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1.
BMC Cardiovasc Disord ; 20(1): 415, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928149

RESUMO

BACKGROUND: Methanol is widely used in industry; however, methanol poisoning is not common. In this regard, a number of outbreaks have been recently reported due to inappropriate processing of alcoholic beverages. Shiraz, a city located in the southern part of Iran, faced one of such outbreaks in 2020 during COVID-19 pandemic. There is no sufficient literature on the electrocardiographic findings in methanol toxicity. This study aimed to address this gap in the literature. METHOD: A total of 356 cases with methanol toxicity referred to Shiraz University of Medical Science Tertiary Hospitals (Faghihi and Namazi) in March and April, 2020. The clinical findings of blindness and impaired level of consciousness, lab data such as arterial blood gas, electrolytes, and creatinine, and the most common findings from ECGs were collected. RESULTS: The most common ECG findings were J point elevation (68.8%), presence of U wave (59.2%), QTc prolongation (53.2% in males and 28.6% in females), and fragmented QRS (33.7%). An outstanding finding in this study was the presence of myocardial infarction in 5.3% of the cases. This finding, to the best of our knowledge, has only been reported in a few case reports. Brugada pattern (8.1%) and Osborn wave (3.7%) were the other interesting findings. In multivariate analysis, when confounding factors were adjusted, myocardial infarction, atrioventricular conduction disturbances, sinus tachycardia, and the prolonged QTC > 500 msecond were four independent factors correlated with methanol toxicity severity measured with arterial blood PH on arterial blood gas measurements, with odds ratios of 12.82, 4.46, 2.32 and 3.15 (P < 0.05 for all), respectively. CONCLUSION: Electrocardiographic variations during methanol intoxication are remarkable and well-correlated with poisoning severity. Myocardial infarction was an egregious and yet a common concerning finding in this sample, which need to be ruled out in methanol toxicity.


Assuntos
Bloqueio Atrioventricular/induzido quimicamente , Cegueira/induzido quimicamente , Transtornos da Consciência/induzido quimicamente , Síndrome do QT Longo/induzido quimicamente , Metanol/envenenamento , Infarto do Miocárdio/induzido quimicamente , Solventes/envenenamento , Taquicardia Sinusal/induzido quimicamente , Adolescente , Adulto , Idoso , Bebidas Alcoólicas , Bloqueio Atrioventricular/sangue , Bloqueio Atrioventricular/fisiopatologia , Betacoronavirus , Cegueira/sangue , Cegueira/fisiopatologia , Gasometria , Síndrome de Brugada/sangue , Síndrome de Brugada/induzido quimicamente , Síndrome de Brugada/fisiopatologia , Transtornos da Consciência/sangue , Transtornos da Consciência/fisiopatologia , Infecções por Coronavirus , Eletrocardiografia , Feminino , Contaminação de Alimentos , Humanos , Concentração de Íons de Hidrogênio , Irã (Geográfico) , Síndrome do QT Longo/sangue , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Pandemias , Pneumonia Viral , Envenenamento/sangue , Envenenamento/fisiopatologia , Fatores Sexuais , Taquicardia Sinusal/sangue , Taquicardia Sinusal/fisiopatologia , Adulto Jovem
2.
Medicine (Baltimore) ; 99(29): e21236, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702900

RESUMO

Sulphonylureas (SUs) subclasses have different risks of all-cause mortality, acute myocardial infarction (AMI), and stroke. Therefore, we assessed these risks in patients with type 2 diabetes mellitus administered gliclazide, glimepiride, or metformin monotherapy with retrospective cohort study design. Total 195,235 subjects were included in the study who were ≥20 years' old and prescribed monotherapy for at least 1 year as a first-line therapy for incident diabetes from January 01, 2009 to December 31, 2013 in the National Health Insurance Service Claim data. Incidence and hazard ratios (HRs) of all-cause mortality, AMI, and stroke were compared with glimepiride monotherapy as a reference. Gliclazide monotherapy increased all-cause mortality compared with glimepiride monotherapy. However, the gliclazide and glimepiride groups showed no difference in AMI and stroke incidences. In line with previous studies, metformin monotherapy showed significant clinical benefits in reducing risks of all-cause mortality, AMI, and stroke compared with glimepiride. This population-based cohort study suggested that gliclazide increases risks of all-cause mortality and has similar risk of AMI and stroke with gliclazide monotherapy in Korean.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Gliclazida/efeitos adversos , Hipoglicemiantes/efeitos adversos , Infarto do Miocárdio/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Compostos de Sulfonilureia/efeitos adversos , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , República da Coreia , Fatores de Risco , Acidente Vascular Cerebral/mortalidade
3.
PLoS One ; 15(5): e0232413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32384080

