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1.
N Z Med J ; 134(1529): 103-108, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33582712

RESUMO

Mr BH was a 53-year-old gentleman who presented to hospital in November 2019 with decompensated heart failure, new-onset paroxysmal atrial tachycardia and increasing left hip pain. Imaging of his hip demonstrated radiographic evidence of bony changes, suggestive of an adverse reaction to metal debris (ARMD), along with a non-traumatic left peri-prosthetic neck-of-femur fracture. Clinically, he had concurrent decompensated cardiomyopathy requiring dopamine and furosemide infusions. His serum cobalt (sCo) levels were 5244nmol/L (normal<12nmol/L). He had previous bilateral total hip arthroplasties using the Birmingham Hip Resurfacing (right side 2006, left side 2012). As part of routine metal-on-metal arthroplasty follow-up, Mr BH had sCo level checks. In 2013, these levels rose to 1981nmol/L. Although there has been no direct correlation between sCo levels and toxicity, levels above 119nmol/L are concerning. Unfortunately, Mr BH moved to a different health district and was subsequently lost to follow-up. In 2015, Mr BH was diagnosed with dilated cardiomyopathy, presumed secondary to viral myocarditis. Despite successful chelating therapy and heart failure treatment, he passed away secondary to cobalt-toxicity induced cardiomyopathy (CTCM).


Assuntos
Artroplastia de Quadril/efeitos adversos , Cardiomiopatias/induzido quimicamente , Cobalto/toxicidade , Prótese de Quadril/efeitos adversos , Artroplastia de Quadril/instrumentação , Cardiomiopatias/diagnóstico , Cobalto/sangue , Ecocardiografia , Evolução Fatal , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Falha de Prótese/efeitos adversos , Radiografia Torácica
2.
Cardiovasc Pathol ; 50: 107266, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32814149

RESUMO

We report a case of a 75-year-old female post orthotopic heart transplantation, who presented to the emergency department with a six-week history of shortness of breath, hand tremor and ultimately delirium. She had lobular breast carcinoma more than 5 years prior to her heart transplant, treated by lumpectomy followed by anthracycline based chemotherapy. The reason for her heart transplant was heart failure that was suspected to be from anthracycline cardiomyopathy, however, her explanted heart actually showed cardiac sarcoidosis. She was placed on long-term immunosuppression with tacrolimus, mycophenolate mofetil and prednisone. Two years after her heart transplant, she underwent bilateral mastectomies for recurrent breast cancer. Her neurological workup, including brain imaging (CT, MRI, LP and EEG) did not show any structural abnormalities, ischemia, mass or neurosarcoidosis as cause for delirium. Tacrolimus was held due to renal dysfunction and hemolytic anemia, and then she developed signs of right heart failure so an endomyocardial biopsy was carried out for suspected allograft rejection. The biopsy did not show any evidence of cellular or antibody medicated rejection; however, it demonstrated infiltration by bland appearing cells with signet ring morphology cells many of which showed intracytoplasmic mucin. The cells were strongly positive with cytokeratins AE1/3, CK7 and mammaglobin. The morphology and immunoprofile were consistent with metastatic lobular breast carcinoma and this was thought to be the cause of her clinical presentation with delirium, hemolytic anemia and renal dysfunction as a paraneoplastic syndrome.


Assuntos
Carcinoma Lobular/secundário , Insuficiência Cardíaca/cirurgia , Neoplasias Cardíacas/secundário , Transplante de Coração , Miocárdio/patologia , Idoso , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Biópsia , Carcinoma Lobular/complicações , Carcinoma Lobular/terapia , Cardiomiopatias/induzido quimicamente , Cardiotoxicidade , Quimioterapia Adjuvante , Feminino , Insuficiência Cardíaca/etiologia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/terapia , Transplante de Coração/efeitos adversos , Humanos , Síndromes Paraneoplásicas/etiologia , Valor Preditivo dos Testes , Fatores de Risco , Sarcoidose/complicações
3.
Kardiologiia ; 60(7): 98-102, 2020 Aug 11.
Artigo em Russo | MEDLINE | ID: mdl-33155947

