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1.
Surg Endosc ; 30(7): 2743-50, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26487206

RESUMO

BACKGROUND: Endoscopically diagnosed early gastric cancers (EGCs) are sometimes revealed to be advanced gastric cancers (AGCs) on pathologic examination of the resected specimen, and also endoscopically diagnosed AGCs are often determined to be EGCs. This study was designed to determine the impact on prognosis of the discordant finding between preoperative endoscopy and postoperative pathology in gastric cancer patients. METHODS: Patients with gastric cancer stages pT1a-T4a who underwent curative gastrectomy between 2004 and 2010 were included in the study. The preoperative endoscopic findings and clinicopathologic features were analyzed. The prognostic impact on recurrence-free survival of discordance between endoscopic and pathologic examinations was analyzed using multivariate analysis. RESULTS: Among 367 patients diagnosed with EGC on preoperative endoscopy, 40 (11 %) had AGC on final pathologic examination; this was more common in female patients, upper one-third location of the cancer, poorly differentiated tumor, combined gross type (elevated and depressed), lymphovascular invasion and lymph node metastasis. Among 350 patients diagnosed with AGC on preoperative endoscopy, 66 (19 %) had EGC pathologically; this was more frequent in patients with tumor in the lower and/or middle third of the stomach, differentiated tumor, Borrmann type 1 and absence of lymph node metastasis. The endoscopic appearance of AGC was identified as a poor prognostic factor related to recurrence-free survival in patients with EGC, whereas discordance did not influence recurrence-free survival in patients with AGC. CONCLUSIONS: Discordant preoperative endoscopic appearance may be an indicator of biologic aggressiveness and a reliable prognostic factor in EGC, but not in AGC.


Assuntos
Adenocarcinoma/patologia , Gastrectomia , Gastroscopia , Linfonodos/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
3.
Dig Dis Sci ; 60(11): 3340-50, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26143342

RESUMO

BACKGROUND AND AIMS: Gut microbiota may be associated with the pathogenesis of nonalcoholic steatohepatitis (NASH). This study aimed to investigate the protective effects and possible mechanisms of Lactobacillus paracasei on NASH. METHODS: Thirty male C57BL/6 mice were randomized into three groups and maintained for 10 weeks: control group (standard chow), NASH model group (high fat + 10 % fructose diet), and the L. paracasei group (NASH model with L. paracasei). Liver histology, serum aminotransferase levels, and hepatic gene expression levels were measured. Intestinal permeability was investigated using urinary (51)Creatinine Ethylenediaminetetraacetic acid ((51)Cr-EDTA) clearance. Total Kupffer cell counts and their composition (M1 vs. M2 Kupffer cells) were measured using flow cytometry with F4/80 and CD206 antibodies. RESULTS: Hepatic fat deposition, serum ALT level, and (51)Cr-EDTA clearance were significantly lower in the L. paracasei group than the NASH group (p < 0.05). The L. paracasei group had lower expression in Toll-like receptor-4 (TLR-4), NADPH oxidase-4 (NOX-4), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin 4 (IL-4), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-δ compared with the NASH group (p < 0.05). The total number of F4/80(+) Kupffer cells was lower in the L. paracasei group than the NASH group. L. paracasei induced the fraction of F4/80(+)CD206(+) cells (M2 Kupffer cells) while F4/80(+)CD206(-) cells (M1 Kupffer cells) were higher in the NASH group (F4/80(+)CD206(+) cell: 44% in NASH model group vs. 62% in L. paracasei group, p < 0.05). CONCLUSIONS: Lactobacillus paracasei attenuates hepatic steatosis with M2-dominant Kupffer cell polarization in a NASH model.


Assuntos
Intestinos/microbiologia , Células de Kupffer/microbiologia , Lactobacillus/fisiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Probióticos , Animais , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Células de Kupffer/imunologia , Células de Kupffer/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia , Permeabilidade , Fenótipo , Transdução de Sinais , Fatores de Tempo
4.
Biochem Biophys Res Commun ; 446(4): 822-9, 2014 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-24569072

RESUMO

Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n=38), early gastric cancer (EGC) (n=38), and advanced gastric cancer (AGC) (n=38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.