RESUMO

BACKGROUND: Acute myocardial infarction (AMI) remains the most common cause of morbidity and mortality worldwide. The present study was directed to investigate the beneficial effects of benfotiamine pre- and post-treatments in isoproterenol (ISO)-induced MI in rats. METHODS: Myocardial heart damage was induced by subcutaneous injection of ISO (150 mg/kg) once daily for two consecutive days. Benfotiamine (100 mg/kg/day) was given orally for two weeks before or after ISO treatment. RESULTS: ISO administration revealed significant changes in electrocardiographic recordings, elevation of levels of cardiac enzymes; creatinine kinase (CK-MB) and troponin-I (cTn-I), and perturbation of markers of oxidative stress; nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and markers of inflammation; protein kinase C (PKC), nuclear factor-kappa B (NF-κB) and metalloproteinase-9 (MMP-9). The apoptotic markers (caspase-8 and p53) were also significantly elevated in ISO groups in addition to histological alterations. Groups treated with benfotiamine pre- and post-ISO administration showed significantly decreased cardiac enzymes levels and improved oxidative stress, inflammatory and apoptotic markers compared to the ISO groups. CONCLUSION: The current study highlights the potential role of benfotiamine as a promising agent for prophylactic and therapeutic interventions in myocardial damage in several cardiovascular disorders via NADPH oxidase inhibition.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , NADPH Oxidases/antagonistas & inibidores , Tiamina/análogos & derivados , Animais , Biomarcadores/metabolismo , Cardiotoxinas/toxicidade , Modelos Animais de Doenças , Eletrocardiografia , Humanos , Mediadores da Inflamação/metabolismo , Isoproterenol/toxicidade , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Tiamina/uso terapêutico
4.
PLoS One ; 15(5): e0232530, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32384091

RESUMO

BACKGROUND: Clinical and animal studies have found that anxiety and depression are significantly more common after acute myocardial infarction (AMI). The medial prefrontal cortex (PFC) has a dual role: in higher brain functions and in cardiovascular control, making it a logical candidate for explaining the perceived bidirectional heart-brain connection. We used parallel Electrocardiography (ECG) and Electrocorticography (ECoG) registration to investigate AMI-induced changes in medial PFC bioelectrical activity in a rat model of AMI. MATERIALS AND METHODS: Adult male Wistar albino rats were used in the study. Gold-plated recording electrodes were implanted over the frontal cortex for ECoG recording. ECG was recorded via two holter electrodes attached on the skin of the back fixed in place by a jacket. Induction of AMI was performed by isoprenaline (150 mg/kg, i.p.). ECoG and ECG signals were registered at baseline, during 3 hours after isoprenaline administration and at 24 hours after isoprenaline administration. RESULTS: Significant increases of theta, alpha, and beta electroencephalographic (EEG) band power were observed in different time intervals after isoprenaline administration. Significant increase of theta band peak frequency was also observed during the first hour after isoprenaline administration. No statistically significant differences in band-power activity were found between the pre-isoprenaline measurements and 24 hours after administration. CONCLUSION: Our results demonstrate significant increases in EEG band power of alpha beta and theta bands during isoprenaline-induced AMI model. These are the first findings to connect heart damage during isoprenaline- induced AMI to disturbances in the cortical bioelectrical activity.


Assuntos
Isoproterenol/farmacologia , Infarto do Miocárdio/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Ondas Encefálicas/fisiologia , Modelos Animais de Doenças , Eletrocardiografia , Eletrocorticografia , Eletroencefalografia , Masculino , Infarto do Miocárdio/induzido quimicamente , Ratos , Ratos Wistar
5.
JAMA Netw Open ; 3(4): e202004, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239221

