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2.
Life Sci ; 262: 118551, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33038370

RESUMO

OBJECTIVE: To explore the effect of urantide on atherosclerotic myocardial injury by antagonizing the urotensin II/urotensin II receptor (UII/UT) system and regulating the mitogen-activated protein kinase (MAPK) signalling pathway. METHODS: Atherosclerosis (AS) was established in rats by administering a high-fat diet and an intraperitoneal injection of vitamin D3. The effect of treatment with urantide (30 µg/kg), a UII receptor antagonist, for 3, 7, or 14 days on AS-induced myocardial damage was evaluated. RESULTS: The heart of rats with AS exhibited pathological changes suggestive of myocardial injury, and the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) were significantly increased. Additionally, significant increases in the levels of UII, its receptor (G protein-coupled receptor 14, GPR14), p-P38, p-extracellular signal-regulated kinase (ERK) and p-c-Jun N-terminal kinase (JNK) were observed in the heart. Urantide improved pathological changes in the heart of rats with AS and reduced the serum CK and LDH levels. Additionally, the UII antagonist decreased the increased levels of UII, GPR14, p-P38, p-ERK and p-JNK in the heart. CONCLUSIONS: Urantide alleviates atherosclerotic myocardial injury by inhibiting the UII-GPR14 interaction and regulating the MAPK signalling pathway. We hypothesized that myocardial injury may be associated with the regulation of the MAPK signalling pathway.


Assuntos
Aterosclerose/tratamento farmacológico , Cardiopatias/prevenção & controle , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Urotensinas/farmacologia , Animais , Aterosclerose/complicações , Cardiopatias/etiologia , Masculino , Miocárdio/patologia , Fragmentos de Peptídeos/administração & dosagem , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas-G/metabolismo , Urotensinas/administração & dosagem , Urotensinas/antagonistas & inibidores
3.
Cardiovasc Ther ; 2020: 1494506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072188

RESUMO

Background: Cardiac adverse events are common among patients presenting with acute stroke and contribute to overall morbidity and mortality. Prophylactic measures for the reduction of cardiac adverse events in hospitalized stroke patients have not been well understood. We sought to investigate the effect of early initiation of high-dose intravenous magnesium sulfate on cardiac adverse events in stroke patients. Methods: This is a secondary analysis of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized phase-3 clinical trial, conducted from 2005-2013. Consecutive patients with suspected acute stroke and a serum magnesium level within 72 hours of enrollment were selected. Twenty grams of magnesium sulfate or placebo was administered in the ambulance starting with a 15-minute loading dose intravenous infusion followed by a 24-hour maintenance infusion in the hospital. Results: Among 1126 patients included in the analysis of this study, 809 (71.8%) patients had ischemic stroke, 277 (24.6%) had hemorrhagic stroke, and 39 (3.5%) with stroke mimics. The mean age was 69.5 (SD13.4) and 42% were female. 565 (50.2%) received magnesium treatment, and 561 (49.8%) received placebo. 254 (22.6%) patients achieved the target, and 872 (77.4%) did not achieve the target, regardless of their treatment group. Among 1126 patients, 159 (14.1%) had at least one CAE. Treatment with magnesium was not associated with fewer cardiac adverse events. A multivariate binary logistic regression for predictors of CAEs showed a positive association of older age and frequency of CAEs (R = 1.04, 95% CI 1.03-1.06, p < 0.0001). Measures of early and 90-day outcomes did not differ significantly between the magnesium and placebo groups among patients who had CAEs. Conclusion: Treatment of acute stroke patients with magnesium did not result in a reduction in the number or severity of cardiac serious adverse events.


