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AIMS: A few studies have reported the effect and safety of pulsed field ablation (PFA) catheters for ablating atrial fibrillation (AF), which were mainly based on basket-shaped or flower-shaped designs. However, the clinical application of a circular-shaped multi-electrode catheter with magnetic sensors is very limited. To study the efficacy and safety of a PFA system in patients with paroxysmal AF using a circular-shaped multi-electrode catheter equipped with magnetic sensors for pulmonary vein isolation (PVI). METHODS AND RESULTS: A novel proprietary bipolar PFA system was used for PVI, which utilized a circular-shaped multi-electrode catheter with magnetic sensors and allowed for three-dimensional model reconstruction, mapping, and ablation in one map. To evaluate the efficacy, efficiency, and safety of this PFA system, a prospective, multi-centre, single-armed, pre-market clinical study was performed. From July 2021 to December 2022, 151 patients with paroxysmal AF were included and underwent PVI. The study examined procedure time, immediate success rate, procedural success rate at 12 months, and relevant complications. In all 151 patients, all the pulmonary veins were acutely isolated using the studied system. Pulsed field ablation delivery was 78.4 ± 41.8 times and 31.3 ± 16.7â ms per patient. Skin-to-skin procedure time was 74.2 ± 29.8â min, and fluoroscopy time was 13.1 ± 7.6â min. The initial 11 (7.2%) cases underwent procedures with deep sedation anaesthesia, and the following cases underwent local anaesthesia. In the initial 11 cases, 4 cases (36.4%) presented transient vagal responses, and the rest were all successfully preventatively treated with atropine injection and rapid fluid infusion. No severe complications were found during or after the procedure. During follow-up, 3 cases experienced atrial flutter, and 11 cases had AF recurrence. The estimated 12-month Kaplan-Meier of freedom from arrhythmia was 88.4%. CONCLUSION: The PFA system, comprised of a circular PFA catheter with magnetic sensors, could rapidly achieve PVI under three-dimensional guidance and demonstrated excellent safety with comparable effects.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Veias Pulmonares/cirurgia , Resultado do Tratamento , Estudos Prospectivos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Catéteres , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Fenômenos Magnéticos , RecidivaRESUMO
The prognosis of patients with nonvalvular atrial fibrillation (NVAF) with a low CHA2DS2-VASc score (0-1) following a stroke is not well studied. In this investigation, stroke risk factors and prognostic markers in low-risk NVAF patients who are nonetheless at risk for stroke were examined.From January 2012 to January 2022, we retrospectively assessed atrial fibrillation (AF) patients at Xiamen University's Zhongshan Hospital for ischemic stroke. Along with a control group of patients with CHA2DS2-VASc scores of 0-1 who weren't suffering from a stroke, patients with CHA2DS2-VASc scores of 0-1 at the time of stroke were included in the study. Using multivariate logistic regression, independent risk factors were identified. To assess the cumulative occurrences of in-hospital mortality in patients with NVAF-related stroke, the Kaplan-Meier method was used.The study included 156 out of 3.237 inpatients with AF-related stroke who had CHA2DS2-VASc ratings of 0-1. Left atrial diameter (LAD) (odds ratio [OR]: 1.858, 95% confidence interval (CI) 1.136-3.036, P = 0.013), D-dimer (OR: 2.569, 95% CI 1.274-5.179, P = 0.008), and NT-proBNP (OR: 4.558, 95% CI 2.060-10.087, P = 0.000) were found to be independent risk factors for stroke in NVAF patients with a low CHA2DS2-VASc score. During hospitalization, nine patients with NVAF-related stroke died. In patients with NVAF-related stroke, NT-proBNP (hazard ratio: 3.504, 95% CI 1.079-11.379, P = 0.037) was an indicator of mortality risk.Patients with NVAF and CHA2DS2-VASc scores of 0-1 had independent risk factors for stroke in the form of LAD, D-dimer, and NT-proBNP. Notably, in low-risk NVAF patients with stroke, NT-proBNP was discovered to be a potent predictor of in-hospital death.
