OR = 0.77; 95% CI = 0.52, 1.15) and compared the results with a meta-analysis of randomized controlled trials (RCTs) (pooled OR = 0.80; 95% CI = 0.74, 0.87). Finally, we present simulation studies to investigate the impact of model selection on bias reduction and variability. CONCLUSION: Ignoring outcome misclassification yielded biased estimates whereas the use of the modified IPW approach produced encouraging results when compared with the meta-analytic RCT findings.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Acidente Vascular Cerebral , Viés , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Probabilidade , Risco , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento
17.
JAMA Dermatol ; 156(11): 1208-1215, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32902568

RESUMO

Importance: Ustekinumab, a monoclonal antibody targeting interleukin 12/23p40 (IL-12/23p40), is effective in the treatment of moderate to severe psoriasis, psoriatic arthritis, and Crohn disease. In 2011, a meta-analysis of randomized clinical trials reported a potential risk of severe cardiovascular events (SCEs) within the first few months after the initiation of anti-IL-12/23p40 antibodies. Objective: To assess whether the initiation of ustekinumab treatment is associated with increased risk of SCEs. Design, Setting, and Participants: This case-time-control study used data from the French national health insurance database, covering 66 million individuals, on all patients exposed to ustekinumab between April 1, 2010, and December 31, 2016, classified according to their cardiovascular risk level (high- and low-risk strata). The risk period was the 6 months before the SCE, defined as acute coronary syndrome or stroke, and the reference period was the 6 months before the risk period. Statistical analysis was performed from September 20, 2017, to July 6, 2018. Exposure: The initiation of ustekinumab treatment was screened during the risk and reference periods. Main Outcomes and Measures: Odds ratios for the risk of SCE after the initiation of ustekinumab treatment were calculated. Results: Of the 9290 patients exposed to ustekinumab (4847 men [52%]; mean [SD] age, 43 [14] years), 179 experienced SCEs (65 cases of acute coronary syndrome, 68 cases of unstable angina, and 46 cases of stroke). Among patients with a high cardiovascular risk, a statisically significant association between initiaton of ustekinumab treatment and SCE occurrence was identified (odds ratio, 4.17; 95% CI, 1.19-14.59). Conversely, no statistically significant association was found among patients with a low cardiovascular risk (odds ratio, 0.30; 95% CI, 0.03-3.13). Conclusions and Relevance: This study suggests that the initiation of ustekinumab treatment may trigger SCEs among patients at high cardiovascular risk. In line with the current mechanistic models for atherosclerotic disease, the period after the initiation of anti-IL-12/23p40 may be associated with atherosclerotic plaque destabilization via the inhibition of helper T cell subtype 17. Although the study interpretation is limited by its observational design, these results suggest that caution may be needed in the prescription of ustekinumab to patients at high cardiovascular risk.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Angina Instável/epidemiologia , Doença de Crohn/tratamento farmacológico , Psoríase/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Ustekinumab/efeitos adversos , Síndrome Coronariana Aguda/induzido quimicamente , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/imunologia , Adulto , Angina Instável/induzido quimicamente , Angina Instável/diagnóstico , Angina Instável/imunologia , Estudos de Casos e Controles , Doença de Crohn/imunologia , Estudos Cross-Over , Seguimentos , França/epidemiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Indução de Remissão/métodos , Medição de Risco/estatística & dados numéricos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/imunologia , Fatores de Tempo
18.
J Stroke Cerebrovasc Dis ; 29(9): 105085, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807481

RESUMO

Ponatinib is a third-generation Tyrosine Kinase Inhibitor (TKI), approved as first-line treatment for Chronic Myeloid Leukaemia (CML) chronic phase. Here we describe a CML patient with a history of subsequent TIAs and an ischemic stroke during Ponatinib treatment. Patient was admitted for a 3-day history of sudden onset left hemiparesis due to an acute ischemic stroke. MRI showed bilaterally the almost total absence of signal in the intracranial tract of anterior circulation and low signal of cerebral posterior circulation. Digital Subtraction Angiography showed multiple steno-occlusions of both anterior and posterior circulation large vessels. The association between cerebrovascular events and TKIs of second and third-generation has been widely described. So Ponatinib was stopped. To our knowledge, this is the first case of multiple ischemic strokes and recurrent TIAs during treatment with Ponatinib, pointing out the importance of accurate quantification of cardiovascular risk before starting Ponatinib.