Assuntos
Cardiopatias/prevenção & controle , Hospitalização , Sulfato de Magnésio/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Esquema de Medicação , Feminino , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Humanos , Incidência , Los Angeles/epidemiologia , Sulfato de Magnésio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento
4.
Eur J Endocrinol ; 183(6): R185-R196, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33077688

RESUMO

Primary aldosteronism is common and contributes to adverse cardiovascular, kidney, and metabolic outcomes. When instituted early and effectively, targeted therapies can mitigate these adverse outcomes. Surgical adrenalectomy is among the most effective treatments because it has the potential to cure, or attenuate the severity of, pathologic aldosterone excess, resulting in a host of biochemical and clinical changes that improve health outcomes. Herein, we review the role of surgical adrenalectomy in primary aldosteronism while emphasizing the physiologic ramifications of surgical intervention, and compare these to other targeted medical therapies for primary aldosteronism. We specifically review the role of curative adrenalectomy for unilateral primary aldosteronism, the role of non-curative adrenalectomy for bilateral primary aldosteronism, and how these interventions influence biochemical and clinical outcomes in relation to medical therapies for primary aldosteronism.


Assuntos
Adrenalectomia/tendências , Aldosterona/sangue , Hiperaldosteronismo/sangue , Hiperaldosteronismo/cirurgia , Adrenalectomia/métodos , Doenças do Sistema Endócrino/sangue , Doenças do Sistema Endócrino/cirurgia , Cardiopatias/sangue , Cardiopatias/prevenção & controle , Humanos , Nefropatias/sangue , Nefropatias/prevenção & controle
6.
Arch Dis Child ; 105(11): 1041-1048, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32994214

RESUMO

OBJECTIVES: Cardiac T2* MRI (T2*CMR), for accurate estimation of myocardial siderosis, was introduced as part of a QI collaborative to optimise chelation therapy in order to improve cardiac morbidity in transfusion dependent thalassaemia (TDT) patients. We report the impact of this QI initiative from two thalassaemia centres from this collaborative. DESIGN AND SETTING: A key driver based quality initiative was implemented to improve chelation in TDT patients registered at these two centres in Karachi, Pakistan. Protocol optimisation and compliance to treatment through training, communication and feedback were used as the drivers for QI intervention. Preintervention variables (demographics, chelation history, T2*CMR, echocardiography and holters) were collected from January 2015 to December 2016) and compared with variables in the post implementation phase (January to December 2019). A standardised adverse event severity for chelators and its management was devised for safe drug therapy as well as ensuring compliance to the regimen. Preintervention and postintervention variables were compared using non-parametric test. P value<0.05 was statistically significant. RESULTS: 100 patients with TDT, median age 17 (9-34) years, were included. An increase or stabilisation of T2*CMR was documented in 82% patients in the postintervention phase especially in patients with severe myocardial iron overload (5.5 vs 5.3 ms, p <0.01). Significantly fewer patients had abnormal echocardiographic findings (3.5% vs 26%, p <0.05) in the postintervention versus preintervention period. CONCLUSION: This QI initiative improved the chelation therapy leading to improved cardiac status in TDT patients at the participating centres.


Assuntos
Terapia por Quelação/métodos , Cardiopatias/prevenção & controle , Coração/diagnóstico por imagem , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/prevenção & controle , Talassemia/terapia , Adolescente , Adulto , Transfusão de Sangue , Criança , Protocolos Clínicos , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Paquistão , Melhoria de Qualidade , Adulto Jovem
7.
Am J Physiol Heart Circ Physiol ; 319(4): H775-H786, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32822209