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Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Prognóstico , Estudos Retrospectivos , Mortalidade Hospitalar , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Medição de RiscoRESUMO
Tertiary lymphoid structures (TLS) are lymphoid aggregates in tumor tissues and their potential significance in clinical applications has not been fully elucidated in gastric cancer. We evaluated TLS and tumor-infiltrating immune cells using H&E and immunohistochemistry staining in the recruited patients with gastric cancer. The prognostic value of TLS was evaluated by Kaplan-Meier analysis and further validated using gene expression profiling. The alterations in gene mutation, copy number variance, and DNA methylation across the TLS signature subtypes were analyzed based on the Cancer Genome Atlas cohort. High TLS density was associated with improved overall survival and disease-free survival. A combination of TLS density and TNM stage obtained higher prognostic accuracy than the TNM stage alone. Tumors with high TLS density showed significantly higher infiltration of CD3+, CD8+, and CD20+ cells but lower infiltration of CD68+ cells. Transcriptomics analysis demonstrated that high TLS signature status was positively associated with the activation of inflammation-related and immune-related pathways. Multi-omics data showed a distinct landscape of somatic mutations, copy number variants, and DNA methylation across TLS signature subtypes. Our results indicated that TLS might link with enhanced immune responses, and represent an independent and beneficial predictor of resected gastric cancer. Multi-omics analysis further revealed key tumor-associated molecular alterations across TLS signature subtypes, which might help explore the potential mechanism of the interaction between TLS formation and cancer cells.
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Neoplasias Gástricas , Estruturas Linfoides Terciárias , Intervalo Livre de Doença , Humanos , Linfócitos do Interstício Tumoral , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Estruturas Linfoides Terciárias/genética , Estruturas Linfoides Terciárias/patologia , Microambiente TumoralRESUMO
Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease of the pancreas, with clinical management determined by the severity of the disease. Diagnosis, severity prediction, and prognosis assessment of AP typically involve the use of imaging technologies, such as computed tomography, magnetic resonance imaging, and ultrasound, and scoring systems, including Ranson, Acute Physiology and Chronic Health Evaluation II, and Bedside Index for Severity in AP scores. Computed tomography is considered the gold standard imaging modality for AP due to its high sensitivity and specificity, while magnetic resonance imaging and ultrasound can provide additional information on biliary obstruction and vascular complications. Scoring systems utilize clinical and laboratory parameters to classify AP patients into mild, moderate, or severe categories, guiding treatment decisions, such as intensive care unit admission, early enteral feeding, and antibiotic use. Despite the central role of imaging technologies and scoring systems in AP management, these methods have limitations in terms of accuracy, reproducibility, practicality and economics. Recent advancements of artificial intelligence (AI) provide new opportunities to enhance their performance by analyzing vast amounts of clinical and imaging data. AI algorithms can analyze large amounts of clinical and imaging data, identify scoring system patterns, and predict the clinical course of disease. AI-based models have shown promising results in predicting the severity and mortality of AP, but further validation and standardization are required before widespread clinical application. In addition, understanding the correlation between these three technologies will aid in developing new methods that can accurately, sensitively, and specifically be used in the diagnosis, severity prediction, and prognosis assessment of AP through complementary advantages.