RESUMO

Importance: Prasugrel was approved at a lower dose in 2014 in Japan than in the West because East Asian patients are considered more susceptible to bleeding than Western patients. However, real-world outcomes with low-dose prasugrel treatment remain unclear. Objective: To investigate the association of low-dose prasugrel vs standard-dose clopidogrel administration with short-term outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). Design, Setting, and Participants: This study used data from the Japan Cardiovascular Database-Keio Interhospital Cardiovascular Studies registry, a large, ongoing, multicenter, retrospective cohort of consecutive patients who underwent PCI. The present cohort study evaluated 2770 patients with acute coronary syndrome who underwent PCI and received either low-dose prasugrel (loading dose, 20 mg; maintenance dose, 3.75 mg) or clopidogrel (loading dose, 300 mg; maintenance dose, 75 mg) in combination with aspirin between 2014 and 2018. Propensity score-matching analysis was conducted to balance the baseline characteristics of patients receiving low-dose prasugrel and those receiving clopidogrel. Data analysis was conducted in June 2019. Exposures: Prescription of either low-dose prasugrel or standard-dose clopidogrel prior to PCI. Main Outcomes and Measures: Primary ischemic events (in-hospital death, recurrent myocardial infarction, and ischemic stroke) and primary bleeding events, defined as bleeding complications within 72 hours after PCI consistent with the National Cardiovascular Data Registry CathPCI Registry definition. Results: Of 2559 patients included in the study, the mean (SD) age was 67.8 (12.7) years, and 78.2% were male. In total, 1297 patients (50.7%) received low-dose prasugrel, and 1262 patients (49.3%) received clopidogrel. After propensity score matching, primary ischemic events among patients receiving low-dose prasugrel and those receiving clopidogrel were comparable (odds ratio [OR], 1.42; 95% CI, 0.90-2.23), but primary bleeding events were significantly higher among patients receiving prasugrel (OR, 2.91; 95% CI, 1.63-5.18). This increase in bleeding events was associated with the presence of a profile of high-bleeding risk (≥75 years of age, body weight <60 kg, or history of stroke or transient ischemic attack) (OR, 4.08; 95% CI, 1.86-8.97), being female (OR, 3.84; 95% CI, 1.05-14.0), or the presence of ST-segment elevation myocardial infarction (OR, 2.07; 95% CI, 1.05-4.09) or chronic kidney disease (OR, 4.78; 95% CI, 1.95-11.7). Conclusions and Relevance: Since its approval, low-dose prasugrel has been used by nearly 80% of patients who undergo PCI. Despite the modified dose, bleeding events were higher among patients receiving low-dose prasugrel than among patients receiving clopidogrel, with no difference in ischemic events between the 2 groups. These results suggest the importance of a risk assessment of bleeding prior to selecting a P2Y12 inhibitor, even for the use of a lower approved dose, when treating patients of East Asian descent.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Síndrome Coronariana Aguda/cirurgia , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/patologia , Estudos de Casos e Controles , Clopidogrel/administração & dosagem , Clopidogrel/uso terapêutico , Morte , Quimioterapia Combinada , Feminino , Hemorragia/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/fisiopatologia , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/uso terapêutico , Sistema de Registros , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Medição de Risco , Acidente Vascular Cerebral/epidemiologia
6.
Curr Opin Anaesthesiol ; 33(3): 417-422, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32324663

RESUMO

PURPOSE OF REVIEW: Although the indications for ß-blockers in the management of patients with congestive heart failure and myocardial infarction are well established, the use of ß-blockers in the perioperative setting remains controversial. RECENT FINDINGS: Since 2008 PeriOperative ISchemic Evaluation Trial, there have been numerous studies suggesting that perioperative ß-blockers are associated with adverse events such as hypotension, bradycardia, increased mortality, and stroke. SUMMARY: In this article, we review the most recent evidence to suggest an approach to perioperative ß-blocker use tailored to patient and surgical risk factors. We also review recent studies on off-label uses for perioperative ß-blockers.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Anestesiologia/métodos , Doenças Cardiovasculares/induzido quimicamente , Cuidados Intraoperatórios/métodos , Complicações Pós-Operatórias/induzido quimicamente , Antagonistas Adrenérgicos beta/uso terapêutico , Bradicardia/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Infarto do Miocárdio/induzido quimicamente , Assistência Perioperatória , Período Perioperatório , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente
7.
Minerva Med ; 111(2): 173-180, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32338843

RESUMO

INTRODUCTION: Clinical data on short mandatory dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy, compared with prolonged DAPT in patients undergoing percutaneous coronary intervention (PCI) are insufficient. We aim to evaluate the effectiveness and safety of P2Y12 inhibitor monotherapy and prolonged DAPT after short mandatory DAPT on cardiovascular events in patients undergoing PCI. EVIDENCE ACQUISITION: A systematic literature search was performed in seven medical databases from building the database until July 2019. Three studies with randomized controlled trial (RCTs), totaling 21,970 patients, were included in this meta-analysis. The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager v. 5.3 software. EVIDENCE SYNTHESIS: Our result of pooled analysis showed that there was noninferior rates of in major adverse cardiac and cerebrovascular events (MACCE), stroke, myocardial infarction and cardiac death between short mandatory DAPT followed by P2Y12 inhibitor monotherapy and prolonged DAPT in patients undergoing PCI. Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5 (OR=0.47, 95% CI: 0.31-0.70, P=0.002), compared with prolonged DAPT in patients undergoing PCI. However, Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy was not associated with BARC type 3-5, compared with prolonged DAPT. CONCLUSIONS: This meta-analysis demonstrated that short mandatory DAPT followed by P2Y12 inhibitor monotherapy compared with prolonged DAPT resulted in noninferior rates of MACCE, all-cause mortality, cardiac death, stroke, myocardial infarction and stent thrombosis. Furthermore, short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5.


