RESUMO
BACKGROUND: Systemic effects of long-term narrowband ultraviolet B (NB-UVB) phototherapy have not been well studied in vitiligo patients. An 11-year nationwide population-based retrospective cohort study was conducted using the Korean National Health Insurance claims database (2007-2017). OBJECTIVES: To investigate the effects of long-term NB-UVB phototherapy on the risk of cardiovascular and cerebrovascular events in vitiligo patients. METHODS: This study included vitiligo patients with ≥100 phototherapy sessions (phototherapy group, n = 3229) and <3 phototherapy sessions (no phototherapy group, n = 9687), in which covariables with age, sex, insurance type and comorbidities such as diabetes, hypertension and hyperlipidemia were matched by 1 : 3 propensity score matching. The outcomes of interest were cardiovascular (ischaemic heart disease and myocardial infarction) and cerebrovascular events (cerebrovascular infraction and haemorrhage). Cox proportional hazards models were used to assess the associations between NB-UVB phototherapy and each event. RESULTS: The risk of cardiovascular or cerebrovascular events was significantly decreased in the phototherapy group compared with the no phototherapy group [hazard ratio (HR) 0.637, 95% confidence interval (CI) 0.523-0.776]. Subgroup analysis revealed that the risk of cardiovascular (HR: 0.682, 95% CI: 0.495-0.940) and cerebrovascular events (HR: 0.601, 95% CI: 0.470-0.769) were significantly lower in the phototherapy group than the no phototherapy group, respectively. CONCLUSIONS: Our findings suggest that long-term NB-UVB phototherapy could decrease the risk of cardiovascular and cerebrovascular events in patients with vitiligo.
Assuntos
Terapia Ultravioleta , Vitiligo , Humanos , Fototerapia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Terapia Ultravioleta/efeitos adversos , Vitiligo/radioterapiaRESUMO
The Notch1 signaling pathway plays a crucial role in determining cell fate, including cell growth and differentiation. In this study, we demonstrated that the antagonistic action of RTK (receptor tyrosine kinase) signaling pathway on the Notch1 signaling pathway is mediated via Ras-PI3K-Akt1. The PI3K-Akt1 signaling pathway was shown to inhibit Notch1 signaling via phosphorylation of RBP-Jk. We observed not only reduced association between Notch1 and RBP-Jk, but also suppression of the Notch1 transcriptional activity. Our results demonstrated that Akt1 functions as a natural inhibitor of the Notch1 signaling pathway via phosphorylation of RBP-Jk.
Assuntos
Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais , Animais , Camundongos , Células NIH 3T3 , Fosforilação , Transcrição GênicaRESUMO
Objective Noninvasive liver fibrosis evaluation is an important issue in chronic hepatitis B infection, and may be assessed using transient elastography (Fibroscan) or with blood markers. We compared the value of Fibroscan with that of a panel of routine serum markers. Materials and methods We recruited 278 chronic hepatitis B patients who underwent Fibroscan and HBV DNA testing. Fibroscan assessments were made, and blood taken for the measurement of the gamma-glutamyl transferase (GGT) to platelet ratio (GPR), platelet count, aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), international normalised ratio (INR), total cholesterol, trigylcerides, bilirubin, mean platelet volume (MPV), AST to platelet ratio index (APRI) and neutrophil to lymphocyte ratio. Results A fibrosis index based on four factors (FIB-4) and GPR were higher and platelets were lower in mild liver fibrosis than in non-liver fibrosis. GGT, AST, ALT, INR, MPV, APRI, FIB-4, GPR, and NLR were higher, and platelet and cholesterol were lower in severe liver fibrosis than in mild liver fibrosis. Elevated GPR (Odds ratio 95% CI 9.1 [1.66-50.0] p = 0.011) and FIB-4 (2.3 [1.2-4.2], p = 0.01) were associated with greater risk of liver fibrosis. The areas under the curve (AUC) were for GPR 0.84 at a cut-off of 0.299 and for FIB-4 0.82 at cut-off 1.571. Conclusions FIB-4 and GPR may be useful blood markers for evaluating the severity of liver fibrosis in chronic hepatitis B patients. Further prospective study is required to validate these noninvasive blood markers in a clinical practice.
