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Objective In general, surface ulceration in gastric gastrointestinal stromal tumor (GIST) is considered a malignant feature; however, the mechanism underlying its formation has not been evaluated in detail. In this study, we analyzed the factors involved in ulceration using resected specimens of gastric GIST. Methods A total of 48 samples were retrospectively analyzed. We examined the association of surface ulceration of gastric GIST with the MIB-1 labeling index, mitotic number, tumor size, endoscopic ultrasound (EUS) findings and growth pattern on computed tomography (CT). Results The proportion of men was significantly higher in the ulceration group than in the non-ulceration group (p=0.04146), whereas age was not significantly different between the groups. Tumor was significantly larger in the ulceration group than in the non-ulceration group (p=0.0048). There was no correlation between tumor size and ulcer number. The MIB-1 index was not related to ulceration, nor were EUS findings. The number of mitotic cells tended to be higher in the ulceration group than in the non-ulceration group (p=0.05988). Intraluminal growth pattern was strongly associated with ulceration (p=0.00019). After a multivariate analysis, the growth pattern was the only factor associated with ulceration of gastric GIST. Conclusion Although formation of surface ulceration in gastric GIST was partially associated with the degree of malignancy, the growth pattern was the most important factor associated with ulceration in gastric GIST.
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Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Masculino , Humanos , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Estudos Retrospectivos , Úlcera/etiologia , Úlcera/complicações , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Endossonografia/métodosRESUMO
BACKGROUND: Functional dyspepsia (FD) is a disorder that presents with chronic dyspepsia, which is not only very common but also highly affects quality of life of the patients. In Japan, FD became a disease name for national insurance in 2013, and has been gradually recognized, though still not satisfactory. Following the revision policy of Japanese Society of Gastroenterology (JSGE), the first version of FD guideline was revised this time. METHOD: Like previously, the guideline was created by the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, the questions were classified to background questions (BQs, 24 already clarified issues), future research questions (FRQs, 9 issues cannot be addressed with insufficient evidence), and 7 clinical questions that are mainly associated with treatment. RESULTS AND CONCLUSION: These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD.
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Dispepsia , Gastroenterologia , Infecções por Helicobacter , Acetilcolinesterase/uso terapêutico , Dispepsia/diagnóstico , Dispepsia/tratamento farmacológico , Endoscopia Gastrointestinal , Humanos , Qualidade de VidaRESUMO
We encountered three cases with incidental penetration of a straight Amsterdam-type bile duct plastic stent into the duodenal papilla. All patients had undergone insertion of a biliary plastic stent due to common bile duct stones. However, in all three cases, we observed penetration of the biliary plastic stent into the duodenal papilla just before the elective surgery or at the time of plastic stent replacement. We, therefore, performed stent dissection using a bipolar snare and were able to safely remove the plastic stents in all three cases. We believe that this is the first report of plastic stent dissection using a bipolar snare.
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Colangiopancreatografia Retrógrada Endoscópica , Plásticos , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/cirurgia , Dissecação , Humanos , StentsRESUMO