RESUMO

Aim      An attempt to prevent the development of diastolic dysfunction (DD) with the mitochondrial antioxidant plastomitin on a model of doxorubicin-induced cardiomyopathy. DD is a type of chronic heart failure. Due to the increasing number of patients with this condition and the absence of effective therapy, development of means for DD correction is a relevant objective.Material and methods  Cardiomyopathy was modeled in 17 rats by two subcutaneous injections of doxorubicin 2 mg/kg/week. The other group (n=17), also administered with doxorubicin, received plastomicin 0.32 mg/kg daily subcutaneously. Left ventricular function was evaluated with echocardiography (EchoCG) and cardiac catheterization with simultaneous pressure and volume monitoring.Results According to EchoCG data the ejection fraction remained unchanged in the experimental groups. Cardiac catheterization showed disorders of both myocardial contractility and relaxability only in the doxorubicin group.Conclusion      A course of plastomitin in combination with the doxorubicin treatment can maintain normal heart contractility and thereby, prevent the known doxorubicin cardiotoxicity.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Animais , Antioxidantes/farmacologia , Cardiomiopatias/induzido quimicamente , Doxorrubicina/efeitos adversos , Humanos , Ratos , Função Ventricular Esquerda
4.
Medicine (Baltimore) ; 99(39): e22301, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991436

RESUMO

RATIONALE: Cardiotoxicity related to osimertinib, including cardiac failure, QT prolongation, and atrial fibrillation, has been reported as an extremely rare incidence in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the occurrence of osimertinib-induced cardiomyopathy. PATIENT CONCERNS: A 76-year old woman was treated with afatinib (40 mg/day) as the 1st line treatment due to recurrence after surgical resection for pulmonary adenocarcinoma. However, she experienced recurrence with positive T790 M, and osimertinib (80 mg/day) was administered as the 2nd line therapy. DIAGNOSIS: Four months after osimertinib initiation, she complained of fever and progressive dyspnea, and a diagnostic endomyocardial biopsy confirmed non-specific cardiomyopathy, indicating osimertinib-induced cardiomyopathy. INTERVENTIONS AND OUTCOMES: She was treated with furosemide, carvedilol, and enalapril, and her cardiac function, her symptoms, and condition improved 3 weeks after the withdrawal of osimertinib. LESSONS: Physicians should be alert of the cardiomyopathy-causing potential of osimertinib in advanced NSCLC patients.


Assuntos
Acrilamidas/efeitos adversos , Compostos de Anilina/efeitos adversos , Cardiomiopatias/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Acrilamidas/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Afatinib/uso terapêutico , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Anilina/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/fisiopatologia , Carvedilol/uso terapêutico , Diuréticos/uso terapêutico , Enalapril/uso terapêutico , Feminino , Furosemida/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Recidiva , Resultado do Tratamento , Suspensão de Tratamento
6.
Internist (Berl) ; 61(8): 854-859, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32504300

RESUMO

A case report is presented of fulminant hydroxychloroquine-induced cardiomyopathy in a 57 year-old female patient with a long history of systemic lupus erythematosus. Diagnosis was established based on clinical findings, imaging (echocardiography and cardiac magnetic resonance imaging) as well as endomyocardial biopsy. Despite immediate discontinuation of the medication, the patient died from heart failure within a few days. Since the rare adverse effect described here might be reversible, early diagnosis and discontinuation of hydroxychloroquine are crucial for the prognosis of these patients.


Assuntos
Cardiomiopatias/induzido quimicamente , Insuficiência Cardíaca/mortalidade , Hidroxicloroquina/efeitos adversos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Doenças Musculares/induzido quimicamente , Biópsia , Cardiomiopatias/mortalidade , Ecocardiografia , Evolução Fatal , Feminino , Coração/efeitos dos fármacos , Insuficiência Cardíaca/induzido quimicamente , Humanos , Hidroxicloroquina/uso terapêutico , Imagem por Ressonância Magnética , Pessoa de Meia-Idade
7.
Cardiovasc Diabetol ; 19(1): 66, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414364