Assuntos
Plaquetas/patologia , Hepatite B Crônica/sangue , Cirrose Hepática/sangue , gama-Glutamiltransferase/sangue , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biópsia , Colesterol/sangue , Feminino , Vírus da Hepatite B/isolamento & purificação , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Coeficiente Internacional Normatizado , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Contagem de Plaquetas , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests. METHODS: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins. RESULTS: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06). CONCLUSIONS: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.
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Anafilaxia/epidemiologia , Anafilaxia/etiologia , Antibacterianos/efeitos adversos , Cefalosporinas/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anafilaxia/diagnóstico , Anafilaxia/mortalidade , Antibacterianos/administração & dosagem , Antibacterianos/química , Cefalosporinas/administração & dosagem , Cefalosporinas/química , Hipersensibilidade a Drogas/diagnóstico , Feminino , Humanos , Incidência , Testes Intradérmicos/métodos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Estudos RetrospectivosRESUMO
To the best of our knowledge, this is the first report to discuss the possible mechanisms of an iatrogenic fracture during operation on an original mandibular fracture in a patient with osteogenesis imperfecta.
Assuntos
Fixação Interna de Fraturas/métodos , Fraturas Mandibulares/etiologia , Fraturas Mandibulares/cirurgia , Osteogênese Imperfeita/cirurgia , Adulto , Humanos , Doença Iatrogênica , Masculino , Má Oclusão Classe III de Angle/diagnóstico por imagem , Fraturas Mandibulares/diagnóstico por imagem , Osteogênese Imperfeita/diagnóstico por imagem , Radiografia PanorâmicaRESUMO
BACKGROUND: Rifaximin might decrease the risk of portal hypertension-related complications by controlling small intestinal bacterial overgrowth. AIM: To evaluate whether rifaximin was associated with the risk of death and cirrhotic complications. METHODS: We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non-HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding. RESULTS: In the non-HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio [aHR], 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile-associated diarrhoea was not different between the groups (aHR, 0.028; P = .338). CONCLUSIONS: In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy.
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Anti-Infecciosos/uso terapêutico , Encefalopatia Hepática/tratamento farmacológico , Rifamicinas/uso terapêutico , Idoso , Infecções Bacterianas/prevenção & controle , Carcinoma Hepatocelular/tratamento farmacológico , Varizes Esofágicas e Gástricas/prevenção & controle , Feminino , Encefalopatia Hepática/complicações , Humanos , Lactulose/uso terapêutico , Cirrose Hepática/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Peritonite/prevenção & controle , Recidiva , Estudos Retrospectivos , Rifaximina , Prevenção SecundáriaRESUMO
The purpose of this study was to determine a practical and cost-effective treatment method for fixing mandibular angle fractures using miniplates. Patients were divided into three groups for comparison, based on the intraoperative plates and maxillomandibular fixation (MMF) used: group A, single miniplate fixation with MMF (n=37); group B, double miniplate fixation with MMF (n=59); group C, double miniplate fixation without MMF (n=38). Details of the characteristics of the fractures and the treatments and outcomes were collected retrospectively and analyzed statistically. This study was based on 134 cases of isolated mandibular angle fracture. Of the surgically treated patients, 78.4% (n=105) were completely free of complications. A detailed complication correlation matrix is given in the text. Besides screw loosening and malocclusion, no statistically significant difference was observed between the groups. The results of this study suggest that treatment with single miniplate fixation and MMF has a low incidence rate of complications, and this method of treatment is considered to be simple.
Assuntos
Placas Ósseas , Técnicas de Fixação da Arcada Osseodentária , Fraturas Mandibulares/cirurgia , Adolescente , Adulto , Criança , Análise Custo-Benefício , Feminino , Fixação Interna de Fraturas , Humanos , Masculino , Mandíbula , Fraturas Mandibulares/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto JovemRESUMO
The role of poly (ADP-ribose) polymerase 1 (PARP1) in cancer has been extensively studied in the context of DNA repair, leading to clinical trials of PARP1 inhibitors in cancers defective in homologous recombination. However, the DNA repair-independent roles of PARP1 in carcinogenesis and metastasis, particularly in lung cancer metastasis, remain largely uncharacterized. Here, we report that PARP1 promotes lung adenocarcinoma relapse to the brain and bones by regulating several steps of the metastatic process in a DNA repair-independent manner. We find that PARP1 expression is associated with overall and distant metastasis-free survival in lung adenocarcinoma patients. Consistent with this, genetic knockdown and pharmacological inhibition of PARP1 significantly attenuated the metastatic potential of lung adenocarcinoma cells. Further investigation revealed that PARP1 potentiates lung adenocarcinoma metastasis by promoting invasion, anoikis resistance, extravasation and self-renewal of lung adenocarcinoma cells and also by modifying the brain microenvironment. Finally, we identified S100A4 and CLDN7 as novel transcriptional targets and clinically relevant effectors of PARP1. Collectively, our study not only revealed previously unknown functions of PARP1 in lung adenocarcinoma metastasis but also delineated the molecular mechanisms underlying the pro-metastatic function of PARP1. Furthermore, these findings provide a foundation for the potential use of PARP1 inhibitors as a new treatment option for lung adenocarcinoma patients with elevated PARP1 expression.