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Pancreatite , Humanos , Pancreatite/diagnóstico por imagem , Pancreatite/terapia , Índice de Gravidade de Doença , Inteligência Artificial , Doença Aguda , Reprodutibilidade dos Testes , Prognóstico , Estudos Retrospectivos , Valor Preditivo dos TestesRESUMO
Mammal caspases have been demonstrated to possess important functions in apoptosis and immune signaling, but there is less knowledge available on abalone caspases. In the present study, a molluscan caspase gene, abCaspase, was cloned for the first time from the variously colored abalone (Haliotis diversicolor) and its full-length cDNA sequence was 2427 bp, with a 1008 bp of open reading frame encoding a protein of 336 aa. The molecular mass of the deduced protein was approximately 36.97 kDa with an estimated pI of 5.28. The predicted amino acid sequence of abCaspase contained two domains of p20 and p10 which were conserved in the caspase family, including the cysteine active site pentapeptide "QSCRG" and the histidine active site signature "HTVYDCVVVIFLTHG". Homology analysis showed that abCaspase shared high similarity with apoptotic caspases and it was grouped together with vertebrate caspase-8s and caspase-10s using phylogenetic analysis, suggesting that abCaspase belonged to a typical apoptotic caspase and might possess the characteristic of human caspase-8 and -10. The mRNA transcripts of abCaspase were widely distributed in various tissues of H. diversicolor. Expression of the abCaspase gene was significantly induced in the tissues tested, especially in the hemocytes, gill and mantle with bacterial challenge. This study suggested that abCaspase may be an initiator caspase associated with the induction of apoptosis which is potentially involved in the immune defense of H. diversicolor.
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Fenômenos Fisiológicos Bacterianos , Caspases/genética , Caspases/metabolismo , Gastrópodes/enzimologia , Gastrópodes/microbiologia , Regulação Enzimológica da Expressão Gênica , Sequência de Aminoácidos , Animais , Sequência de Bases , Caspases/química , Clonagem Molecular , Feminino , Gastrópodes/classificação , Gastrópodes/genética , Perfilação da Expressão Gênica , Dados de Sequência Molecular , Filogenia , RNA Mensageiro/metabolismo , Alinhamento de SequênciaRESUMO
BACKGROUND: The platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have been found to be associated with prognosis in several solid tumours. However, the prognostic roles of PLR and NLR in gastrointestinal stromal tumours (GISTs) remain controversial. The aim of this meta-analysis was to assess the prognostic roles of PLR and NLR in GISTs. METHODS: We searched MEDLINE, EMBASE and the Cochrane Library for relevant articles. A systematic review was performed to calculate pooled hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS) by fixed-effects/random-effects models. RESULTS: Fourteen studies containing 3,151 subjects were finally enrolled in this meta-analysis. Eight studies including 2,560 patients investigated the prognostic effect of PLR, and thirteen studies with 2,751 subjects explored the prognostic effect of NLR. Both elevated PLR (HR: 1.29, 95% CI: 1.10-1.52, P=0.002) and NLR (HR: 1.37, 95% CI: 1.15-1.63, P=0.0005) were significantly associated with decreased DFS. The pooled HR for PLR was not significantly different from that for NLR. High PLR and NLR correlated with increased tumour sizes, more advanced tumour stages and mitotic index (>5/50 HPF). In addition, elevated PLR was related to adjuvant tyrosine kinase inhibitor (TKI) therapy. CONCLUSIONS: Elevated preoperative PLR and NLR are associated with poor outcomes in patients with GISTs.
