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Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.
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This study investigated the effects of amygdalin (AMY, a cyanogenic glycoside widely distributed in the fruits and seeds of Rosaceae plants) on cardiac performance and ventricular remodeling in a rat model of myocardial infarction (MI). We also investigated whether the combination of AMY with exercise training (ExT) has a beneficial synergistic effect in treating MI rats. MI was induced by the ligation of the left anterior descending coronary artery in male SD rats. ExT or AMY treatment was started 1 week after MI and continued for 1 week (short-term) or 8 weeks (long-term). Cardiac function was evaluated by echocardiographic and hemodynamic parameters. Heart tissues were harvested and subjected to 2,3,5-triphenyl-tetrazolium chloride, Masson's trichrome, hematoxylin-eosin, and immunohistochemical staining. Gene expression was determined by quantitative polymerase chain reaction. Western blot gave a qualitative assessment of protein levels. AMY or ExT improved cardiac function and reduced infarct size in MI rats. AMY or ExT also suppressed myocardial fibrosis and attenuated inflammation in the infarct border zone of hearts from MI rats, as evidenced by inhibition of collagen deposition, inflammatory cell infiltration, and pro-inflammatory markers (interleukin 1ß, interleukin 6, tumor necrosis factor-α, and cyclooxygenase 2). Notably, the effects of AMY combined with ExT were superior to those of AMY alone or ExT alone. Mechanistically, these beneficial functions were correlated with the inhibition of MI-induced activation of the transforming growth factor-ß/Smad pathway. Collectively, AMY and ExT exert a synergistic effect on improving cardiac performance and ameliorating cardiac inflammation and fibrosis after MI, and the effects of long-term intervention were better than short-term intervention.
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Amigdalina , Infarto del Miocardio , Animales , Ratas , Ratas Sprague-Dawley , Amigdalina/farmacología , Infarto del Miocardio/terapia , Inflamación/terapia , FibrosisRESUMEN
BACKGROUND: The diagnosis of constrictive pericarditis (CP) is challenging as there are currently no standard echocardiographic diagnostic criteria. In this retrospective case series, we analyzed and summarized the features of 25 patients with CP and proposed echocardiographic diagnostic criteria. It is hoped that the suggested criteria help professionals make decisions in their daily practice so that patients receive timely diagnosis and effective treatment. METHODS: Twenty-five patients with CP were selected for this retrospective study. The clinical and echocardiographic imaging data were analyzed and summarized, and echocardiographic diagnostic criteria for CP were proposed. RESULTS: The main clinical manifestations were fatigue, breathlessness, exertional dyspnea (88%), lower-limb edema (84%), hepatomegaly, and jugular vein filling (84%). Echocardiographic features comprised pericardial thickening (88%) and calcification (60%), pulmonary hypertension (52%), inferior vena cava dilation (80%), left and/or right atrial enlargement (100%), diastolic flattening of the left ventricular (LV) posterior wall (72%), septal shudder and bounce (64%), restrictive LV and right ventricular diastolic filling pattern (100%), early filling changes of mitral and tricuspid flow (80% and 60%, respectively), and mitral annulus reversus (73%). CONCLUSIONS: Echocardiography is a simple and valuable examination for CP. The echocardiographic diagnostic criteria are valid and worth promoting.
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Pericarditis Constrictiva , Humanos , Pericarditis Constrictiva/diagnóstico por imagen , Estudios Retrospectivos , Ecocardiografía , Pericardio/diagnóstico por imagen , Válvula Mitral/diagnóstico por imagenRESUMEN
Background: Ischemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat. Methods: Rat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed. Results: Pre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators. Conclusion: Our result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.