Assuntos
Aspirina/efeitos adversos , Cardiopatias/mortalidade , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Acidente Vascular Cerebral/mortalidade , Aspirina/uso terapêutico , Causas de Morte , Cardiopatias/induzido quimicamente , Humanos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Stents/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Trombose/induzido quimicamente , Trombose/mortalidade
8.
Arterioscler Thromb Vasc Biol ; 40(6): 1454-1463, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32295420

RESUMO

Prostanoids are a group of bioactive lipids that are synthesized de novo from membrane phospholipid-released arachidonic acid and have diverse functions in normal physiology and disease. NSAIDs (non-steroidal anti-inflammatory drugs), which are among the most commonly used medications, ameliorate pain, fever, and inflammation by inhibiting COX (cyclooxygenase), which is the rate-limiting enzyme in the biosynthetic cascade of prostanoids. The use of NSAIDs selective for COX-2 inhibition increases the risk of a thrombotic event (eg, myocardial infarction and stroke). All NSAIDs are associated with an increased risk of heart failure. Substantial variation in clinical responses to aspirin exists and is associated with cardiovascular risk. Limited clinical studies suggest the involvement of prostanoids in vascular restenosis in patients who received angioplasty intervention. mPGES (microsomal PG [prostaglandin] E synthase)-1, an alternative target downstream of COX, has the potential to be therapeutically targeted for inflammatory disease, with diminished thrombotic risk relative to selective COX-2 inhibitors. mPGES-1-derived PGE2 critically regulates microcirculation via its receptor EP (receptor for prostanoid E) 4. This review summarizes the actions and associated mechanisms for modulating the biosynthesis of prostanoids in thrombosis, vascular remodeling, and ischemic heart disease as well as their therapeutic relevance.


Assuntos
Anti-Inflamatórios , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Descoberta de Drogas , Prostaglandinas/fisiologia , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Humanos , Infarto do Miocárdio/induzido quimicamente , Traumatismo por Reperfusão Miocárdica/induzido quimicamente , Prostaglandina-E Sintases/efeitos dos fármacos , Prostaglandinas/biossíntese , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Remodelação Vascular
9.
Nat Biomed Eng ; 4(4): 446-462, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32284552

RESUMO

Environmental factors are the largest contributors to cardiovascular disease. Here we show that cardiac organoids that incorporate an oxygen-diffusion gradient and that are stimulated with the neurotransmitter noradrenaline model the structure of the human heart after myocardial infarction (by mimicking the infarcted, border and remote zones), and recapitulate hallmarks of myocardial infarction (in particular, pathological metabolic shifts, fibrosis and calcium handling) at the transcriptomic, structural and functional levels. We also show that the organoids can model hypoxia-enhanced doxorubicin cardiotoxicity. Human organoids that model diseases with non-genetic pathological factors could help with drug screening and development.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Coração/efeitos dos fármacos , Modelos Cardiovasculares , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Organoides/efeitos dos fármacos , Cardiotoxicidade/metabolismo , Cardiotoxicidade/patologia , Desenvolvimento de Medicamentos , Humanos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/genética , Organoides/metabolismo , Organoides/patologia , Oxigênio/metabolismo
10.
Oxid Med Cell Longev ; 2020: 2432918, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32215169

RESUMO

The present study was directed to investigate the effect of precotreatment with (E)-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide (7-hyd.HC), a novel potent synthesized coumarin, on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. The hydrazone compound was characterized by IR, 1D, and 2D NMR analyses. Experimental induction of MI in rats was established by ISO (85 mg/kg/day, s.c) for two consecutive days (6th and 7th days). 7-hyd.HC or sintrom was given for 7 days prior and simultaneous to ISO injection. 7-hyd.HC offered a cardiopreventive effect by preventing heart injury marker leakage (LDH, ALT, AST, CK-MB, and cTn-I) from cardiomyocytes and normalizing cardiac function and ECG pattern, as well as improving lipid profile (TC, TG, LDL-C, and HDL-C), which were altered by ISO administration. Moreover, 7-hyd.HC precotreatment significantly mitigated the oxidative stress biomarkers, as evidenced by the decrease of lipid peroxidation and the increased level of the myocardial GSH level together with the SOD, GSH-Px, and catalase activities. 7-hyd.HC inhibited the cardiac apoptosis by upregulating the expression of Bcl-2 and downregulating the expression of Bax and caspase-3 genes. In addition, 7-hyd.HC reduced the elevated fibrinogen rate and better prevented the myocardial necrosis and improved the interstitial edema and neutrophil infiltration than sintrom. Overall, 7-hyd.HC ameliorated the severity of ISO-induced myocardial infarction through improving the oxidative status, attenuating apoptosis, and reducing fibrinogen production. The 7-hyd.HC actions could be mediated by its antioxidant, antiapoptotic, and anti-inflammatory capacities.