Objective: This study aimed to clarify the association of MAFK polymorphisms (rs4268033, rs3735656, and rs10226620) with the degree of gastric mucosal atrophy and CDKN2A CpG methylation status. Methods: A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). Methods: A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). Results: Either rs3735656 or rs10226620, located in the 3'-UTR of MAFK, was significantly associated with the severity of gastric mucosal atrophy using a dominant genetic model (odds ratio [OR], 2.10; p = 0.0012, and OR, 1.98; p = 0.0027, respectively). However, using a recessive genetic model, no significant association was found between three polymorphisms and gastric mucosal atrophy. The serum pepsinogen I/II ratio was significantly lower in subjects with minor alleles of rs3735656 and rs10226620 than in subjects with the wild homozygous allele (p = 0.018 and 0.013, respectively). In a subgroup including 400 of the 491 subjects, the CpG of p14ARF and p16 INK4a were methylated in 132 and 112 subjects, respectively. Fifty subjects had both CpG methylations and 206 subjects had neither methylation. When comparing the groups with both and neither methylations, there were no significant associations between three polymorphisms and CDKN2A methylation using a dominant genetic model. However, all polymorphisms investigated in this study (rs4268033, rs3735656, and rs10226620) were significantly associated with CDKN2A methylation in a recessive genetic model (OR, 3.58; p = 0.0071, OR, 4.49; p = 0.0004, and OR, 3.45; p = 0.0027, respectively). Conclusions: Our results indicate that carrying the minor allele of the MAFK polymorphisms, particularly when they are located in the 3'-UTR, has a high risk for the severity of gastric mucosal atrophy; furthermore, CDKN2A CpG methylation may develop in subjects with homozygous minor allele of these polymorphisms.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Mucosa Gástrica/metabolismo , Fator de Transcrição MafK/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Atrofia/genética , Atrofia/metabolismo , Atrofia/patologia , Ilhas de CpG , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Metilação de DNA , Feminino , Mucosa Gástrica/patologia , Frequência do Gene , Predisposição Genética para Doença , Humanos , Fator de Transcrição MafK/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: CpG methylation of tumor suppressor genes occurs in the early stage of carcinogenesis. Detecting risk factors for aberrant CpG methylation is clinically important for predicting cancer development. DNA methyltransferase (DNMT) 3a is considered to play critical roles in the DNA methylation process during pathogenesis. In this study, we evaluated the association between DNMT3A polymorphisms (rs6733868 and rs13428812) and CpG methylation status in non-cancerous gastric mucosa. METHODS: We determined the DNMT3A genotype and CpG methylation status of 4 genes (p14ARF, p16INK4a, DAPK, and CDH1) in 510 subjects without gastric cancer. Helicobacter pylori (HP) infection status was determined by the rapid urease test, urea breath test, speculum examination, or serum antibody test. We determined the DNMT3A genotype using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). CpG methylation status was determined by methylation-specific polymerase chain reaction (MSP). When the methylated band was stronger than 10 ng/µL according to the DNA marker, we judged CpG island hypermethylation (CIHM) to be present. Associations between genotypes and susceptibilities were assessed by logistic regression analysis. RESULTS: The minor allele frequencies of both polymorphisms (rs6733868 and rs13428812) were lower in the CpG methylated groups of each of the 4 genes (p14ARF, p16INK4a, DAPK, and CDH1). Using a dominant genetic model, rs6733868 was significantly associated with the hypermethylation of each gene, whereas rs13428812 was associated with the methylation of 3 genes (all except p14ARF). When low-CIHM was defined as 1 or 2 CpG islands methylated and high-CIHM was defined as 3 or more CpG islands methylated, carrying the minor allele of rs6733868 was associated with both decreased low- and high-CIHM, and that of rs13428812 also was associated with a decrease. Comparing low-CIHM with high-CIHM, carrying the minor alleles of rs6733868 or rs13428812 was related to decreased susceptibility to high-CIHM. In HP-infected subjects, carrying the minor alleles of rs6733868 or rs13428812 had a significantly greater association with decreased susceptibility to high-CIHM. CONCLUSIONS: Our study indicates that polymorphisms of DNMT3A are associated with the accumulation of gene methylation in gastric mucosa. Carrying the minor alleles of rs6733868 or rs13428812 inhibits aberrant gene methylations, which are typically enhanced by HP infection.