Assuntos
Adenoma/patologia , Leptina/análise , Leptina/metabolismo , Neoplasias Gástricas/patologia , Estômago/patologia , Adenoma/etiologia , Adenoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Mucosa Gástrica/metabolismo , Humanos , Imuno-Histoquímica , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Receptores para Leptina/análise , Receptores para Leptina/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Endoscopy ; 46(10): 845-50, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25111136

RESUMO

BACKGROUND AND STUDY AIMS: Preoperative pathological diagnosis may improve clinical management decisions in patients with upper gastrointestinal subepithelial tumors (SETs). The aims of this study were to evaluate the diagnostic yield of deep biopsy via an endoscopic submucosal dissection (ESD) technique, the complications associated with the procedure, and the impact on management of patients with upper gastrointestinal SETs. PATIENTS AND METHODS: A total of 68 patients with SETs in the stomach or esophagus were voluntarily assigned to two groups. One group underwent endoscopic ultrasound (EUS) and endoscopic deep biopsy using the ESD technique (40 patients), and the other group (28 patients) underwent surgical resection after EUS without obtaining preoperative pathological diagnosis, in accordance with accepted clinical management algorithms. RESULTS: The diagnostic yield of deep biopsy was 90 % (36/40). The results of deep biopsy changed the treatment plans in 14/40 patients (35 %). One patient with lymphoepithelial carcinoma was scheduled for surgical resection, and 13 patients with benign SETs of diameter ≥  2 cm avoided surgery. Of the 28 patients who underwent surgical resection without preoperative pathological diagnosis, 12 (42.9 %) were confirmed to have benign lesions. The mean procedure time for deep biopsy was 13.7 minutes. There were no procedure-related complications in the deep biopsy group.  CONCLUSIONS: Deep biopsy by the ESD technique is a safe, high-yield, diagnostic method in patients with upper gastrointestinal SETs. Pathologic confirmation could improve clinical decision making in the management of patients with upper gastrointestinal SETs. CLINICAL TRIAL REGISTRATION: NCT 01993199.


Assuntos
Biópsia/métodos , Carcinoma/patologia , Coristoma/patologia , Neoplasias Esofágicas/patologia , Tumores do Estroma Gastrointestinal/patologia , Leiomioma/patologia , Lipoma/patologia , Pâncreas , Neoplasias Gástricas/patologia , Procedimentos Desnecessários , Adolescente , Adulto , Idoso , Carcinoma/cirurgia , Dissecação/métodos , Endoscopia Gastrointestinal , Endossonografia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Esôfago/patologia , Feminino , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/terapia , Conduta Expectante , Adulto Jovem
6.
Scand J Gastroenterol ; 49(5): 604-10, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24646220

RESUMO

BACKGROUND: In neurophysiological studies, P300, is well known for reflecting early cognitive impairment in minimal hepatic encephalopathy (MHE). Although P300 is investigated extensively, other early event-related potential (ERP) parameters have not been studied in MHE. METHODS: The subjects were 21 adult cirrhotic patients without clinical encephalopathy and 29 normal controls. For neuropsychological testing, number connection tests, A and B (NCT-A, NCT-B), the line tracing test, the serial dotting test (SDT), and the digit symbol test (DST) were performed. For ERP testing, auditory oddball paradigms were used. The N100, P200, N200, and P300 parameters were measured. RESULTS: Cirrhosis had longer neuropsychological performance scores on NCT-A, SDT, and DST than the control group. In neurophysiological test, cirrhotic patients showed longer latencies for N100, P200, N200, and P300 than the control group. Although P300 alteration was not seen in patients without MHE compared to the control group (325.4±43.3 vs. 345.21±35.1, p=0.25), N200 latency was significantly prolonged in cirrhotic patients without MHE compared to the healthy group (242.1±30.3 vs. 259.58±33.3, p=0.006). N200 also showed good correlation with psychometric hepatic encephalopathy score and critical flicker frequency. CONCLUSIONS: N200 is a useful tool for assessing early changes of cognitive dysfunction in cirrhosis. It suggests that slower auditory cortical processing is the first sign of cerebral deterioration in patients with hepatic encephalopathy.