Assuntos
Anti-Inflamatórios/uso terapêutico , Benzopiranos/uso terapêutico , Cumarínicos/uso terapêutico , Hidrazonas/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Apoptose/efeitos dos fármacos , Benzopiranos/síntese química , Benzopiranos/química , Biomarcadores/metabolismo , Cumarínicos/síntese química , Cumarínicos/química , Hidrazonas/síntese química , Hidrazonas/química , Inflamação/metabolismo , Isoproterenol/toxicidade , Masculino , Estrutura Molecular , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Resultado do Tratamento
11.
Chem Biol Interact ; 318: 108970, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32007421

RESUMO

Cardiovascular disorders constitute the principal cause of deaths worldwide and will continue as the major disease-burden by the year 2060. A significant proportion of heart failures occur because of use and misuse of drugs and most of the investigational agents fail to achieve any clinical relevance. Here, we investigated rosuvastatin and retinoic acid for their "pharmacological pleiotropy" against high dose ß-adrenergic agonist (isoproterenol)-induced acute myocardial insult. Rats were pretreated with rosuvastatin and/or retinoic acid for seven days and the myocardial injury was induced by administering isoproterenol on the seventh and eighth day. After induction, rats were anaesthetized for electrocardiography, then sacrificed and different samples were collected/stored for various downstream assays. Myocardial injury with isoproterenol resulted in increased cardiac mass, decreased R-wave amplitude, increased QRS and QT durations; elevated levels of cardiac markers like cTnI, CK-MB, ALT and AST; increased lipid peroxidation, protein carbonylation and tissue nitric oxide levels; decreased endogenous antioxidants like SOD, CAT, GR, GST, GPx and total antioxidant activity; increased inflammatory markers like TNF-α and IL-6; decreased the mRNA expression of Nrf2 and Bcl-2; increased the mRNA expression of Bax, eNOS and iNOS genes. Pretreatment with rosuvastatin and/or retinoic acid mitigated many of the above biochemical and pathological alterations. Our results demonstrate that rosuvastatin and retinoic acid exert cardioprotective effects and may act as potential agents in the prevention of ß-adrenergic agonist-induced acute myocardial injury in rats. Cardioprotective potential of rosuvastatin and retinoic acid could be attributed to their influence on the redox pathways, immunomodulation, membrane stability, Nrf2 preservation, iNOS and Bax expression levels. Thus, they may act directly or indirectly at various steps, the breakpoints, in the pathophysiological cascade responsible for cardiac injury. Our study gives insights about the pharmacological pleiotropism of rosuvastatin and retinoic acid.


Assuntos
Isoproterenol/toxicidade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/prevenção & controle , Rosuvastatina Cálcica/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tretinoína/farmacologia , Agonistas Adrenérgicos beta/toxicidade , Animais , Anticolesterolemiantes/farmacologia , Antineoplásicos/uso terapêutico , Peso Corporal/efeitos dos fármacos , Coração/anatomia & histologia , Coração/efeitos dos fármacos , Masculino , Tamanho do Órgão , Distribuição Aleatória , Ratos , Ratos Wistar
12.
Food Funct ; 11(1): 965-976, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31960866

RESUMO

Emerging evidence demonstrates that NLRP3 inflammasome activation, lysosomal dysfunction, and impaired autophagic flux play a crucial role in the pathophysiology of myocardial infarction (MI). Therapeutic strategies targeting NLRP3 activation, lysosomal enzyme release and correcting autophagy have shown beneficial effects in suppressing early inflammatory responses in cardiovascular diseases. Thus, the agents, which inhibit NLRP3 activation and correct lysosome dysfunction and impaired autophagic flux, can be potential drugs for MI. The present study evaluated the effects and elucidated the NLRP3 inflammasome mediated mechanism of α-bisabolol, a dietary sesquiterpene alcohol in a rat model of isoproterenol (ISO)-induced MI. In the present study, male albino Wistar rats were pre- and co-treated with intraperitoneal injection of α-bisabolol (25 mg kg-1) daily for 10 days along with the subcutaneous injection of ISO (85 mg kg-1) at an interval of 24 h for two days (9th and 10th day). ISO injections induced MI as evidenced by the elevated cardiac marker enzyme in serum and altered oxidative stress markers in the total heart and lysosomal fractions. ISO also caused activation of NLRP3 inflammasomes mediating TLR4-NFκB/MAPK signaling pathways and lysosomal dysfunction along with induction and release of proinflammatory cytokines. Interestingly, treatment with α-bisabolol favorably corrected the morphological, histopathological, ultrastructural, biochemical and molecular abnormalities induced by ISO-induced MI in rats. Furthermore, the ultrastructural studies also confirmed the improvement in the autophagic mechanism. The findings of the present study clearly demonstrate that α-bisabolol attenuates oxidative stress and inflammation by inhibiting NLRP3 inflammasome activation and TLR4-NFκB/MAPK signaling pathways along with correcting lysosomal dysfunction and impaired autophagic flux. The underlying pharmacological and molecular mechanism of cardioprotection was attributed to its antioxidant, free radical scavenging and anti-inflammatory properties.


