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1.
Anticancer Res ; 39(8): 4285-4289, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366519

RESUMO

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a cancer with poor prognosis due to therapy resistance, locoregional recurrences, and distant metastases. There is on increased interest in profiling the androgen receptor (AR) in cancer biology. The aim of this study was to compare AR and Ki-67 levels in the neoplastic epithelium and stroma between non-metastatic and metastatic stages of OSCC. PATIENTS AND METHODS: Tissue specimens of 101 non-metastatic and 95 metastatic OSCC patients were analyzed by immunohistochemistry. RESULTS: More than 20% of AR-positive cytoplasmic staining of OSCC epithelium was significantly associated with nuclear AR levels in the epithelium and increased AR levels in the stroma. In metastatic OSCC patients, Ki-67 was significantly higher than in non-metastatic OSCC patients. CONCLUSION: More than 20% of AR-positive cytoplasmic staining in neoplastic OSSC epithelium is a significant predictor of OSCC progression risk.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Antígeno Ki-67/genética , Neoplasias Bucais/genética , Receptores Androgênicos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Fatores de Risco
2.
Anticancer Res ; 39(8): 4325-4328, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366524

RESUMO

BACKGROUND/AIM: The significance of second transurethral resection (TUR), and identification of predictive factors for residual cancer remain unrevealed. This study aimed to find residual cancer and up-staging rates, as well as predictive factors for residual cancer, in patients who undergo second TUR for non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patients who underwent second TURs for NMIBC between 2015 and 2017, were included in the study and their clinicopathological characteristics were analyzed for predictors of residual cancer. RESULTS: Among 143 Japanese patients whose tumors were initially diagnosed as high-risk NMIBC, residual cancers detected at second TURs were, Tis: n=22 (15.4%), Ta: n=15 (10.5%) and T1: n=29 (20.3%). No patients showed up-staging from NMIBC to MIBC. The presence of carcinoma-in situ at initial TUR was an independent risk factor for any residual cancer (Tis, Ta and T1), non-flat residual cancer (Ta and T1), and flat residual cancer (Tis). CONCLUSION: The presence of carcinoma-in situ is suggested to be an independent predictor of residual cancer. This may help guide decisions to perform second TUR.


Assuntos
Carcinoma in Situ/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasia Residual/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Cistectomia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasia Residual/diagnóstico , Neoplasia Residual/patologia , Fatores de Risco , Resultado do Tratamento , Uretra/patologia , Uretra/cirurgia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Procedimentos Cirúrgicos Urológicos
3.
J Cancer Res Clin Oncol ; 145(9): 2261-2271, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31367836

RESUMO

PURPOSE: To investigate the role of sonic hedgehog (Shh) signaling and epithelial-mesenchymal transition (EMT) in bladder cancer progression and invasion. METHODS: We cultured three bladder cancer cell lines, muscle-invasive T24 and 5637, and non-muscle-invasive KK47, in the presence of a recombinant-Shh (r-Shh) protein or cyclopamine, a Shh signaling inhibitor, to investigate proliferation and expression of EMT markers. Wound-healing assays and transwell assay were performed to evaluate cell invasion and migration. Mice were then inoculated with bladder cancer cells and treated with cyclopamine. Mouse tumor samples were stained for Shh signaling and EMT markers. RESULTS: R-Shh protein enhanced cell proliferation, whereas cyclopamine significantly suppressed cell proliferation, especially in invasive cancer (5637 and T24) (p < 0.05). R-Shh protein promoted EMT, suppressed E-cadherin and enhanced N-cadherin and vimentin and Gli1, an Shh downstream molecule, while cyclopamine blocked EMT, especially in 5637 and T24. Cyclopamine also inhibited cell invasion and migration in vitro. In the animal study, intraperitoneal injection of cyclopamine significantly suppressed tumor growth in 5637 and T24 in mice (p = 0.01 and p = 0.004, respectively) and slightly suppressing KK47 tumor growth (p = 0.298). Significant cyclopamine-induced suppression of Gli1 in 5637 and T24 mouse tumors (both p = 0.03) was seen, suggesting that muscle-invasive bladder cancer may be more dependent on Shh signaling than non-muscle-invasive bladder cancer. CONCLUSIONS: Shh signaling and EMT were especially enhanced in muscle-invasive bladder cancer progression and invasion, and suppressed by the inhibition of Shh signaling.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Proteínas Hedgehog/fisiologia , Neoplasias Musculares/secundário , Neoplasias da Bexiga Urinária/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Proteínas Hedgehog/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Musculares/metabolismo , Invasividade Neoplásica , Transdução de Sinais/fisiologia , Neoplasias da Bexiga Urinária/metabolismo
4.
J Cancer Res Clin Oncol ; 145(9): 2251-2259, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31385026