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BACKGROUND: Accumulating evidence indicates that tumour-infiltrating lymphocytes (TILs) are the primary determinant of survival outcomes in various tumours. Thus, we sought to investigate the TIL distribution and density in gastrointestinal stromal tumours (GISTs) and to develop an immune infiltration (II)-based signature to predict prognosis. METHODS: The expression of 8 immune features in the tumour centre (TC) and tumour margin (TM) and PD-L1 in 435 GIST patients was investigated by immunohistochemistry. Then, a 4-feature-based II-GIST signature integrating the CD3+ TC, CD3+ TM, CD8+ TM and CD45RO+ TM parameters was developed using a LASSO Cox regression model in the training cohort and was validated in two separate validation cohorts. FINDINGS: High CD3+ TC, CD3+ TM, CD8+ TC, CD8+ TM, CD45RO+ TM, NKp46+ TM and CD20+ TM correlated with improved survival. Patients with high II-GIST scores have better RFS and OS outcomes than those with low II-GIST scores. Multivariable analyses demonstrated that the II-GIST signature is an independent prognostic factor. The receiver operating characteristic (ROC) curve demonstrated that the prognostic accuracy of the II-GIST signature is superior to that of the NIH risk criteria. Further analysis showed that moderate- and high-risk GIST patients with high II-GIST scores could gain survival benefits from adjuvant imatinib therapy. INTERPRETATION: The novel II-GIST signature accurately predicted the survival outcomes of GIST patients. In addition, the II-GIST signature was a useful predictor of survival benefit from imatinib therapy amongst moderate- and high-risk patients with GIST. FUNDING: This project was supported by National Natural Science Foundation of China (81702325), Natural Science Foundation of Guangdong Province (2017A030310565), and 3&3 Project of the First Affiliated Hospital of Sun Yat-sen University.
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Tumores do Estroma Gastrointestinal/genética , Proteínas de Neoplasias/genética , Prognóstico , Transcriptoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Feminino , Tumores do Estroma Gastrointestinal/epidemiologia , Tumores do Estroma Gastrointestinal/patologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos ProporcionaisRESUMO
Abalones are considered to be the most precious delicacy from the sea, and become very important commercial seafood in aquaculture worldwide. Variously colored abalone (Haliotis diversicolor Reeve, 1846) has been widely cultured on the southeast coast for more than twenty years. However, abalone culture frequently suffers from bacterial infection and mass mortality of reared abalones causes serious economic losses. Unfortunately, knowledge of the defense mechanism in this animal is still lacking. In this study, using suppression subtractive hybridization (SSH) technology, a forward SSH library was constructed from haemocytes of H. diversicolor, with the content of 1.37x10(6) pfu and the recombinant rate of 98.18%. After the recombinant plasmids were sequenced, partial cDNA of macrophage expressed protein (MEP) was recognized based on BLAST searches in NCBI, with the size of 1,551 bp, and continuously encoding 517 amino acids. Semi-quantitative PCR and quantitative real-time PCR results showed that MEP cDNA was distinctly up-regulated in haemocytes of the bacterial-challenged group compared to the unchallenged group. The gene information obtained from this library will provide new insights into the immune mechanism of H. diversicolor and facilitate future study of target genes involved in the response to invading microorganisms.
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Gastrópodes/microbiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA Complementar/genética , Macrófagos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Proteínas/química , Proteínas/genética , Proteínas/metabolismo , Alinhamento de SequênciaRESUMO
The current study investigated the electrophysiological characteristics and radiofrequency ablation in patients with localized reentry within the left atrial appendage during repeated ablation for recurrent atrial fibrillation (AF). A total of 76 patients (21 paroxysmal, 55 persistent) undergoing repeated catheter ablation for recurrent AF were enrolled in this study. Local reentry tachycardia within the left atrial appendage (LAA) was identified through combining activation and entrainment mapping. Left atriography was performed prior to radiofrequency ablation to identify the focus in the LAA. Three patients (1 paroxysmal, 2 persistent) with sustained atrial tachycardias (ATs) were identified during repeated ablation in this cohort. Combined activation and entrainment mapping were applied to localize the reentry. Postpacing interval-tachycardia cycle length differences were <30 msec at the possible site of reentry in varying segments with macro-reentry. This difference was only determined at the base of LAA for local reentry within the LAA. All 3 patients were free of atrial arrhythmias without any complications at the 6-month follow-up following the ablation in the LAA. Combining activation and entrainment mapping were necessary in approaching ATs within the LAA. Performing entrainments in opposite segments of possible loops were valuable in precluding macro-reentry. Focal ablation was safe and effective in this cohort. Therefore localized reentry within the LAA was not uncommon during repeat AF ablation. The present study may thus provide valuable information for clinicians to manage this type of arrhythmia.