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Ilhas de CpG/genética , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA , Mucosa Gástrica/metabolismo , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Antígenos CD/genética , Caderinas/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA Metiltransferase 3A , Proteínas Quinases Associadas com Morte Celular/genética , Feminino , Mucosa Gástrica/microbiologia , Frequência do Gene , Genótipo , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: CDKN2A hypermethylation is among the major events associated with carcinogenesis and is also observed in non-neoplastic colonic mucosa in patients with ulcerative colitis (UC). Macrophage migration inhibitory factor (MIF) plays a crucial role in promoting gastrointestinal inflammation characteristic of UC. The aim of this study is to explore associations between CDKN2A methylation status and MIF polymorphisms (rs755622 and rs5844572). METHODS: One hundred and fifty-nine patients diagnosed with UC were enrolled in this study. The methylation status of p14ARF and p16INK4a was determined by MSP; MIF genotypes were identified by PCR-SSCP. RESULTS: We found no differences with respect to mean age, gender, clinical type (chronic continuous or relapse/remitting), or extent of disease among the patients with methylated and unmethylated p14ARF or p16INK4a. Carrying the rs755622 C allele indicated a significantly higher risk for p14ARF methylation (odds ratio (OR), 2.16; 95% confidence interval (CI), 1.08-4.32; p = 0.030); similarly, carrying the rs5844572 7-repeat allele indicated a significantly higher risk for p16INK4a methylation (OR, 2.57; 95% CI, 1.26-5.24; p = 0.0094) after an adjusted regression analysis. The carriers of the rs755662 C allele or the rs5844572 7-repeat allele were both at a significantly higher risk for methylation of both p14ARF and p16INK4a when compared to the cohort in which neither of the genes were methylated (OR, 2.70; 95% CI, 1.22-6.01; p = 0.015 and OR, 2.87; 95% CI, 1.25-6.62; p = 0.013, respectively). Additionally, carrying rs755622 C allele was significantly associated with CIHM in chronic continuous of clinical type and total colitis (OR, 25.9; 95% CI, 2.55-262.6; p = 0.0059 and OR, 4.38; 95% CI, 1.12-17.2; p = 0.034, respectively), and carrying 7-repeat allele of rs5844572 was significantly associated in chronic continuous type (OR, 14.5; 95%CI, 1.46-144.3; p = 0.022). CONCLUSIONS: Taken together, our findings suggest that MIF genotypes associated with inflammation may also be involved in promoting carcinogenesis via CDKN2A hypermethylation in patients diagnosed with UC.
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Colite Ulcerativa/genética , Ilhas de CpG/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Colite Ulcerativa/diagnóstico , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
We herein report the case of a 79-year-old patient with unresectable stage III non-small cell lung cancer who developed immune-related hepatitis caused by durvalumab administration. Durvalumab was administered at 10 mg/kg every two weeks after the treatment with carboplatin (AUC2), paclitaxel (35 mg/m2), and 60 Gy radiation. At the day 208 in which the 14th durvalumab administration was scheduled, the patient was urgently hospitalized due to CTCAE Grade 4 hepatic dysfunction detected during the an outpatient blood sampling test. He was diagnosed with immune-related hepatitis and started on methylprednisolone 60 mg/day. After 51 days, his liver dysfunction improved and he was discharged.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas , Hepatite/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina/uso terapêutico , Feminino , Hepatite/etiologia , Hepatite/imunologia , Humanos , Japão , Masculino , Paclitaxel/uso terapêuticoRESUMO
A 65-year-old man was admitted complaining of high fever and pain in the right lower abdomen. An ileocolonic side-to-end anastomosis had been performed 38 years previously for an abscess in a colonic diverticulum. On the current admission, findings on contrast-enhanced computed tomography suggested an amebic liver abscess and intestinal amebiasis. Colonoscopy revealed an irregularly shaped ulcer and false membrane in the ileal blind end of the ileocolonic anastomosis. Amebic trophozoites were seen by rapid microscopy. Amebiasis in the blind end of the ileum has rarely been reported. This case is of particular interest because the intestinal amebiasis also led to a liver abscess.
Assuntos
Amebíase , Disenteria Amebiana/diagnóstico , Abscesso Hepático Amebiano/diagnóstico , Idoso , Anastomose Cirúrgica , Colonoscopia , Humanos , MasculinoRESUMO
The aim of the present study was to investigate whether single nucleotide polymorphisms in the DNMT3A gene are associated with susceptibility to gastric cancer in the Japanese population. The present case-control study examined the associations between single nucleotide polymorphisms (rs6733868 and rs13428812) in DNMT3A and cancer susceptibility in 343 patients with gastric cancer and 708 subjects without gastric malignancies on upper gastro-duodenal endoscopy. Of 708 controls, 409 were classified into two groups histologically: 99 cases with and 310 cases without gastric mucosal atrophy. Overall, homozygosity for the DNMT3A rs6733868 minor allele was significantly associated with a reduced risk of gastric cancer (odds ratio [OR], 0.621; 95% confidence interval [CI], 0.402-0.958; P=0.031), especially of the intestinal type (OR, 0.494; 95% CI, 0.274-0.890; P=0.019). In subjects >60 years, rs6733868 minor allele homozygosity was significantly associated with gastric cancer susceptibility. Carriers of the rs6733868 minor allele had a reduced risk of severe gastric mucosal atrophy (OR, 0.495; 95% CI, 0.299-0.826; P=0.0069). In addition, the number of minor alleles of both rs6733868 and rs13428812 was significantly correlated with the risk of Helicobacter pylori (HP) infection (P=0.0070 and P=0.0050, respectively). However, rs13428812 was not associated with severe gastric mucosal atrophy or gastric carcinogenesis. The present results suggest that DNMT3A polymorphisms serve roles in the progression from HP infection to gastric mucosal atrophy and gastric carcinogenesis in terms of degree and manner.
