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1.
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
2.
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
3.
Eur J Ophthalmol ; 30(1): 66-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30618282

RESUMO

BACKGROUND: Systemic complications of intravitreal anti-vascular endothelial growth factor agents are relatively uncommon but highly significant. OBJECTIVES: Primary objective: To assess the risk for thromboembolic events following intravitreal bevacizumab injection in neovascular age-related macular degeneration patients by a large population-based study. Secondary objective: To analyze the association between injection frequency and the risk for thromboembolic events, the time interval between the injection and the thromboembolic events, and the influence of chronic diseases on complications rate. DESIGN: A retrospective cohort study. METHODS: Consecutive neovascular age-related macular degeneration patients receiving intravitreal bevacizumab at Soroka University Medical Center from December 2005 to December 2013 were included. Thromboembolic events analyzed included acute coronary syndrome, acute myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism. The thromboembolic event rate was compared 2 years prior and 2 years after the initial intravitreal bevacizumab injection. RESULTS: A total of 2102 patients were included. Acute coronary syndrome and stroke rate were higher 2 years after intravitreal bevacizumab (p = 0.03 and p = 0.01, respectively). No statistical significant difference was found for the rest of thromboembolic events. Patients older than 80 years and patients receiving less than six intravitreal bevacizumab injections were more likely to experience stroke. Patients with known cardiovascular risk factors before starting injections did not develop significant more thromboembolic events. CONCLUSION: In our study population, patients treated with intravitreal bevacizumab were significantly more likely to experience stroke during 2 years after first injection.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Bevacizumab/efeitos adversos , Neovascularização de Coroide/tratamento farmacológico , Tromboembolia/induzido quimicamente , Degeneração Macular Exsudativa/tratamento farmacológico , Síndrome Coronariana Aguda/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neovascularização de Coroide/fisiopatologia , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Embolia Pulmonar/induzido quimicamente , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Tromboembolia/diagnóstico , Tromboembolia/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Trombose Venosa/induzido quimicamente , Degeneração Macular Exsudativa/fisiopatologia
4.
Ann Hematol ; 99(2): 359-361, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31872359
5.
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
6.
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
7.
PLoS One ; 14(12): e0226637, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31881052

RESUMO

BACKGROUND: Although studies reported increased cardiovascular (CV) risks in patients treated with macrolides, the risks remain controversial among clarithromycin (CLR) users. We aimed to summarize the association between CLR use and the risks of mortality and CV events. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) and observational studies with population exposed to CLR published until December 31st, 2018. These studies reported either all-cause mortality (primary outcome) or CV adverse events (secondary outcomes) based on multivariate models. Effect measures were synthesized by study design and follow-up duration (long-term, ≥ 1 year; short-term, ≤ 3 months; and immediate, ≤ 2 weeks). This study has been registered on PROSPERO (ID: CRD42018089605). RESULTS: This meta-analysis included 13 studies (3 RCTs and 10 observational studies) and 8,351,815 subjects (1,124,672 cases and 7,227,143 controls). Overall, CLR use was not associated with increased long-term all-cause mortality (pooled rate ratio RR = 1.09, 95% CI = 0.91-1.32), either among patients with or without comorbidities of cardiovascular diseases. Comparing CLR users to placebo, there is no additional risks of cardiac mortality (pooled RR = 1.03, 95% CI = 0.53-2.01), acute myocardial infarction (pooled RR = 1.29, 95% CI = 0.98-1.68), and arrhythmia (pooled RR = 0.90, 95% CI = 0.62-1.32). CONCLUSIONS: Our findings suggested no significant association between CLR use and subsequent long-term all-cause mortality, regardless having comorbidity of cardiovascular diseases or not. Further RCTs investigating the short-term CV risks of CLR use compared to alternative antibiotics are warranted, particularly in high-risk populations.