RESUMO

BACKGROUND: Empagliflozin showed efficacy in controlling glycaemia, leading to reductions in HbA1c levels, weight loss and blood pressure, compared to standard treatment. Moreover, the EMPA-REG OUTCOME trial demonstrated a 14% reduction of major adverse cardiovascular events (MACE), a 38% reduction in cardiovascular (CV) death and a 35% reduction in the hospitalization rate for heart failure (HF). These beneficial effect on HF were apparently independent from glucose control. However, no mechanistic in vivo studies are available to explain these results, yet. We aimed to determine the effect of empagliflozin on left ventricular (LV) function in a mouse model of doxorubicin-induced cardiomyopathy (DOX-HF). METHODS: Male C57Bl/6 mice were randomly assigned to the following groups: controls (CTRL, n = 7), doxorubicin (DOX, n = 14), DOX plus empagliflozin (DOX + EMPA, n = 14), or DOX plus furosemide (DOX + FURO group, n = 7). DOX was injected intraperitoneally. LV function was evaluated at baseline and after 6 weeks of treatment using high-resolution echocardiography with 2D speckle tracking (Vevo 2100). Histological assessment was obtained using Haematoxylin and Eosin and Masson's Goldner staining. RESULTS: A significant decrease in both systolic and diastolic LV function was observed after 6 weeks of treatment with doxorubicin. EF dropped by 32% (p = 0.002), while the LS was reduced by 42% (p < 0.001) and the CS by 50% (p < 0.001). However, LV function was significantly better in the DOX + EMPA group, both in terms of EF (61.30 ± 11% vs. 49.24 ± 8%, p = 0.007), LS (- 17.52 ± 3% vs. - 13.93 ± 5%, p = 0.04) and CS (- 25.75 ± 6% vs. - 15.91 ± 6%, p < 0.001). Those results were not duplicated in the DOX + FURO group. Hearts from the DOX + EMPA group showed a 50% lower degree of myocardial fibrosis, compared to DOX mice (p = 0.03). No significant differences were found between the DOX + FURO and the DOX group (p = 0.103). CONCLUSION: Empagliflozin attenuates the cardiotoxic effects exerted by doxorubicin on LV function and remodelling in nondiabetic mice, independently of glycaemic control. These findings support the design of clinical studies to assess their relevance in a clinical setting.


Assuntos
Compostos Benzidrílicos/farmacologia , Cardiomiopatias/prevenção & controle , Doxorrubicina , Glucosídeos/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Disfunção Ventricular Esquerda/prevenção & controle , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/metabolismo , Cardiomiopatias/fisiopatologia , Cardiotoxicidade , Diástole , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibrose , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Sístole , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia
8.
Eur Heart J Acute Cardiovasc Care ; 9(3): 215-221, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32372695

RESUMO

More than 2,000,000 individuals worldwide have had coronavirus 2019 disease infection (COVID-19), yet there is no effective medical therapy. Multiple off-label and investigational drugs, such as chloroquine and hydroxychloroquine, have gained broad interest due to positive pre-clinical data and are currently used for treatment of COVID-19. However, some of these medications have potential cardiac adverse effects. This is important because up to one-third of patients with COVID-19 have cardiac injury, which can further increase the risk of cardiomyopathy and arrhythmias. Adverse effects of chloroquine and hydroxychloroquine on cardiac function and conduction are broad and can be fatal. Both drugs have an anti-arrhythmic property and are proarrhythmic. The American Heart Association has listed chloroquine and hydroxychloroquine as agents which can cause direct myocardial toxicity. Similarly, other investigational drugs such as favipiravir and lopinavir/ritonavir can prolong QT interval and cause Torsade de Pointes. Many antibiotics commonly used for the treatment of patients with COVID-19, for instance azithromycin, can also prolong QT interval. This review summarizes evidenced-based data regarding potential cardiac adverse effects due to off-label and investigational drugs including chloroquine and hydroxychloroquine, antiviral therapy, monoclonal antibodies, as well as common antibiotics used for the treatment of COVID-19. The article focuses on practical points and offers a point-of-care protocol for providers who are taking care of patients with COVID-19 in an inpatient and outpatient setting. The proposed protocol is taking into consideration that resources during the pandemic are limited.


