Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin‐3 knockout mice

Aim: Nonalcoholic fatty liver disease (NAFLD) represents a growing health concern due to its rapidly increasing prevalence worldwide. Nonalcoholic steatohepatitis (NASH) is a progressing form of NAFLD, and recently many studies have reported that it could eventually develop into hepatocellular carcinoma (HCC). We previously reported that 6‐month‐old male galectin‐3 knockout (gal3^?/?) mice developed clinicopathological features similar to those of NAFLD in humans. Our aim was to investigate the changes in liver histology in gal3^?/? mice by long‐term observation. Methods: We initially investigated three 15‐month‐old gal3^?/? mice, of which two developed multiple liver nodules with dysplastic changes. Then, we histopathologically examined the liver specimens of the 15‐, 20‐ and 25‐month‐old gal3^?/? mice and attempted to evaluate the liver morphology by contrast enhanced computed tomography (CT) before sacrifice. Results: At the age of 15 months or later, gal3^?/? mice developed liver nodules with varying degrees of architectural and nuclear atypia based on mild to moderate delicate zone 3 fibrosis. In addition, we successfully confirmed the presence of some of the liver nodules by CT. We report herein that gal3^?/? mice develop dysplastic liver nodules and HCC. Conclusions: We believe that it would be interesting to use this murine model to investigate liver carcinogenesis based on a natural history of NAFLD. Furthermore, CT scanning might be a useful tool for longitudinal evaluation of morphological changes in vivo.     

Clinical and angiographic follow-up of small vessel lesions treated with paclitaxel-eluting stents (from the TRUE Registry)

Several randomized trials have shown that sirolimus-eluting stents and paclitaxel-eluting stents (PES) are effective in reducing restenosis in respect to bare-metal stents, including the subset of small vessels. The objective of this study was to evaluate "real world" angiographic and clinical outcomes of a large series of patients enrolled in the TRUE registry and treated with PES for both small vessel and very small vessel lesions. A consecutive series of 675 patients (926 lesions) with reference vessel diameter <2.75 mm measured by quantitative coronary angiography analysis were analyzed. The primary end point was the rate of angiographic in-stent restenosis and 1-year major adverse cardiac events. In this study 390 lesions were identified as small vessel (reference vessel diameter >or=2.25 and <2.75 mm) and 536 lesions as very small vessel (reference vessel diameter <2.25 mm). Overall in-stent restenosis was 15.5% (n = 96). Compared with small vessel, the very small vessel lesions had more in-stent restenosis (21.7% vs 11.4%, p <0.001) and in-segment restenosis (29.3% vs 22.5%, p = 0.055). The majority of the restenotic lesions (n = 125) were focal (57%, n = 71). At 1 year, cardiac death was 1.6% (n = 11), acute myocardial infarction 0.5% (n = 4.), and the target lesion revascularization 12.8% (n = 86). Cumulative major adverse cardiac events rate was 17.3% (n = 119). The rate of definite and probable stent thrombosis was 0.9% (n = 8). In conclusion, in comparison with historical bare-metal stent controls, this large series of small vessel lesions treated with PES confirms previous results reporting the efficacy of PES in small vessels. The rate of subacute and late stent thrombosis was low in this subgroup of patients.     

Rapid,sensitive detection of myoglobinemia by improved counterimmunoelectrophoresis in cases of acute myocardial infarction

A counterimmunoelectrophoresis technique for detection of serum myoglobin (Mb) was improved using non-ionic polymer dextran. Precipitin lines were graded according to their strength, which was ascertained by radioimmunoassay data. By this method, serum Mb in concentrations of 500 ng./ml. before stain and of 200 ng./ml. after stain were detected. Electrophoretic time was 60 minutes. Among 32 cases of acute myocardial infarction (AMI) whose blood samples were collected within 24 hours after disease onset, precipitin lines were detected in 25 cases (78 per cent) before stain and 31 cases (97 per cent) after stain. Considering the early peak concentration time (approximately 10 hours) of serum Mb after AMI onset, diagnosis becomes more rapid and exact with this method, especially in severe cases.     