Assuntos
Agonistas Adrenérgicos beta/efeitos adversos , Inflamassomos/metabolismo , Sesquiterpenos Monocíclicos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Autofagia , Inflamação , Masculino , Infarto do Miocárdio/induzido quimicamente , NF-kappa B/metabolismo , Estresse Oxidativo , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Receptor 4 Toll-Like/metabolismo
13.
AAPS PharmSciTech ; 21(3): 81, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974855

RESUMO

Myocardial infarction (MI) is the principal cause of death in many countries. Silymarin (SM) is a herbal antioxidant and can be efficiently used in preventing cardiovascular diseases (CVDs). The study is aimed to enhance the absorption rate and biological activity of SM by using liquisolids besides investigating the cardioprotective activity of SM and its selected liquisolid formula against isoproterenol prompted cardiotoxicity in rats. Eight formulae were prepared according to (23) full-factorial design. The effect of viscosity increasing agent type and concentration, as well as the carrier/coat ratio on the dissolution rate and angle of repose were studied. All formulae were tested for content uniformity, micromeritic properties, dissolution performance besides the evaluation of its physicochemical properties, and scanning electron microscopy (SEM). Based on the factorial design outcomes, the highest desirability was obtained from F3 with excipient ratio value (R) of 20%, dissolution rate at Q5 min of 26.9%, and angle of repose of 19. Oral administration of F3 liquisolid and SM revealed a significant protective efficacy against the modification of cardiac plasma markers, brain natriuretic peptide (BNP), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-ß1 besides cardiac superoxide dismutase (SOD), malondialdehyde (MDA), and total protein kinase-1 (Akt-1) levels. Additionally, they minimized cardiac inducible nitric oxide synthase (iNOS), microRNA-34a (miR-34a), and p38 mitogen-activated protein kinase (p38-MAPK) levels. In conclusion, F3 liquisolid compact possessed an overall pronounced results over pure SM reckoned to its enhanced solubility and efficacy.


Assuntos
Isoproterenol/toxicidade , Infarto do Miocárdio/tratamento farmacológico , Silimarina/administração & dosagem , Animais , Infarto do Miocárdio/induzido quimicamente , Ratos , Silimarina/química , Silimarina/farmacologia , Solubilidade
15.
Neurology ; 94(5): e497-e510, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31852816

RESUMO

OBJECTIVE: To examine the cardiovascular, cerebrovascular, and peripheral vascular safety of erenumab across migraine prevention studies. METHODS: Vascular adverse events (AEs) and blood pressure data were integrated across 4 double-blind, placebo-controlled studies of erenumab and their open-label extensions in patients with chronic or episodic migraine. Subgroup analyses were conducted by acute migraine-specific medication use and number of vascular risk factors at baseline. Standardized search terms were used to identify vascular AEs (cardiovascular, cerebrovascular, or peripheral). An independent committee adjudicated whether targeted events were vascular in origin. RESULTS: In placebo-controlled studies, 2,443 patients received placebo (n = 1,043), erenumab 70 mg (n = 893), or erenumab 140 mg (n = 507) subcutaneously once monthly. Regardless of acute migraine-specific medication use or vascular risk factors at baseline, AE incidence was similar across the placebo and erenumab treatment groups. Hypertension AEs were reported for 0.9% (placebo), 0.8% (erenumab 70 mg), and 0.2% (erenumab 140 mg) of patients. Vascular AEs, which were similar across double-blind and open-label treatment, generally were confounded, with plausible alternative etiologies. In 18 patients with events reviewed by the independent committee, 4 events were positively adjudicated as cardiovascular in origin: 2 deaths and 2 vascular events. All 4 positively adjudicated cardiovascular events occurred during open-label erenumab treatment. CONCLUSION: Selective blockade of the canonical calcitonin gene-related peptide receptor with erenumab for migraine prevention had a vascular safety profile comparable to that of placebo over 12 weeks, with no increased emergence of events over time. Further study of long-term safety of erenumab in patients with migraine is needed. CLINICALTRIALSGOV IDENTIFIERS: NCT02066415, NCT02456740, NCT01952574, NCT02483585, NCT02174861, and NCT01723514. CLASSIFICATION OF EVIDENCE: This analysis provides Class II evidence that for patients with migraine, erenumab does not increase the risk of vascular AEs.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Transtornos de Enxaqueca/prevenção & controle , Adulto , Angina Instável/induzido quimicamente , Angina Instável/epidemiologia , Angina Instável/cirurgia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Ataque Isquêmico Transitório/induzido quimicamente , Ataque Isquêmico Transitório/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/cirurgia , Revascularização Miocárdica/estatística & dados numéricos , Doença Arterial Periférica/induzido quimicamente , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia , Procedimentos Cirúrgicos Vasculares/estatística & dados numéricos
16.
Biomed Pharmacother ; 121: 109157, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731195