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OBJECTIVE: To assess the efficacy, safety, procedural success and long-term clinical outcome in patients underwent percutaneous carotid stenting with distal device. METHODS: Percutaneous carotid stents with distal device were implanted to 58 patients with 59 significant (> 75%) carotid artery stenosis (49 men, mean age 68 years) between January 2000 to December 2005. Forty-five out of 58 patients were symptomatic, 35 had coronary artery diseases and 10 had previous strokes. RESULTS: Sixty one carotid stenting were implanted to 59 lesions in 58 patients. Stents with filter devices were successfully implanted in 57 out of 58 (98%) patients. Angioplasty success rate was 100%. Aspirin (300 mg/d) and Clopidogrel (75 mg x 2/d) were administered 3 days prior operation and clopidogrel was discontinued 30 days post stenting and aspirin was continued at dose of 100 mg/d. The percentage of stenotic carotid artery reduced from 85.3% to 6.2% after stenting and the diameter increased from 1.3 +/- 0.9 mm to 5.2 +/- 1.1 mm. Two minor strokes (3.4%) occurred during operation and at 14 days post stenting. All patients were discharged from the hospital after an average of 2.5 days hospitalization. At 14 +/- 2 months follow up, all patients survived and there were 2 asymptomatic restenosis (50% and 70% and the latter underwent successful balloon angioplasty), 2 myocardial infarctions (1 non-Q wave and 1 Q wave myocardial infarction, all underwent successful emergent PCI) and 2 minor strokes occurred at 6 and 8 months post stenting. CONCLUSION: Carotid stenting with distal device appears to be safe and effective in treating patients with carotid artery stenosis.
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Implante de Prótese Vascular/métodos , Estenose das Carótidas/terapia , Acidente Vascular Cerebral/prevenção & controle , Idoso , Angioplastia com Balão , Implante de Prótese Vascular/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , StentsRESUMO
N25, a novel histone deacetylase inhibitor, was created through structural modification of suberoylanilide hydroxamic acid. To evaluate the anti-tumor activity of N25 and clarify its molecular mechanism of inducing autophagy in glioma cells, we investigated its in vitro anti-proliferative effect and in vivo anticancer effect. Moreover, we detected whether N25 induces autophagy in glioma cells by transmission electron microscope and analyzed the protein expression level of HDAC3, Tip60, LC3 in glioma samples by western blot. We additionally analyzed the protein expression level of HDAC3, Tip60, ULK1 (Atg1), and Beclin-1 (Atg6) after treatment with N25 in glioma cells. Our results showed that the anti-tumor activity of N25 in glioma cells is slightly stronger than SAHA both in vitro and in vivo. We found that N25 induced autophagy, and HDAC3 was significantly elevated and Tip60 and LC3 significantly decreased in glioma samples compared with normal brain tissues. Nevertheless, N25 inhibited HDAC3 and up-regulated the protein expression of Tip60, ULK1 (Atg1), and Beclin-1 (Atg6) after treatment of glioma cells with N25. In conclusion, these data suggest that N25 has striking anti-tumor activity in part due to inhibition of HDAC3. Additionally, N25 may induce autophagy through inhibiting HDAC3.
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N1- (2, 5-dimethoxyphenyl)-N(8)-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of RNHCO(CH2)6CONHOH (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and LD50. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations (0.5-30 µM). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose- dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice (LD50: 240.840 mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.