Assuntos
Adenocarcinoma/genética , Claudinas/genética , Proteínas de Ligação a DNA/genética , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Carcinogênese/genética , Linhagem Celular Tumoral , Reparo do DNA/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Recombinação Homóloga , Humanos , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Proteína A4 de Ligação a Cálcio da Família S100/genéticaRESUMO
BACKGROUND: The performance of Xpert(®) MTB/RIF assay, an automated nucleic acid amplification test (NAAT) that was developed for the detection of tuberculosis (TB), has been evaluated in various clinical settings. However, few studies have compared Xpert with other NAATs, especially its performance using lower respiratory tract specimens (LRTS). OBJECTIVE: To compare the practical diagnostic performance of the Xpert assay with that of the AdvanSure™ TB/NTM RT-PCR kit in the detection of pulmonary TB (PTB), using LRTS obtained through bronchoscopy. RESULTS: Of 249 patients included, 105 had culture-confirmed PTB. Using culture as reference, the overall sensitivity of Xpert and AdvanSure was respectively 92.4% and 83.8%. When acid-fast bacilli smear results were taken into consideration, the sensitivity of Xpert for smear-positive and smear-negative LRTS was respectively 100% and 88.9%, while that of the AdvanSure was 100% and 76.4%. Xpert showed better results than AdvanSure in terms of sensitivity in smear-negative LRTS (P = 0.012), but no difference in smear-positive LRTS. CONCLUSIONS: Xpert may be advantageous in the detection of PTB using LRTS, particularly in low microbiological burden settings.
Assuntos
Técnicas de Diagnóstico Molecular/normas , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Adulto , Idoso , Broncoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , República da Coreia , Estudos RetrospectivosRESUMO
AIM: To investigate the relationship between mammographic breast density (MGD) and background parenchymal enhancement (BPE) at breast MRI and histopathological features of invasive breast cancers. MATERIALS AND METHODS: A total of 178 women with unilateral invasive breast cancer who preoperatively underwent mammography and breast MRI were included in the study. Two radiologists rated MGD and BPE according to BI-RADS criteria in consensus. The relationship between MGD and BPE was investigated, and compared with histopathological features of invasive breast cancers according to the level of MGD and BPE. RESULTS: At MRI, there is no significant difference in the distribution of MGD and BPE of the contralateral breast in women with invasive breast cancer according to menopausal status (p=0.226, 0.384). Women with high MGD (>50% glandular) were more likely to have oestrogen-receptor (ER)-positive breast cancer (p=0.045) and progesterone receptor (PR)-positive breast cancer (p=0.020). With regard to BPE, PR positivity correlated with moderate or marked BPE with borderline significance (p=0.054). Multivariate logistic regression analyses revealed that women with high MGD were less likely to have triple-negative (i.e., a cancer that is ER negative, PR negative, and human epidermal growth factor receptor type 2 [HER2] negative) breast cancer compared with ER (+)/HER2 (-) cancer (OR=0.231, 95% CI: 0.070, 0.760; p=0.016). No association between the histological tumour characteristics and BPE was observed. CONCLUSION: In women with invasive breast cancer, high MGD is associated with ER positivity of the invasive breast cancer. However, at MRI, BPE of the contralateral breast seems to be independent of tumour characteristics.
Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Fatores Etários , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Fatores de RiscoRESUMO
Because there are no available molecular markers for pulmonary mucormycosis (PM), which has low culture sensitivity, early diagnosis and treatment rely heavily on imaging modes such as computed tomography (CT). However, there are limited data comparing CT findings for PM with those for invasive pulmonary aspergillosis (IPA). Adult patients who met the modified criteria for proven and probable PM (over an 11-year period) and IPA (over a 6-year period, owing to the availability of the galactomannan assay) according to the modified European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions were retrospectively enrolled. IPA cases were selected at a 1 : 4 (PM/IPA) ratio. Thoracic CT scans were reviewed by two experienced radiologists blinded to the patients' demographics and clinical outcomes. A total of 24 patients with PM, including 20 (83%) with proven PM and four (17%) with probable PM, and 96 patients with IPA, including 12 (13%) with proven IPA and 84 (87%) with probable IPA, were eventually analysed. The reverse halo sign was more common in patients with PM (54%) than in those with IPA (6%, p < 0.001), whereas some airway-invasive features, such as clusters of centrilobular nodules, peribronchial consolidations, and bronchial wall thickening, were more common in patients with IPA (IPA 52% vs. PM 29%, p 0.04; IPA 49% vs. PM 21%, p 0.01; IPA 34% vs. PM 4%, p 0.003, respectively). The reverse halo sign was more common, and airway-invasive features were less common, in patients with PM than in those with IPA. These findings may help physicians to initiate Zygomycetes-active antifungal treatment earlier.
Assuntos
Aspergilose Pulmonar Invasiva/diagnóstico , Pneumopatias Fúngicas/diagnóstico , Pulmão/patologia , Mucormicose/diagnóstico , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico por imagem , Aspergilose Pulmonar Invasiva/patologia , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/patologia , Masculino , Pessoa de Meia-Idade , Mucormicose/diagnóstico por imagem , Mucormicose/patologia , Radiografia Torácica , Estudos Retrospectivos , Adulto JovemRESUMO
Conventional methods for studying paracrine signaling in vitro may not be sensitive to short-range effects resulting from signal dilution or decay. We employ a microfabricated culture substrate to maintain two cell populations in microscale proximity. Individual populations can be quickly retrieved for cell-specific readouts by standard high-throughput assays. We show that this platform is sensitive to short-range interactions that are not detectable by common methods such as conditioned media transfer or porous cell culture inserts, as revealed by gene expression changes in a tumor-stromal crosstalk model. In addition, we are able to detect population-specific gene expression changes that would have been masked in mixed co-cultures. We thus demonstrate a tool for investigating an important class of intercellular communication that may be overlooked in conventional biological studies.
Assuntos
Técnicas de Cocultura/métodos , Perfilação da Expressão Gênica/métodos , Comunicação Parácrina/fisiologia , Linhagem Celular Tumoral , Técnicas de Cocultura/instrumentação , Fibroblastos , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Telomerase/genéticaRESUMO
A 49-year-old white man with blood group AB, D+ was found to have alloanti-Jk(a) and -K when he developed a delayed hemolytic transfusion reaction before allogeneic hematopoietic stem cell transplant (HSCT). Given that his stem cell donor was blood group O, D+, Jk(a+), K-, rituximab was added to his conditioning regimen of fludarabine and melphalan to prevent hemolysis of engrafting Jk(a+) donor red blood cells. The patient proceeded to receive a peripheral blood stem cell transplant from a matched unrelated donor with no adverse events. To our knowledge, this is the first case of successful management of major non-ABO incompatibility caused by anti-Jk(a) in a patient receiving an allogeneic HSCT reported in the literature.
Assuntos
Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos , Transplante de Células-Tronco Hematopoéticas , Reações Antígeno-Anticorpo , Bilirrubina/sangue , Hemoglobinas/análise , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To evaluate the rate of human papillomavirus (HPV) infection in pregnant women and their neonates, and the risk factors associated with vertical transmission of HPV infection from mothers to neonates. STUDY DESIGN: Cervical HPV testing was undertaken in pregnant women over 36 weeks of gestation, and mouth secretions and oral mucosa of neonates were tested for HPV immediately after delivery. HPV-positive neonates were rechecked 2 months postpartum to identify the persistence of HPV infection. In HPV-positive mothers, the placenta, cord blood and maternal peripheral blood were also analysed for HPV to confirm whether transplacental HPV infection occurred. RESULTS: HPV was detected in 72 of 469 pregnant women (15.4%) and in 15 neonates (3.2%). Maternal HPV positivity was associated with primiparity and abnormal cervical cytology. The rate of vertical transmission was 20.8%, and all HPV-positive neonates were born from HPV-positive mothers. Vertical transmission was associated with vaginal delivery and multiple HPV types in the mother. Neonates with HPV showed a tendency for higher maternal total HPV copy number than neonates without HPV, but this difference was not significant (p=0.081). No cases of HPV infection were found in the infants at 2 months postpartum, and no HPV was detected in placenta, cord blood or maternal blood. CONCLUSIONS: Vertical transmission of HPV is associated with vaginal delivery and multiple HPV types in the mother; however, neonatal HPV infection through vertical transmission is thought to be a transient.