RESUMO

PURPOSE: Fibroblast Growth Factor Receptor 4 (FGFR4) was proposed to hold prognostic significance in high-grade serous ovarian carcinoma (HGSOC). However, information on this deriving from large, representative patient panels is still missing, though such data would be indispensable to validate suitability of FGFR4 as prognostic marker or even pharmacological target. METHODS: 1063 ovarian cancer cases were included in this study. Immunohistochemistry (IHC) was performed using two different anti-FGFR4 specific antibodies (HPA027273, sc-124) on an automated staining system. IHC data of both FGFR4 antibodies were available from 995 cases. FGFR4 immunostaining was correlated to prognostic factors including survival using uni- and multivariate proportional hazard models. RESULTS: FGFR4 was positively associated with advanced FIGO stage, high grade and presence of residual disease. When progression free (PFS) of FGFR4 negative vs. positive patients was compared, patients scored as FGFR4 positive had significantly shortened PFS as compared to those that stained negative. All associations of FGFR4 and shortened PFS were lost during multivariate testing. No significant associations were found in terms of OS. CONCLUSIONS: We were not able to confirm FGFR4 as an independent negative prognosticator as described before. However, FGFR4 was highly prevalent in those cases harboring residual disease after debulking surgery. Since especially patients that could only be debulked sub-optimally may benefit from targeted adjuvant treatment, tyrosine kinase inhibitors targeting FGFRs might turn out to be an interesting future treatment option.


Assuntos
Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/cirurgia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasia Residual , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Análise Serial de Tecidos , Resultado do Tratamento
5.
Adv Exp Med Biol ; 1121: 57-59, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31392652

RESUMO

Hypertension, obesity and metabolic syndromes are leading risk factors for the development of chronic kidney disease (CKD). Considering the high prevalence of hypertension and obesity in children and adolescents and it's risk of progression to cardiovascular disease, CKD should be considered a serious long-term health issue in children with metabolic syndrome. Prevention of CKD requires a professional teamwork consisting of primary care physicians, nephrologists, nutritionist, pharmacist, and social work to identify and manage children at risk of developing CKD in order to provide a highly valuable management strategies. This review focuses on the principles underlying the importance of a team approach for CKD prevention.


Assuntos
Falência Renal Crônica , Progressão da Doença , Humanos , Hipertensão , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/prevenção & controle , Obesidade Pediátrica , Prevalência , Insuficiência Renal Crônica , Fatores de Risco
6.
Wiad Lek ; 72(7): 1265-1268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31398153

RESUMO

OBJECTIVE: Introduction: Chronic obstructive pulmonary disease (COPD) with hypertension occupy a leading position in morbidity and mortality in the world. The question of studying a single pathological way of their development, the search for diagnostic markers and therapeutic targets in this comorbid pathology remains relevant. The aim of the study was to study cardiopulmonary parameters in patients with chronic obstructive pulmonary disease with concomitant hypertension, depending on the level of vasoactive intestinal peptide (VIP). PATIENTS AND METHODS: Materials and methods: 99 patients with COPD GOLD 2 were examined, 54 of whom had concomitant hypertension II stage, in which the dependence of lipid metabolism, spirometry and hemodynamic parameters, depending on the level of VIP in blood serum. RESULTS: Results and conclusions: It was established that the smallest values of VIP and the greatest changes in cardiopulmonary parameters, lipid metabolism were found in the cohort of persons with concomitant hypertension. There was a significant decrease in spirometry values and an increase in hemodynamic parameters, respectively, a decrease in VIP levels in patients with COPD in combination with hypertension, which may indicate its role in the formation of these pathologies due to a decrease in its protective function, both in relation to apoptosis of alveolar cells and in relation to progression atherosclerosis and high blood pressure. It was also noted that in patients with the lowest VIP serum levels, a more rapid formation of COPD was observed. The data obtained make it possible to consider VIP as a diagnostic marker and a potential therapeutic target for the comorbid pathology examined.