Assuntos
Antimaláricos/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Cloroquina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Antibacterianos/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antimaláricos/farmacocinética , Antimaláricos/toxicidade , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/complicações , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/complicações , Cardiotoxicidade/epidemiologia , Cloroquina/farmacocinética , Cloroquina/toxicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Humanos , Hidroxicloroquina/farmacocinética , Hidroxicloroquina/toxicidade , Uso Off-Label/estatística & dados numéricos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia
9.
BMC Complement Med Ther ; 20(1): 112, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293408

RESUMO

BACKGROUND: Shenmai injection (SMI) has been used in the treatment of cardiovascular disease (CVD), such as heart failure, myocardial ischemia and coronary heart disease. It has been found to have efficacy on doxorubicin (DOX)-induced cardiomyopathy. The aims of this study were to explore the underlying molecular mechanisms of SMI treatment on CVD by using network pharmacology and its protective effect on DOX-induced cardiotoxicity by in vitro and in vivo experiment based on network pharmacology prediction. METHODS: Network pharmacology method was used to reveal the relationship between ingredient-target-disease and function-pathway of SMI on the treatment of CVD. Chemical ingredients of SMI were collected form TCMSP, BATMAN-TCM and HIT Database. Drugbank, DisGeNET and OMIM Database were used to obtain potential targets for CVD. Networks were visualized utilizing Cytoscape software, and the enrichment analysis was performed using IPA system. Finally, cardioprotective effects and predictive mechanism confirmation of SMI were investigated in H9c2 rat cardiomyocytes and DOX-injured C57BL/6 mice. RESULTS: An ingredient-target-disease & function-pathway network demonstrated that 28 ingredients derived from SMI modulated 132 common targets shared by SMI and CVD. The analysis of diseases & functions, top pathways and upstream regulators indicated that the cardioprotective effects of SMI might be associated with 28 potential ingredients, which regulated the 132 targets in cardiovascular disease through regulation of G protein-coupled receptor signaling. In DOX-injured H9c2 cardiomyocytes, SMI increased cardiomyocytes viability, prevented cell apoptosis and increased PI3K and p-Akt expression. This protective effect was markedly weakened by PI3K inhibitor LY294002. In DOX-treated mice, SMI treatment improved cardiac function, including enhancement of ejection fraction and fractional shortening. CONCLUSIONS: Collectively, the protective effects of SMI on DOX-induced cardiotoxicity are possibly related to the activation of the PI3K/Akt pathway, as the downstream of G protein-coupled receptor signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Cardiomiopatias/tratamento farmacológico , Cardiotoxicidade/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Animais , Cardiomiopatias/induzido quimicamente , Linhagem Celular , Modelos Animais de Doenças , Doxorrubicina/toxicidade , Combinação de Medicamentos , Injeções , Camundongos , Camundongos Endogâmicos C57BL , Mapas de Interação de Proteínas , Ratos
10.
Ecotoxicol Environ Saf ; 197: 110605, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32311614

RESUMO

Fluorosis is a worldwide public health problem, and its adverse effects on the heart have been confirmed by many studies. Abnormal myocardial contractions are often associated with impairment of cardiac function as a cause or consequence. We designed two-part experiments to search for biomarkers and clarify the underlying molecular mechanism of fluoride on myocardial contraction. First, we used Pressure-volume Loop analysis to evaluate changes in myocardial function indexes with multiple fluoride exposure levels in mice (0, 30, 70, and 150 mg/L) exposed for 4 weeks. The results showed that fluoride exposure affects the heart pump function and reduces cardiac contractility. Then, we established a rat model of fluoride exposure (0, 30, 60, and 90 mg/L) for 6 months to carry out proteomic analysis of fluoride-induced myocardial contractile injury. Hematoxylin-eosin (H&E) staining was used to determine the severity of myocardial injury, and myocardial tissue samples were submitted for isobaric tags for relative and absolute quantitation (ITRAQ) analysis. A total of 1607 proteins were successfully identified with 294 differentially expressed proteins (DEPs) in fluoride treated groups. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, 12 DEPs were confirmed to be involved in pathways related to myocardial contraction. Furthermore, we constructed a protein-protein interaction (PPI) network for these 12 core DEPs to illustrate the role and location of each DEP in the myocardial contraction pathway. The results of this study are helpful for identify a potential mechanism and biomarkers of fluoride-induced myocardial contraction function damage, moreover, which can provide a new insight into the heart toxicity of fluoride in animals at the proteomics level.