Assuntos
Transmissão Vertical de Doenças Infecciosas , Infecções por Papillomavirus/transmissão , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Infecções por Papillomavirus/epidemiologia , Gravidez , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco , Carga ViralRESUMO
BACKGROUND/OBJECTIVES: Gestational diabetes mellitus (GDM) risk factors are well established for Caucasians, but not for Asians. We hypothesized that nutrient intakes, plasma adipokines and/or gestational hormones might be linked to GDM development among pregnant Korean women. This study sought to identify new risk factors for GDM and adverse pregnancy outcomes according to body weight at prepregnancy. SUBJECTS/METHODS: All subjects were pregnant women visiting the Cheil General Hospital and Women's Healthcare Center between June 2006 and March 2009. Non-GDM (n=531) and GDM (n=215) participants were divided into normal-weight and overweight groups according to prepregnancy body mass index (BMI) above or below 23 kg/m(2) at 24-28th week of gestation. At that time, glucose tolerance, insulin resistance as homeostatic model assessment for insulin resistance, insulin secretory capacity as homeostatic model assessment for ß-cell function, anthropometric measurement, nutrient intakes, and plasma levels of adipokines and gestational hormones were determined. RESULTS: GDM women gained more weight in early pregnancy than non-GDM among normal-weight women. GDM was mainly associated with increased insulin resistance in overweight women and decreased insulin secretory capacity in normal-weight women. Plasma visfatin and adiponectin were lower and progesterone levels higher in GDM than non-GDM independent of BMI while plasma resistin levels were higher in non-GDM, but not GDM, overweight women. Energy and saturated fat intakes were higher in GDM independent of body weight, whereas taurine intakes were lower in GDM than non-GDM only in normal-weight women. CONCLUSIONS: Low visfatin and adiponectin and high progesterone levels in the circulation and high energy and saturated fat intakes were common risk factors for GDM and pregnancy outcome such as large for gestational age. Daily reference intakes for energy and fat during pregnancy need to be re-evaluated according to prepregnancy BMI.
Assuntos
Adiponectina/sangue , Índice de Massa Corporal , Diabetes Gestacional/etiologia , Gorduras na Dieta/efeitos adversos , Ingestão de Energia , Ácidos Graxos/efeitos adversos , Nicotinamida Fosforribosiltransferase/sangue , Diabetes Gestacional/sangue , Dieta/efeitos adversos , Feminino , Humanos , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Sobrepeso , Gravidez , Progesterona/sangue , Valores de Referência , Fatores de Risco , Taurina/farmacologia , Aumento de PesoRESUMO
Although endoscopic submucosal dissection (ESD) is increasingly utilized to treat early neoplasms of the gastrointestinal tract, its use for duodenal neoplasms is limited by the thin wall and narrow lumen of the duodenum. We have reviewed cases where ESD was used to treat sessile, nonampullary duodenal neoplasms. To do this, we retrospectively reviewed the medical records of patients treated with ESD for adenomas of the duodenum from January 2001 to December 2010, assessing the curative outcomes and complication rates. A total of 14 cases were reviewed. Mean patient age was 56.4 years. The mean size of tumors and mean size of the specimens were 17.1 mm and 26.4 mm, respectively. The en bloc resection rate with ESD was 78.6%, and the complete (R0) resection rate was 85.7%. No patient in the study experienced major bleeding. However, second-look endoscopy revealed minor bleeding requiring endoscopic homeostasis in one case (7.1%). Perforations were observed in five cases (35.7%). Two of the five patients with perforation underwent surgery. The ESD methods yielded acceptable curative resection rates for duodenal adenomas, although ESD was associated with a higher rate of perforation. Therefore, duodenal ESD should be performed with care and only in selected patients to avoid serious complications.
