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OBJECTIVE: The aim of this study was to determine the prevalence of mesenteric panniculitis (MP) and to describe its clinical characteristics, therapy, and outcome. SUBJECTS AND METHODS: This retrospective study was carried out among patients with MP based on computed tomography (CT) scans from January 2012 to December 2015. The CT images were reanalyzed by study radiologists to confirm the previous MP diagnosis. Patients were divided into 2 groups, i.e., idiopathic and secondary, based on the presence or absence of associated predisposing factors such as trauma, malignancy, autoimmune disorders, ischemia, or previous abdominal surgery. The clinical characteristics of the 2 groups, as well as treatments, were assessed. RESULTS: Among the 19,869 CT scans, 36 patients (0.18%) with MP were identified (i.e., 19 [53%] females and 17 [47%] males). The median age was 54 years (range 26 - 76). Twenty-four patients (67%) were categorized into the idiopathic group. Malignancy was the predisposing factor in 8 (22%) of those patients. Furthermore, abdominal pain was the cardinal symptom observed in 22 patients (92%) in the idiopathic group. In the idiopathic group, 15 patients (63%) were treated with antibiotics and 16 (67%) were treated with nonsteroidal anti-inflammatory drugs (NSAID). One unresponsive patient was treated with colchicine. Symptomatic relief was achieved in all of the treated patients. CONCLUSION: In this study, a symptomatic idiopathic subgroup of patients with MP did not have any associated disorder. The response to treatment with antibiotics and NSAID was effective in most of the patients. Based on these findings, anti-inflammatory treatments beyond NSAID and surgery should be reserved for patients who are unresponsive to antibiotics and NSAID.
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Paniculite Peritoneal/fisiopatologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paniculite Peritoneal/diagnóstico , Paniculite Peritoneal/tratamento farmacológico , Paniculite Peritoneal/epidemiologia , Prevalência , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The occurrence of spontaneous bacterial peritonitis (SBP) is significantly increased in carriers of nucleotide-binding oligomerization domain-containing protein 2 (NOD2) variants, suggesting that local immune alterations might be implicated in bacterial translocation (BT). AIMS: We aimed to assess the role of the NOD2 gene in conferring susceptibility to SBP. We also sought to determine whether levels of serum interleukin-6 (IL-6), lipopolysaccharide-binding protein, and soluble TNF-α receptor, along with the presence of bacterial DNA (bactDNA) in ascitic fluid, are appropriate markers for BT in patients with liver cirrhosis and SBP. METHODS: A cohort of 171 patients was divided into two groups: patients with SBP (n = 82) and those without SBP (n = 89). The presence of the most common NOD2 variants (p.R702W, p.G908R, and c.3020insC) was determined in these patients. RESULTS: We detected the p.G908R variant in four patients (4.9 %) of the SBP group. No significant difference was observed between the SBP and non-SBP groups for NOD2 risk variants. The frequency of bactDNA in ascitic fluid was higher for patients with NOD2 variants than for patients without variants (p = 0.021). Serum IL-6 levels in the SBP group were higher than those in the non-SBP group. CONCLUSIONS: The frequent detection of bactDNA in ascites of patients with the p.G908R variant suggests there is a strong association between NOD2 risk variants and BT in SBP patients. In addition, increased serum IL-6 levels and bactDNA in ascitic fluid could be considered surrogate markers for BT in patients with cirrhosis.