RESUMO

INTRODUCTION: Bone marrow mesenchymal stem cells (BMSCs) have been extensively investigated from a perspective on cardiac regeneration therapy. The current study aimed to investigate the protective effect conferred by BMSCs in subacute myocardial injury, and to identify an appropriate BMSC reinfusion time. METHODS: BMSCs were isolated from human bone marrow blood. Daunorubicin (DNR)-induced subacute myocardial models were subsequently established. The rats with DNR-induced subacute myocardial injury were injected with dexrazoxane (DZR) and/or BMSCs at varying time points, after which cardiac function was evaluated by assessing left ventricular ejection fraction (LVEF) and fraction shortening (FS). The myocardial structural changes were analyzed, after which the levels of CD3 and human leukocyte antigen DR (HLA-DR) were examined to further validate the mechanism by which BMSCs could influence subacute myocardial injury. RESULTS: BMSCs combined with DZR treatment enhanced the cardiac function of rats with DNR-induced myocardial injury, as reflected by increased LVEF and FS. DNR-induced myocardial injuries were mitigated via the application of BMSCs combined with treatment of DZR, accompanied by diminished infiltration or vacuolization. Moreover, BMSCs were observed to alleviate infiltration of T lymphocyte and antigen-presenting cells, as evidenced by reduced expression of CD3 and HLA-DR. CONCLUSION: Taken together, this study demonstrates that BMSCs could protect against DNR-induced myocardial injury, especially in the first three days of DNR administration. BMSCs combined with DZR exert a better therapeutic effect, but there are individual differences.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Daunorrubicina/farmacologia , Células-Tronco Mesenquimais/imunologia , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/imunologia , Miocárdio/imunologia , Linfócitos T/imunologia , Animais , Células da Medula Óssea/imunologia , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/imunologia , Ratos , Ratos Sprague-Dawley
17.
Mol Med Rep ; 21(1): 508-516, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746394

RESUMO

Depression is often triggered by prolonged exposure to psychosocial stressors and associated with coronary heart disease (CHD). Matrix metalloproteinases (MMPs) are involved in the pathogenesis of various emotional and cardiovascular disorders. The purpose of this study was to investigate whether Kai­Xin­San (KXS), which may terminate the signaling of MMPs, exerts antidepressant­like and cardioprotective effects in a myocardial infarction (MI) plus depression rat model. Rats were randomly assigned to five groups: A normal control (control group), a celisc­injection of isopropyl adrenaline group (ISO group), depression (depression group), an ISO + depression (depression + ISO group), and an ISO + depression group treated with intragastric administration of 1,785 mg/kg KXS (KXS group). Behavioral changes, echocardiography, biochemical index, matrix metalloproteinase (MMP) and apoptosis­related proteins were assessed. Compared with the depression + ISO group, KXS significantly improved stress­induced alterations of behavioral parameters and protected the heart by enlarging the left ventricular (LV) fractional shortening (FS) and LV ejection fraction (EF). Moreover, KXS significantly attenuated ISO + depression­induced MMP­2 and MMP­9 expression at the mRNA and protein level and decreased TIMP in the heart compared to the complex model group. Myocardial apoptosis was significantly attenuated by KXS by regulating the Bcl­2/Bax axis. These results indicated that MI comorbid with depression may damage the MMP balance in the central and peripheral system, and KXS may have a direct anti­depressive and cardio­protective effect by regulating the level of MMPs and associated myocardial apoptosis. It is promising to further explore the clinical potential of KXS for the therapy or prevention of MI plus depression comorbidity disease.


Assuntos
Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Infarto do Miocárdio/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Depressão/induzido quimicamente , Depressão/genética , Depressão/patologia , Modelos Animais de Doenças , Epinefrina/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Humanos , Metaloproteinases da Matriz/genética , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
18.
J Photochem Photobiol B ; 202: 111705, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31812087

RESUMO

The procurance of gold nanoparticles in the plant extracts is an excellent way to attain nanomaterials natural and eco-friendly nanomaterials. The Dehydrated roots of Chinese Euphorbia fischeriana flowering plant are called "Lang-Du". In this study, the retrieving of gold nanoparticles from Euphorbia fischeriana root was amalgamated by standard procedure. Fabricated gold nanoparticles were portrayed through the investigations of ultraviolet and visible spectrophotometry (UV-Vis), Fourier transform infrared spectroscopy (FTIR), High resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The UV-Vis and FTIR results explicated the obtained particles were sphere-shaped and the terpenoids of Euphorbia fischeriana had strong communications with gold surface. The HRTEM and XRD images exposed the produced gold nanoparticles had an extreme composition of crystal arrangement and excellent uniformed size of particles. In our study, the Isoprenaline induced myocardial damage established the elevation in TBARS, LOOH of heart tissues and notable decline in antioxidant enzymes SOD, CAT, GPx, and GSH. This biochemical result was additionally proved by histopathological assessment. Remarkably, the pretreatment with EF-AuNps(50 mg/kg b.w) illustrated stabilized levels of serum creatine and cardiotropins in myocardial infarcted animals. And further we understood the essential function of NF-ƙB, TNF-α, IL-6 signaling molecules and its way progression in the development of vascular tenderness.