Assuntos
Adenoma/cirurgia , Neoplasias Duodenais/cirurgia , Duodenoscopia , Duodeno , Mucosa Intestinal/cirurgia , Perfuração Intestinal/etiologia , Adenoma/patologia , Dissecação/efeitos adversos , Neoplasias Duodenais/patologia , Duodenoscopia/efeitos adversos , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Estudos RetrospectivosRESUMO
AIMS/HYPOTHESIS: Many of the effects of resveratrol are consistent with the activation of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1) and peroxisome proliferator-activated receptor (PPAR)γ co-activator 1α (PGC-1α), which play key roles in the regulation of lipid and glucose homeostasis, and in the control of oxidative stress. We investigated whether resveratrol has protective effects on the kidney in type 2 diabetes. METHODS: Four groups of male C57BLKS/J db/m and db/db mice were used in this study. Resveratrol was administered via gavage to diabetic and non-diabetic mice, starting at 8 weeks of age, for 12 weeks. RESULTS: The db/db mice treated with resveratrol had decreased albuminuria. Resveratrol ameliorated glomerular matrix expansion and inflammation. Resveratrol also lowered the NEFA and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK and the activation of SIRT1-PGC-1α signalling and of the key downstream effectors, the PPARα-oestrogen-related receptor (ERR)-1α-sterol regulatory element-binding protein 1 (SREBP1). Furthermore, resveratrol decreased the activity of phosphatidylinositol-3 kinase (PI3K)-Akt phosphorylation and class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production. Consequently, resveratrol reversed the increase in renal apoptotic cells and oxidative stress, as reflected by renal 8-hydroxy-deoxyguanosine (8-OH-dG), urinary 8-OH-dG and isoprostane concentrations. Resveratrol prevented high-glucose-induced oxidative stress and apoptosis in cultured mesangial cells through the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling and the downstream effectors, PPARα-ERR-1α-SREBP1. CONCLUSIONS/INTERPRETATION: The results suggest that resveratrol prevents diabetic nephropathy in db/db mice by the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling, which appear to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Rim/efeitos dos fármacos , Células Mesangiais/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Estilbenos/uso terapêutico , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/química , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Ativação Enzimática/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipotrópicos/farmacologia , Lipotrópicos/uso terapêutico , Masculino , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Interferência de RNA , Resveratrol , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/química , Sirtuína 1/genética , Sirtuína 1/metabolismo , Estilbenos/farmacologia , Fatores de Transcrição/agonistas , Fatores de Transcrição/metabolismoRESUMO
AIMS/HYPOTHESIS: Transcription factor E3 (TFE3) has been shown to increase insulin sensitivity by activating insulin-signalling pathways. However, the role of TFE3 in glucose homeostasis is not fully understood. Here, we explored the possible therapeutic potential of TFE3 for the control of hyperglycaemia using a streptozotocin-induced mouse model of diabetes. METHODS: We achieved overabundance of TFE3 in streptozotocin mice by administering an adenovirus (Ad) or adeno-associated virus serotype 2 (AAV2). We also performed an oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). To explore molecular mechanisms of blood glucose control by TFE3, transcriptional studies on the regulation of genes involved in hepatic glucose metabolism were performed using quantitative real-time PCR and chromatin immunoprecipitation assay. The binding site of TFE3 in the liver Gck gene promoter was identified using deletion and site-specific mutation studies. RESULTS: Overabundance of TFE3 resulted in reduced hyperglycaemia as shown by the OGTT and ITT in streptozotocin-treated mice. We observed that TFE3 can upregulate Gck in a state of insulin deficiency. However, glucose-6-phosphatase and cytosolic phosphoenolpyruvate carboxykinase mRNA levels were decreased by Ad-mediated overexpression of Tcfe3. Biochemical studies revealed that the anti-hyperglycaemic effect of TFE3 is due to the upregulation of Gck. In primary cultured hepatocytes, TFE3 increased expression of Gck mRNA. Conversely, small interfering RNA-mediated knockdown of TFE3 resulted in a decrease in Gck mRNA. CONCLUSIONS/INTERPRETATION: This study demonstrates that TFE3 counteracts hyperglycaemia in streptozotocin-treated mice. This effect could be due to the upregulation of Gck by binding of TFE3 to its cognitive promoter region.