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BACKGROUND: Hypertension is the the primary cause of diastolic heart failure. Oxidative stress plays an important role in cardiac diastolic dysfunction caused by hypertension. The occurrence of oxidative stress is related to the level of nitric oxide (NO) in the body. Tetrahydrobiopterin (BH4) is an essential cofactor for NO synthesis. Nebivolol can reduce myocardial oxidative stress and increase NO activity. Therefore, we investigated the effects of monotherapy or combination therapy of different doses of BH4 and nebivolol on cardiac diastolic function in spontaneously hypertensive rats, and preliminarily expounded the related mechanisms. METHODS: Left ventricular function was evaluated by non-invasive echocardiographic assessment and invasive right carotid artery catheterization methods. ELISA was used to measure myocardial 3-nitrotyrosine content, NO production, and cyclic guanosine monophosphate (cGMP) concentration in the myocardium; quantitative real-time PCR (qRT-PCR) was used to determine endothelial nitric oxide synthase (eNOS), phospholamban and sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) mRNA expression levels; Western blot was used to detect the protein expression levels of eNOS and eNOS dimers in myocardial tissue, and immunohistochemical detection of cGMP expression in the myocardium was performed. RESULTS: Studies have shown that compared with those in the control group, NO generation and the expression level of myocardial eNOS mRNA, eNOS expression of dimers, phospholamban, SERCA2a and cGMP increased significantly after the combined intervention of BH4 and nebivolol, while the expression of 3-nitrotyrosine was significantly decreased. CONCLUSIONS: The combined treatment group had a synergistic effect on reducing myocardial oxidative stress, increasing eNOS content, and increasing NO production, and had a more obvious protective effect on diastolic dysfunction through the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway.
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Biopterinas/análogos & derivados , Presión Sanguínea/efectos de los fármacos , Guanosina Monofosfato/metabolismo , Hipertensión/metabolismo , Nebivolol/administración & dosificación , Óxido Nítrico/metabolismo , Animales , Biopterinas/administración & dosificación , Presión Sanguínea/fisiología , Diástole/efectos de los fármacos , Diástole/fisiología , Quimioterapia Combinada , Hipertensión/tratamiento farmacológico , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVES: This study aimed to assess right ventricular (RV) diastolic dysfunction in patients with obstructive sleep apnea syndrome (OSAS) using velocity vector imaging (VVI) and to evaluate the application of VVI technology. METHODS: According to the apnea-hypopnea index (AHI), 69 patients with OSAS were divided into three groups: mild, moderate, and severe. A total of 35 cases of healthy subjects were enrolled as the control group. Digital images of apex four-chamber views were acquired to measure the peak early diastolic strain rate (RV-SRe), late diastolic strain rate(RV-SRa), and RV-SRe/RV-SRa using VVI. RESULTS: RV-SRe, RV-Sra, and RV-SRe/RV-SRa were decreasing along with the disease severity. RV-SRe, RV-SRe/RV-SRa in moderate and severe OSAS group showed lower than control and mild OSAS groups. RV-SRa in severe OSAS group showed lower than control group. RV-SRe had the best correlation with AHI than other parameters. CONCLUSIONS: Right ventricular diastolic dysfunction starts before the development of heart failure and pulmonary hypertension in patients with OSAS. RV-SRe was the parameter that may reflect subclinical myocardial dysfunction and can better reflect RV diastolic dysfunction.
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Hipertensión Pulmonar , Apnea Obstructiva del Sueño , Disfunción Ventricular Derecha , Humanos , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/diagnóstico por imagen , Disfunción Ventricular Derecha/complicaciones , Disfunción Ventricular Derecha/diagnóstico por imagenRESUMEN
Heart failure (HF) is one of the most severe heart conditions, which lacks effective therapies. Therefore, it is necessary to develop more efficient drugs for HF. In this study, we investigated the cardioprotective effects of hyperoside against the pathological progression of HF. Thoracic aortic constriction (TAC) was performed to induce HF in rats. Hyperoside treatment improved cardiac function, decreased cardiomyocyte cross-sectional area and heart weight to body weight (HW/BW) ratio in HF rats. Moreover, hyperoside administration repressed apoptosis as evidenced by changing apoptosis-related protein levels, and promoted autophagy in TAC rats and angiotensin II (AngII)-induced H9C2 cells. Inhibition of autophagy by 3-methyladenine (3-MA) attenuated the beneficial effect of hyperoside against apoptosis in H9C2 cells. In summary, these data confirm that hyperoside effectively alleviates HF via suppressing apoptosis and inducing autophagy, which provides evidence that hyperoside may serve as a promising natural drug for treating HF.