Assuntos
Hipertensão , Doença Pulmonar Obstrutiva Crônica , Progressão da Doença , Humanos , Peptídeo Intestinal Vasoativo
7.
Wiad Lek ; 72(7): 1310-1314, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31398161

RESUMO

OBJECTIVE: Introduction: Nowadays, the number of chronic carriers of hepatitis C virus (HCV) is considered to be from around 150 to 500 million by the most of infectionists and epidemiologists. Being one of the most dangerous diseases of the liver of viral etiology hepatitis C increases annually. The aim: To determine the level of general immunological reactivity of patients with chronic hepatitis C. PATIENTS AND METHODS: Materials and methods: This study does not contradict the principles of the Helsinki Declaration (2013), the European Convention on Human Rights and Biomedicine. A clinical and laboratory examination of 31 patients with chronic hepatitis C was conducted during 2014-2015 on the basis of the infectious department of Chernivtsi Regional Clinical. RESULTS: Results: The initial condition of clinical and laboratory examination of patients with chronic hepatitis C is normally considered to be a clinical examination of each patient and first of all hemograms where absolute and relative number of major populations of immunocompetent cells, platelets, erythrocytes and erythrocyte sedimentation rates (ESR) were determined. CONCLUSION: Conclusions: General immunological reactivity in patients with chronic hepatitis C increased to 30,07% and the factors activation and mechanisms of nonspecific anti-infection protection decreased that create a condition for prolonged persistence of hepatitis C virus and the progression of a chronic infectious process in patients' organism.


Assuntos
Hepatite Crônica , Progressão da Doença , Hepacivirus , Humanos
8.
JAMA ; 322(6): 546-556, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31408135

RESUMO

Importance: While air pollutants at historical levels have been associated with cardiovascular and respiratory diseases, it is not known whether exposure to contemporary air pollutant concentrations is associated with progression of emphysema. Objective: To assess the longitudinal association of ambient ozone (O3), fine particulate matter (PM2.5), oxides of nitrogen (NOx), and black carbon exposure with change in percent emphysema assessed via computed tomographic (CT) imaging and lung function. Design, Setting, and Participants: This cohort study included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) Air and Lung Studies conducted in 6 metropolitan regions of the United States, which included 6814 adults aged 45 to 84 years recruited between July 2000 and August 2002, and an additional 257 participants recruited from February 2005 to May 2007, with follow-up through November 2018. Exposures: Residence-specific air pollutant concentrations (O3, PM2.5, NOx, and black carbon) were estimated by validated spatiotemporal models incorporating cohort-specific monitoring, determined from 1999 through the end of follow-up. Main Outcomes and Measures: Percent emphysema, defined as the percent of lung pixels less than -950 Hounsfield units, was assessed up to 5 times per participant via cardiac CT scan (2000-2007) and equivalent regions on lung CT scans (2010-2018). Spirometry was performed up to 3 times per participant (2004-2018). Results: Among 7071 study participants (mean [range] age at recruitment, 60 [45-84] years; 3330 [47.1%] were men), 5780 were assigned outdoor residential air pollution concentrations in the year of their baseline examination and during the follow-up period and had at least 1 follow-up CT scan, and 2772 had at least 1 follow-up spirometric assessment, over a median of 10 years. Median percent emphysema was 3% at baseline and increased a mean of 0.58 percentage points per 10 years. Mean ambient concentrations of PM2.5 and NOx, but not O3, decreased substantially during follow-up. Ambient concentrations of O3, PM2.5, NOx, and black carbon at study baseline were significantly associated with greater increases in percent emphysema per 10 years (O3: 0.13 per 3 parts per billion [95% CI, 0.03-0.24]; PM2.5: 0.11 per 2 µg/m3 [95% CI, 0.03-0.19]; NOx: 0.06 per 10 parts per billion [95% CI, 0.01-0.12]; black carbon: 0.10 per 0.2 µg/m3 [95% CI, 0.01-0.18]). Ambient O3 and NOx concentrations, but not PM2.5 concentrations, during follow-up were also significantly associated with greater increases in percent emphysema. Ambient O3 concentrations, but not other pollutants, at baseline and during follow-up were significantly associated with a greater decline in forced expiratory volume in 1 second per 10 years (baseline: 13.41 mL per 3 parts per billion [95% CI, 0.7-26.1]; follow-up: 18.15 mL per 3 parts per billion [95% CI, 1.59-34.71]). Conclusions and Relevance: In this cohort study conducted between 2000 and 2018 in 6 US metropolitan regions, long-term exposure to ambient air pollutants was significantly associated with increasing emphysema assessed quantitatively using CT imaging and lung function.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Pulmão/fisiologia , Enfisema Pulmonar , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Carbono/efeitos adversos , Carbono/análise , Estudos de Coortes , Progressão da Doença , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Óxidos de Nitrogênio/efeitos adversos , Óxidos de Nitrogênio/análise , Ozônio/efeitos adversos , Ozônio/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Enfisema Pulmonar/epidemiologia , Enfisema Pulmonar/fisiopatologia , Testes de Função Respiratória , Tomografia Computadorizada por Raios X , Estados Unidos/epidemiologia
9.
Braz J Med Biol Res ; 52(8): e8341, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365693