Assuntos
Antibacterianos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Claritromicina/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/epidemiologia , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Humanos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/epidemiologia , Fatores de Risco
8.
Life Sci ; 235: 116841, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31494173

RESUMO

Indanyloxyacetic acid-94 (IAA-94), an intracellular chloride channel blocker, is shown to ablate cardioprotection rendered by ischemic preconditioning (IPC), N (6)-2-(4-aminophenyl) ethyladenosine or the PKC activator phorbol 12-myristate 13-acetate and cyclosporin A (CsA) in both ex-vivo and in-vivo ischemia-reperfusion (IR) injury. Thus signifying the role of the IAA-94 sensitive chloride channels in mediating cardio-protection upon IR injury. Although IAA-94 sensitive chloride currents are recorded in cardiac mitoplast, there is still a lack of understanding of the mechanism by which IAA-94 increases myocardial infarction (MI) by IR injury. Mitochondria are the key arbitrators of cell life and death pathways. Both oxidative stress and calcium overload in the mitochondria, elicit pathways resulting in the opening of mitochondrial permeability transition pore (mPTP) leading to cell death. Therefore, in this study we explored the role of IAA-94 in MI and in maintaining calcium retention capacity (CRC) of cardiac mitochondria after IR. IAA-94 inhibited the CRC of the isolated cardiac mitochondria in a concentration-dependent manner as measured spectrofluorimetrically using calcium green-5 N. Interestingly, IAA-94 did not change the mitochondrial membrane potential. Further, CsA a blocker of mPTP opening could not override the effect of IAA-94. We also showed for the first time that IAA-94 perfusion after ischemic event augments MI by reducing the CRC of mitochondria. To conclude, our results demonstrate that the mechanism of IAA-94 mediated cardio-deleterious effects is via modulating the mitochondria CRC, thereby playing a role in mPTP opening. These findings highlight new pharmacological targets, which can mediate cardioprotection from IR injury.


Assuntos
Cálcio/metabolismo , Glicolatos/efeitos adversos , Infarto do Miocárdio/metabolismo , Animais , Ciclosporina/farmacologia , Relação Dose-Resposta a Droga , Glicolatos/antagonistas & inibidores , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Infarto do Miocárdio/induzido quimicamente , Ratos
9.
Molecules ; 24(15)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374848

RESUMO

Curcumin from Curcuma longa is a nutraceutical compound reported to possess strong antioxidant activity that makes it a candidate for use in counteracting oxidative stress-induced damage. The effect of pre-treatment with curcumin nanoparticles (nC) compared to conventional curcumin (Cs) on blood pressure, electrocardiogram, and biological changes on isoproterenol (ISO)-induced myocardial infarction (MI) in rats had been investigated. The Cs doses of 150 and 200 mg/kg bw and all nC doses (100, 150 and 200 mg/kg bw) significantly reduced heart rate before ISO administration and prevented QRS complex enlargement after MI induction (p < 0.026). All doses of Cs and nC prevented prolongation of the QT and QT corrected (QTc) intervals, with better results for higher doses (p < 0.048). The nC solution had more significant results than Cs in all metabolic parameters assessed (lactate dehydrogenase, glycaemia, aspartate transaminase, and alanine transaminase, p < 0.009). nC was more efficient than Cs in limiting myocardial oxidative stress and enhancing antioxidative capacity (p < 0.004). Compared to Cs, nC better prevented myocardial damage extension, reduced interstitial oedema, and inflammation. Curcumin nanoparticles as compared to conventional curcumin exert better antioxidative effects. Moreover, nC better prevent cardiomyocytes damage, and electrocardiogram alterations, in the case of ISO-induced MI in rats.