Assuntos
Antineoplásicos/efeitos adversos , Imidazóis/efeitos adversos , Trombose Intracraniana/induzido quimicamente , Ataque Isquêmico Transitório/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Piridazinas/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Tomada de Decisão Clínica , Humanos , Trombose Intracraniana/diagnóstico por imagem , Ataque Isquêmico Transitório/diagnóstico por imagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Resultado do Tratamento
19.
Am Heart J ; 228: 1-7, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32739652

RESUMO

BACKGROUND: Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is the cornerstone for prevention ischemic events in patients with acute coronary syndromes (ACS) and undergoing percutaneous coronary intervention. However, the optimal antiplatelet strategy for ACS patients with both high bleeding and high ischemic risks is unclear. STUDY DESIGN: The OPT-BIRISK trial is a multicenter, double-blinded, placebo-controlled randomized study designed to test the superiority of extended antiplatelet therapy with clopidogrel monotherapy compared with aspirin and clopidogrel for reduction of bleeding events in ACS patients with both high bleeding and high ischemic risks ("bi-risk"). A total of 7,700 patients who completed 9- to 12-month dual antiplatelet therapy after new-generation drug-eluting stent implantation for the treatment of ACS will be randomized to receive clopidogrel monotherapy or aspirin plus clopidogrel for 9 months followed by aspirin monotherapy for 3 months. The primary end point is Bleeding Academic Research Consortium type 2, 3, or 5 bleedings at 9 months after randomization. The key secondary end point is major adverse cardiac and cerebral events at 9 months after randomization, defined as a composite of all-cause death, myocardial infarction, stroke, or coronary artery revascularization. CONCLUSIONS: OPT-BIRISK is the first large-scale randomized trial aimed to explore the optimal antiplatelet strategy for bi-risk ACS patients after percutaneous coronary intervention in current clinical practice. The results will add evidence regarding de-escalation antiplatelet therapy for patients at special risk.


Assuntos
Síndrome Coronariana Aguda , Aspirina , Clopidogrel , Hemorragia , Risco Ajustado/métodos , Acidente Vascular Cerebral , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Adulto , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Método Duplo-Cego , Stents Farmacológicos/efeitos adversos , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/métodos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
20.
Exp Mol Pathol ; 116: 104512, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32745469

RESUMO

The miRNAs and mRNAs are found to play a crucial role in modulating different diseases including stroke, according to the recent evidence. The current study is aimed at assessing the functional role played by miR-188-5p in the regulation of cell apoptosis and viability in OGD-induced human neural cell line HNC. With the help of RT-qPCR, the authors determined miR-188-5p as well as its putative target PTEN among OGD-treated cells in different treatment times. The cell viability was assessed through CCK-8 assay while the cell transfection either upregulated or may have silenced the genes. Both Western Blot as well as RT-qPCR found the proliferation biomarkers such as Ki87 and PCNA in addition to apoptosis biomarkers such as caspase-8 and caspase-3. The luciferase activity was tracked by conducting luciferase assay. The researchers observed an elevation in the expression of miR-188-5p while the PTEN got downregulated in Human Neural Cell line HNC with increase in the time span. The expressions of miR-188-5p and PTEN got increased with increasing OGD treatment time while the Luciferase reassured the binding site. The cell viability was suppressed by the overexpression of miR-188-5p which further inhibited the apoptosis biomarkers too. Meanwhile, it was understood that the results could be reversed to some extent with the inhibition of PTEN. The study findings from in vitro investigations yielded promising results and provided excellent insights about the fundamental molecular mechanisms of miR-188-5p involved in stroke via PTEN. This could be considered as a potential therapeutic axis among stroke patients in the near future.


Assuntos
Apoptose/genética , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Acidente Vascular Cerebral/genética , Caspase 8/genética , Linhagem Celular , Sobrevivência Celular/genética , Glucose/efeitos adversos , Humanos , Neurônios/metabolismo , Neurônios/patologia , Oxigênio/efeitos adversos , Transdução de Sinais/genética , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia
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