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In biological systems, extracellular vesicles including exosomes have recently been revealed to play a significant role in the communication between various cells, and the number of papers on this subject has dramatically increased. In current conventional exosome studies, the standard research method is to use liquid biopsies to analyze extracts of various disease exosomes. However, exosomes are only one of many key players in natural cellular interactions. Reproducing the phenomena occurring in vivo and investigating the interactions are required in order to examine their role fully. For exosome research, an alternative to the liquid biopsy method for observing natural interactions is the co-culturing technique. It does not require an exosome extraction procedure, and while the technique has been used in many studies thus far, its application to exosome research has been limited. However, the use of co-culturing technologies is necessary to examine the essential interactions of exosomes. An overview of exosome research methodologies and co-culturing systems is thus provided here.
Assuntos
Exossomos , Animais , Pesquisa Biomédica , Técnicas de Cocultura , HumanosRESUMO
The aim of the present study was to investigate an association of genetic polymorphism (rs7521584) located in miR200a200b429 cluster, which has tumor suppressor and proinflammatory function, with the development of gastric mucosal atrophy and metaplasia as a premalignant condition. Gastric mucosa samples were obtained from the antrum of 393 patients with no malignancies. The rs7521584 genotype was determined using the polymerase chain reactionsinglestrand conformation polymorphism analysis method. The degree of gastritis was assessed histologically in all subjects and serum levels of pepsinogen (PG) I/II were quantified in 123 out of 393 patients. Patients with an atrophy score ≥1 and metaplasia score ≥1 were classified into the atrophic gastritis group (AG group). The rs7521584 TT genotype was significantly associated with the development of atrophic gastritis [odds ratio (OR), 2.41; 95% confidence interval (CI), 1.105.25; P=0.027), particularly in patients with H. pylori infection (OR, 3.31; 95% CI, 1.358.12; P=0.0089). In addition, in patients younger than 60 years of age, this genotype was associated with atrophic gastritis (OR, 3.15; 95% CI 1.039.61; P=0.044)]. In patients with H. pylori infection, the metaplasia score was significantly higher in the TT homozygote compared with the GG+GT genotype. In the rs7521584 TT homozygote, serum PG I/II ratio was significantly reduced with increasing age (P=0.0084). No significant trend was identified between the GG+GT genotype and age. The results of the current study indicated that the rs7521584 minor allele homozygote was associated with the development of chronic gastritis under the influence of H. pyloriinduced inflammation, particularly with the severity of metaplastic alterations.
Assuntos
Gastrite Atrófica/genética , Predisposição Genética para Doença , Infecções por Helicobacter/genética , MicroRNAs/genética , Adulto , Idoso , Feminino , Gastrite Atrófica/complicações , Gastrite Atrófica/microbiologia , Estudos de Associação Genética , Genótipo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de DoençaRESUMO
The present study aimed to investigate whether single nucleotide polymorphisms in receptor interacting serine/threonine kinase 2 (RIPK2), which encodes a component of the nucleotide binding oligomerization domain containing 2-RIP2 pathway, may compromise the innate immune response to Helicobacter pylori infection, leading to increased susceptibility to gastric cancer in the Japanese population. The present case control study investigated the associations between RIPK2 single nucleotide polymorphisms and gastric mucosal inflammation, atrophy and cancer susceptibility in 528 patients with gastric cancer and 697 patients without gastric malignancies on upper gastro-duodenal endoscopy. Overall, the RIPK2 rs16900627 minor allele was significantly associated with the susceptibility to gastric cancer [OR, 1.37; 95% confidence interval (CI), 1.06-1.77; P=0.016], particularly of the intestinal type (OR, 1.53; 95% CI, 1.13-2.07; P=0.0062). It was also significantly associated with gastric mucosal atrophy (OR, 1.83; 95% CI, 1.14-2.93; P=0.011). When assessing the severity of chronic gastritis using the updated Sydney system, the activity and inflammation scores, as well as atrophy and metaplasia scores, were significantly higher in rs16900627 minor allele carriers compared with wild-type homozygotes. In patients younger than 60 years old, the pepsinogen I/II ratio was significantly lower in rs16900627 minor allele carriers compared with wild-type homozygotes (P=0.037). The rs16900627 minor allele is associated with the severity of gastric mucosal inflammation and the development of gastric mucosal atrophy. Carriers of this allele may have an increased risk for the development of gastric cancer, particularly of the intestinal type.