Assuntos
Cardiomiopatias/induzido quimicamente , Fluoretos/toxicidade , Contração Miocárdica/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Ontologia Genética , Masculino , Camundongos , Mapeamento de Interação de Proteínas , Proteínas/metabolismo , Proteômica/métodos , Ratos
11.
Circ Res ; 126(7): 926-941, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32213135

RESUMO

Anthracycline-based chemotherapy can result in the development of a cumulative and progressively developing cardiomyopathy. Doxorubicin is one of the most highly prescribed anthracyclines in the United States due to its broad spectrum of therapeutic efficacy. Interference with different mitochondrial processes is chief among the molecular and cellular determinants of doxorubicin cardiotoxicity, contributing to the development of cardiomyopathy. The present review provides the basis for the involvement of mitochondrial toxicity in the different functional hallmarks of anthracycline toxicity. Our objective is to understand the molecular determinants of a progressive deterioration of functional integrity of mitochondria that establishes a historic record of past drug treatments (mitochondrial memory) and renders the cancer patient susceptible to subsequent regimens of drug therapy. We focus on the involvement of doxorubicin-induced mitochondrial oxidative stress, disruption of mitochondrial oxidative phosphorylation, and permeability transition, contributing to altered metabolic and redox circuits in cardiac cells, ultimately culminating in disturbances of autophagy/mitophagy fluxes and increased apoptosis. We also suggest some possible pharmacological and nonpharmacological interventions that can reduce mitochondrial damage. Understanding the key role of mitochondria in doxorubicin-induced cardiomyopathy is essential to reduce the barriers that so dramatically limit the clinical success of this essential anticancer chemotherapy.


Assuntos
Cardiomiopatias/metabolismo , Doxorrubicina/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Animais , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/envenenamento , Apoptose/efeitos dos fármacos , Cardiomiopatias/induzido quimicamente , Doxorrubicina/envenenamento , Humanos , Mitocôndrias Cardíacas/metabolismo , Mitofagia/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo
12.
PLoS One ; 15(3): e0229772, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126131

RESUMO

BACKGROUND: Fatigue is a common adverse event during lenvatinib treatment in patients with hepatocellular carcinoma. One mechanism contributing to development of fatigue might involve abnormal adenosine triphosphate synthesis that is caused by carnitine deficiency. To address this possibility, we examined the relationship between carnitine levels and fatigue during lenvatinib treatment. METHODS: This prospective study evaluated 20 patients with hepatocellular carcinoma who underwent lenvatinib treatment. Both blood and urine samples were collected from the patients before starting lenvatinib therapy (day 0), and on days 3, 7, 14, and 28 thereafter. Plasma and urine concentrations of free and acyl carnitine (AC) were assessed at each time point. The changes in daily fatigue were evaluated using the Brief Fatigue Inventory (BFI). RESULTS: Plasma levels of free carnitine (FC) at days 3 and 7 were significantly higher compared with baseline (p = 0.005, p = 0.005, respectively). The urine FC level at day 3 was significantly higher compared with baseline (p = 0.030) and that of day 7 tended to be higher compared with baseline (p = 0.057). The plasma AC concentration at days 14 and 28 was significantly higher compared with that of baseline (p = 0.002, p = 0.005, respectively). The plasma AC-to-FC (AC/FC) ratio on days 14 and 28 was significantly higher compared with baseline (p = 0.001, p = 0.003, respectively). There were significant correlations between the plasma AC/FC ratio and the change in the BFI score at days 14 and 28 (r = 0.461, p = 0.041; r = 0.770, p = 0.002, respectively). CONCLUSIONS: Longitudinal assessments of carnitine and fatigue in patients with hepatocellular carcinoma suggest that lenvatinib affects the carnitine system in patients undergoing lenvatinib therapy and that carnitine insufficiency increases fatigue. The occurrence of carnitine insufficiency may be a common cause of fatigue during the treatment.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Cardiomiopatias/induzido quimicamente , Carnitina/deficiência , Fadiga/etiologia , Hiperamonemia/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Doenças Musculares/induzido quimicamente , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/urina , Cardiomiopatias/sangue , Cardiomiopatias/complicações , Cardiomiopatias/dietoterapia , Carnitina/administração & dosagem , Carnitina/sangue , Carnitina/urina , Suplementos Nutricionais , Fadiga/sangue , Fadiga/diagnóstico , Fadiga/prevenção & controle , Feminino , Humanos , Hiperamonemia/sangue , Hiperamonemia/complicações , Hiperamonemia/dietoterapia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/urina , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doenças Musculares/sangue , Doenças Musculares/complicações , Doenças Musculares/dietoterapia , Estudos Prospectivos , Resultado do Tratamento
15.
Food Chem Toxicol ; 137: 111138, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31981685