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Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Cardiotónicos/farmacología , Insuficiencia Cardíaca/prevención & control , Miocardio/patología , Quercetina/análogos & derivados , Angiotensina II/farmacología , Animales , Células Cultivadas , Masculino , Quercetina/farmacología , Ratas , Ratas WistarRESUMEN
This study aimed to evaluate the effects of combined use of tetrahydrobiopterin (BH4) and nebivolol on cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs). Twelve-week-old male SHRs were treated with BH4, nebivolol, or a combination of both. Left ventricle function was evaluated, and reactive oxygen species (ROS) production (including dihydroethidium (DHE) and 3-nitrotyrosine (3-NT)), nitric oxide synthase (NOS) activity and the level of NO in myocardial tissue were determined. The expression levels of endothelial NOS (eNOS), phospholamban (PLN), sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ß3-adrenoceptor, cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) were assayed. Treatment with BH4, nebivolol, or both reversed the noninvasive indexes of diastolic function, including E/E' and E'/A', and the invasive indexes, including time constant of isovolumic left ventricle (LV) relaxation (tau), -dP/dtmin, -dP/dtmin/LV systolic pressure (LVSP), and LV end-diastolic pressure (LVEDP) in SHRs. mRNA and protein expression levels of eNOS dimer, phosphorylated PLN, SERCA2a, cGMP, and PKG in the myocardium of treated SHRs were significantly up-regulated compared with those in control rats (p < 0.05 or p < 0.01). The expression levels of 3-NT and DHE were reduced in all treated groups (p < 0.05 or p < 0.01). Notably, combined use of BH4 and nebivolol had better cardioprotective effects than monotherapies. BH4 or nebivolol has a protective effect on diastolic dysfunction in SHRs, and BH4 combined with nebivolol may exert a synergistically cardioprotective effect through activation of ß3-adrenoceptor and the NO/cGMP/PKG signaling pathway.
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Antihipertensivos/farmacología , Biopterinas/análogos & derivados , Cardiotónicos/farmacología , Diástole/efectos de los fármacos , Nebivolol/farmacología , Animales , Biopterinas/farmacología , GMP Cíclico/metabolismo , Sinergismo Farmacológico , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Masculino , Miocardio/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Especies Reactivas de Oxígeno/metabolismo , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
BACKGROUND: Brain metastases (BM) are a common consequence of lung cancer and surgery is effective; however, the factors affecting survival after surgery are unclear. The aim of this study was to identify the outcomes and prognoses of post-metastasectomy patients with BM from non-small cell lung cancer (NSCLC) at a single institution over a 15-year period. METHODS: NSCLC patients who had undergone BM surgery were retrospectively identified. Survival was analyzed using the Kaplan-Meier curve, and univariate and multivariate factors associated with survival were identified using the Cox proportional hazards model. RESULTS: The median overall survival was 9.8 months, 18 (14.8%) patients survived > 24 months, and 6 (4.9%) > 36 months. The one and two-year survival rates were 41% and 18.6%, respectively. Univariate analysis revealed that recursive partitioning analysis (RPA) classification, Karnofsky Performance Scale (KPS) scores, BM number, extracranial metastasis status, different lesion locations, resection extent, postoperative treatment, and salvage therapy after recurrence significantly influenced patient survival. The different treatment modalities for primary lesions also affected postoperative survival. KPS ≥ 70, RPA class I/II, and postoperative chemotherapy were independent factors that decreased the risk of death from BM. Interestingly, the initial onset of intracranial lesions could increase the risk of death from BM. CONCLUSION: A KPS score ≥ 70, RPA class I/II, and postoperative chemotherapy could benefit post-metastasectomy patients with BM from NSCLC. Conversely, the initial onset of intracranial lesions is an unfavorable factor that increases the risk of death. These findings support the use of personalized therapy for patients with BM from NSCLC.