Assuntos
Curcumina/farmacologia , Coração/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Nanopartículas/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Cardiotônicos/química , Cardiotônicos/farmacologia , Curcuma/química , Curcumina/química , Modelos Animais de Doenças , Glutationa/química , Coração/fisiopatologia , Humanos , Isoproterenol/toxicidade , Infarto do Miocárdio/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos
10.
BMJ ; 366: l4772, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467044

RESUMO

OBJECTIVE: To investigate the cardiovascular effectiveness of sodium glucose cotransporter 2 (SGLT2) inhibitors in routine clinical practice. DESIGN: Cohort study using data from nationwide registers and an active-comparator new-user design. SETTING: Denmark, Norway, and Sweden, from April 2013 to December 2016. PARTICIPANTS: 20 983 new users of SGLT2 inhibitors and 20 983 new users of dipeptidyl peptidase 4 (DPP4) inhibitors, aged 35-84, matched by age, sex, history of major cardiovascular disease, and propensity score. MAIN OUTCOME MEASURES: Primary outcomes were major cardiovascular events (composite of myocardial infarction, stroke, and cardiovascular death) and heart failure (hospital admission for heart failure or death due to heart failure). Secondary outcomes were the individual components of the cardiovascular composite and any cause death. In the primary analyses, patients were defined as exposed from treatment start throughout follow-up (analogous to intention to treat); additional analyses were conducted with an as-treated exposure definition. Cox regression was used to estimate hazard ratios. RESULTS: Mean age of the study cohort was 61 years, 60% were men, and 19% had a history of major cardiovascular disease. Of the total 27 416 person years of follow-up in the SGLT2 inhibitor group, 22 627 (83%) was among patients who initiated dapagliflozin, 4521 (16%) among those who initiated empagliflozin, and 268 (1%) among those who initiated canagliflozin. During follow-up, 467 SGLT2 inhibitor users (incidence rate 17.0 events per 1000 person years) and 662 DPP4 inhibitor users (18.0) had a major cardiovascular event, whereas 130 (4.7) and 265 (7.1) had a heart failure event, respectively. Hazard ratios were 0.94 (95% confidence interval 0.84 to 1.06) for major cardiovascular events and 0.66 (0.53 to 0.81) for heart failure. Hazard ratios were consistent among subgroups of patients with and without history of major cardiovascular disease and with and without history of heart failure. Hazard ratios for secondary outcomes, comparing SGLT2 inhibitors with DPP4 inhibitors, were 0.99 (0.85 to 1.17) for myocardial infarction, 0.94 (0.77 to 1.15) for stroke, 0.84 (0.65 to 1.08) for cardiovascular death, and 0.80 (0.69 to 0.92) for any cause death. In the as-treated analyses, hazard ratios were 0.84 (0.72 to 0.98) for major cardiovascular events, 0.55 (0.42 to 0.73) for heart failure, 0.93 (0.76 to 1.14) for myocardial infarction, 0.83 (0.64 to 1.07) for stroke, 0.67 (0.49 to 0.93) for cardiovascular death, and 0.75 (0.61 to 0.91) for any cause death. CONCLUSIONS: In this large Scandinavian cohort, SGLT2 inhibitor use compared with DPP4 inhibitor use was associated with reduced risk of heart failure and any cause death, but not with major cardiovascular events in the primary intention-to-treat analysis. In the additional as-treated analyses, the magnitude of the association with heart failure and any cause death became larger, and a reduced risk of major cardiovascular events that was largely driven by the cardiovascular death component was observed. These data help inform patients, practitioners, and authorities regarding the cardiovascular effectiveness of SGLT2 inhibitors in routine clinical practice.


Assuntos
Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Insuficiência Cardíaca/epidemiologia , Infarto do Miocárdio/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Idoso , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Seguimentos , Insuficiência Cardíaca/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Noruega/epidemiologia , Sistema de Registros/estatística & dados numéricos , Acidente Vascular Cerebral/induzido quimicamente , Suécia/epidemiologia
12.
Mayo Clin Proc ; 94(7): 1374-1377, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31272579

RESUMO

Women presenting to the cardiac catheterization laboratory with normal coronary arteries without significant atherosclerotic disease is a common presentation. In such patients, it is important to maintain a wide differential and consider alternate diagnoses. We present two cases of women presenting with chest pain found to have severe coronary vasospasm in the setting of recent initiation of phentermine. Phentermine may have vasospastic proprieties which are important to consider when prescribing to patients.