RESUMO

The efficacy of an anthracycline antibiotic doxorubicin (DOX) as a chemotherapeutic agent is limited by dose-dependent cardiotoxicity. DOX is associated with activation of intracellular stress signaling pathways including p38 MAPKs. While previous studies have implicated p38 MAPK signaling in DOX-induced cardiac injury, the roles of the individual p38 isoforms, specifically, of the alternative isoforms p38γ and p38δ, remain uncharacterized. We aimed to determine the potential cardioprotective effects of p38γ and p38δ genetic deletion in mice subjected to acute DOX treatment. Male and female wild-type (WT), p38γ-/-, p38δ-/-, and p38γ-/-δ-/- mice were injected with 30 mg/kg DOX and their survival was tracked for 10 days. During this period, cardiac function was assessed by echocardiography and electrocardiography and fibrosis by Picro Sirius Red staining. Immunoblotting was performed to assess the expression of signaling proteins and markers linked to autophagy. Significantly improved survival was observed in p38δ-/- female mice post-DOX relative to WT females, but not in p38γ-/- or p38γ-/-δ-/- male or female mice. The improved survival in DOX-treated p38δ-/- females was associated with decreased fibrosis, increased cardiac output and LV diameter relative to DOX-treated WT females, and similar to saline-treated controls. Structural and echocardiographic parameters were either unchanged or worsened in all other groups. Increased autophagy, as suggested by increased LC3-II level, and decreased mammalian target of rapamycin activation was also observed in DOX-treated p38δ-/- females. p38δ plays a crucial role in promoting DOX-induced cardiotoxicity in female mice by inhibiting autophagy. Therefore, p38δ targeting could be a potential cardioprotective strategy in anthracycline chemotherapy.NEW & NOTEWORTHY This study for the first time identifies the sex-specific roles of the alternative p38γ and p38δ MAPK isoforms in promoting doxorubicin (DOX) cardiotoxicity. We show that p38δ and p38γ/δ systemic deletion was cardioprotective in female but not in male mice. Cardiac structure and function were preserved in DOX-treated p38δ-/- females and autophagy marker was increased.


Assuntos
Doxorrubicina , Cardiopatias/prevenção & controle , Proteína Quinase 13 Ativada por Mitógeno/deficiência , Miocárdio/enzimologia , Animais , Autofagia/efeitos dos fármacos , Cardiotoxicidade , Modelos Animais de Doenças , Feminino , Fibrose , Técnicas de Inativação de Genes , Cardiopatias/enzimologia , Cardiopatias/genética , Cardiopatias/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína Quinase 12 Ativada por Mitógeno/deficiência , Proteína Quinase 12 Ativada por Mitógeno/genética , Proteína Quinase 13 Ativada por Mitógeno/genética , Miocárdio/patologia , Fatores Sexuais , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos
8.
Life Sci ; 260: 118216, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768582

RESUMO

AIMS: Doxorubicin (DOX) is a potent anticancer drug with severe dose-dependent cardiotoxicity. To address this issue, previous research primarily focused on DOX-induced toxicity on cardiomyocytes. However, more recent research has looked into the endothelium as a therapeutic target due to the emerging role of endothelial cells in the support of cardiomyocyte survival and function. MAIN METHODS: We investigated a novel role of endothelial cell (EC) primary cilia in the prevention of DOX-mediated cardiotoxicity. Mice lacking EC primary cilia, via the deletion of EC-specific intraflagellar protein 88 (IFT88) expression, were administered DOX (20 mg/kg i.p.), and assessed for survival, cardiac function, cardiac structure changes, and indices of cardiomyocyte injury. KEY FINDINGS: DOX-treatment resulted in reduced survival and cardiac function (ejection fraction and fractional shortening) in EC-IFT88-/- mice vs. their similarly treated wild-type littermates. Cardiomyocyte vacuolization, cardiac fibrosis, and serum CK-MB levels were also increased in DOX-treated mice compared to saline-treated controls. However, these parameters were not significantly different when comparing WT and EC-IFT88-/- mice after DOX treatment. SIGNIFICANCE: The loss of EC primary cilia accelerated DOX-mediated mortality and reduced cardiac function, suggesting pathways downstream of ciliary-mediated signal transduction as potential targets to promote EC support of cardiomyocyte function during DOX treatment.


