Selective adsorption of human CD4 T cells

The pathogenesis of most autoimmune diseases directly involves CD4(+) helper T cells. To remove CD4(+) T cells selectively from the circulation, we designed a new column in which an anti-CD4 monoclonal antibody was immobilized on the activated substance. Nearly 90% of CD4(+) T cells were selectively adsorbed from whole blood with a single passage through the column in vitro, resulting in depletion of the antigen-specific T cell responses. We conclude that this new column would be potentially useful for treatment of T cell-mediated autoimmune diseases.     

Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitis

BACKGROUND: The clinical efficacy of corticosteroids in the treatment of ulcerative colitis (UC) is well-established. However, prolonged usage of these drugs can result in serious complications. Rebamipide {2-(4-chlorobenzoylamino)-3[2-(1H)-quinolinon-4-yl] propionic acid}, a cytoprotective agent, has been reported to have anti-inflammatory activity and to repair mucosal injury in animal colitis models. The aim of the present study was to assess the clinical efficacy and safety of a novel Rebamipide enema therapy in UC patients. METHODS: Twenty patients with the active distal type of UC in whom corticosteroid treatment had been unsuccessful were treated with rectal administration of Rebamipide twice a day for 3 weeks, during which corticosteroid dosage was kept constant. The efficacy of treatment was assessed from clinical symptoms and endoscopic findings. The anti-inflammatory effect of Rebamipide was also examined by monitoring changes in the intensity of histological inflammation and levels of cytokine activity in the rectal mucosa. RESULTS: At 3 weeks after the initiation of Rebamipide enema therapy, 11 patients (55%) achieved clinical remission. Sixteen (80%) were colonoscopically judged to be responders, with decreased levels of interleukin (IL)-1beta but not of IL-8, and an increased ratio of IL-1 receptor antagonist/IL-1beta in organ cultures of mucosal tissues. The change in the number of infiltrating neutrophils was not significantly correlated with the clinical response to this therapy. No side-effects were noted in any patients. CONCLUSION: Rebamipide enema therapy proved to be safe and useful in corticosteroid-refractory patients with the active distal type of UC.     

Regular exercise reduces 8-oxodG in the nuclear and mitochondrial DNA and modulates the DNA repair activity in the liver of old rats

Exercise is often said to increase the generation of reactive oxygen species that are potentially harmful. On the other hand, regular exercise has various health benefits even late in life. The specific aim of this study was to explore effects of regular exercise on oxidative status of DNA in aged animals. We report that 2 months of regular treadmill running of aged rats (21 month old) significantly reduced 8-oxodG content to the level of young adult animals (11 month old) in both nuclear and mitochondrial DNA of the liver. The mitochondrial DNA showed 10-fold higher content of the oxidative lesion than the nuclear DNA. The levels in old animals were 2- and 1.5-fold higher than that in young adults for the nucleus and mitochondria, respectively. The activity of the repair enzyme OGG1 was upregulated significantly in the nucleus but not in mitochondria by the exercise. To our knowledge, this is the first report demonstrating that regular exercise can reduce significantly oxidative damage to both the nuclear and mitochondrial DNA. We suggest that the apparent beneficial outcomes in reducing the DNA damage by regular exercise can be interpreted in terms of hormetic effect by moderate oxidative stress and potential adaptation to stronger stresses.     

Successful catheter ablation of left ventricular epicardial tachycardia originating from the great cardiac vein: a case report and review of the literature.

A patient underwent radiofrequency (RF) catheter ablation for a drug-refractory ventricular tachycardia, but RF energy application at an endocardial site of the left ventricular outflow tract and at the left sinus of Valsalva could not eliminate the tachycardia. The earliest ventricular activation during the arrhythmia, which preceded the onset of the QRS complex by 32 ms, was found within the great cardiac vein and complete elimination of the tachycardia was finally achieved with RF application at that site.     

Impact of early elevation of serum bilirubin during treatment with pegylated interferon and ribavirin in patients with chronic hepatitis C

Aim: Hemolytic anemia is a well‐known adverse effect of interferon and ribavirin combination treatment. Herein, we analyzed the impact of early elevation of serum bilirubin level as a marker for predicting severe anemia during treatment. Methods: We studied 245 chronic hepatitis C patients who received pegylated interferon and ribavirin combination treatment, and divided them using two different threshold levels: (i) elevation of total bilirubin of 0.5 mg/dL or more within 1 week of starting treatment; and (ii) drop of hemoglobin (Hb) by 3 g/dL or more within 4 weeks of starting treatment. We compared the dynamics in each group and then investigated independent factors for predicting a severe Hb drop (≥3 g/dL) at 4 weeks after beginning treatment and dose reduction of ribavirin. Results: Total bilirubin levels at 1 week were significantly higher in patients with a Hb drop of 3 g/dL or more as compared to those with a drop of less than 3 g/dL (P < 0.0001). Hb levels at 4 weeks were significantly lower in the group of 0.5 mg/dL or more increase of total bilirubin levels than in the group with a less than 0.5 mg/dL increase (P < 0.0001). Therefore, elevation of total bilirubin after 1 week of treatment was shown to be an independent factor for predicting severe Hb drop (≥3 g/dL) at 4 weeks (P < 0.0001), and dose reduction of ribavirin during treatment (P = 0.0321). Conclusion: Early elevation of serum bilirubin level was found to be a possible predictive marker of both a severe drop of Hb in the early phase of treatment and dose reduction of ribavirin.     