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Adenocarcinoma del Pulmón/mortalidad , Neoplasias Encefálicas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/mortalidad , Neoplasias Pulmonares/mortalidad , Neumonectomía/mortalidad , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND AND OBJECTIVES: This study aimed to assess the changes of RA function in patients with obstructive sleep apnea syndrome (OSAS) using velocity vector imaging (VVI) and to evaluate the application of VVI technology. METHODS: According to the apnea-hypopnea index (AHI), 71 patients with OSAS were divided into three groups: mild, moderate, and severe. A total of 30 cases of healthy subjects were enrolled as the control group. Digital images of apex four-chamber views were acquired to measure the right atrium (RA) linear dimensions and volume parameters including RA longitudinal diameter (RAL), transverse diameter (RAT), RA maximum volume (Vmax), RA minimum volume (Vmin), right atrial volume before contraction (Vpre). Right atrial volume parameters were corrected by body surface area (VImax, VImin, VIpre). The total right atrial emptying fraction (RATEF), right atrial passive emptying fraction (RAPEF), right atrial active contraction emptying fraction (RAAEF) were calculated. The VVI data measuring right atrial global strain (RA-GLS), right atrial strain rate in ventricular systolic phase (RA-SRs), right atrial strain rate in ventricular early diastolic phase (RA-SRe), right atrial strain rate in ventricular late diastolic phase (RA-SRa). RESULTS: 1. RA linear dimensions and volume parameters in severe OSAS were higher than those of control group. RAPEF in severe group was lower than control group and mild OSAS group (t = 2.681, P = 0.021; t = 2.985, P = 0.011; respectively). RAAEF in OSAS moderate group was higher than that of control group (t = 3.006, P = 0.02), and without statistical difference (P > 0.05) in the severe OSAS group and the control group. 2. RA-GLS in moderate OSAS group was significantly lower than that of control group (t = 2.333, P = 0.040) and reduced more obvious in the severe OSAS group (vs control, t = 3.25, P = 0.008, vs mild; t = 3.011, P = 0.012; respectively). RA-SRe in moderate and severe OSAS groups were lower than control group (t = 2.466, P = 0.031; t = 3.547, P = 0.005; respectively). RA-SRs of OSAS in severe group was lower than that of control and mild groups (t = 3.665, P = 0.004; t = 3.204, P = 0.008; respectively). RA-SRa in severe OSAS group was lower than that of control group (t = 2.425, P = 0.034). 3. Multivariate regression analysis showed that RA-GLS and RA-SRe were independently correlated with AHI (t = - 2.738, P = 0.010; t = - 2.191, P = 0.036; respectively). CONCLUSION: RA function was impaired in patients with OSAS. On hemodynamics, the change of RA function performed increased of reserve function, reduced pipeline function and increased of contraction function. However, the strain and strain rate reduced in different degree. RA-GLS and RA-SRe decreased the earliest, which suggested that strain and strain rate were the parameters which can reflect myocardial function damage earliest. VVI can more earlier and accurately detect myocardial dysfunction of right atrium in patients with OSAS, which is expected to be a worthy technique for early clinical therapy in patients with OSAS.
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Función del Atrio Derecho/fisiología , Atrios Cardíacos/fisiopatología , Flujometría por Láser-Doppler/métodos , Apnea Obstructiva del Sueño/diagnóstico por imagen , Adulto , Estudios de Casos y Controles , Ecocardiografía/métodos , Femenino , Atrios Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polisomnografía/métodos , Valores de Referencia , Análisis de Regresión , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/fisiopatologíaRESUMEN
Objective A patent foramen ovale (PFO) is detected frequently by echocardiography. However, a thrombus trapped in a PFO is relatively rare. We herein describe a rare case of a 51-year-old patient with pulmonary embolism in which a large thrombus-in-transit through a PFO was found by echocardiography and disappeared after treatment. Methods A 51-year-old woman presented with a 1-week history of chest tightness, unspecified chest pain, and shortness of breath. Echocardiography revealed a large thrombus trapped in a PFO with increased pulmonary artery pressure, which is a very rare and critical condition. Results The patient was treated with thrombolysis and anticoagulation and discharged from the hospital with an uneventful recovery. Conclusion Our treatment of the present patient achieved a satisfactory result, but it may not be applicable to every patient. Echocardiography is a readily available and safe tool for demonstrating the size, location, and extent of a thrombus, and it plays an important role in the early diagnosis and treatment evaluation for patients with a thrombus trapped in a PFO with concurrent pulmonary embolism.