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Infecções Bacterianas/microbiologia , Predisposição Genética para Doença , Variação Genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Peritonite/microbiologia , Adulto , Idoso , Infecções Bacterianas/genética , Translocação Bacteriana , Feminino , Regulação da Expressão Gênica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Adaptadora de Sinalização NOD2/genética , Peritonite/genéticaRESUMO
AIM/BACKGROUND: Pistacia terebinthus is used as a coffee substitute in the East and Southern Anatolia regions of Turkey. It contains unsaturated fatty acids, tocopherols, polyphenols and carotenoids. P. terebinthus has anti-inflammatory and potential antioxidant activity. In this study we evaluated the protective effects of P. terebinthus coffee (PTC) on thioacetamide (TAA)-induced liver injury in rats. MATERIALS AND METHODS: Twenty-eight male Sprague-Dawley rats were equally randomized into four groups. Chronic liver injury was induced with TAA (100 mg/kg i.p. three times weekly). The first group of rats served as control and received only tap water (G1), and the remaining groups of rats received PTC, p.o (G2); TAA (G3); TAA plus PTC, p.o (G4), respectively. RESULTS: After 8 weeks, PTC intake significantly reduced fibrosis/inflammation scores (p PTC intake reduced transforming growth factor beta (TGF-ß) concentrations in the liver (p PTC intake. DISCUSSION AND CONCLUSION: PTC intake provided beneficial effects against TAA-induced liver injury in rats. PTC probably suppresses the proinflammatory cytokines through NF-κB signaling pathway.
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Inflamação/tratamento farmacológico , Cirrose Hepática Experimental , Fígado , Estresse Oxidativo/efeitos dos fármacos , Pistacia , Chás de Ervas , Triterpenos/farmacologia , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/fisiopatologia , Cirrose Hepática Experimental/prevenção & controle , Masculino , Noxas/toxicidade , Ratos , Ratos Sprague-Dawley , Tioacetamida/toxicidade , Fator de Crescimento Transformador beta/metabolismo , Resultado do TratamentoRESUMO
Introduction: In the present study, we aimed to examine the effects of the administration of whey protein through rectal enema to rats with acetic acid-induced ulcerative colitis on the pathways of nuclear-related factor-2 (Nrf-2), haem oxygenase-1 (HO-1), nuclear factor κB (NF-κB), active protein kinase-1 (AP-1), tumour necrotising factor-α (TNF-α), and cyclooxygenase-2 (COX-2), IL-6, IL-10. Material and methods: Twenty-eight rats were employed for the trial. Ulcerative colitis was induced through the use of acetic acid. The therapeutic doses of whey protein were administered rectally. Ulcerative colitis was subjected to histopathological examination and protein levels in colon tissue were measured with the Western blot method. Results: The significant increases observed in the levels of AP-1, COX-2, IL-6, IL-10, NF-κB, and TNF-α as markers of inflammation following the development of ulcerative colitis showed remarkable decreases along with the administration of whey protein (p < 0.05). On the other hand, we identified a decrease in the Nrf2-ARE signal pathway and HO-1 protein having protective roles in the colon inflammatory response along with the development of ulcerative colitis and activation of the Nrf2-HO-1 pathway by the whey protein. Conclusions: Whey protein modulates Nrf2/HO-1 and NF-kB pathways, thereby creating a therapeutic effect against colonic inflammation induced by acetic acid (AA) due to its anti-inflammatory effects.
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BACKGROUND AND AIM: The epithelial cells are the strongest determinants of the physical intestinal barrier. Tight junctions (TJs) hold the epithelial cells together and allow for selective paracellular permeability. Larazotide acetate (LA) is a synthetic octapeptide that reduces TJ permeability by blocking zonulin receptors. In this study, we aimed to investigate the effects of LA, a TJ regulator, on the liver and intestinal histology in the model of acute liver failure (ALF) in rats. MATERIALS AND METHODS: The thioacetamide (TAA) group received intraperitoneal (ip) injections of 300 mg/kg TAA for 3 days. The TAA+LA(dw) (drinking water) group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of TAA. The LA(dw) group received 0.01 mg/mL LA orally. The TAA + LA(g) (gavage) group received prophylactic 0.01 mg/mL LA via oral gavage for 7 days before the first dose of TAA. The LA(g) group received 0.01 mg/mL LA via oral gavage. While liver tissue was evaluated only with light microscopy, intestinal samples were examined with light and electron microscopy. RESULTS: Serum ammonia, AST, and ALT levels in the TAA group were significantly higher than in control groups (all p < 0.01). Serum ALT levels in the TAA + LA(dw) group were significantly lower than in the TAA group (p < 0.05). However, serum ammonia and ALT levels did not differ between the TAA and other groups. Serious liver damage in the TAA group was accompanied by marked intestinal damage. There was no significant difference between the TAA and TAA + LA(dw) groups and TAA and TAA + LA(g) groups for liver damage scores. However, intestinal damage scores significantly decreased in the TAA + LA(dw) group compared to the TAA group. In the TAA + LA(dw) group, fusion occurred between the surface epithelial cells of neighboring villi and connecting regions formed as epithelial bridges between the villi. CONCLUSION: Our findings suggest that LA reduced intestinal damage by acting on TJs in the TAA-induced ALF model in rats.