Assuntos
Estimulantes do Sistema Nervoso Central/efeitos adversos , Vasoespasmo Coronário/induzido quimicamente , Infarto do Miocárdio/induzido quimicamente , Fentermina/efeitos adversos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Dor no Peito/etiologia , Vasoespasmo Coronário/diagnóstico , Vasoespasmo Coronário/tratamento farmacológico , Eletrocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Nitroglicerina/uso terapêutico , Fentermina/administração & dosagem , Vasodilatadores/uso terapêutico
13.
Oxid Med Cell Longev ; 2019: 7847142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205590

RESUMO

Curcumin has anti-inflammatory, antioxidative, anticarcinogenic, and cardiovascular protective effects. Our study is aimed at evaluating the effects of pretreatment with curcumin nanoparticles (CCNP) compared to conventional curcumin (CC) on isoproterenol (ISO) induced myocardial infarction (MI) in rats. Fifty-six Wistar-Bratislava white rats were randomly divided into eight groups of seven rats each. Curcumin and curcumin nanoparticles were given by gavage in three different doses (100 mg/kg body weight (bw), 150 mg/kg bw, and 200 mg/kg bw) for 15 days. The MI was induced on day 13 using 100 mg/kg bw ISO administered twice, with the second dose 24 h after the initial dose. The blood samples were taken 24 h after the last dose of ISO. The antioxidant, anti-inflammatory, and cardioprotective effects were evaluated in all groups. All doses of CC and CCNP offered a cardioprotective effect by preventing creatine kinase-MB leakage from cardiomyocytes, with the best result for CCNP. All the oxidative stress parameters were significantly improved after CCNP compared to CC pretreatment. CCNP was more efficient than CC in limiting the increase in inflammatory cytokine levels (such as TNF-α, IL-6, IL-1α, IL-1ß, MCP-1, and RANTES) after MI. MMP-2 and MMP-9 levels decreased more after pretreatment with CCNP than with CC. CCNP better prevented myocardial necrosis and reduced interstitial edema and neutrophil infiltration than CC, on histopathological examination. Therefore, improving the bioactivity of curcumin by nanotechnology may help limit cardiac injury after myocardial infarction.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Isoproterenol/toxicidade , Infarto do Miocárdio/tratamento farmacológico , Nanopartículas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Agonistas Adrenérgicos beta/toxicidade , Animais , Antioxidantes/farmacologia , Feminino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/patologia , Nanopartículas/química , Ratos , Ratos Wistar
14.
Can J Physiol Pharmacol ; 97(7): 661-674, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31157553

RESUMO

Diabetes increases the sensitivity of myocardium to ischemic damage and impairs response of the myocardium to cardioprotective interventions. The present study aimed to elucidate the potential cardioprotective effect provided by ranolazine during myocardial infarction in nondiabetic and diabetic male rats. As AMP-activated protein kinase (AMPK) has been shown to be involved in the cellular response to ischemic injury, in this context, the present animal study evaluated the modulating role of ranolazine in the AMPK expression in isoprenaline-induced myocardial ischemic rat model. Male rats were divided into 2 experiments: experiment I and II (nondiabetic and diabetic rats) and assigned to normal control, saline control for isoprenaline, isoprenaline control, and ranolazine-treated groups. Ranolazine administration revealed effectiveness in attenuating the severity of isoprenaline-induced myocardial injury in both nondiabetic and diabetic rats as revealed by ECG signs, histopathological score, and apoptotic markers via abrogating the increments in the inflammatory and oxidative stress markers and modulating AMPK expression. Therefore, the current cardioprotective effect of ranolazine was, at least in part, mediated through inhibition of apoptosis and modulation of AMPK expression, encouraging considering the utility of ranolazine in protection from acute myocardial infarction.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Diabetes Mellitus Experimental/complicações , Isoproterenol/efeitos adversos , Infarto do Miocárdio/patologia , Ranolazina/farmacologia , Doença Aguda , Animais , Glicemia/metabolismo , Eletrocardiografia , Hemoglobina A Glicada/metabolismo , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
15.
J Ethnopharmacol ; 242: 112037, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31247239