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Foramen Oval Permeable/complicaciones , Embolia Pulmonar/etiología , Trombosis/diagnóstico por imagen , Anticoagulantes/uso terapéutico , Angiografía por Tomografía Computarizada , Ecocardiografía Transesofágica , Femenino , Fibrinolíticos/uso terapéutico , Foramen Oval Permeable/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico por imagen , Terapia Trombolítica , Trombosis/complicaciones , Trombosis/tratamiento farmacológico , Tromboembolia Venosa/complicaciones , Tromboembolia Venosa/diagnóstico por imagen , Tromboembolia Venosa/tratamiento farmacológicoRESUMEN
Measles is caused by measles virus belonging to genus Morbillivirus of the family Paramyxoviridae. Vaccination has played a critical role in controlling measles infection worldwide. However, in the recent years, outbreaks of measles infection still occur in many developing countries. Here, we report an outbreak of measles among healthcare workers and among the 60 measles infected patients 50 were healthcare workers including doctors, nurses, staff, and medics. Fifty-one patients (85%) tested positive for IgM antibodies against the measles virus and 50 patients (83.3%) tested positive for measles virus RNA. Surprisingly, 73.3% of the infected individuals had been previously immunized against measles. Since there is no infection division in our hospital, the fever clinics are located in the Emergency Division. In addition, the fever and rash were not recognized as measles symptoms at the beginning of the outbreak. These factors result in delay in isolation and early confirmation of the suspected patients and eventually a measles outbreak in the hospital. Our report highlights the importance of following a two-dose measles vaccine program in people including the healthcare workers. In addition, vigilant attention should be paid to medical staff with clinical fever and rash symptoms to avoid a possible nosocomial transmission of measles infection.
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Prostate cancer is a type of cancer that occurs in the male prostate, a gland in the male reproductive system. Because prostate cancer cells may spread to other parts of the body and can influence human reproduction, understanding the mechanisms underlying this disease is critical for designing effective treatments. The identification of as many genes and chemicals related to prostate cancer as possible will enhance our understanding of this disease. In this study, we proposed a computational method to identify new candidate genes and chemicals based on currently known genes and chemicals related to prostate cancer by applying a shortest path approach in a hybrid network. The hybrid network was constructed according to information concerning chemical-chemical interactions, chemical-protein interactions, and protein-protein interactions. Many of the obtained genes and chemicals are associated with prostate cancer.
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Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Ontología de Genes/estadística & datos numéricos , Humanos , Masculino , Redes y Vías Metabólicas/genética , Modelos Genéticos , Modelos Estadísticos , Oncogenes , Mapas de Interacción de ProteínasRESUMEN
Discovering potential indications of novel or approved drugs is a key step in drug development. Previous computational approaches could be categorized into disease-centric and drug-centric based on the starting point of the issues or small-scaled application and large-scale application according to the diversity of the datasets. Here, a classifier has been constructed to predict the indications of a drug based on the assumption that interactive/associated drugs or drugs with similar structures are more likely to target the same diseases using a large drug indication dataset. To examine the classifier, it was conducted on a dataset with 1,573 drugs retrieved from Comprehensive Medicinal Chemistry database for five times, evaluated by 5-fold cross-validation, yielding five 1st order prediction accuracies that were all approximately 51.48%. Meanwhile, the model yielded an accuracy rate of 50.00% for the 1st order prediction by independent test on a dataset with 32 other drugs in which drug repositioning has been confirmed. Interestingly, some clinically repurposed drug indications that were not included in the datasets are successfully identified by our method. These results suggest that our method may become a useful tool to associate novel molecules with new indications or alternative indications with existing drugs.
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Algoritmos , Minería de Datos/métodos , Bases de Datos Farmacéuticas , Diseño de Fármacos , Interacciones Farmacológicas , Reposicionamiento de Medicamentos/métodos , Diccionarios Farmacéuticos como AsuntoRESUMEN
OBJECTIVE: To evaluate the non-inferiority of pramipexole extended-release (ER) versus immediate-release (IR) in Chinese patients with Parkinson's disease (PD) in a double-blind, randomized, parallel-group study. METHODS: Subjects were Chinese patients with idiopathic PD with diagnosis ≥ 2 years prior to trial, age ≥ 30 years old at diagnosis, and Modified Hoehn and Yahr score 2-4 during 'on'-time. Subjects received treatment with pramipexole ER (n=234) or IR (n=239). Non-inferiority was based on the primary endpoint, the change from baseline to end of maintenance (week 18) in the UPDRS (Parts II + III) total score. RESULTS: For the primary endpoint, the adjusted mean changes (standard error) of UPDRS Parts II + III at week 18 were -13.81 (0.655) and -13.05 (0.643) for ER and IR formulations, respectively, using ANCOVA adjusted for treatment and centre (fixed effect) and baseline (covariate). The adjusted mean between group difference was 0.8 for the 2-sided 95% CI (-1.047, 2.566). Since the lower limit of the 2-sided 95% CI (-1.047) for treatment difference was higher than the non-inferiority margin of -4, non-inferiority between pramipexole ER and IR was demonstrated. The incidence of adverse events (AEs) was 68.8% in the ER arm and 73.6% in the IR arm with few severe AEs (ER: 2.1%; IR: 3.8%). CONCLUSION: Based on the UPDRS II + III score, pramipexole ER was non-inferior to pramipexole IR. The safety profiles of pramipexole ER and IR were similar. These results were based on comparable mean daily doses and durations of treatment for both formulations.