Assuntos
Euphorbia/química , Ouro/química , Nanopartículas Metálicas/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Animais , Antioxidantes/química , Catalase/genética , Catalase/metabolismo , Creatina Quinase/sangue , Citocinas/metabolismo , Euphorbia/metabolismo , Química Verde , Isoproterenol/toxicidade , Nanopartículas Metálicas/química , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Extratos Vegetais/química , Raízes de Plantas/química , Ratos , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
19.
J Ethnopharmacol ; 247: 112284, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31604137

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Herb pair, the most fundamental and simplest form of herb compatibility, serves as the basic building block of traditional Chinese medicine formulae. The Danshen-Honghua herb pair (DH), composed of Salviae Miltiorrhizae Radix et Rhizoma (Danshen in Chinese) and Carthami Flos (Honghua in Chinese), has remarkable clinical efficacy to cure cardio-cerebrovascular diseases. This study was designed to investigate the pharmacodynamics of DH in comparison with single herbs and pharmacokinetics of DH relative to Danshen in acute myocardial ischemic injury. MATERIALS AND METHODS: Sixty male Wistar rats were divided into control, model and drug treated groups. The acute myocardial ischemia rat model was induced by administering 85 mg/kg/d isoproterenol (ISO) subcutaneously for two consecutive days. For pharmacodynamic study, histopathological and biochemical analysis were performed to assess the anti-myocardial ischemic effects. While for pharmacokinetic study, a UPLC-MS/MS method was developed for determination of nine main active ingredients, namely danshensu, protocatechuic acid, protocatechualdehyde, caffeic acid, lithospermic acid, rosmarinic acid, salvianolic acid B, salvianolic acid A and salvianolic acid C in rat plasma. RESULTS: The histopathological and biochemical analysis revealed that DH exerted enhanced anti-myocardial ischemic effects against the ISO-induced myocardial ischemia compared with single herbs. The pharmacokinetic study indicated that DH could significantly increase the t1/2z of danshensu, Tmax, AUC0-∞ and MRT0-t of protocatechuic acid in comparison with Danshen alone in normal rats, but more importantly elevate systemic exposure level and prolong t1/2z of protocatechualdehyde, caffeic acid, Tmax of danshensu in acute myocardial ischemia rats. CONCLUSIONS: Our findings demonstrated the greater effects of DH after the compatibility in ISO-induced acute myocardial ischemia rats at pharmacodynamic and pharmacokinetic levels and provided valuable information for clinical application of herb pairs.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Salvia miltiorrhiza/química , Administração Oral , Animais , Carthamus tinctorius , China , Modelos Animais de Doenças , Combinação de Medicamentos , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Etnofarmacologia , Humanos , Isoproterenol/toxicidade , Masculino , Infarto do Miocárdio/induzido quimicamente , Ratos
20.
J Ethnopharmacol ; 247: 112266, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31580943

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zygophyllum album is widely used to treat many cardiovascular diseases (CVDs) and as anti-inflammatory plant. AIM OF THE STUDY: This study aimed to investigate the mechanism of the potential protective effects of Zygophyllum album roots extract (ZARE) against myocardial damage and fibrosis induced by a chronic exposure to deltamethrin (DLM) in rats. MATERIALS AND METHODS: Bioactive compounds present in ZARE were analyzed by HPLC-DAD-ESI-QTOF-MS/MS. In vivo, DLM (4 mg/kg body weight), ZARE (400 mg/kg body weight) and DLM with ZARE were administered to rats orally for 60 days. Biochemical markers (LDH, ALT, CK, CK-MB and cTn-I) were assessed in the plasma by an auto-analyzer. Pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) were evaluated by a sandwich ELISA. NF-κB was quantified at mRNA levels by real time PCR. Heart tissue was used to determine cardiac oxidative stress markers (MDA, PC, SOD, CAT, and GPx). Masson's Trichrome (MT) and Sirius Red (SR) stainings were used for explored fibrosis statues. RESULTS: Phytochemical analysis using HPLC-DAD-ESI-QTOF-MS/MS revealed the presence of twenty six molecules including phenolic compounds and saponins. ZARE significantly improved the heart injury markers (LDH, ALT, CK, CK-MB and cTn-I), lipid peroxidation (MDA), protein oxidation (PC), antioxidant capacity (SOD, CAT, and GPx), and DNA structure, which were altered by DLM exposure. Moreover, ZARE cotreatment reduced the expressions of NF-κB, decreased plasmatic pro-inflammatory cytokines concentration (TNF-α, IL-1ß and IL-6), and suppressed the myocardial collagen deposition, as observed by Sirius Red and Masson's Trichrome staining. CONCLUSION: ZARE ameliorated the severity of DLM-induced myocardial injuries through improving the oxidative status and reducing profibrotic cytokines production. The ZARE actions could be mediated by downregulation of NF-κB mRNA.


Assuntos
Anti-Inflamatórios/farmacologia , Cardiotônicos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Extratos Vegetais/farmacologia , Zygophyllum/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Cardiotônicos/química , Cardiotônicos/isolamento & purificação , Cardiotônicos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Etnofarmacologia , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/patologia , Miocárdio/imunologia , Miocárdio/patologia , NF-kappa B/metabolismo , Nitrilos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Raízes de Plantas/química , Piretrinas/toxicidade , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas em Tandem , Tunísia
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