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: The leaves of Alpinia zerumbet is used in folk medicine in Brazil to treat hypertension. However, the cardioprotective effect of this plant has not been studied yet. AIM OF THIS STUDY: To evaluate the cardioprotective effects of the hydroalcoholic extract of the leaves of Alpinia zerumbet (AZE) against isoproterenol (ISO)-induced myocardial infarction in rats. MATERIAL AND METHODS: Rats were pretreated orally with AZE (300 mg/kg) for 30 days prior to ISO-induced myocardial infarction. The rats were sacrificed and hearts were collected and homogenized for biochemical analysis. At the end of the experiment, cardiac marker enzyme levels, histological and morphometric parameters, and hemodynamic measurements were assessed. Phytochemical compounds were verified by gas chromatography-mass spectrometry (GC-MS). RESULTS: Rats administered with ISO showed a significant increase in cardiac marker enzymes, i.e., in creatine kinase-NAC (CK-NAC) and CK-MB. Triphenyltetrazolium chloride (TTC) staining exhibited an increase in infarct areas. In the animals treated with ISO induced a significant increase in heart rate. Pretreatment with AZE significantly inhibited these effects of ISO. Moreover, biochemical findings were supported by histopathological observations. The GC-MS analyses of AZE identified volatile oils, kavalactones, and phytosterols. CONCLUSIONS: Haemodynamic, biochemical alteration and histopathological results suggest a cardioprotective protective effect of oral administration of AZE in isoproterenol induced cardiotoxicity.


Assuntos
Alpinia , Cardiotônicos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Creatina Quinase/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Isoproterenol , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Folhas de Planta , Ratos Wistar
16.
Mayo Clin Proc ; 94(7): 1190-1198, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31036352

RESUMO

OBJECTIVE: To determine whether levothyroxine (L-T4) preparation (generic vs brand) affected hospitalization for cardiovascular events. PATIENTS AND METHODS: We performed a retrospective analysis using a large administrative claims database, OptumLabs Data Warehouse, creating two 1-to-1 propensity score-matched cohorts initiating generic or brand L-T4. Patients were followed for a mean of 1.0±1.2 years (range, 0-9.3 years). We included 87,902 propensity score-matched patients (43,951 patients per cohort) initiating generic or brand L-T4. Variables included in matching were age, sex, race/ethnicity, residence region, selected comorbidities, and Charlson-Deyo comorbidity score. Patients with previous use of any thyroid preparation, amiodarone, or lithium were excluded. Primary outcomes were the event rates for hospitalizations for incident atrial fibrillation, myocardial infarction, congestive heart failure, or stroke. RESULTS: In the generic L-T4 cohort, 35,242 (80.2%) were women and 7327 (16.7%) were 65 years of age or older; in the brand L-T4 cohort, 34,633 (78.8%) were women and 8092 (18.4%) were 65 years of age or older. We found no differences in event rates (events per 1000 person-years) for 4 outcomes comparing generic and brand L-T4 therapy: (1) atrial fibrillation (1.82 vs 2.19; hazard ratio [HR], 1.22; 95% CI, 0.90-1.65; P=.19); (2) myocardial infarction (2.12 vs 1.83; HR, 0.86; 95% CI, 0.64-1.17; P=.35); (3) congestive heart failure (2.27 vs 2.00; HR, 0.88; 95% CI, 0.66-1.18; P=.41); and (4) stroke (3.10 vs 2.38; HR, 0.77; 95% CI, 0.59-1.00; P=.05). Stratification by age group revealed no differences. CONCLUSION: In patients with newly treated hypothyroidism, cardiovascular event rates were similar for generic and brand L-T4.