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Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are representative types of fatty liver disease (FLD) and have similar histologic features. In this study, we aimed to compare the associations of the two FLD types with hypertension (HT), diabetes mellitus (DM), and dyslipidemia (DL). A nationwide survey investigating FLD status included 753 Japanese subjects (median age 55 years; male 440, female 313) with biopsy-proven ASH (n = 172) or NASH (n = 581). We performed a multiple logistic regression analysis to identify the factors associated with HT, DM, or DL. Older age and a higher body mass index were significant factors associated with HT. Older age, female sex, a higher body mass index, advanced liver fibrosis, and the NASH type of FLD (odds ratio 2.77; 95% confidence interval 1.78-4.31; P < 0.0001) were significant factors associated with DM. Finally, the NASH type of FLD (odds ratio 4.05; 95% confidence interval 2.63-6.24; P < 0.0001) was the only significant factor associated with DL. Thus, the associations of NASH with DM and DL were stronger than those of ASH with DM and DL. In the management of FLD subjects, controlling DM and DL is particularly important for NASH subjects.
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AIM: To investigate whether single nucleotide polymorphisms in maf protein K (MAFK), which encodes the MAFK, lead to increased susceptibility to ulcerative colitis in the Japanese population. METHODS: This case control study examined the associations between MAFK single nucleotide polymorphisms (rs4268033 G>A, rs3735656 T>C and rs10226620 C>T) and ulcerative colitis susceptibility in 174 patients with ulcerative colitis (UC) cases, and 748 subjects without no lower abdominal symptoms, diarrhea or hematochezia (controls). In addition, as the second controls, we set 360 subjects, who have an irregular bowel movement without abnormal lower endoscopic findings (IBM controls). RESULTS: The genotype frequency of rs4268033 AA and allelic frequency of the rs4268033A allele were significantly higher in the UC cases than in both controls (P = 0.0005 and < 0.0001, P = 0.015 and 0.0027 vs controls and IBM controls, respectively). Logistic regression analysis after adjustment for age and gender showed that the rs4268033 AA and rs3735656 CC genotypes were significantly associated with susceptibility to UC development (OR = 2.63, 95%CI: 1.61-4.30, P = 0.0001 and OR = 1.81; 95%CI: 1.12-2.94, P = 0.015, respectively). Similar findings were observed by the comparison with IBM controls. In addition, the rs4268033 AA genotype was significantly associated with all phenotypes of UC except early onset. There was no significant association between rs10226620 and ulcerative colitis. CONCLUSION: Our results provide the first evidence that MAFK genetic polymorphisms are significantly associated with susceptibility to UC development. In particular, rs4268033 is closely associated with an increased risk for the development of UC.
