Anti-inflammatory Effects of Flavonoids on TNBS-induced Colitis of Rats

It has been shown that the extracts including eupatilin and quercetin-3-β-D-glucuronopyranoside had mucoprotective effects on the esophagus and stomach through their antioxidant activities. This study was designed to investigate the anti-inflammatory effect of these flavonoid compounds in an animal model of inflammatory bowel disease induced by 2,4,6-trinitrobenzene sulfonic acid. Experimental colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid. Extracts including eupatilin or quercetin-3-β-D-glucuronopyranoside were orally administered to animals 48, 24, and 1 h prior to the induction of colitis and then again 24 h later. The animals were sacrificed 48 h after by 2,4,6-trinitrobenzene sulfonic acid treatment and the macroscopic appearance of the colonic lesions was scored in a blinded manner on a scale of 1 to 10. The inflammatory response to colitis induction was assessed by measuring myeloperoxidase activity, nitric oxide production, tumor necrosis factor-α expression, total glutathione levels, and malondialdehyde concentrations in the colon. The results indicated that extracts including eupatilin and extracts including quercetin-3-β-D-glucuronopyranoside dose-dependently improved the morphology of the lesions induced by 2,4,6-trinitrobenzene sulfonic acid and reduced the ulcer index accordingly. In addition, rats receiving extracts including eupatilin and extracts including quercetin-3-β-D-glucuronopyranoside showed significantly decreased levels of mucosal myeloperoxidase activity, nitric oxide production, tumor necrosis factor-α expression, and malondialdehyde levels, and increased total glutathione levels. Extracts including eupatilin and extracts including quercetin-3-β-D-glucuronopyranoside ameliorated the inflammatory response and colonic injury in acute colitis by decreasing oxidative stress and neutrophil activation. Extracts including eupatilin and extracts including quercetin-3-β-D-glucuronopyranoside may inhibit acute colitis.     

Prognostic Value of Renal Function for Cardiac Events in Patients Without Significant Stenosis on Coronary Computed Tomography Angiography

This study was conducted to determine clinical parameters predicting future major adverse cardiovascular events (MACEs) in patients without significant stenosis on coronary computed tomographic angiography (CCTA). A total of 625 patients with suspected coronary artery disease (CAD) who underwent CCTA that revealed insignificant (< 50%) CAD was reviewed in three cardiac centers. The MACEs including cardiac death, non-fatal myocardial infarction (MI), unstable angina and late (> 90 days after CCTA) revascularization were assessed. During the mean follow-up period of 819 ± 529 days (median 837 days), there were 28 cases of MACEs (4.5%). In multivariable Cox regression analysis, independent predictors for MACEs were male sex (hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.01-5.69; P = 0.046) and low estimated creatinine clearance (eCCr) (< 60 mL/min/1.73 m²) (HR, 3.07; 95% CI, 1.22-7.74; P = 0.017). Low eCCr was the only independent predictor for hard events including cardiac death and MI (HR, 17.6, 95% CI, 1.44-215.7; P = 0.025). In conclusion, renal function is an independent predictor for cardiovascular events among patients without significant CAD by CCTA. Careful monitoring and preventive strategy are warranted in patients with impaired renal function even without significant CAD.

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Prognostic significance of bcl-2, bax,and p53 expression in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLCL) exhibits heterogeneous clinical features and varies markedly in response to treatment and prognosis. Because apoptosis-related proteins may play an important role in predicting the prognosis of DLCL, the current study investigated the prognostic significance of a high level of bcl-2, bax, and p53 expression in relation to clinical characteristics in patients with DLCL. Paraffin-embedded specimens from 94 patients with de novo DLCL were analyzed immunohistochemically for bcl-2, bax, and p53 gene expression. Cases with a positive immunohistological stain in more than 50% of the tumor cells were considered to have DLCL-positive expression. Patients were treated optimally, i.e., with radiotherapy including brief cycles of CHOP or CHOP-like regimens for patients with stage 1-2A diseases and with at least 6 cycles of CHOP or CHOP-like regimens for stage 2B-4 diseases. The responses to therapy and survival were then analyzed in 94 uniformly staged patients. bcl-2 expression was identified in 24 patients (26.4%), bax expression in 35 patients (37.6 %), and p53 expression in 21 patients (22.6%). bax expression proved to be a statistically significant prognostic factor in predicting the overall survival (OS) (P = 0.0015) and disease-free survival (DFS) (P = 0.0052), regardless of other clinical factors or immunohistological results. There was no significant difference in the OS (P = 0.0682) or DFS (P = 0.088) between the bcl-2-positive (n = 24) and bcl-2-negative (n = 67) groups. However, bcl-2 expression was found to be unfavorably associated with the OS (P = 0.0054) in a confined group with low (n = 51) or low intermediate (n = 22) IPI scores. The expression of p53 exhibited no statistical correlation with the OS or DFS. A multivariate analysis revealed that IPI score, bulky mass, and bax expression were all significantly associated with the DFS or OS. bax and bcl-2 should be considered as independent biologic prognostic parameters in DLCL, thereby aiding in the identification of patient risk groups. As such, bcl-2-positive patients with a low or low intermediate IPI score, or without a high level of bax expression could be candidates for more intensive therapy or alternative therapeutic approaches.     