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Intestinos/efeitos dos fármacos , Falência Hepática Aguda/tratamento farmacológico , Fígado/efeitos dos fármacos , Oligopeptídeos/farmacologia , Junções Íntimas/efeitos dos fármacos , Animais , Masculino , Oligopeptídeos/uso terapêutico , Ratos , Ratos WistarRESUMO
Objective To compare clinical and laboratory features of elderly patients with and without diverticulosis and assess factors related to hepatosteatosis. Method This retrospective case-control study analysed the clinical and laboratory data, colonoscopy and abdominal ultrasonography records of patients >65 years who underwent colonoscopies. Subjects were categorized according to the presence and absence of colonic diverticulosis. Univariate/multivariate logistic regression analyses were performed to evaluate the independent predictive factors of hepatosteatosis. Results A total of 355 patients were enrolled in the study: 169 had colonic diverticulosis; and 186 without colonic diverticulosis formed the control group. Age, sex and chronic disorders associated with the metabolic syndrome did not differ between the diverticulosis and control groups. The rate of hepatosteatosis was lower in patients with diverticulosis compared with the control group (27% versus 42%, respectively). Diabetes mellitus, hyperlipidaemia and hepatosteatosis were more common among patients aged <75 years. In the multivariate logistic regression analysis, diverticulosis remained an independent predictor of hepatosteatosis (odds ratio 0.529; 95% confidence interval 0.323, 0.866). Other independent predictive factors in the multivariate analysis were triglyceride and albumin. Conclusion Diverticulosis in the elderly was found to be a negative predictor of hepatosteatosis. Higher values of albumin and triglyceride in conjunction with the absence of diverticulosis may be suggestive of nonalcoholic fatty liver disease in the elderly.
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Divertículo/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Idoso , Demografia , Feminino , Humanos , Modelos Logísticos , Masculino , Análise MultivariadaRESUMO
OBJECTIVE: This prospective study aimed to determine the prevalence of anti-HDV seropositivity among subjects who had previous hepatitis B virus (HBV) infection. METHODS: Subjects who were admitted to the gastroenterology inpatient clinic of our hospital between August 2016 and July 2017 were screened for previous HBV infection. The subjects who had HBV serology compatible with resolved HBV infection were recruited in the study, and the seroprevalance of anti-HDV was studied. Participants answered a short questionnaire regarding their family history of chronic hepatitis B (CHB) and chronic hepatitis D (CHD) infection and risk factors for transmission. Subjects who were anti-HDV positive were recalled for a control visit, and HBV-DNA and HDV-RNA were assayed in the blood samples of the responders. RESULTS: Among 554 subjects who had previous HBV infection, 53 (9.6%) were anti-HDV positive. The mean age was 63.1±15.4 years in the anti-HDV-positive group and 65.9±15.6 years in the anti-HDV-negative group (p=0.19). The most common risk factor for both groups was dental procedures (89% vs 80%, p=0.33). Anti-Hbc IgG, anti-Hbs, and anti-HBeAg seropositivity did not differ between the anti-HDV-positive and -negative groups (for all, p>0.05). Although HDV-RNA was not detectable in all studied samples, only one subject had detectable HBV-DNA in the anti-HDV-positive group. CONCLUSION: This study highlighted the prevalence of anti-HDV among subjects who had resolved HBV infection. Long-term follow-up studies, including after the resolution of both infections, are needed to explore HBV-HDV interactions and the behavioral patterns of these viruses.