Assuntos
Cílios/fisiologia , Doxorrubicina/toxicidade , Células Endoteliais/fisiologia , Cardiopatias/induzido quimicamente , Proteínas Supressoras de Tumor/fisiologia , Animais , Cruzamentos Genéticos , Células Endoteliais/ultraestrutura , Cardiopatias/fisiopatologia , Cardiopatias/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteínas Supressoras de Tumor/deficiência
9.
BMC Surg ; 20(1): 193, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854681

RESUMO

BACKGROUND: Open surgical repair (OSR) for thoracoabdominal aortic aneurysms (TAA) is associated with a high pulmonary and renal morbidity rate. Ischemic preconditioning (IPC) is a mechanism of protection against the deleterious effects of ischemia-reperfusion. To our knowledge IPC has never been tested during OSR for TAA. METHODS: The primary objective of the study is to evaluate the efficacy of IPC during OSR for TAA with respect to acute kidney injury (AKI) according to KDIGO and pneumonia/prolonged ventilation-time during the first 8 postoperative days. The secondary objectives are to compare both arms with respect to cardiac complications within 48 h, renal and pulmonary complications within 21 days and mortality at 60 days. To assess the efficacy of IPC with respect to pulmonary and renal morbidity, a cox model for competing risks will be used. Assuming that the event occurs among 36% of the patients when no IPC is performed, the allocation of 55 patients to each arm should allow detecting a hazard ratio of at least 2.75 with a power of 80% when admitting 5% for an error of first kind. This means that 110 patients, enrolled in this multicenter study, may be randomised within 36 months of the first randomization. Randomization will be performed to allocate patients either to surgery with preconditioning before aortic cross clamping (Arm 1) or to surgery without preconditioning before aortic cross clamping (Arm 2). Randomization takes place during the intervention after intravenous injection of heparin, or after the start of femoral assistance. The procedure for IPC will be a supra-visceral thoracic aortic cross clamping for 5 min followed by an unclamping period of 5 min. This procedure will be repeated twice before starting thoracic aortic cross clamping needed to perform surgery. CONCLUSIONS: Our hypothesis is that ischemic preconditioning could reduce clinical morbidity and the incidence of lung damage associated with supra-visceral aortic clamping. TRIAL REGISTRATION: EPICATAStudy registered in ClinicalTrial.gov / number: NCT03718312 on Oct.24.2018 URL number.


Assuntos
Aneurisma da Aorta Torácica , Precondicionamento Isquêmico , Traumatismo por Reperfusão/prevenção & controle , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/prevenção & controle , Aorta/cirurgia , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular , Ponte Cardiopulmonar , Constrição , Cardiopatias/etiologia , Cardiopatias/prevenção & controle , Humanos , Hipotermia Induzida , Isquemia/etiologia , Isquemia/prevenção & controle , Precondicionamento Isquêmico/métodos , Pneumopatias/etiologia , Pneumopatias/prevenção & controle , Morbidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Traumatismo por Reperfusão/etiologia , Resultado do Tratamento
10.
Am J Physiol Endocrinol Metab ; 319(2): E320-E329, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603601

RESUMO

Complex organisms rely heavily on intercellular communication. The rapidly expanding field of extracellular vesicle biology has made it clear that the necessary intercellular communication occurs partly through their paracrine and endocrine actions. Extracellular vesicles are nanoscale lipid membranes (30-2,000 nm in diameter) that shuttle functional biological material between cells. They are released from numerous tissues and are isolated from nearly all biofluids and cell cultures. Although their biogenesis, cell targeting, and functional roles are incompletely understood, they appear to have crucial roles in physiological and disease processes. Their enormous potential to serve as sensitive biomarkers of disease and also new therapeutic interventions for diseases have gained them considerable attention in recent years. Regular physical exercise training confers systemic health benefits and consequently prevents many age-related degenerative diseases. Many of the molecular mechanisms responsible for the salubrious effects of exercise are known, yet a common underlying mechanism potentially responsible for the holistic health benefits of exercise has only recently been explored (i.e., via extracellular vesicle transport of biological material). Here, we provide an overview of extracellular vesicle biology before outlining the current evidence on the capacity for a single bout and chronic exercise to elicit changes in extracellular vesicle content and modulate their molecular cargo (e.g., small RNAs). We highlight areas for future research and emphasize their potential utility as biomarkers and therapeutic strategies of disease and its prevention.