RESUMO

T-2 toxin, A trichothecenes mycotoxin, is immunotoxic to animals and humans. Although it is highly cardiotoxic, the pathogenesis of cardiomyopathy caused by T-2 toxin is not entirely clear. Hence, in our research, cardiomyopathy was induced by a single injection of T-2 mycotoxin (0.23 mg/kg s.c., 1 LD50) to Wistar rats. The cardiac tissue was carefully examinated by using basic histopathology, semiquantitative (tissue grading score scales) and imaging (a total number of mast cells - MCs) analyses on days 1, 7, 14, 21, 28 and 60 of the study. The most intensive myocardial alterations (cardiac damage score, CDS = 4.20-4.40), irregular glycogen distribution (glycogen distribution score, GDS = 4.07-4.17), haemorrhagic foci (vascular damage score, VDS = 4.57-4.90), diffuse accumulation and degranulation of MCs were observed on day 28 and 60 after treatment (p < 0.001 vs. control and 1st T-2-toxin-treated group, respectively). Besides, statistically significant positive correlations were obtained regarding myocardial injury, glycogen distribution and intensity of haemorrhage, and a negative correlation was found in the case of MCs. Obtained results are essential and crucial for further in vivo experimental studies, including the development of medications able to reduce T-2 toxin-induced cardiotoxicity.


Assuntos
Cardiomiopatias/etiologia , Cardiotoxicidade/etiologia , Toxina T-2/toxicidade , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Cardiotoxicidade/patologia , Glicogênio/metabolismo , Masculino , Mastócitos/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Ratos Wistar
16.
Life Sci ; 245: 117330, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31962130

RESUMO

AIMS: The purpose of this study was to investigate mechanisms of chronic alcohol-induced cardiac remodeling and dysfunction. We also sought to determine the role of cardiac fibroblasts, which play a dynamic role in cardiac remodeling, in mediating these effects. MAIN METHODS: Adult male Wistar rats were exposed to ethanol (EtOH) vapor inhalation for 16 weeks. Echocardiography was performed to assess terminal cardiac structure and function. Cardiac fibroblasts were isolated from the left ventricle (LV) for both ex vivo and in vitro analysis. Cultured H9C2 cells were also exposed to conditioned media from alcohol-exposed cardiac fibroblasts. Gene expression in whole LV tissue, isolated cardiac fibroblasts, or cultured H9C2 cells was determined by real-time PCR, and protein expression was determined by Western blot. KEY FINDINGS: EtOH led to LV wall thinning and impaired systolic function, and decreased contractile protein mRNA levels. EtOH increased LV inflammatory markers, JNK and Akt activation, and decreased mTOR expression. EtOH induced myofibroblast activation as assessed by flow cytometry, and increased LV collagen III expression. EtOH increased expression of several inflammatory mediators in cardiac fibroblasts both ex vivo and in vitro. Administration of conditioned media from EtOH-treated fibroblasts decreased contractile protein mRNA levels and impaired Akt and mTOR signaling in differentiated H9C2 cardiomyocytes. SIGNIFICANCE: Our results indicate that EtOH-induced cardiac atrophy and dysfunction is associated with activation of inflammatory pathways. Furthermore, EtOH may induce a pro-inflammatory cardiac fibroblast phenotype, leading to aberrant fibroblast-myocyte cross-talk. Thus, EtOH may promote cardiac muscle wasting in part by activation of pro-inflammatory fibroblasts.