Assuntos
Potenciais Evocados/fisiologia , Encefalopatia Hepática/fisiopatologia , Cirrose Hepática/fisiopatologia , Adulto , Idoso , Área Sob a Curva , Estudos de Casos e Controles , Cognição/fisiologia , Eletroencefalografia , Feminino , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/psicologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/psicologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Curva ROC
7.
Scand J Gastroenterol ; 49(1): 43-51, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24256141

RESUMO

BACKGROUND: Recent studies have shown that mast cells play an important role in irritable bowel syndrome (IBS). We investigated the relationship between mast cells and the gut hormones substance P and vasoactive intestinal peptide (VIP) in irritable bowel syndrome with diarrhea (IBS-D). METHODS: Colonoscopic biopsies were performed on the rectal mucosa of 43 subjects (IBS-D patients: 22, healthy volunteers: 21) diagnosed according to the Rome III criteria. Mast cells, and substance P & VIP were evaluated by quantitative immunohistology and image analysis. Mast cells were counted as tryptase-positive cells in the lamina propria, and substance P and VIP levels were expressed as percentages of total areas of staining. RESULTS: Mast cell counts were higher in IBS-D patients than healthy volunteers (9.6 ± 3.3 vs. 5.7 ± 2.5/high power field (HPF), p < 0.01). Substance P was also elevated (0.11 ± 0.08% vs. 0.03 ± 0.02 %, p < 0.01) while VIP was only high in women with IBS-D. Mast cell counts were positively correlated with levels of substance P & VIP in women but not men (women: r = 0.625, p < 0.01 for substance P and r = 0.651, p < 0.01 for VIP). However, mast cell counts were not correlated with IBS symptoms including abdominal pain. CONCLUSION: Mast cells are activated leading to the raised levels of substance P & VIP in IBS-D patients. However, the correlation between mast cells and levels of substance P & VIP differs according to gender.


Assuntos
Síndrome do Intestino Irritável/patologia , Mastócitos , Substância P/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Contagem de Células , Diarreia/etiologia , Feminino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/metabolismo , Masculino , Pessoa de Meia-Idade , Reto/metabolismo , Reto/patologia , Fatores Sexuais , Adulto Jovem
8.
J Gastroenterol Hepatol ; 29(1): 52-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23829297

RESUMO

BACKGROUND AND AIM: The efficacy of treatment with multispecies probiotics on irritable bowel syndrome (IBS) symptoms and the alterations of gut microbiota in patients who have taken probiotics were investigated. METHODS: This randomized, double-blind, placebo-controlled trial involved 49 IBS patients (probiotics: 25, placebo: 24) diagnosed according to the Rome III criteria. Patients were randomly assigned to two groups: either to receive multispecies probiotics (a mixture of Bifidobacterium longum, B. bifidum, B. lactis, Lactobacillus acidophilus, L. rhamnosus, and Streptococcus thermophilus) twice a day for 4 weeks or to receive a placebo twice a day for 4 weeks. The primary efficacy end-point was the proportion of participants whose IBS symptoms were substantially relieved at week 4. Secondary end-points were the intensity of abdominal pain/discomfort, bloating, stool frequency/consistency, alterations in fecal microflora over the 4 weeks. Fecal microflora were analyzed in 34 patients (probiotics: 17, placebo: 17) by quantitative real-time polymerase chain reaction assays. RESULTS: The proportion of patients whose IBS symptoms were substantially relieved at week 4 was significantly higher in the probiotics group than in the placebo group: 68.0% (17/25) versus 37.5% (9/24) (P < 0.05). Secondary end-points such as improvement in abdominal pain/discomfort and bloating occurred in the probiotics group but not in the placebo group. Fecal analysis revealed that B. lactis, L. rhamnosus, and S. thermophilus had increased significantly in the probiotics group after 4 weeks and that B. lactis had increased in the placebo group. CONCLUSIONS: Multispecies probiotics are effective in IBS patients and induce the alterations in the composition of intestinal microbiota.