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OBJECTIVE: To explore the effects of gender on treatment strategies for elderly patients with acute coronary syndrome (ACS). METHODS: March 2009 to March 2012, consecutive 619 aged ACS patients undergoing coronary angiography (CA) were screened at our hospital. There were 273 females and 346 males. Risk factors, ACS diagnosis, CA results, treatments and prognosis were compared between female and male groups. RESULTS: The risk factors of body mass index, stroke history, smoking history, hemoglobin (Hb), serum cholesterol (TC), low density lipoprotein (LDL-C) and blood uric acid (UA) levels were significantly lower in female group than those in male group (P < 0.05). The morbidity of diabetes in female group was obviously higher than that in male group (27.8% vs 18.5%, P < 0.05). The prevalence of myocardial infarction history, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) history in male group were significantly greater than that in female group (48.0% vs 39.9%, P < 0.05; 30.6% vs 22.3%, P < 0.05; 19.9% vs 10.3%, P < 0.01). The rate of combined multiple risk factors (3 or higher) increased significantly in female group (41.8% vs 29.8%, P < 0.05). The incidence of unstable angina pectoris (UAP) and non-ST segment elevation myocardial infarction (NSTEMI) in female group was greater, but there was no statistical significance. The rate of 3-vessel and calcification lesions in female group was significantly elevated compared with male group (36.26% vs 28.61%, P < 0.05). Regarding the choice of treatment strategy, conservative treatment was common in females, but there was no statistical significance between them. PCI, emergency PCI and selective CABG operation were performed more frequently in female group compared with male group (26.0% vs 14.2%, P < 0.01; 14.7% vs 6.6%, P < 0.01; 19.1% vs 7.7%, P < 0.01). The prognosis had no statistical significance between two groups. CONCLUSION: The treatment strategies have certain limitations for female ACS patients. And an more aggressive treatment should be offered to improve the prognosis.
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Síndrome Coronario Agudo/terapia , Factores Sexuales , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Pronóstico , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: This study investigates the influence of hepatic arterial occlusion (HAO) on blood perfusion of transplanted cancer in rat's liver, and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1) and explores the mechanisms involved in transcatheter arterial embolization (TAE)-induced metastasis of liver cancer preliminarily. METHODOLOGY: Walker 256 carcinosarcoma was transplanted into rat's liver to create the liver cancer model. Hepatic arterial ligation (HAL) was used to block the hepatic arterial blood supply and simulate TAE. Rats bearing tumor were divided into three groups: control, laparotomy control, and HAL groups. Blood perfusion of tumor was analyzed by a Hoechst 33342 labeling assay. The level of serum VEGF was assayed by ELISA; and the expression of VEGF and MMP-1 mRNA was detected by in situ hybridization. RESULTS: Two days after HAL, the number of Hoechst 33342 labeled cells which represent the blood perfusion of the tumor directly and hypoxia of tumor indirectly in the HAL group decreased significantly compared with that in the control group (329.1+/-29.3 vs. 383.6+/-19.2, P<0.01). The level of serum VEGF in the HAL group increased significantly compared with that of the control group (92.5+/-43.9 pg/mL vs. 54.9+/-19.3 pg/mL, P<0.05). The expression of VEGF and MMP-1 mRNA in the tumor tissue of the HAL group increased significantly compared with that of the control and the laparotomy control groups (P<0.05). The blood perfusion data of the tumor, represented by number of Hoechst 33342 labeled cells, showed an inverse correlation with the expression of VEGF mRNA in tumor tissue (P<0.05). While 6 days after HAL, the blood perfusion of tumor in HAL group decreased and the expression of VEGF and MMP-1 increased only slightly, not significantly, compared with that in the control group. CONCLUSIONS: In conclusion, blockage of hepatic arterial blood supply results in transient decreased blood perfusion and increased expression of metastasis-associated genes VEGF and MMP-1 of transplanted liver cancer in rats. Decreased blood perfusion and hypoxia may be the major reason for up-regulated expression of VEGF. Better understanding of the mechanisms involved with TAE-induced metastasis may lead to the enhancement of the long-term effects of TAE for liver cancer.