RESUMO

MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.


Assuntos
Carcinoma/patologia , Histona Desacetilases/metabolismo , MicroRNAs/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/patologia , Apoptose , Carcinogênese/genética , Carcinoma/genética , Carcinoma/metabolismo , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
10.
Vasc Health Risk Manag ; 15: 221-227, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410012

RESUMO

Background: High sensitivity C-reactive protein (hsCRP) predicts myocardial dysfunction after acute coronary syndromes. We aimed to study the association of hsCRP estimation at first acute myocardial infarction (AMI) with myocardial dysfunction and heart failure. Methods: This research was carried out at the Department of Physiology and Department of Emergency Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia. In this prospective study, 227 patients were studied. hsCRP levels were estimated when patients came to the emergency department at AMI, 7 days post AMI, and at 12 weeks of follow up after AMI. The outcome was change in myocardial functions, especially heart failure, 12 months after the attack. Results: Based on a cutoff mean value of hsCRP levels at admission (10.05±12.68 mg/L), patients were grouped into high and low C-reactive protein (CRP.) The ejection fraction was significantly lower at follow up in the high CRP group (37.29±12.97) compared to the low CRP group (43.85±11.77, p<0.0198). hsCRP had significant inverse correlation with left ventricular ejection fraction (r=-0.283, p<0.01). About 38.1% patients showed heart failure, with 23.6% in the high CRP group and 14.5% in the low CRP group (OR 2.4, p=0.028). Receiver operating characteristic curve analysis showed that CRP levels at AMI had a specificity of 79% and sensitivity of 83% to predict heart failure. Conclusion: A high hsCRP level measured at first AMI predicts myocardial dysfunction and heart failure. It is suggested that hsCRP plays an important role in the development of heart failure after myocardial infarction.


Assuntos
Proteína C-Reativa/análise , Insuficiência Cardíaca/etiologia , Infarto do Miocárdio/sangue , Adulto , Idoso , Biomarcadores/sangue , Progressão da Doença , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Admissão do Paciente , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Arábia Saudita , Volume Sistólico , Fatores de Tempo , Função Ventricular Esquerda
11.
Stud Health Technol Inform ; 264: 168-172, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437907