Assuntos
Síndrome do Intestino Irritável/tratamento farmacológico , Probióticos/administração & dosagem , Adulto , Idoso , Bifidobacterium/isolamento & purificação , Método Duplo-Cego , Fezes/microbiologia , Feminino , Humanos , Síndrome do Intestino Irritável/microbiologia , Lactobacillus/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Streptococcus thermophilus/isolamento & purificação , Adulto Jovem
9.
Dig Dis Sci ; 59(1): 117-25, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24142070

RESUMO

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a commonly performed procedure for patients with severe dysphagia leading to malnutrition. Improved knowledge of risk factors for PEG-related complications might decrease patient discomfort and healthcare costs. AIM: The aim of the present study was to investigate factors associated with complications after PEG. METHODS: A retrospective review was performed for all patients referred for PEG placement from December 2002 to December 2012 in single-tertiary care center. PEG-related complications and risk factors were evaluated through chart reviews, endoscopic reports, and endoscopic and radiologic images. RESULTS: Among a total of 245 consecutive individuals (146 male, mean age 59.2 ± 12.6 years) enrolled, 43 major complications had developed. Multivariate analysis revealed that patients with an internal bolster of a PEG tube in the upper body of stomach were at significant risk for early [OR 6.127 (95 % CI 1.447-26.046)] and late complications [OR 6.710 (95 % CI 1.692-26.603)]. Abnormal leukocyte counts [OR 3.198 (95 % CI 1.174-8.716)], stroke as an indication for PEG [OR 3.047 (95 % CI 1.174-8.882)], and PEG tube placement by an inexperienced endoscopist [OR 3.401 (95 % CI 1.073-10.779)] were significantly associated with early complications. CONCLUSIONS: A PEG tube should not be inserted into the upper body of stomach to reduce complication risk, and PEG procedures should be performed by skilled endoscopists to prevent early complications. An abnormal leukocyte count can be a predictor of early complication, and care is needed when PEG is performed for patients with stroke.


Assuntos
Gastroscopia/efeitos adversos , Gastrostomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
10.
Liver Int ; 33(4): 535-43, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23362947

RESUMO

BACKGROUND: 5-hydroxytryptamine (5-HT) receptors are upregulated in activated hepatic stellate cells (HSCs), and are therefore thought to play an important role in their activation. AIM: The aim of this study was to determine whether 5-HT2A receptor antagonists affect the activation or apoptosis of HSCs in vitro and/or in vivo. METHODS: For the in vitro experiments, the viability, apoptosis and wound healing ability of LX-2 cells were examined after treatment with various 5-HT2A receptor antagonists. Levels of HSC activation markers (procollagen type I, α-SMA, TGF-ß and Smad 2/3) were measured. For in vivo experiments, rats were divided into three groups: (i) a control group, (ii) a disease group, in which cirrhosis was induced by thioacetamide (iii) a treatment group, in which cirrhosis was induced and a 5-HT2A receptor antagonist (sarpogrelate, 30 mg/kg) was administered. RESULTS: 5-HT2A , but not 5-HT2B receptor mRNA increased with time upon HSC activation. 5-HT2A receptor antagonists (ketanserin and sarpogrelate) inhibited viability and wound healing in LX-2 cells and induced apoptosis. Expression of α-SMA and procollagen type I was also inhibited. In the in vivo study, lobular inflammation was reduced in the sarpogrelate-treated group, but there was only slight and statistically insignificant attenuation of periportal fibrosis. Expression of α-SMA, TGF-ß and Smad 2/3 was also reduced in the treatment group. CONCLUSIONS: 5-HT2A receptor antagonists can reduce inflammation and the activation of HSCs in this cirrhotic model.