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Data evaluating the presence and characteristics of mesenteric lymph nodes (LNs) in patients with ulcerative colitis (UC) are scarce. The aim of this study is to determine the presence and characteristics of LNs in UC. The LN characteristics in computed tomography (CT), including LN dimension and attenuation, were evaluated retrospectively in 100 patients with UC (61 active and 39 inactive cases). Clinical characteristics and laboratory parameters, including CBC, biochemical analysis, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were also compared. Mesenteric LNs were evident in all patients with UC. The attenuation and dimension of mesenteric LNs did not differ between active and inactive patients with UC. No correlation was found among patients with UC in terms of LN dimension, attenuation, ESR, CRP, leucocyte, and albumin (all with p > 0.05). The current study suggested that inflammation results in the development of mesenteric LN in UC, similar to Crohn’s disease and other inflammatory disorders.
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INTRODUCTION: Pegylated-interferon alpha (Peg-IFN α) is the therapy most commonly used to treat chronic hepatitis delta virus (HDV) infection. In the present study, we planned to investigate effect of IL28B polymorphism on response to Peg-IFN α therapy and disease progression in patients with chronic HDV. METHODOLOGY: A total of 47 patients who received Peg-IFNα therapy for at least one year were investigated. The patients were divided into three groups based on their response to treatment: sustained viral response (SVR) (32%), unresponsive (53%), and relapse (15%). The groups were compared in terms of age, gender, blood biochemistry (albumin, total bilirubin, lactic acid dehydrogenase, ALT, AST, ALP, GGT), complete blood count, HBeAg, HBsAg, HBV-DNA, HDV-RNA, IL28B genotypes (CC, CT, TT), and results of liver biopsy. RESULTS: Regarding the investigation of IL28B genotype, the prevalence of CC, CT, and TT showed no difference among the three groups. In the SVR group, the prevalence of CC was 53%, CT was 47%, but there was no patient with TT. In the unresponsive group, prevalence of CC was 52%, CT was 32%, and TT was 16%. In the relapse group, prevalence of CC was 43%, CT was 57%, but there was no patient with TT genotype. No significant difference was found among the groups with sustained response, no response, and relapse in terms of CC and CT polymorphisms (p>0.05). CONCLUSIONS: No relationship was found between IL28B rs12979860 polymorphism and response to treatment and disease severity in patients with chronic HDV infection.
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Hepatite D/tratamento farmacológico , Hepatite D/patologia , Vírus Delta da Hepatite/imunologia , Interferon-alfa/uso terapêutico , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Biópsia , Feminino , Humanos , Interferons , Fígado/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND/AIMS: Steroids have been shown to prevent intestinal oxidative stress. We investigated the effects of methylprednisolone on intestinal oxidative damage and bacterial translocation in thioacetamide-induced liver failure in rats. MATERIALS AND METHODS: Group 1 (n=8) was the control group. In group 2 (n=8), the thioacetamide group, rats received 300 mg/kg intraperitoneal thioacetamide daily for 2 days. In group 3 (n=8), the thioacetamide+methylprednisolone group, treatment with methylprednisolone (30 mg/kg intraperitoneal) was commenced 48 h before the first dose of thioacetamide. In group 4 (n=8), the methylprednisolone group, the rats received only methylprednisolone (30 mg/kg intraperitoneal). RESULTS: Serious hepatic and intestinal oxidative damage and high bacterial translocation frequencies were observed in the thioacetamide group compared with those of the controls. Bacterial translocation frequency in the thioacetamide+methylprednisolone group was significantly lower than that in the thioacetamide group (p<0.05). Intestinal thiobarbituric acid-reactive substances and myeloperoxidase levels and tissue damage scores for the intestines in the thioacetamide+methylprednisolone group were lower than those in the thioacetamide group (p<0.01, p<0.01, and p<0.0001, respectively). CONCLUSION: Our findings suggest that methylprednisolone reduces bacterial translocation by preventing intestinal oxidative damage in this model of acute liver failure in rats.