RESUMO

Early detection of Alzheimer's disease (AD) has become increasingly important. Healthy monitoring technology focusing on behavioral changes is a promising approach in this vein. Among such technologies, handwriting features measured by digital tablet devices have attracted attention as potential indicators for detecting AD and mild cognitive impairment (MCI). However, previous studies have mainly investigated features in single tasks, and it remains unclear whether combining the features of multiple tasks could improve the performance of detecting AD and MCI. In this study, we investigated features in five representative tasks used in neuropsychological tests collected from 71 seniors including some diagnosed with MCI and AD. We found that our three-class classification model improved diagnosis accuracy by up to 11.3% by combining features of multiple tasks, for a final accuracy of 74.6%. We also suggested that drawing behaviors during multiple tasks might be useful for estimating disease progression simply by utilizing the labels of disease groups.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico , Progressão da Doença , Diagnóstico Precoce , Escrita Manual , Humanos , Testes Neuropsicológicos
12.
Stud Health Technol Inform ; 264: 920-924, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438058

RESUMO

Understanding the progression of chronic diseases, such as chronic obstructive pulmonary disease (COPD), is important to inform early diagnosis, personalized care, and health system management. Data from clinical and administrative systems have the potential to advance this understanding, but traditional methods for modelling disease progression are not well-suited to analyzing data collected at irregular intervals, such as when a patient interacts with a healthcare system. We applied a continuous-time hidden Markov model to irregularly-spaced healthcare utilization events and patient-level characteristics in order to analyze the progression through discrete states of 76,888 patients with COPD. A 4-state model allowed classification of patients into interpretable states of disease progression and generated insights about the role of comorbidities, such as cardiovascular diseases, in accelerating severe trajectories. These results can improve the understanding of the evolution of COPD and point to new hypotheses about chronic disease management and comorbidity.


Assuntos
Doenças Cardiovasculares , Doença Pulmonar Obstrutiva Crônica , Doença Crônica , Comorbidade , Progressão da Doença , Humanos
13.
Nihon Yakurigaku Zasshi ; 154(2): 61-65, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31406044

RESUMO

Non-alcoholic steatohepatitis (NASH), one of the most common chronic liver diseases (CLD), is getting the most important cause of cirrhosis and hepatocellular carcinoma. Iron is an essential micronutrient for organisms. Once excess iron is accumulated in vital organs, dysfunctions of these organs can occur via the generation of reactive oxygen species. Hepatic iron overload is often seen in CLD patients. In NASH patients, iron accumulation in the liver is positively correlated with histological severity. Thus iron overload can contribute to progression of nonalcoholic fatty liver disease (NAFLD) to NASH. In a rat model of NASH, feeding of high-fat and high-iron diet increases hepatic inflammation with increased hepatic cytokine expression compared with feeding of high-fat diet only. In this model, iron is intensely accumulated in Kupffer cells/macrophages within the lesion, raising the possibility that iron-laden Kupffer cells/macrophages can play a key role in the enhancement of hepatic inflammation in NASH condition. On the other hand, in a rat model of liver cirrhosis, dietary iron overload clearly abrogates the development and progression of liver cirrhosis induced by repeated administration of thioacetamide (TAA). These findings suggest that iron overload can promote or suppress chronic liver diseases depending on the tissue microenvironment. Here we review and introduce the recent findings on the pathological roles of iron overload in the development and progression of NAFLD/NASH.


Assuntos
Sobrecarga de Ferro/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Progressão da Doença , Humanos , Ferro , Ratos
14.
Methodist Debakey Cardiovasc J ; 15(2): 145-148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384378

RESUMO

Steady advances in the diagnosis and management of congenital heart disease over the last few decades has resulted in a growing population of adults with congenital heart disease (ACHD). Consequently, there has been a parallel increase in the number of ACHD patients plagued with end-stage heart failure. Even so, the transplantation rate for these patients has remained low, at about 3% of all adult heart transplants. This review discusses the scope of transplantation for ACHD, including indications and contraindications, specific challenges and nuances, and post-transplant outcomes.


Assuntos
Cardiopatias Congênitas/cirurgia , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Adulto , Fatores Etários , Tomada de Decisão Clínica , Progressão da Doença , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/fisiopatologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Humanos , Seleção de Pacientes , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Listas de Espera
17.
Results Probl Cell Differ ; 67: 413-440, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31435806

RESUMO

Centrosome amplification is a feature of multiple tumour types and has been postulated to contribute to both tumour initiation and tumour progression. This chapter focuses on the mechanisms by which an increase in centrosome number might lead to an increase or decrease in tumour progression and the role of proteins that regulate centrosome number in driving tumorigenesis.