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Anilidas/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Acetilação , Anilidas/farmacocinética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/genética , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Histona Desacetilases , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacocinética , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Simulação de Acoplamento Molecular , Proteínas Repressoras/antagonistas & inibidores , Proteína Supressora de Tumor p53/biossíntese , VorinostatRESUMO
Our previous study reports that short-term exposure to sublethal concentrations of benzo[a]pyrene (BaP) induces immunomodulation in the gastropod abalone, Haliotis diversicolor. In the present study, it was further observed that long-term chronic exposure to sublethal concentrations of BaP modulated the immunocompetence of abalones in terms of the change in activity of the antioxidant and immune associated parameters tested. In addition, the effect of tributyltin (TBT), another important genotoxicant in the aquatic environment, was investigated. Exposure of abalones to sublethal concentrations of TBT and BaP for 21 days resulted in significant decrease of total hemocyte count, phagocytosis, membrane stability and lysozyme activity. Conversely induction of extra and intra cellular superoxide generation, nitric oxide, nitric oxide synthase and myeloperoxidase activity was present when the abalones were exposed to TBT and BaP. Most of the immune associated parameters tested showed clear time dependent response to both toxicants. Within 14 days after the 21 day exposure to BaP, recovery was observed as evidenced by most of the parameters returning to their normal level. However, no recovery was observed within 14 days after the 21 day exposure to TBT as evidenced by continued elevation of intra cellular superoxide and nitrite production and decrease in THC, membrane stability and lysozyme activity. This suggested a prolonged TBT-induced impact on the immune reaction and possibly more damage than that caused by BaP. Overall the results suggest that chronic exposure to sublethal concentrations of TBT or BaP causes modulations in the immunocompetence of abalones with most of the immune associated parameters tested being stimulated, and this might be harmful to the host.
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Benzo(a)pireno/toxicidade , Gastrópodes/fisiologia , Hemócitos/efeitos dos fármacos , Imunomodulação/efeitos dos fármacos , Compostos de Trialquitina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Contagem de Células , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Relação Dose-Resposta a Droga , Hemócitos/imunologia , Hemócitos/metabolismo , Imunomodulação/fisiologia , Muramidase/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Espécies Reativas de Oxigênio/metabolismo , Fatores de TempoRESUMO
OBJECTIVE: To evaluate the value of cardiac troponin I (CTnI) measurement in predicting anthracycline-induced cardiotoxicity in patients with breast cancer. METHODS: This study was conducted among 186 breast cancer patients receiving anthracycline-based chemotherapy. Serum cTnI concentrations before and after each cycle of the chemotherapy and the left ventricular ejection fraction (LVEF) before and at the 2nd, 4th and 6th months of the treatment were recorded. According to serum cTnI concentration, the patients were divided into CTnI+ group (with serum CTnI concentration of no less than 0.1 ng/ml, n=60) and CTnI- (<0.1 ng/ml) group (n=126). RESULTS: No patients in this series experienced cardiac heart failure (CHF). The number of patients with a LVEF reduction by over 10% from the baseline was 16 (26.7%) in CTnI+ group, as compared to 7 (5.6%) in CTnI- group, showing a significant difference between the two groups (P<0.01). CONCLUSION: CTnI can be a useful marker for early prediction of anthracycline-induced cardiotoxicity in patients with breast cancer.
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Antraciclinas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxinas/efeitos adversos , Miocárdio/metabolismo , Troponina I/sangue , Adulto , Idoso , Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Biomarcadores/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Adulto JovemRESUMO
It has been reported that environmental pollutants in the aquatic ecosystem could weaken immune competence of organisms. The purpose of the present study was to investigate the effects of benzo(a)pyrene [B(a)P] on immunomodulation in marine gastropods and to see if these effects are caused by or related to the generation of reactive oxygen species. In our present study, the marine gastropod Haliotis diversicolor was exposed to sublethal concentrations (0.01, 0.02, 0.04 and 0.08 mg L(-1)) of B(a)P for 7d under laboratory conditions and the alterations of hematological parameters like haemocyte count, haemocyte viability, protein content and immune components like phenoloxidase, phagocytosis and superoxide anion generation were measured. In addition, the changes in lysozyme activity, antibacterial activity due to the effect of B(a)P on abalone were analysed. B(a)P was found to decrease significantly the total number of circulating haemocytes. Intracellular superoxide anion generation and phenoloxidase significantly increased on exposure to B(a)P, whereas phagocytic activity was decreased significantly at higher concentration. Significant alterations were found in the uptake of neutral red and the observed alterations of hematological parameters and immune components tested indicated the generation of immunotoxicological effects on abalone due to B(a)P exposure. The results demonstrate a possible relationship between B(a)P and the immunological parameters of abalone studied.