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Translocação Bacteriana/efeitos dos fármacos , Glucocorticoides/farmacologia , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/microbiologia , Metilprednisolona/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glutationa/metabolismo , Íleo/metabolismo , Íleo/microbiologia , Íleo/patologia , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Masculino , Peroxidase/metabolismo , Ratos , Ratos Wistar , Tioacetamida , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
BACKGROUND/AIMS: Gingko biloba is an antioxidant substance which has antagonistic activity on platelet-activating factor. We aimed to investigate the antioxidant effect and the histopathologic changes caused by Gingko biloba on acetic acid-induced colitis. METHODS: Totally 22 rats were divided into three groups. Group 1 (n=7) served as the control group. Group 2 (n=7) and Group 3 (n=8) were given 2 ml/day of 4% acetic acid by intracolonic instillation for three days. Gingko biloba (100 mg/kg) was then given only to Group 3 intraperitoneally for three days. Oxidative stress was assessed by determinate tissue and serum malondialdehyde (MDA) levels, and colonic damage was assessed by histologic examination. RESULTS: Depth of necrosis, extent of necrosis, degree of inflammation, extent of inflammation, fibrosis and total histologic scores in Group 2 were significantly higher than in the control group (p<0.05). The same parameters were lower in Group 3 versus Group 2, but the difference was not significant. Tissue and serum MDA levels in Group 2 were significantly higher than Group 1 (p<0.01 and 0.05, respectively). Again, the same parameters in Group 3 were lower than in Group 2, but the difference was not significant statistically. CONCLUSIONS: Gingko biloba did not significantly affect histopathological and oxidative stress parameters in experimental colitis.
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Ácido Acético/efeitos adversos , Colite/tratamento farmacológico , Ginkgo biloba , Fitoterapia , Animais , Antioxidantes/farmacologia , Biomarcadores/sangue , Colite/induzido quimicamente , Colite/patologia , Modelos Animais de Doenças , Fibrose/induzido quimicamente , Fibrose/prevenção & controle , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Malondialdeído/sangue , Necrose/induzido quimicamente , Necrose/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fator de Ativação de Plaquetas/efeitos dos fármacos , Fator de Ativação de Plaquetas/metabolismo , Ratos , Ratos WistarRESUMO
INTRODUCTION: In this study, we aimed to investigate the histological and clinical effect of angiotensin-converting enzyme (ACE) and ACE gene polymorphism in nonalcoholic fatty liver disease (NAFLD) and their roles in the progression of the disease. MATERIALS AND METHODS: Liver function tests, body mass index, waist circumference, lipid parameters, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), homeostasis model assessment-IR (HOMA-IR), ACE, and ACE gene polymorphism were evaluated in the NAFLD group and control group. The study group was evaluated by dividing the group into four subgroups by ACE gene polymorphism (D/D homozygous, I/I homozygous, D/I heterozygous, I/D heterozygous). Liver biopsies were evaluated according to Brunt Classification. RESULTS: A total of 31 patients who were diagnosed with NAFLD and 40 healthy individuals were included in the study. The ACE level was found to be 11.69 ± 1.99 in the NAFLD group and 11.52 ± 1.72 in the control group (p = 0.70). There was a negative correlation between ACE levels and HOMA-IR levels (p = 0.008, r= -0.512). Biochemical parameters were not different among ACE gene polimorphism subgroups, except FBG (between D/D, I/D and D/I, I/D; p = 0.02). When the ACE levels were compared in terms of grade and stage, no significant difference was found (for stage and grade p = 0.68). The ACE gene polymorphism subgroups did not differ by histopathologic findings; grade and stage (for grade p = 0.42, for stage p = 0.92). CONCLUSION: In this study, we could not find a correlation of ACE and ACE gene polymorphism with metabolic risk factors and the disease severity in NAFLD. HOW TO CITE THIS ARTICLE: Tekatas DD, Bahcecioglu IH, Ispiroglu M, Sahin A, Ilhan N, Yalniz M, Demirel U. Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):137-142.