Assuntos
Comunicação Celular/fisiologia , Exercício Físico/fisiologia , Espaço Extracelular/fisiologia , Vesículas Extracelulares/fisiologia , Animais , Vesículas Extracelulares/química , Promoção da Saúde , Cardiopatias/prevenção & controle , Humanos , MicroRNAs/fisiologia , Condicionamento Físico Animal/fisiologia , Prevenção Primária/métodos
12.
Heart Vessels ; 35(12): 1664-1671, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32572567

RESUMO

Myocardial injury is a problem associated with percutaneous coronary intervention (PCI). This study aimed to clarify the role of nicorandil administration in preventing myocardial injury. This study included patients with stable angina who underwent PCI from November 2013 to June 2016. Of 58 consecutive patients, the first 20 patients received only saline infusion after PCI (control group); the other 38 patients received a continuous intravenous infusion of nicorandil and saline after PCI (nicorandil group). Troponin I and brain natriuretic peptide (BNP) levels were measured. Vascular parameters, such as blood pressure (BP), cardiac output, cardio-ankle vascular index (CAVI), and estimated systemic vascular resistance (eSVR), were measured. Troponin I of both groups increased 12 h after PCI. Changes in BNP levels between immediately after PCI and 12 h after PCI were significantly higher in the control than in the nicorandil group (10.8 ± 44.2 vs. - 2.6 ± 14.6 pg/ml, p = 0.04). In the nicorandil group, BP, eSVR, and CAVI decreased significantly at 12 h after PCI compared with those immediately after PCI (p < 0.0001), whereas no change was observed in the control group. In a single linear analysis, the change in BP (r = 0.36, p < 0.01) and nicorandil administration (r = - 0.47, p < 0.001) was significantly correlated with the change in CAVI, multiple regression analysis revealed that the changes in CO and eSVR were significant contributing factors for the changes in CAVI. PCI could result in myocardial injury and/or cardiac burden in patients with stable angina. Nicorandil administration after PCI may be effective in relieving the burden by decreasing arterial stiffness (CAVI).


Assuntos
Angina Estável/terapia , Doença da Artéria Coronariana/terapia , Cardiopatias/prevenção & controle , Hemodinâmica/efeitos dos fármacos , Nicorandil/administração & dosagem , Intervenção Coronária Percutânea/efeitos adversos , Rigidez Vascular/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Idoso , Angina Estável/diagnóstico por imagem , Angina Estável/fisiopatologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Feminino , Cardiopatias/diagnóstico por imagem , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Nicorandil/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Vasodilatadores/efeitos adversos
13.
Hosp Pract (1995) ; 48(5): 282-288, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32597257

RESUMO

OBJECTIVE: Farshchian Heart Center is the fifth health-promoting hospital and the first center of its type in Western Iran that officially joined the International Network of Health Promoting Hospitals and Health Services (HPH) in 2016. The purpose of the present study is to evaluate the health promotion standards at this center in 2018. METHODS: We conducted this cross-sectional study at Farshchian Heart Center of Hamadan. The main data collection instruments included questionnaires obtained from indicators of five different main standards of health-promoting hospitals developed by the World Health Organization (WHO) which were evaluated from three different perspectives: Management staff, hospital employees, and patients. The data were analyzed by SPSS version 21 software. RESULTS: We evaluated 111 hospital employees, 109 patients, and 6 management staff. Nurses (46.8%) comprised the majority of the hospital staff respondents. Less than half (42.3%) of the hospital staff expressed awareness of hospital health promotion policies; however, only 13.5% had attended various health promotion programs. Only 51.4% of patients knew about the hospital health promotion policies and 17.4% of them participated in relevant programs. The mean score for patient satisfaction with the hospital health promotion programs according to the visual analogue scale (VAS, range: 0-10) was 7.16 ± 2.45, which was significantly higher in outpatients (8.16 ± 1.85) compared to inpatients (6.44 ± 2.59, p = 0.001). Two thirds (66.7%) of the management staff expressed awareness of implementation of these programs. CONCLUSION: The results of this study demonstrated that health promotion policies based on WHO standards were not well-recognized among patients, hospital employees, and management staff in Farshchian Heart Center of Hamadan, Iran.