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Benzo(a)pireno/toxicidade , Poluentes Ambientais/toxicidade , Gastrópodes/imunologia , Animais , Benzo(a)pireno/farmacologia , Exposição Ambiental , Poluentes Ambientais/farmacologia , Gastrópodes/efeitos dos fármacos , Hemócitos/efeitos dos fármacos , Monofenol Mono-Oxigenase/metabolismo , Fagocitose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismoRESUMO
Glutathione S-transferases (GSTs) are a multigene family of xenobiotic metabolizing phase II detoxification enzymes which take part in many pathological and physiological processes, and which can potentially be used as indicators and biomarkers for cancer diagnoses and organic or inorganic pollutant exposure. In this study, a full-length cDNA of a sigma class GST (abGSTsigma) (GenBank accession number EF546619) from variously colored abalone (Haliotis diversicolor) was identified. It was 1328bp containing an open reading frame of 624bp, encoding 208 amino acid residues with a predicted protein molecular weight of 23.67kDa and an estimated pI of 5.67. Sequence analysis showed that the predicted protein sequence of abGSTsigma cDNA contained the conserved domain of the GST_N_Sigma_like (PSSM: cd03039) and GST_C_Sigma_like (PSSM: cd03192). Alignment analysis demonstrated that the abGSTsigma of H. diversicolor was in a branch position with other known class sigma GSTs from different organisms. The abGSTsigma mRNA was distributed in multiple tissues tested and was highly demonstrated in the gill and mantle of normal abalones. In bacteria-challenged abalone, the abGSTsigma gene was significantly expressed in the hemocytes, gill, mantle and digestive gland and the total GSTs enzyme and SOD were also induced in the four tissues. The increased activities of SOD and GSTs can result in the elimination of reactive oxygen species (ROS) indicating antioxidant activities involved. The preliminary work revealed that the sigma class glutathione S-transferase gene abGSTsigma, a phase II detoxification enzyme, had a positive response to bacterial challenge, and that will lead to an insightful study on elucidating the interactions between immune responses and biotransformation exerted by abGSTsigma.
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Gastrópodes/imunologia , Gastrópodes/microbiologia , Glutationa Transferase/biossíntese , Sequência de Aminoácidos , Animais , Bactérias , Sequência de Bases , Clonagem Molecular , Feminino , Gastrópodes/enzimologia , Glutationa Transferase/genética , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência , Superóxido Dismutase/biossínteseRESUMO
PURPOSE: The study was designed to determine whether relationships exist among knee muscle spasticity, isometric knee muscle strength, knee muscle balance, gross motor function, and walking efficiency in children with spastic cerebral palsy and to evaluate the relative contributions of impairment measures to functional outcome measures. METHODS: Twenty-seven children with spastic diplegic cerebral palsy participated. Knee muscle strength and spasticity were measured by a hand-held dynamometer and the Ashworth Scale, respectively. Functional abilities were assessed by the Gross Motor Function Measure and by calculating the energy expenditure index from data collected during two three-minute walk tests (comfortable and fast speeds). RESULTS: Significant relationships were found between impairments and functional abilities (r = 0.42-0.85, p < 0.05). Isometric hamstring strength and quadriceps spasticity explained 81.5% of total Gross Motor Function Measure score variance. Quadriceps spasticity explained 56.7% of energy expenditure index variance during comfortable walking. CONCLUSION: Hamstring strength and quadriceps spasticity explain much of the variance in gross motor function and comfortable walking efficiency.