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BACKGROUND: The only established therapy for chronic viral delta hepatitis, the most severe form of viral hepatitis is treatment with pegylated-interferon α (Peg IFN α). OBJECTIVES: In this study, we aimed to determine the efficacy of pegylated-interferon α 2a (Peg-IFN α 2a) and 2b (Peg IFN α 2b) in the treatment of patients infected with chronic delta hepatitis virus. PATIENTS AND METHODS: The sample size was based on available patients potentially to be recruited. Data of 63 patients receiving either Peg IFN alpha 2a or Peg IFN alpha 2b were retrospectively assessed in the present cohort study performed in Turkey. Of 56 patients completed the study, 41 received Peg IFN α 2a and 15 received Peg IFN α 2b for 12 months. Patients were evaluated for biochemical and virological responses at the end of given treatment and six months after the treatment. RESULTS: Stage of fibrosis was found high in both groups (85.4% vs. 86.7%), while cirrhosis was higher in the group of Peg IFN α 2b (53.3% vs. 34.1%). At the end of treatment, either hepatitis delta virus RNA (HDV RNA) alone or both HDV RNA and hepatitis b virus DNA (HBV DNA) had negative results in 32% of patients. Although HDV RNA negativity was sustained in 30.3% of patients, negativity of both HDV RNA and HBV DNA was decreased to 19.6% six months after completion of the treatment. HBV DNA became positive in one third of patients with response at six months after completion of the treatment (10.7% of all patients). HDV RNA negativity at month six was found as a predictor of positive response. No significant difference was found between Peg IFN α 2a and Peg IFN α 2b for virological response rate. CONCLUSIONS: Treatment with Peg IFN α achieved a sustained negativity of HDV RNA in about one third of patients. Duration of Peg IFN α therapy might be prolonged to at least 24 months or more to prevent the occurrence of Hepatitis B virus (HBV) relapse encountered six months after completion of the treatment.
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The aims of our work were to determine the presence of the cag pathogenicity-island (cag PAI) and other virulence genes of Helicobacter pylori recovered from patients with gastritis and peptic ulcer, and to investigate the correlation of these virulence genes with clinical outcome. The presence of the cagA, the promoter regions of cagA, cagE, cagT, and the left end of cag-PAI (LEC), cag right junction (cagRJ), the plasticity region open reading frames (ORFs), vacA and oipA genes among 69 H. pylori isolates were determined by polymerase chain reaction. Intact cag PAI was detected in only one (1.4%) isolate. The cagA gene was identified in 52.1% and 76.2% of isolates from patients with dyspepsia (gastritis and peptic ulcer), respectively. The plasticity region ORFs i.e. JHP912 and JHP931 were predominantly detected in isolates from peptic ulcer. Less than 25% of the isolates carried other ORFs. Types I, II and III were the most commonly found among the isolates. None of the isolates possessed type Ib, 1c, IIIb, IV and V motifs. The most commonly vacA genotypes were s1am1a and s1m2 in isolates with peptic ulcer and gastritis, respectively. The results confirmed that the prevalence of oipA (Hp0638) gene was 75% and 85.7% in patients with gastritis and peptic ulcer, respectively. Furthermore, vacA s1am1a positivity was significantly related to peptic ulcer (p < 0.05).