Assuntos
Guias como Assunto , Pessoal de Saúde/psicologia , Pessoal de Saúde/estatística & dados numéricos , Promoção da Saúde/estatística & dados numéricos , Promoção da Saúde/normas , Cardiopatias/prevenção & controle , Administração Hospitalar/estatística & dados numéricos , Administração Hospitalar/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
14.
J Nutr ; 150(9): 2353-2363, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32510147

RESUMO

BACKGROUND: Although the combination of doxorubicin (DOX) and trastuzumab (TRZ) reduces the progression and recurrence of breast cancer, these anticancer drugs are associated with significant cardiotoxic side effects. OBJECTIVE: We investigated whether prophylactic administration of flaxseed (FLX) and its bioactive components, α-linolenic acid (ALA) and secoisolariciresinol diglucoside (SDG), would be cardioprotective against DOX + TRZ-mediated cardiotoxicity in a chronic in vivo female murine model. METHODS: Wild-type C57BL/6 female mice (10-12 wk old) received daily prophylactic treatment with one of the following diets: 1) regular control (RC) semi-purified diet; 2) 10% FLX diet; 3) 4.4% ALA diet; or 4) 0.44% SDG diet for a total of 6 wks. Within each arm, mice received 3 weekly injections of 0.9% saline or a combination of DOX [8 mg/(kg.wk)] and TRZ [3 mg/(kg.wk)] starting at the end of week 3. The main outcome was to evaluate the effects of FLX, ALA, and SDG on cardiovascular remodeling and markers of apoptosis, inflammation, and mitochondrial dysfunction. Significance between measurements was determined using a 4 (diet) × 2 (chemotherapy) × 2 (time) mixed factorial design with repeated measures. RESULTS: In the RC + DOX + TRZ-treated mice at week 6 of the study, the left ventricular ejection fraction (LVEF) decreased by 50% compared with the baseline LVEF (P < 0.05). However, the prophylactic administration of the FLX, ALA, or SDG diet was partially cardioprotective, with mice in these treatment groups showing an ∼68% increase in LVEF compared with the RC + DOX + TRZ-treated group at week 6 (P < 0.05). Although markers of inflammation (nuclear transcription factor κB), apoptosis [poly (ADP-ribose) polymerase-1 and the ratio of BCL2-associated X protein to B-cell lymphoma-extra large], and mitochondrial dysfunction (BCL2-interacting protein 3) were significantly elevated by approximately 2-fold following treatment with RC + DOX + TRZ compared with treatment with RC + saline at week 6, prophylactic administration of FLX, ALA, or SDG partially downregulated these signaling pathways. CONCLUSION: In a chronic in vivo female C57BL/6 mouse model of DOX + TRZ-mediated cardiotoxicity, FLX, ALA, and SDG were partially cardioprotective.


Assuntos
Suplementos Nutricionais , Doxorrubicina/efeitos adversos , Linho , Cardiopatias/induzido quimicamente , Cardiopatias/prevenção & controle , Trastuzumab/efeitos adversos , Animais , Antineoplásicos/efeitos adversos , Cardiotoxicidade , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Função Ventricular Esquerda
16.
Medicine (Baltimore) ; 99(19): e19987, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384451