Assuntos
Medicamentos Genéricos , Hipotireoidismo/tratamento farmacológico , Tiroxina , Adulto , Idoso , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/epidemiologia , Medicamentos Genéricos/efeitos adversos , Medicamentos Genéricos/uso terapêutico , Feminino , Humanos , Revisão da Utilização de Seguros/tendências , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/epidemiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia , Tiroxina/efeitos adversos , Tiroxina/uso terapêutico
17.
Ann Hematol ; 98(8): 1885-1890, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31044260

RESUMO

There is little information about cardiovascular adverse event (CV-AE) incidence in chronic myeloid leukemia (CML) patients treated with bosutinib in the real-life practice. We identified 54 consecutive CML patients treated with bosutinib, stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 40-month cumulative incidence of CV-AEs was 25.2 ± 8.1%. Patients with the SCORE of high-very high showed a significantly higher incidence of CV-AEs (55 ± 12.9% vs 9 ± 9.5%; p = 0.002). Overall, 9 CV-AEs were reported, with 2 deaths attributed to CV-AE. In conclusion, the SCORE assessment before starting treatment is helpful in identifying CV-AE high-risk patients during bosutinib treatment.


Assuntos
Compostos de Anilina/efeitos adversos , Antineoplásicos/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Infarto do Miocárdio/induzido quimicamente , Nitrilos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/induzido quimicamente , Angina Pectoris/diagnóstico , Angina Pectoris/fisiopatologia , Compostos de Anilina/administração & dosagem , Antineoplásicos/administração & dosagem , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Suscetibilidade a Doenças , Esquema de Medicação , Feminino , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Nitrilos/administração & dosagem , Doenças Vasculares Periféricas/induzido quimicamente , Doenças Vasculares Periféricas/diagnóstico , Doenças Vasculares Periféricas/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Quinolinas/administração & dosagem , Estudos Retrospectivos
18.
Drugs Aging ; 36(Suppl 1): 15-24, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31073921

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recommended and prescribed to treat pain in osteoarthritis. While measured to have a moderate effect on pain in osteoarthritis, NSAIDs have been associated with wide-ranging adverse events affecting the gastrointestinal, cardiovascular, and renal systems. Gastrointestinal toxicity is found with all NSAIDs, which may be of particular concern when treating older patients with osteoarthritis, and gastric adverse events may be reduced by taking a concomitant gastroprotective agent, although intestinal adverse events are not ameliorated. Cardiovascular toxicity is associated with all NSAIDs to some extent and the degree of risk appears to be pharmacotherapy specific. An increased risk of acute myocardial infarction and heart failure is observed with all NSAIDs, while an elevated risk of hemorrhagic stroke appears to be restricted to the use of diclofenac and meloxicam. All NSAIDs have the potential to induce acute kidney injury, and patients with osteoarthritis with co-morbid conditions including hypertension, heart failure, and diabetes mellitus are at increased risk. Osteoarthritis is associated with excess mortality, which may be explained by reduced levels of physical activity owing to lower limb pain, presence of comorbid conditions, and the adverse effects of anti-osteoarthritis medications especially NSAIDs. This narrative review of recent literature identifies data on the safety of non-selective NSAIDs to better understand the risk:benefit of using NSAIDs to manage pain in osteoarthritis.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Artralgia/tratamento farmacológico , Diclofenaco/efeitos adversos , Meloxicam/efeitos adversos , Osteoartrite/tratamento farmacológico , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Diclofenaco/administração & dosagem , Diclofenaco/uso terapêutico , Gastroenteropatias/induzido quimicamente , Humanos , Meloxicam/administração & dosagem , Meloxicam/uso terapêutico , Infarto do Miocárdio/induzido quimicamente , Risco
19.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(2): 278-282, 2019 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-31060687

RESUMO

Multi-target anticancer drugs have a more comprehensive and extensive range of action,and there is an uncertain risk in the combination of two drugs.A case of acute toxicity induced by erlotinib combined with cabozantinib is reported in this article.


Assuntos
Anilidas/efeitos adversos , Erupção por Droga/etiologia , Cloridrato de Erlotinib/efeitos adversos , Infarto do Miocárdio/induzido quimicamente , Piridinas/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Humanos
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