Assuntos
Apoptose/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Receptor 5-HT2A de Serotonina/efeitos dos fármacos , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Actinas/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Relação Dose-Resposta a Droga , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Ketanserina/farmacologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/tratamento farmacológico , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptor 5-HT2A de Serotonina/genética , Receptor 5-HT2A de Serotonina/metabolismo , Ritanserina/farmacologia , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Succinatos/farmacologia , Tioacetamida , Fatores de Tempo , Fator de Crescimento Transformador beta/metabolismo , Cicatrização/efeitos dos fármacos
11.
J Gastroenterol Hepatol ; 28(3): 522-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22497339

RESUMO

BACKGROUND AND AIM: The widely accepted range of upper limits of normal (ULN) alanine aminotransferase (ALT) levels (ULN < 40 U/L) was recently challenged by several reports. Both ALT and aspartate aminotransferase (AST) are commonly used as surrogate markers of liver disease, but almost all studies of aminotransferase activity were conducted on ALT. We investigated not only ULN of ALT but also AST activity and to identify factors modulating them in healthy Korean. METHODS: A cross-sectional study of 411,240 registered blood donors in all nationwide blood banks belonging to the Korean Red Cross were conducted. ULN of ALT and AST was evaluated adjusting their age according to the national population census database. "Decision tree model" was used to identify the affecting factors of ALT and AST and optimal cut-off points of affecting factors. RESULTS: "ULN of ALT" was 34 U/L in men and 24 U/L in women and "ULN of AST" was 32 U/L in men and 26 U/L in women in the blood donor database. Decision tree analysis showed that ALT levels were mostly influenced by body mass index level and its critical two cut-off points were 23.5 kg/m2 and 25.8 kg/m2 , respectively. The most affecting factor of AST was gender. CONCLUSION: Upper limits of normal of ALT and AST in Koreans were lower than conventional accepted values (< 40 U/L) but higher than recently suggested values (male < 30 U/L and female < 19 U/L). Body mass index was the most determining factor for ALT and gender was the most influencing factor for AST activity.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Doadores de Sangue , Índice de Massa Corporal , Estudos Transversais , Árvores de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , República da Coreia , Fatores Sexuais , Adulto Jovem
12.
J Gastroenterol Hepatol ; 28(12): 1877-84, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23808892

RESUMO

BACKGROUND AND AIM: Several epidemiological studies have shown that coffee intake attenuates the progression of liver fibrosis; however, the mechanism is unclear. AIMS: We investigated the direct effects of caffeine on hepatic stellate cells (HSCs) and assessed whether caffeine attenuated intrahepatic fibrosis in rat model of liver cirrhosis. METHODS: Human hepatic stellate cell line, an immortalized human HSCs line, was used in in vitro assay system. Cell migration and proliferation were assessed in presence of various caffeine concentrations (0, 1, 5, and 10 mmol), and levels of procollagen type Ic and α-smooth muscle actin (α-SMA) were measured by Western blot. Severity of liver inflammation and fibrosis were compared between thioacetamide-treated rats with and without caffeine supplementation. RESULTS: Caffeine increased HSCs apoptosis and intracellular F-actin and cyclic adenosine monophosphate expression. Caffeine also inhibited procollagen type Ic and α-SMA expression in a dose- and time-dependent manner. In rat model, caffeine decreased periportal inflammation, levels of inflammatory cells (1.4 ± 0.52 vs 2.6 ± 0.46, P < 0.05), and fibrosis (2.1 ± 0.35 vs 2.9 ± 0.84, P < 0.05). Transforming growth factor-ß and α-SMA expressions were also reduced by caffeine. CONCLUSION: Caffeine attenuates the progression of liver fibrosis by inhibiting HSCs adhesion and activation.