Assuntos
Colite Ulcerativa/genética , Predisposição Genética para Doença , Fator de Transcrição MafK/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Colite Ulcerativa/diagnóstico por imagem , Colite Ulcerativa/epidemiologia , Colo/diagnóstico por imagem , Colonoscopia , Feminino , Frequência do Gene , Genótipo , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , RiscoRESUMO
Ischemia-reperfusion (IR) injury is a major clinical problem and is associated with numerous adverse effects. GGsTop [2-amino-4{[3-(carboxymethyl)phenyl](methyl)phosphono}butanoic acid] is a highly specific and irreversible γ-glutamyl transpeptidase (γ-GT) inhibitor. We studied the protective effects of GGsTop on IR-induced hepatic injury in rats. Ischemia was induced by clamping the portal vein and hepatic artery of left lateral and median lobes of the liver. Before clamping, saline (IR group) or saline containing 1 mg/kg body wt of GGsTop (IR-GGsTop group) was injected into the liver through the inferior vena cava. At 90 min of ischemia, blood flow was restored. Blood was collected before induction of ischemia and prior to restoration of blood flow and at 12, 24, and 48 h after reperfusion. All the animals were euthanized at 48 h after reperfusion and the livers were harvested. Serum levels of alanine transaminase, aspartate transaminase, and γ-GT were significantly lower after reperfusion in the IR-GGsTop group compared with the IR group. Massive hepatic necrosis was present in the IR group, while only few necroses were present in the IR-GGsTop group. Treatment with GGsTop increased hepatic GSH content, which was significantly reduced in the IR group. Furthermore, GGsTop prevented increase of hepatic γ-GT, malondialdehyde, 4-hydroxynonenal, and TNF-α while all these molecules significantly increased in the IR group. In conclusion, treatment with GGsTop increased glutathione levels and prevented formation of free radicals in the hepatic tissue that led to decreased IR-induced liver injury. GGsTop could be used as a pharmacological agent to prevent IR-induced liver injury and the related adverse events.
Assuntos
Aminobutiratos/farmacologia , Inibidores Enzimáticos/farmacologia , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Organofosfonatos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , gama-Glutamiltransferase/antagonistas & inibidores , Alanina Transaminase/sangue , Aldeídos/metabolismo , Animais , Aspartato Aminotransferases/sangue , Citoproteção , Modelos Animais de Doenças , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Fígado/enzimologia , Fígado/patologia , Hepatopatias/enzimologia , Hepatopatias/patologia , Masculino , Malondialdeído/metabolismo , Necrose , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa/metabolismo , gama-Glutamiltransferase/sangueRESUMO
Telomere shortening occurs with human aging in many organs and tissues and is accelerated by rapid cell turnover and oxidative injury. We measured average telomere length using quantitative real-time PCR in non-neoplastic gastric mucosa and assessed its relationship to H. pylori-related gastritis, DNA methylation, ulcer disease, and nonsteroidal anti-inflammatory drug (NSAID) usage. Gastric biopsies were obtained from 151 cancer-free subjects including 49 chronic NSAID users and 102 nonusers. Relative telomere length in genomic DNA was measured by real-time PCR. H. pylori infection status, histological severity of gastritis, and serum pepsinogens (PGs) were also investigated. E-cadherin (CDH1) methylation status was determined by methylation-specific PCR (MSP). Average relative telomere length of H. pylori-infected subjects was significantly shortened when compared to H. pylori-negative subjects (p = 0.002) and was closely associated with all histological parameter of gastritis (all p values <0.01) and CDH1 methylation (p = 0.0002). In H. pylori-negative subjects, NSAID users presented significantly shorter telomere length than nonusers (p = 0.028). Shorter telomere length was observed in duodenal and gastric ulcer patients compared with non-ulcer subjects among NSAID users. Telomere shortening is closely associated with severity of H. pylori-induced gastritis and CDH1 methylation status. Also, telomere shortening is accelerated by NSAID usage especially in H. pylori-negative subjects.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Caderinas/genética , Mucosa Gástrica/efeitos dos fármacos , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Telômero/genética , Anti-Inflamatórios não Esteroides/farmacologia , Antígenos CD , Metilação de DNA/efeitos dos fármacos , Feminino , Gastrite/genética , Infecções por Helicobacter/genética , Humanos , Masculino , Pessoa de Meia-Idade , Pepsinogênios/sangue , Regiões Promotoras Genéticas/efeitos dos fármacos , Telômero/efeitos dos fármacos , Encurtamento do Telômero/efeitos dos fármacosRESUMO
DNA methylation plays a significant role in gastric carcinogenesis. The CpG island methylator phenotype (CIMP) characterizes distinct subtypes of gastric cancer (GC) and the relationship between specific methylation patterns and clinicopathological features has been evaluated. Altered DNA methylation is also observed in Helicobacter pylori-infected gastric mucosa, and its potential utility for GC risk estimation has been suggested. The ability to detect small amounts of methylated DNA among tissues allows us to use DNA methylation as a molecular biomarker in GC in a variety of samples, including serum, plasma and gastric washes. The DNA methylation status of nontargeted tissue, particularly blood, has been associated with predisposition to GC. We focus on the recent development of DNA methylation-based biomarkers in GC.