Expression of cyclooxygenase-2 in cholangiocarcinoma: correlation with clinicopathological features and prognosis

BACKGROUND AND AIMS: No information is available on the nature of the correlation between cyclooxygenase-2 (COX-2) expression and the clinicopathological features and prognosis of cholangiocarcinoma (CC). The goal of the present study was to determine the possible roles and clinical significance of COX-2 expression in CC. METHODS: We investigated the immunohistochemical expression of COX-2 in 102 patients with CC with respect to clinicopathological characteristics, namely evidence of Clonorchis sinensis infection, proliferation index (PI, assessed by Ki-67 expression), apoptotic index (AI, assessed by TUNEL stain), and microvessel density (MVD, assessed by CD34 expression). Evidence of C. sinensis infection was assessed by the microscopic examination of stools for C. sinensis ova, serological testing (ELISA), and the detection of peripheral bile duct dilations by imaging studies. RESULTS: An immunohistochemical investigation demonstrated the immunolabeling of tumor cells, mainly in the cytoplasmic and perinuclear regions, in 53 (52%) of the 102 patients with CC. No significant differences were found in terms of age, sex, tumor differentiation, involvement of the resection margin, presence of lymph nodes or liver metastases, or in pTNM stage between COX-2 positive and COX-2 negative patients. However, evidence of C. sinensis infection was more common in COX-2 positive patients (P < 0.05). No significant differences were found for PI, AI, MVD, or cumulative survival between COX-2 positive and COX-2 negative patients. CONCLUSION: Clonorchis sinensis infection is related to aberrant COX-2 expression in patients with CC. However, COX-2 expression is not related to clinical outcome in CC patients.     

Correlation between inhalant allergen-specific IgE and pulmonary function in children with asthma

Sensitization to aeroallergens is associated with diminished lung function in adults. Little has been studied on the relationship between the inhalant allergen-specific IgE and pulmonary function in asthmatic children. This study was focused on four major inhalant allergens found in Korea, including Dermatophagoides pteronyssinus (Der p.), Dermatophagoides farinae (Der f.), and Alternaria- and German cockroach-specific IgEs, with evaluation of pulmonary function in relation to the amount of allergens. The parents or legal guardians of participants enrolled in this study gave informed consent. Fifty-five asthmatic patients and 48 nonasthmatic children were included. The amounts of specific IgE for the four specified inhalant allergens were determined by employing the CAP system FEIA. Forced expiratory volume in 1 sec (FEV(1))/forced vital capacity (FVC), FEV(1), and forced expiratory flow between 25% and 75% of FVC (FEF(25-75)) of subjects were evaluated through pulmonary function tests. In the asthmatic group, FEV(1), FEV(1)/FVC, and FEF(25-75) were significantly reduced (P < 0.05): reduction in FEV(1) (r = -0.44) and FEF(25-75) (r = -0.33) in association with the Der f.-specific allergen, and reduction in FEV(1) (r = -0.37) and FEF(25-75) (r = -0.34) in association with the Der p.-specific allergen, were observed. However, there was no significant correlation with German cockroach and Alternaria allergen. In the control group, no significant correlation was detectable between the allergen-specific IgE titers and the results of pulmonary function tests. In asthmatic patients, Der p.- and Der f.-specific IgEs, and not German cockroach and Alternaria, seem to play a considerable role in reduced pulmonary function among asthmatic children.     