Assuntos
Cafeína/uso terapêutico , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática Experimental/prevenção & controle , Actinas/antagonistas & inibidores , Actinas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cafeína/administração & dosagem , Cafeína/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , AMP Cíclico/metabolismo , Progressão da Doença , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Masculino , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/metabolismo , Pró-Colágeno/antagonistas & inibidores , Pró-Colágeno/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismo , Cicatrização/efeitos dos fármacos
13.
J Korean Med Sci ; 28(6): 901-7, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23772156

RESUMO

Whether hydrogen and methane gas produced during lactulose breath test (LBT) are associated with symptoms of irritable bowel syndrome (IBS) is not determined. We aimed to investigate whether hydrogen and methane on LBT are associated with IBS symptoms. Sixty-eight IBS patients meeting the Rome III criteria for IBS, and 55 healthy controls, underwent LBT. The IBS subjects recorded their customary gastrointestinal symptoms on a questionnaire using visual analogue scales. LBT positivity was defined to be above 20 ppm rise of hydrogen or 10 ppm rise of methane within 90 min. Gas amounts produced during LBT were determined by calculating area under the curve of hydrogen and methane excretion. Symptom severity scores were not different between the LBT (+) IBS and LBT (-) IBS subjects and also between methane producers and non-methane producers. Gas amounts produced during LBT were not associated with IBS symptoms, except a weak correlation between total gas amounts and a few IBS symptoms such as bloating (r = 0.324, P = 0.039), flatulence (r = 0.314, P = 0.046) and abdominal pain (r = 0.364, P = 0.018) only in LBT (+) IBS. In conclusion, hydrogen and methane gas on LBT are not useful for predicting the customary symptoms and subtypes of IBS.


Assuntos
Hidrogênio/análise , Síndrome do Intestino Irritável/diagnóstico , Lactulose/metabolismo , Metano/análise , Dor Abdominal/etiologia , Adulto , Área Sob a Curva , Testes Respiratórios , Feminino , Flatulência/etiologia , Gases/análise , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco
14.
Gut Liver ; 17(2): 226-233, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35730245

RESUMO

Background/Aims: Efficacy of proton pump inhibitors is limited in patients with nonerosive reflux disease (NERD). The aim of this study was to comparatively evaluate the efficacy and safety of esomeprazole with sodium bicarbonate and esomeprazole alone. Methods: This was a multicenter, randomized, double-blind, active-controlled, noninferiority comparative study. A total of 379 patients with NERD were randomly allocated to receive either EsoduoⓇ (esomeprazole 20 mg with sodium bicarbonate 800 mg) or NexiumⓇ (esomeprazole 20 mg) once daily for 4 weeks from January 2019 to December 2019. The patients had a history of heartburn for at least 2 days in the week before randomization as well as in the last 3 months and no esophageal mucosal breaks on endoscopy. The primary endpoint was a complete cure of heartburn at week 4. The secondary and exploratory endpoints as well as the safety profiles were compared in the groups at weeks 2 and 4. Results: A total of 355 patients completed the study (180 in the EsoduoⓇ group and 175 in the NexiumⓇ group). The proportions of patients without heartburn in the entire 4th week of treatment were not different between the two groups (33.33% in the EsoduoⓇ group and 35% in the NexiumⓇ group, p=0.737). There were no significant differences in most of the secondary and exploratory endpoints as well as the safety profiles. Conclusions: EsoduoⓇ is as effective and safe as NexiumⓇ for managing typical symptoms in patients with NERD (ClinicalTrial.gov identifier: NCT03928470).