Assuntos
Etanol/efeitos adversos , Coração/efeitos dos fármacos , Miocárdio/patologia , Animais , Atrofia , Western Blotting , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Ecocardiografia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Coração/fisiopatologia , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Miocárdio/citologia , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Remodelação Ventricular/efeitos dos fármacos
17.
Am J Ther ; 27(2): e142-e150, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30648987

RESUMO

BACKGROUND: Anthracyclines remain the cornerstone of the treatment in many cancers including lymphomas, leukemia and sarcomas, and breast cancer. The cardiomyopathy that develops from anthracyclines can lead to heart failure and decreased survival. Multiple mechanisms are involved in the pathophysiology of anthracycline-induced heart failure. STUDY QUESTION: We hypothesize that anthracycline-induced cardiac (AIC) pathology can be monitored using a panel of blood biomarkers including high-sensitive cardiac troponin T (hs-cTnT) for myocyte necrosis and N-terminal prohormone brain natriuretic peptide (NT-proBNP) for parietal stress. STUDY DESIGN: A prospective, institutionally approved study recruited all patients with cancer scheduled to start anthracycline chemotherapy in the Transylvania University cancer clinics. MEASURES AND OUTCOMES: Transthoracic 2D echocardiography and the measurements of NT-proBNP and hs-cTnT plasma levels were performed at the beginning of the study and 3 months and 6 months after anthracycline treatment initiation. RESULTS: The plasma levels of hs-cTnT at 3 months (rho = 0.439, P = 0.0001) and 6 months (rho = 0.490, P = 0.0001) are correlated with AIC occurrence. For a cutoff value of hs-cTnT at 3 months > 0.008 ng/mL, we obtained 66.7% sensitivity and 67.9% specificity for developing AIC at 6 months, with a 54.5% positive predictive value and a 87.8% negative predictive value. The NT-proBNP serum levels at 3 months (rho = 0.495, P = 0.0001) and 6 months (rho = 0.638, P = 0.0001) are correlated with an AIC diagnosis at 6 months. For a cutoff value of NT-proBNP at 3 months >118.5 pg/mL, we obtained 80% sensitivity and 79.2% specificity for evolution to AIC at 6 months, with 52.2% positive predictive value and 93.3% negative predictive value. CONCLUSIONS: In anthracycline-treated cancer patients, the increase in plasma levels of NT-proBNP and of hs-cTnT can predict the development of anthracycline-induced cardiomyopathy. Early identification of at-risk patients will potentially allow for targeted dose reductions and will diminish the number of patients developing cardiac pathology.


Assuntos
Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Cardiomiopatias/sangue , Cardiomiopatias/induzido quimicamente , Peptídeo Natriurético Encefálico/sangue , Precursores de Proteínas/sangue , Troponina T/sangue , Adulto , Idoso , Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores/sangue , Cardiomiopatias/diagnóstico por imagem , Doxorrubicina/efeitos adversos , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Valor Preditivo dos Testes , Estudos Prospectivos , Volume Sistólico , Resultado do Tratamento , Adulto Jovem
18.
J Oncol Pharm Pract ; 26(2): 478-480, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31142233

RESUMO

INTRODUCTION: Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase, has altered the treatment perspective of chronic lymphocytic leukemia and showed modest activity against several types of non-Hodgkin's lymphomas. According to phase studies and real-world data, reported serious adverse effects included atrial fibrillation, diarrhea, and bleeding diathesis. However, heart failure was not reported to be a probable adverse effect linked with ibrutinib. CASE REPORT: In this paper, we present a 66-year-old female chronic lymphocytic leukemia patient who developed significant and symptomatic left ventricular dysfunction at the 13th month of ibrutinib treatment. MANAGEMENT AND OUTCOME: Following cessation of ibrutinib, ejection fraction and clinical findings of the left ventricular dysfunction alleviated. DISCUSSION: Although the use of ibrutinib is generally well tolerated, cardiac functions should be monitored occasionally in all patients.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Cardiomiopatias/induzido quimicamente , Transtornos de Início Tardio/induzido quimicamente , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Idoso , Cardiomiopatias/diagnóstico , Feminino , Humanos , Transtornos de Início Tardio/diagnóstico , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Disfunção Ventricular Esquerda/diagnóstico
19.
Cardiovasc Toxicol ; 20(3): 222-234, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31435888