Early time course of neointima formation and vascular remodelling following percutaneous coronary intervention and vascular brachytherapy of in-stent restenotic lesions as assessed by intravascular ultrasound analysis

Summary In-stent restenosis (ISR) represents the major limitation of stent implantation. Treatment, although of relative technical ease, is unsatisfactory due to a high incidence of recurrent restenosis. Vascular brachytherapy (VBT) has emerged as a powerful adjunct therapeutic modality to treat ISR. Inhibition of neointima formation has been regarded as the relevant mechanism of action. Yet, positive remodelling has been suspected as another contributing factor. Since only very few precise analyses of the extent, distribution and time course of the respective mechanims exist, the goal of the present study was to describe the changes of the vessel geometry at the target lesion and at the reference site following angioplasty and VBT of ISR in 42 patients by means of quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) before and after the index procedure and at the 3 and 6 month follow-up.By QCA the acute lumen gain measured 2.2±0.8 mm, the late lumen loss at 3 months was 0.1±0.5 mm and at 6 months 0.4±0.7 mm. By IVUS luminal cross-sectional area increased from 1.5±1.2 mm² to 7.9±1.9 mm² (p<0.001). The intima hyperplasia cross-sectional area at 3 months was only 0.2±1.0 mm² (p=0.191), but increased to 0.7±0.6 mm² (p<0.001) at 6 months resulting in a lumen cross-sectional area of 7.1±1.7 mm². Stent dimensions did not show any significant changes over time. The external elastic membrane cross-sectional area at 3 months increased by 1.3±1.9 mm² (p<0.001), and showed a further increase by 0.7±2.9 mm² at 6 months. Positive remodelling could be demonstrated also at the reference segment.In conclusion the absolute amount of intima hyperplasia during a 6-month follow-up period after VBT of ISR is low and most pronounced between the third and sixth month. Besides this, predominantly within the first 3 months of follow-up, significant positive remodelling could be demonstrated at the target lesion and at the reference site. Both observed effects may contribute to the preservation of the vessel lumen.Diese Publikation enthält die Ergebnisse der Promotionsarbeit von Frau Andrea Zimmermann     

Absence of postprandial surge in coronary blood flow distal to significant stenosis: a possible mechanism of postprandial angina

OBJECTIVES: This study was designed to investigate a possible mechanism of postprandial angina. BACKGROUND: Postprandial angina has been recognized for more than two centuries; however, its mechanism is still controversial. The most widely accepted mechanism involves increased myocardial oxygen demand after food intake. Recently, the redistribution in coronary blood flow (CBF) was suggested as a possible mechanism. METHODS: Twenty young, healthy volunteer controls and 20 patients with significant stenosis in the left anterior descending (LAD) or left main coronary artery were enrolled in the study. Coronary blood flow was evaluated in the distal LAD by using transthoracic Doppler echocardiography before and 15, 30, 45, and 60 min after food intake. In the CBF curve, the time velocity integral of diastolic flow (Dtvi) and the product of Dtvi and heart rate (HR) were measured. In six patients, these measurements were repeated after successful coronary intervention. RESULTS: In the healthy volunteer controls, Dtvi and Dtvi x HR increased after food intake with a peak value at 15 min, which indicates the presence of postprandial surge in the CBF. Fasting values and peak values at 15 min were significantly different (Dtvi: 15.1 +/- 4.9 cm/s vs. 18.9 +/- 5.9 cm/s, p = 0.04, Dtvi x HR: 862.2 +/- 261.5 cm/min vs. 1,174.2 +/- 307.5, p = 0.002). In contrast with the controls, despite postprandial increase in double product (HR x blood pressure), Dtvi and Dtvi x HR in the patient group decreased after food intake, with a nadir value at 45 min. Fasting values and nadir values at 45 min were significantly different (Dtvi: 24.0 +/- 19.6 cm/s vs. 19.3 +/- 17.1 cm/s, p < 0.001, Dtvi x HR: 1,449.6 +/- 1,044.0 cm/min vs. 1,273.4 +/- 1,000.9 cm/min, p = 0.002). In six patients, the CBF pattern resumed the normal pattern of postprandial surge in the CBF after successful coronary intervention. CONCLUSIONS: Results of our study suggest that "steal phenomenon" may play a role in the mechanism of postprandial angina.     

Mucinous Cystadenoma: Pitfalls of Differential Diagnosis

Cystic neoplasms of the pancreas often are difficult to differentiate from pseudocysts. It has been proposed that a history of clinical pancreatitis, elevated serum pancreatic enzymes, elevated cyst fluid amylase, and a communication with the pancreatic duct suggest the diagnosis of a pseudocyst. We report the case of a young woman who presented with a cystic mass in the pancreas and was thought to have a pseudocyst because of the above; at surgery, a mucinous cystadenoma was documented. The pitfalls of differentiating neoplastic cysts of the pancreas from pseudocysts are discussed.