Assuntos
Esomeprazol , Refluxo Gastroesofágico , Humanos , Esomeprazol/efeitos adversos , Azia/tratamento farmacológico , Azia/etiologia , Bicarbonato de Sódio , Resultado do Tratamento , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/complicações , Inibidores da Bomba de Prótons , Método Duplo-Cego
15.
World J Gastroenterol ; 28(44): 6294-6309, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36504556

RESUMO

BACKGROUND: Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner. AIM: To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE). METHODS: Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups. RESULTS: Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups. CONCLUSION: Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Esofagite , Úlcera Péptica , Adulto , Humanos , Esomeprazol/efeitos adversos , Gastrinas , Qualidade de Vida , ATPase Trocadora de Hidrogênio-Potássio
16.
Liver Int ; 31(9): 1315-24, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22093454

RESUMO

BACKGROUND: Mitochondria are the main sites for fatty acid oxidation and play a central role in lipotoxicity and nonalcoholic steatohepatitis. AIMS: We investigated whether carnitine prevents free fatty acid (FFA)-induced lipotoxicity in vitro and in vivo. METHODS: HepG2 cells were incubated with FFA, along with carnitine and carnitine complexes. Mitochondrial ß-oxidation, transmembrane potential, intracellular ATP levels and changes in mitochondrial copy number and morphology were analysed. Otsuka Long-Evans Tokushima Fatty and Long-Evans Tokushima Otsuka rats were segregated into three experimental groups and fed for 8 weeks with (i) normal chow, (ii) a methionine choline-deficient (MCD) diet or (iii) an L-carnitine-supplemented MCD diet. RESULTS: Carnitine prevented FFA-induced apoptosis (16% vs. 3%, P < 0.05). FFA treatment resulted in swollen mitochondria with increased inner matrix density and loss of cristae. However, mitochondria co-treated with carnitine had normal ultrastructure. The mitochondrial DNA copy number was higher in the carnitine treatment group than in the palmitic acid treatment group (375 vs. 221 copies, P < 0.05). The carnitine group showed higher mitochondrial ß-oxidation than did the control and palmitic acid treatment groups (597 vs. 432 and 395 ccpm, P < 0.05). Carnitine treatment increased the mRNA expression of carnitine palmitoyltransferase 1A and peroxisome proliferator-activated receptor-γ, and carnitine-lipoic acid further augmented the mRNA expression. In the in vivo model, carnitine-treated rats showed lower alanine transaminase levels and lesser lobular inflammation than did the MCD-treated rats. CONCLUSIONS: Carnitine and carnitine-lipoic acid prevent lipotoxicity by increasing mitochondrial ß-oxidation and reducing intracellular oxidative stress.


Assuntos
Carnitina/farmacologia , Ácidos Graxos não Esterificados/metabolismo , Fígado Gorduroso/prevenção & controle , Fígado/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Ácido Tióctico/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Carnitina/análogos & derivados , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Deficiência de Colina/complicações , DNA Mitocondrial/metabolismo , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Fígado/metabolismo , Fígado/patologia , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Metionina/deficiência , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos OLETF , Ratos Long-Evans , Ácido Tióctico/análogos & derivados , Fatores de Tempo
17.
Hepatogastroenterology ; 58(107-108): 775-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21830388

RESUMO

BACKGROUND/AIMS: Traditionally, patients fast from midnight the night before to just prior to the colonoscopy. Many patients find it extremely inconvenient to have to fast for a full day. We sought to compare: a group in which diet was restricted and a group in which diet was not restricted. METHODOLOGY: Patients who attended inpatient clinics of Hanyang University Hospital who were scheduled to undergo colonoscopy were considered eligible to participate in this study. The subjects were randomly assigned to either eat lunch before colonoscopy or to fast before the colonoscopy. RESULTS: There were no significant differences between the study groups with respect to age, gender distribution, previous abdominal surgery, or bowel movements. The two groups showed no significant differences in bowel cleanliness scores or fluid volume scores. Patients' unwillingness to undergo the same procedure in the future was 10.0% in group A compared to 33.3% in group B. With regard to the patients' opinion about lunch before colonoscopy, most of the subjects in group A answered that they would eat lunch before colonoscopy again if given the choice. CONCLUSIONS: Eating lunch before afternoon colonoscopy had no negative impact on the quality of the bowel preparation.