Assuntos
Adenoviridae/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Diabetes Mellitus Experimental/terapia , Glucoquinase/metabolismo , Hiperglicemia/terapia , Fígado/enzimologia , Fígado/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Imunoprecipitação da Cromatina , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/metabolismo , Glucoquinase/genética , Teste de Tolerância a Glucose , Células Hep G2 , Humanos , Hiperglicemia/enzimologia , Hiperglicemia/metabolismo , Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/genética , RNA Interferente PequenoRESUMO
BACKGROUND/AIM: Little is known about exposures to low radiation doses in the first trimester of pregnancy and deterministic adverse effects in the offspring, and risks are extrapolated from catastrophic events or from exposures to radiotherapy. The study aimed to assess the foetal and neonatal outcomes of pregnant women exposed to radiodiagnostic procedures with abdominal or lumbar irradiation. METHODS: In a prospective cohort design, we studied the foetal and neonatal outcomes in 115 singleton pregnant women who required abdominal or lumbar radiodiagnostic procedures without the administration of radionucleotides, and in 527 age-matched (± 2 years) control pregnant women. RESULTS: In the exposed group, lumbar spine radiography (33.9%), plain abdominal radiography (16.5%) and upper gastrointestinal tract radiography with abdominal irradiation (15.7%) were the most common radiodiagnostic procedures. Major congenital malformations were identified in two (1.9%) babies born in the exposed group and in two (0.4%) babies born in the control group (odds ratio = 4.7; 95% confidence interval 0.7-33.6; P = 0.15). The rest of the foetal and neonatal outcomes was similar in the two groups except by a marginally higher rate of admissions to the neonatal intensive care unit among babies born to exposed women (odds ratio = 2.9; 95% confidence interval 1.0-9.4; P = 0.06). CONCLUSION: Our results indicate that X-ray and computed tomography scan exposure involving abdominal irradiation without the administration of radionucleotides is not associated with adverse foetal and neonatal deterministic outcomes. Efforts are required to reduce the use of radiodiagnostic procedures for general check-ups in childbearing age women.
Assuntos
Anormalidades Congênitas/epidemiologia , Feto/efeitos da radiação , Resultado da Gravidez/epidemiologia , Primeiro Trimestre da Gravidez/efeitos da radiação , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Radiografia Abdominal , Adulto , Estudos de Coortes , Anormalidades Congênitas/diagnóstico , Feminino , Humanos , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Estudos Prospectivos , Doses de Radiação , Radiografia Abdominal/efeitos adversosRESUMO
BACKGROUND AND STUDY AIMS: Following noncurative endoscopic resection of early gastric cancer (EGC), the patient should be observed when the underlying disease is severe, the patient is elderly, or the patient refuses further treatment. The aim of this study was to analyze the clinical outcomes of patients with differentiated EGC who underwent noncurative endoscopic resection without additional treatment. PATIENTS AND METHODS: Included patients underwent noncurative endoscopic resection for differentiated EGC without additional treatment at the Asan Medical Center between July 1994 and January 2009.âClinical and oncological outcomes were analyzed. RESULTS: A total of 159 patients were included in the analysis. The median follow-up period was 33 months (interquartile range [IQR] 22â-â52 months). In total, 40 patients died (25.2â%)â-â3 due to stomach cancer, 34 due to other causes, and 3 from unknown causes; the median survival time after endoscopic treatment for these patients was 27.5 months (IQR 13.8â-â48.3 months). Multivariate analysis showed that the rates of underlying disease (Pâ<â0.001) and lymphovascular invasion (Pâ=â0.005) were higher among the 40 patients who died than among the 119 survivors. The overall 3- âand 5-year survival rates were 82.9â% and 77.1â%, respectively; the rates of the patients with lymphovascular invasion were 61.9â% and 42.4â%, respectively, and the rates of patients without lymphovascular invasion were 86.1â% and 81.8â%, respectively (Pâ<â0.001). CONCLUSIONS: Additional treatment provides fewer benefits to patients who do not have long life expectancies. Additional surgery can be considered for patients with lymphovascular invasion because of its high mortality rate; however, the benefits and risks of surgery should be considered carefully.