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Dispepsia/microbiologia , Dispepsia/patologia , Ilhas Genômicas , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Fatores de Virulência/genética , DNA Bacteriano/genética , Variação Genética , Genótipo , Helicobacter pylori/isolamento & purificação , Humanos , Reação em Cadeia da Polimerase , Resultado do Tratamento , TurquiaRESUMO
Effects of nadroparin sodium, a low molecular weight heparin, in colitis was investigated by analyzing proteins implicated in nuclear factor E2-related factor-2/heme oxygenase-1 (Nrf2/HO-1) and nuclear factor kappa B (NF-κB) pathways. Twenty-eight rats were used. Colitis was induced by acetic acid (AA). Nadroparin sodium was given to prevention and treatment groups in addition to AA. Colitis was assessed histologically and levels of proteins were analyzed with Western blot. Nadroparin not only prevented and ameliorated the AA-induced colitis histopathologically but also decreased expression of colon NF-κB, activator protein-1, cyclooxygenase-2, tumor necrosis factor-alpha, and IL-6, which were significantly increased in group AA compared to control. The accumulation of Nrf2 in nuclear fraction and HO-1 found low in group AA was increased with nadroparin (p < 0.05). The mean malondialdehyde level increased with AA and was decreased significantly with nadroparin prevention and treatment (p < 0.001). Nadroparin sodium has both protective and therapeutic effects against colonic inflammation via exerting anti-oxidative and anti-inflammatory effects by modulating Nrf2/HO-1 and NF-κB pathways.
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Colite/tratamento farmacológico , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Nadroparina/farmacologia , Ácido Acético , Animais , Colite/induzido quimicamente , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Ciclo-Oxigenase 2/biossíntese , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Interleucina-6/biossíntese , Masculino , Malondialdeído/análise , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Nadroparina/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição AP-1/biossíntese , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Oxidative stress plays important role in the development of acute liver failure. In this study, we investigated effects of allopurinol (AP) upon thioacetamide (TAA)-induced liver injury and the potential mechanisms leading to amelioration in inflammation with AP treatment. Acute liver failure was induced by intraperitoneal administration of TAA (300 mg/kg/day for 2 days). Thirty-five rats were divided into five groups as control (group 1), TAA (group 2), TAA + 25AP (group 3), TAA + 50 AP (group 4), and TAA + 100AP (group 5). The number of animals in each group was seven. At the end of the study, histopathological, biochemical, and western blot analysis were done. TAA treatment significantly increased serum levels of aminotransferases, liver malondialdehyde (MDA), nuclear factor-kappa B (NF-ÒB ), activator protein-1 (AP-1), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels, and the necro-inflammation scores. Nevertheless, nuclear factor E2-related factor-2 and heme oxygenase-1 (HO-1) expressions in the liver were decreased by TAA. AP treatment significantly lowered the serum levels of aminotransferases (P < 0.01) and liver MDA, NF-κB, AP-1, TNF-α, COX-2, and IL-6 expressions (P < 0.05). Moreover, AP restored the liver Nrf2 and HO-1 expressions and improved the necro-inflammation scores significantly. AP improves oxidative stress-induced liver damage by regulating cellular redox-sensitive transcriptor factors and expression of pro-inflammatory and antioxidant defense mechanisms. AP probably exerts these beneficiary features by its free radical scavenging ability in a dose-dependent manner.
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Alopurinol/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Inflamação/tratamento farmacológico , Falência Hepática Aguda/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Animais , Antioxidantes , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ciclo-Oxigenase 2/sangue , Heme Oxigenase-1/biossíntese , Interleucina-6/sangue , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Masculino , Malondialdeído/análise , Fator 2 Relacionado a NF-E2/biossíntese , NF-kappa B/sangue , Oxirredução , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Tioacetamida , Transaminases/sangue , Fator de Transcrição AP-1/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Intestinal bacterial overgrowth (IBO) and increased mucosal permeability are suggested to increase bacterial translocation (BT) in liver injury. Rifaximin (RIF) is a minimally absorbed oral antimicrobial agent that restores gut microflora imbalance. The aim of the present study was to investigate the effects of RIF on BT frequency in thioacetamide (TAA)-induced liver injury. Group 1 was the control. In group 2 (TAA), rats received TAA daily for 3 days. In group 3 (TAA + RIF), RIF was commenced on the same day as the first dose of TAA. In group 4 (RIF), rats received only RIF. Ileal aspirate Escherichia coli counts were significantly lower in the TAA + RIF group than in TAA group. There was no difference in BT frequency between the TAA and TAA + RIF groups. Our results suggest that factors such as intestinal barrier dysfunction and impaired host immune shield, apart from IBO, play an important role in BT in this model.