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Carcinoma 256 de Walker/metabolismo , Carcinoma 256 de Walker/terapia , Embolización Terapéutica/efectos adversos , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/terapia , Metaloproteinasa 1 de la Matriz/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Carcinoma 256 de Walker/irrigación sanguínea , Carcinoma 256 de Walker/secundario , Arteria Hepática/cirugía , Hibridación in Situ , Ligadura , Neoplasias Hepáticas Experimentales/irrigación sanguínea , Neoplasias Hepáticas Experimentales/patología , Masculino , Distribución Aleatoria , Ratas , Ratas Endogámicas , Regulación hacia ArribaRESUMEN
OBJECTIVE: We investigated the value of resting energy expenditure (REE) in healthy neonates and evaluated the impact factors on REE. METHODS: One hundred eighty healthy neonates (95 boys and 85 girls) with birth weights above 2500 g were measured by indirect calorimetry, and the effect of birth weight evaluated. Measured and predicted REEs were compared, and the effects of sex and delivery method on REE were examined in 154 newborn infants with birth weights of approximately 2500 to 4000 g. RESULTS: Birth weight had a significant effect on REE. There was a negative relation between REE and birth weight (r = -0.289). The REEs of newborn infants weighing more than 4000 g were statistically lower than those of infants weighing 2500 to 4000 g (44.5 +/- 5.9 versus 48.3 +/- 6.1 kcal x kg(-1) x d(-1), P = 0.01). The measured and predicted REEs of 154 newborn infants were 48.3 +/- 6.1 and 54.1 +/- 1.1 kcal x kg(-1) x d(-1), respectively. There was a significant difference between the two values. Sex and delivery methods had no effect on REE in healthy neonates. CONCLUSIONS: The value from the predicted equation is not suitable for neonatal energy supplementation in clinical practice. The normal REE value for healthy neonates with birth weights of 2500 to 4000 g is 48.3 +/- 6.1 kcal x kg(-1) x d(-1).
Asunto(s)
Metabolismo Energético/fisiología , Descanso/fisiología , Peso al Nacer/fisiología , Calorimetría Indirecta , Parto Obstétrico/estadística & datos numéricos , Ingestión de Energía/fisiología , Femenino , Humanos , Recién Nacido , Masculino , Valores de Referencia , Distribución por SexoRESUMEN
OBJECTIVE: To establish the value of the resting energy expenditure (REE) in healthy newborns and evaluate relative factors of REE. METHODS: One hundred and fifty-four healthy newborns (75 boys, 79 girls; birth-weight 2,500-3,999 g) were enrolled in this study. The Apgar score at the 5th minute was equal to or more than 8; the postnatal age was equal to or more than 5 days. The newborns had no apparent defect. The mothers had no history of metabolic and endocrine diseases. REE was measured by Deltatrac II in child canopy mode for 30-45 minutes during asleep or quiet awake status. RESULTS: The average REE was (201.8 +/- 25.4) kJ/(kg.d), which was significantly lower than the predicted REE by Schofield formula[(226.1 +/- 4.8) kJ/(kg.d), P = 0.000], the predicted REE was 12.04% higher than the measured REE. There were no differences in sex and ways of delivery. The newborns whose birth-weight was between 2,500-2,999 g were measured in two modes: baby and child mode, and the REE values were significantly higher (122.6 +/- 25.0) kJ/(kg.d) and (208.8 +/- 26.4) kJ/(kg.d), respectively (P = 0.000). CONCLUSIONS: The prediction formula might be improper for calculating the REE in newborn infants. The indirect calorimetry was the better way to know the actual REE of newborns. The authors recommended that in child mode the measurement of REE in newborns would be the indirect calorimetry, and the REE in healthy newborns was (201.8 +/- 25.4) kJ/(kg.d).