Assuntos
Carcinogênese , Centrossomo/metabolismo , Neoplasias/patologia , Progressão da Doença , Humanos
18.
Ophthalmologe ; 116(8): 797-810, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31372724

RESUMO

Corneal nerves are responsible for the reception of pain, temperature, and touch and are an important component of homeostasis of the ocular surface. When the corneal innervation is reduced, degenerative changes can be manifested as neurotrophic keratopathy (NK). In a stage-dependent course, corneal epithelial alterations and ulcers may occur, even leading to perforation. The cause of NK is predominantly damage to the trigeminal nerve, which can be caused by infections (especially herpesviruses), metabolic diseases (such as diabetes mellitus) and by surgical procedures. The diagnosis of NK requires a detailed medical and ocular history, assessment of corneal sensitivity, and a complete ocular examination. The treatment of NK is oriented to the clinical severity and aims to restore the integrity of the ocular surface in order to prevent further disease progression.


Assuntos
Distrofias Hereditárias da Córnea , Ceratite , Doenças do Nervo Trigêmeo , Córnea , Progressão da Doença , Humanos
19.
Medicine (Baltimore) ; 98(34): e16837, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441856

RESUMO

INTRODUCTION: Alkaptonuria (AKU) is a rare disease caused by deficiency of homogentisate 1,2-dioxygenase which results in deposition of homogentisic acid (HGA). Ochronotic arthritis, the deposition of excess oxidized HGA in the connective tissues, causes pigmentation and degeneration of the joint tissues ultimately resulting in chronic inflammation and osteoarthritis. The ochronotic arthritis has similar clinical features with osteoarthritis. There is currently no specific treatment for AKU and management is usually symptomatic. In severe cases, total joint arthroplasty is the major treatment approaches. It is rarely reported in China. PATIENT CONCERNS: Here we reported a case of a patient with bilateral knee pain for more than 1 year. He complained of a 20-year history of chronic, nonspecific low back pain and stiffness. His urine was black since he was a child. Six years after the knee surgery, his Achilles tendon ruptured. DIAGNOSIS: Specific radiographic and magnetic resonance imaging manifestations were observed. Darkly pigmented full-thickness cartilage and subchondral bone were found during the operation. Histological investigation also manifested dark stains in meniscus and synovial tissues. Black-denatured tendon tissue was also found during the operation. The patient was diagnosed as AKU. INTERVENTIONS: Total knee arthroplasty and Achilles tendon repair were operated separately after the disease was diagnosed. OUTCOMES: The patient recovered very well after the second surgery. He returned to full activities, described no knee pain, and presented to the clinic walking without any aid. Physical examination revealed 0 to 20 of plantar flexion and 0 to 15 of dorsiflexion of the ankle. CONCLUSIONS: Ochronosis is a very rare disease in Asia. This paper supplies new information for study of this disease. The mechanism is still unknown right now. Further studies will be necessary.


Assuntos
Tendão do Calcâneo/lesões , Alcaptonúria/complicações , Ocronose/complicações , Tendão do Calcâneo/cirurgia , Alcaptonúria/urina , Artroplastia do Joelho , Cartilagem Articular/patologia , Cartilagem Articular/cirurgia , Progressão da Doença , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Articulação do Joelho/cirurgia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ruptura Espontânea/etiologia , Ruptura Espontânea/cirurgia
20.
N Engl J Med ; 381(8): 716-726, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31433919

RESUMO

BACKGROUND: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 µg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).


Assuntos
Doenças Cardiovasculares/mortalidade , Insuficiência Cardíaca/tratamento farmacológico , Relaxina/uso terapêutico , Vasodilatadores/uso terapêutico , Doença Aguda , Idoso , Pressão Sanguínea/efeitos dos fármacos , Progressão da Doença , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Incidência , Infusões Intravenosas , Masculino , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Relaxina/efeitos adversos , Relaxina/farmacologia , Falha de Tratamento , Vasodilatadores/efeitos adversos
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