Shape of Barrett��s epithelium is associated with prevalence of erosive esophagitis

AIM: To test the hypothesis that the shape and length of Barrett’s epithelium are associated with prevalence of erosive esophagitis.METHODS: A total study population comprised 869 patients who underwent endoscopy during a health checkup at our hospital. The presence and extent of Barrett’s epithelium were diagnosed based on the Prague C & M Criteria. We originally classified cases of Barrett’s epithelium into two types based on its shape, namely, flame-like and lotus-like Barrett’s epithelium, and into two groups based on its length, its C extent < 2 cm, and ≥ 2 cm. Correlation of shape and length of Barrett’s epithelium with erosive esophagitis was examined.RESULTS: Barrett’s epithelium was diagnosed in 374 cases (43%). Most of these were diagnosed as short-segment Barrett’s epithelium. The prevalence of erosive esophagitis was significantly higher in subjects with flame-like than lotus-like Barrett’s epithelium, and in those with a C extent of ≥ 2 cm than < 2 cm.CONCLUSION: Flame-like rather than lotus-like Barrett’s epithelium, and Barrett’s epithelium with a longer segment were more strongly associated with erosive esophagitis.     

Inhibition of shear-induced platelet aggregation in rat by tetramethylpyrazine and salvianolic acid B

Tetramethylpyrazine (TMP) and salvianolic acid B (SAB) are effective ingredients of Rhizoma Ligustici chuanxiong Hort. and Radix Salviae miltiorrhizae Bge., accordingly. The inhibitive effects of TMP, SAB and their combination on shear-induced platelet aggregation (SIPA) were investigated in the present study. SD rats were used as blood donors to collect anticoagulated blood, the concentration of platelet-rich-plasma (PRP) was adjusted to 5 x 10(5) microl. HAAKE rheometer RS 600 with sensor C60/0.5 degrees was used as shear generator. Different doses of TMP and SAB and their combinations were added to the PRP. After constant shear of 15 Pa at 37 degrees C for 360 seconds, PRP was transferred to a platelet aggregometer and SIPA was determined by turbidity. SIPA was inhibited by TMP and SAB in a dose-dependent manner. SIPA was decreased from 48.6 +/- 4.6% of the control to 12.5 +/- 2.1% in the presence of TMP (1.46 mM) and SAB (10 microM) (P < 0.0001). In conclusion, TMP and SAB have additive effects on inhibiting platelet aggregation induced by high shear stress.     

Use of color Doppler ultrasonography in the diagnosis of anomalous connection in pancreatobiliary disease

AIM: To estimate the detectability of anomalous connection in pancreatobiliary disease (ACPBD) cases, measuring gallbladder wall blood flow (GWBF). METHODS: In the retrospective study, we enrolled 42 subjects with gallbladder wall thickening. GWBF velocity was determined as an average value of the peak velocity of color signals on the gallbladder wall, three times in each case. Based on the findings on endoscopic ultrasonography (EUS) or endoscopic retrograde cholangiopancreatography (ERCP), the 42 subjects were divided into 11 cases with ACPBD and 31 cases without ACPBD, In the prospective study, the subjects were 92 cases with gallbladder wall thickening. Using the cut-off level of the flow velocity obtained in the retrospective study, the usefulness of measuring GWBF velocity in diagnosing ACPBD was evaluated. RESULTS: In the retrospective study, imaging of GWBF was obtained in 40 of the 42 subjects. The mean GWBF velocity of the ACPBD cases was 29.4±3.9 cm/s (mean±SD), which was significantly different (P<0.0001; 95% CI 5.48-13.2) from that of the without ACPBD cases (20.1±5.9 cm/s). Based on this result, we prepared a receiver operating characteristic curve, and the cut-off level appropriate for diagnosing ACPBD was estimated to be 25 cm/s. In the prospective study, GWBF was detected in 86 of the 92 subjects. Based on the EUS or ERCP findings, the 92 subjects were divided into 15 cases with ACPBD and 77 cases without ACPBD. When a cut-off level of 25 cm/s was employed, ACPBD could be diagnosed with a sensitivity of 87.0% (13/15) and a specificity of 87.3% (62/71). CONCLUSION: Meas urement of GWBF velocity, which is less invasive and provides objective values, is very useful for diagnosing ACPBD prior to the development of malignant tumors in cases with gallbladder wall thickening.