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Translocação Bacteriana/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/microbiologia , Escherichia coli/crescimento & desenvolvimento , Íleo/microbiologia , Rifamicinas/farmacologia , Tioacetamida/toxicidade , Animais , Carga Bacteriana , Doença Hepática Induzida por Substâncias e Drogas/patologia , Escherichia coli/isolamento & purificação , Íleo/efeitos dos fármacos , Fígado/microbiologia , Masculino , Ratos , Ratos Wistar , Rifamicinas/uso terapêutico , RifaximinaRESUMO
Tumor necrosis factor (TNF)-α antibodies have been shown to reduce liver damage in different models. We investigated the effects of infliximab (a TNF-α antibody) on liver damage in thioacetamide (TAA)-induced hepatotoxicity in rats. Group 1 (n = 8) was the control group. In group 2 (n = 8), the TAA group, the rats received 300 mg/kg intraperitoneal (ip) TAA daily for 2 days. In group 3 (n = 8), the TAA + Infliximab (INF) group, infliximab (5 mg/kg ip daily) was administered 48 hours before the first dose of TAA daily for 2 days and was maintained for 4 consecutive days. In group 4 (n = 8), the INF group, the rats received only ip infliximab (5 mg/kg) daily. Livers were excised for histopathological and biochemical tests (thiobarbituric-acid-reactive substances [TBARS], and myeloperoxidase [MPO]). Serum ammonia, aspartate transaminase (AST), alanine transaminase (ALT), TNF-α, liver TBARS and MPO levels, and liver necrosis and inflammation scores in the TAA group were significantly higher than in the control and INF groups (all p < 0.01). All parameters except AST were not significantly different between TAA and TAA + INF. In conclusion, our results suggest that oxidative stress plays an important role in TAA-induced hepatotoxicity, and infliximab does not improve oxidative liver damage.
Assuntos
Anticorpos Monoclonais/farmacologia , Antídotos/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Tioacetamida/toxicidade , Fator de Necrose Tumoral alfa/imunologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Antagonismo de Drogas , Infliximab , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangueAssuntos
2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Antiulcerosos/uso terapêutico , Úlcera Duodenal/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Omeprazol/uso terapêutico , Adolescente , Adulto , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Quimioterapia Combinada , Úlcera Duodenal/complicações , Úlcera Duodenal/microbiologia , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol , Inibidores da Bomba de Prótons , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
The aims of our work were to determine the presence of the cag pathogenicity-island (cag PAI) and other virulence genes of Helicobacter pylori recovered from patients with gastritis and peptic ulcer, and to investigate the correlation of these virulence genes with clinical outcome. The presence of the cagA, the promoter regions of cagA, cagE, cagT, and the left end of cag-PAI (LEC), cag right junction (cagRJ), the plasticity region open reading frames (ORFs), vacA and oipA genes among 69 H. pylori isolates were determined by polymerase chain reaction. Intact cag PAI was detected in only one (1.4%) isolate. The cagA gene was identified in 52.1% and 76.2% of isolates from patients with dyspepsia (gastritis and peptic ulcer), respectively. The plasticity region ORFs i.e. JHP912 and JHP931 were predominantly detected in isolates from peptic ulcer. Less than 25% of the isolates carried other ORFs. Types I, II and III were the most commonly found among the isolates. None of the isolates possessed type Ib, 1c, IIIb, IV and V motifs. The most commonly vacA genotypes were s1am1a and s1m2 in isolates with peptic ulcer and gastritis, respectively. The results confirmed that the prevalence of oipA (Hp0638) gene was 75% and 85.7% in patients with gastritis and peptic ulcer, respectively. Furthermore, vacA s1am1a positivity was significantly related to peptic ulcer (p < 0.05).