Assuntos
Colonoscopia/métodos , Adulto , Idoso , Jejum , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
J Korean Med Sci ; 26(8): 1074-80, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21860559

RESUMO

In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 µg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Úlcera Duodenal/prevenção & controle , Misoprostol/efeitos adversos , Extratos Vegetais/efeitos adversos , Úlcera Gástrica/prevenção & controle , Adolescente , Adulto , Método Duplo-Cego , Úlcera Duodenal/induzido quimicamente , Endoscopia Gastrointestinal , Feminino , Mucosa Gástrica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Gástrica/induzido quimicamente
19.
J Korean Med Sci ; 26(10): 1339-43, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22022188

RESUMO

The aim of this study was to examine the relationship of complications related to diverticulitis and visceral obesity. The study was based on a retrospective case note review conducted at the Hanyang University Hospital. Patients were diagnosed with diverticulitis based on clinical symptoms and abdominal computed tomography (CT) findings and divided into two groups: those admitted with complicated diverticulitis and those with a simple diverticulitis episode. We compared the body mass index (BMI) and degree of visceral obesity, measured by abdominal CT. The study included 140 patients, 87 (62.1%) were simple diverticulitis and 53 (37.9%) were complicated diverticulitis. In the complicated diverticulitis group, 9 (6.4%) cases were recurrent, 29 (20.7%) were perforation or abscess patients, and 28 (20%) were patients with systemic inflammatory response syndrome (SIRS). Of the SIRS patients, 13 were involved in other complication groups. When comparing in the two groups, the complicated diverticulitis group had a significantly higher visceral fat area (128.57 cm(2) vs 102.80 cm(2), P = 0.032) and a higher ratio of visceral fat area/subcutaneous fat area (0.997 vs 0.799, P = 0.014). Visceral obesity is significantly associated with complications of diverticulitis.


Assuntos
Diverticulite/complicações , Gordura Intra-Abdominal , Lipídeos/sangue , Obesidade Abdominal/complicações , Tecido Adiposo , Adulto , Idoso , Composição Corporal , Índice de Massa Corporal , Diverticulite/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Resposta Inflamatória Sistêmica
20.
Gut Liver ; 15(1): 109-116, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32066208

RESUMO

Background/Aims: To date, studies on various noninvasive techniques have been suggested to evaluate the degree of liver fibrosis. We aimed to investigate the diagnostic performance of serum asialo α1-acid glycoprotein (AsAGP) in the diagnosis of liver cirrhosis compared with chronic hepatitis for clinically useful result. Methods: We conducted a case-control study of 96 patients with chronic liver disease. Chronic hepatitis was defined as the presence of chronic liver disease on ultrasonography, with a liver stiffness of less than 5.0 kPa as shown on magnetic resonance elastography (MRE). Liver cirrhosis was defined as liver stiffness of more than 5.0 kPa on MRE. The serum AsAGP concentration was compared between the two groups. Results: Serum AsAGP levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis (1.83 µg/mL vs 1.42 µg/mL, p<0.001). Additionally, when comparing patients in each cirrhotic group (Child-Pugh grades A, B, and C) to those with chronic hepatitis, AsAGP levels were significantly higher in all the cirrhotic groups (p<0.05, p<0.01, p<0.001, respectively). The sensitivity and specificity of AsAGP for detecting cirrhosis were 79.2% and 64.6%, respectively, and the area under the curve value was 0.733. The best diagnostic cutoff to predict cirrhosis was 1.4 µg/mL. AsAGP and bilirubin were found to be independent risk factors for the prediction of cirrhosis in the logistic regression analysis. Conclusions: Serum AsAGP showed an acceptable diagnostic performance in predicting liver cirrhosis.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatias , Estudos de Casos e Controles , Glicoproteínas , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Hepatopatias/patologia , Curva ROC
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