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Metilação de DNA , Epigênese Genética , Neoplasias Gástricas/genética , Biomarcadores Tumorais , Ilhas de CpG , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Regulação Neoplásica da Expressão Gênica , Marcadores Genéticos , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Helicobacter pylori , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiologiaRESUMO
BACKGROUND/AIMS: Artificial ulcers remain a major complication after Endoscopic submucosal dissection (ESD). The development of more effective treatment regimen for this ulcer is required than the use of proton pump inhibitor (PPI) alone. METHODOLOGY: Patients with ESD-derived artificial ulcers were randomly assigned to two groups: a group of patients who received rabeprazole 20 mg daily for 8 weeks (PPI group) and a group of patients who received a combination of rebamipide 300 mg daily for 8 weeks and rabeprazole 20 mg dairy for the first 4 weeks (reb+PPI group). The area reduction ratio and healing status of ulcers were evaluated endoscopically on postoperative 7, 28 and 56 days. RESULTS: The overall ulcer area reduction ratio was higher in the reb+PPI group than in the PPI group, especially at an early stage. The ratio of progression to the H1 stage in the reb+PPI group was significantly higher than that in the PPI group, especially at an early stage. CONCLUSIONS: Treatment with 8 weeks of rebamipide plus the first 4 weeks of PPI demonstrated a reduction ratio of artificial ulcers superior to that with 8 weeks of PPI mono-therapy. This combination treatment is, therefore, one of the candidate treatment strategies against ESD-derived artificial ulcers.
Assuntos
Alanina/análogos & derivados , Antiulcerosos/administração & dosagem , Dissecação/efeitos adversos , Gastrectomia/efeitos adversos , Gastroscopia/efeitos adversos , Inibidores da Bomba de Prótons/administração & dosagem , Quinolonas/administração & dosagem , Rabeprazol/administração & dosagem , Neoplasias Gástricas/cirurgia , Úlcera Gástrica/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Idoso , Alanina/administração & dosagem , Alanina/efeitos adversos , Antiulcerosos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Gastrectomia/métodos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Quinolonas/efeitos adversos , Rabeprazol/efeitos adversos , Neoplasias Gástricas/patologia , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Taste is an important element in food preferences. Gastroesophageal reflux disease (GERD) is related to lifestyles including eating habits. We aimed to investigate the relationship between responses to specific tastes and GERD. METHODS: Altogether 280 patients including 170 men with a mean age of 58.6 years were included in the study to determine the relationship between their liking for specific tastes and GERD using a new self-administered questionnaire (responses to various tastes and participants' sensitivity to taste and hot food and on the frequency of stomatitis). Another self-administrated questionnaire was administrated for a diagnosis of GERD (the frequency scale for the symptoms of GERD cut-off score of 10). Furthermore, 142 of 280 patients who had received esophagogastroduodenoscopy (EGD) were investigated on the association between endoscopic esophagitis and their favorite tastes. RESULTS: In the association analyses between responses to specific tastes and GERD, the group liking salty food and the group with a high frequency of stomatitis had a significantly higher incidence of GERD (salty food: odds ratio [OR] 2.059, 95% confidence interval [CI] 1.215-3.488, P = 0.0073; stomatitis: OR 2.861, 95% CI 1.558-5.253, P = 0.0007, respectively). In association analyses with endoscopic esophagitis, the groups liking salty and sour food had a significantly higher incidence rate of endoscopic esophagitis (salty: OR 2.718, 95% CI 1.330-5.555, P = 0.0061; sour: OR 3.267, 95% CI 1.491-7.160, P = 0.0031, respectively). CONCLUSIONS: Sensitivity and response to specific food taste were associated with GERD. The results of a preference to hot or salty food and endoscopic esophagitis suggest that physical stimuli are important for esophageal injuries.