RESUMO

In the present study, we investigated the cardioprotective effects of coenzyme Q10 (Q10) against doxorubicin (DOXO) induced cardiomyopathy. Twenty adult rats were distributed in four experimental groups: group 1 received NaCl 0.9% at 1 ml/day for 14 days; group 2 received Q10 at 1 mg/kg/day for 14 days; group 3 received initial 7 days of treatment with NaCl 0.9% followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of NaCl; and group 4 received initial 7 days of Q10 1 mg/kg/day, followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of Q10. At the end of 14 days, systolic, diastolic and mean blood pressure, electrocardiogram (ECG), complete blood count, and serum biochemical profile were evaluated. We also analyzed heart histological and ultrastructure analysis, and estimated heart's oxidative stress and lipid peroxidation. DOXO administration altered ECG, with increase heart rate, P-wave duration, PR interval duration, and T-wave amplitude. All the parameters were significantly reduced following Q10 treatment. DOXO also caused increase in CK, CK-MB, LDH, and urea levels, which were not mitigated by Q10 treatment. However, Q10 reduced oxidative stress by interfering with superoxide dismutase, significantly decreasing lipid peroxidation in heart tissue. DOXO administration also leads to several histological and ultrastructure alterations including cardiomyocyte degeneration and intense intracelullar autophagosomes, all minimized by Q10 treatment. Q10 treatment prevented the ECG changes, minimized oxidative stress, lipid peroxidation, and DOXO-induced heart tissue alterations. Our findings suggest that pre- and post-treatment with Q10 exerts potential cardioprotective effect against the DOX-induced cardiotoxicity.


Assuntos
Antioxidantes/farmacologia , Cardiomiopatias/prevenção & controle , Doxorrubicina , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ubiquinona/análogos & derivados , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Cardiotoxicidade , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/ultraestrutura , Ratos Wistar , Ubiquinona/farmacologia
20.
J Oncol Pharm Pract ; 26(3): 680-687, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31500517

RESUMO

BACKGROUND: Acute myeloid leukemia patients receive anthracycline-containing induction chemotherapy. Anthracyclines cause cardiotoxicity; however, there is a paucity of data reflecting the risk of cardiotoxicity in the acute myeloid leukemia population, and risk factors for development of reduced left ventricular ejection fraction are not well established in this population. METHODS: A retrospective cohort study of adult acute myeloid leukemia patients receiving anthracycline-containing induction chemotherapy between March 2011 and August 2017 was performed. Baseline and all additional cardiac monitoring within one year of induction were collected. Home medications and new medication initiation were determined via the electronic health record and new outpatient prescriptions. RESULTS: Of 97 evaluable patients, 25 (25.8%) developed reduced left ventricular ejection fraction and 18 (18.6%) experienced clinical heart failure within one year of induction. The median difference from baseline to lowest left ventricular ejection fraction was -5.0 percentage points, with a range of +10.0 to -52.5. The median time to onset of reduced left ventricular ejection fraction was 27 days, at a median cumulative anthracycline dose of 270 mg/m2. No patient-specific or medication-specific factors were significantly associated with the risk of developing reduced left ventricular ejection fraction. Of 14 patients started on medical management for reduced left ventricular ejection fraction, 10 (71%) responded to therapy. CONCLUSIONS: In this retrospective analysis, we observed that acute myeloid leukemia patients experienced reduced left ventricular ejection fraction more quickly and at lower doses than previously reported in the solid tumor population. Reduced left ventricular ejection fraction was at least partially reversible in most patients started on medical management. Although no factors were significantly associated with decreased cardiomyopathy risk, future assessment of cardioprotective medications may be warranted.


Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Cardiomiopatias/induzido quimicamente , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Cardiotoxicidade/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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