RESUMO

This study aimed to investigate the inner linkage and mechanism of Mycoplasma pneumoniae (MP) infection and Kawasaki disease (KD), as well as the risk factors of outcome in this cohort of patients.A retrospective study was performed in 210 patients diagnosed with KD complicated with community acquired pneumonia (CAP) in Children's Hospital, Zhejiang University School of Medicine from January 2014 to December 2017. They were divided into two groups based on MP infection: MP infection group (n = 97) and non-MP infection group (n = 113). We compared the variables of these two groups based on medical records.The MP infection group had higher ESR than the non-MP infection group. During hospitalization, the non-MP infection group had higher levels of WBC during hospital, LDH, PCT, and lower HB when compared to the MP infection group. No differences were found in the hs-CRP level, N%, PLT, ALT, CKMB, and cytokine levels (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) between MP and non-MP infection group. Likewise, no difference was found in fever duration or hospital stays between them. Totally 19 patients in the infection group had CAA with a rate of 19.59%; and 27 (23.89%) patients had CAA in the non-MP infection group. Unfortunately, no difference was found in CAA rate between the two groups.MP infection may occur simultaneously in children with Kawasaki disease. KD patients with MP infection tended to occur in older population. MP infection may not increase the risk of CAA, which still needs further large-scaled studies to confirm. Clinicians should be alert to KD patients with high level of ESR. MP should be screened and early treatment with macrolides should be given timely.


Assuntos
Sedimentação Sanguínea , Cardiopatias , Macrolídeos/administração & dosagem , Síndrome de Linfonodos Mucocutâneos , Pneumonia por Mycoplasma , Antibacterianos/administração & dosagem , Pré-Escolar , China/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Comorbidade , Citocinas/sangue , Intervenção Médica Precoce/métodos , Feminino , Cardiopatias/etiologia , Cardiopatias/prevenção & controle , Humanos , Lactente , Contagem de Leucócitos/métodos , Contagem de Leucócitos/estatística & dados numéricos , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/terapia , Pneumonia por Mycoplasma/sangue , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/epidemiologia , Estudos Retrospectivos , Avaliação de Sintomas/métodos , Avaliação de Sintomas/estatística & dados numéricos
18.
Cardiovasc Drugs Ther ; 34(5): 651-657, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32444994

RESUMO

BACKGROUND: The high surgical risk in redo cardiac surgery is largely attributed to adhesions around the epicardium and the great vessels. BAX602 is an adhesion prevention reagent composed of two synthetic polyethylene glycols. Spraying BAX602 over the epicardium and the great vessels reportedly contributes to adhesion prevention after pediatric cardiac surgery. The present study aims to evaluate the safety and effectiveness of BAX602 spray in patients undergoing extracorporeal ventricular assist device implantation surgery to treat refractory congestive heart failure. METHODS AND DESIGN: This investigator-initiated, multicenter, pivotal, two-arm, open-label, randomized trial will include a total of 30 patients. The primary outcome measure is the severity of adhesions, which will be evaluated during re-sternotomy surgery performed 2-12 weeks after the primary extracorporeal ventricular assist device implantation surgery. The adhesion severity will be evaluated at five predefined sites using a four-grade adhesion evaluation score (0 = no adhesion; 1 = filmy and avascular adhesion; 2 = dense/vascular adhesion; 3 = cohesive adhesion). This measure will be summarized in two ways to evaluate the effect of BAX602: (1) the total score of the severity of adhesions at all five sites (ranging from 0 to 15), and (2) the total number of sites with dense/vascular or cohesive adhesions (ranging from 0 to 5). ETHICS AND DISSEMINATION: The study findings will be disseminated at regional, national, and international conferences and through peer-reviewed scientific journals. TRIAL REGISTRATION: The trial was registered in the UMIN Clinical Trials Registry (UMIN-CTR: UMIN000038998) on 6 January 2020.


Assuntos
Cardiopatias/prevenção & controle , Insuficiência Cardíaca/terapia , Coração Auxiliar , Polietilenoglicóis/administração & dosagem , Implantação de Prótese/instrumentação , Função Ventricular Esquerda , Adolescente , Adulto , Aerossóis , Idoso , Feminino , Cardiopatias/etiologia , Cardiopatias/patologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/síntese química , Desenho de Prótese , Implantação de Prótese/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Aderências Teciduais , Resultado do Tratamento , Adulto Jovem
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