Effect of TT virus co‐infection on interferon response in chronic hepatitis C patients

Abstract: Aim: TT virus (TTV) is a single stranded DNA virus found in serum of patients with post‐transfusion non‐A to ‐G hepatitis. TTV‐DNA has been investigated in sera of patients with various liver diseases. This study aimed at finding whether co‐infection with TTV in HCV patients, may influence the effect of interferon (IFN) in complete elimination of HCV, and analysed the correlation between HCV and TTV by semi‐quantification of both HCV RNAs and TTV DNA. Methods: In 28 chronic hepatitis C (CH‐C) patients with TTV co‐infection, the presence of TTV DNA was checked in sera six months before and after the end of IFN therapy. Result: Five out of 28 patients became negative for both HCV‐RNA and TTV‐DNA following IFN therapy. But 10 out of 28 patients persistently remained positive for both. Among the remaining 13 patients, 5 tested negative for HCV‐RNA but positive for TTV‐DNA. Post IFN therapy changes in serum alanine aminotransferase (ALT) levels did not appear to be influenced by the presence of TTV co‐infection. HCV‐RNA was found to be the most important predictor of IFN response in CH‐C patients with TTV co‐infection. TTV DNA level in sera had no correlation with IFN response. In addition, there was no relationship between HCV RNA and TTV DNA. Conclusion: Based on these results, it can be concluded that the effectiveness of IFN in eliminating HCV does not seem to be influenced by co‐infection.     

Therapeutic effects of the combination of methotrexate and bucillamine in early rheumatoid arthritis: a multicenter, double-blind, randomized controlled study

Disease-modifying antirheumatic drug (DMARD) combination therapies are used widely, but there have been few reports clearly demonstrating that combination therapy is more effective than DMARD monotherapy. We conducted a multicenter, double-blind controlled trial in order to clarify that the combination of methotrexate and bucillamine is more effective than either alone. The subjects of this study were 71 patients with active rheumatoid arthritis within 2 years of onset. Dosages were 8 mg methotrexate with 5 mg folic acid per week (MTX group), 200 mg bucillamine per day (BUC group), or both MTX and BUC (combination group). Clinical effects and adverse reactions were observed for 96 weeks. The ACR 20 response rate was 79.2% in the combination group, significantly higher than the rates of 43.5% for the MTX group (P = 0.008) and 45.8% for the BUC group (P = 0.0178). The cumulative survival curve of maintaining the ACR 20 response was significantly higher in the combination group than in the MTX and BUC groups (P = 0.0123 and P = 0.0088, respectively). The mean increase in the total Sharp score over 96 weeks was 12.6 ± 9.0 in the combination group, significantly lower (P = 0.0468) than the value of 28.0 ± 28.3 for the single DMARD (combined MTX and BUC) group. The incidence of adverse reactions did not differ significantly between the three groups. It was concluded that the combination therapy with MTX and BUC showed significantly higher clinical efficacy than either of the single DMARD therapies.     

Gadopentetate dimeglumine as a potential alternative contrast medium during percutaneous coronary intervention: a case report.

BACKGROUND: There have not been previous reports of patients undergoing percutaneous coronary intervention (PCI) using a gadolinium chelate. METHODS AND RESULTS: A 74-year-old woman, who had a history of anaphylactic shock 4 times in response to iodinated contrast media despite preprocedural intravenous administration of hydrocortisone, was hospitalized because of unstable angina refractory to intensive medical treatment. Fully considering the risks of iodinated agents, digital subtraction coronary angiography and PCI were performed using gadopentetate dimeglumine without any side effects or complications. CONCLUSIONS: Gadolinium chelates can be an alternative contrast media during PCI in particular patients with contraindications to iodinated media.     

A significant reduction in serum alanine aminotransferase levels after 3-month iron reduction therapy for chronic hepatitis C: a multicenter, prospective, randomized, controlled trial in Japan

Background Increasing evidence indicates that iron cytotoxicity plays an important role in the pathogenesis of chronic hepatitis C (CHC). However, the biochemical effects of iron reduction therapy on CHC remain to be confirmed in a controlled study. This study aimed to test whether iron removal by repeated phlebotomy improves serum alanine aminotransferase (ALT) levels in patients with CHC.Methods Patients were randomly assigned to an iron reduction therapy or control group. The patients in the treatment group received 3-month iron reduction therapy by biweekly phlebotomy, while the patients in the control group were followed up for 3 months with regular blood tests alone.Results Thirty-three patients completed the 3-month treatment, while 29 patients received the complete follow-up. The serum ALT levels were reduced from 118 ± 79 to 73 ± 39IU/L in the treatment group, but did not change in the control group (106 ± 45 versus 107 ± 48IU/L). Posttreatment enzyme activity was decreased significantly from the baseline. Furthermore, it was significantly lower than the 3-month control level. Although 5 patients withdrew from the study, none was affected by any side effects of repeated phlebotomy that required them to discontinue the treatment.Conclusions This short-term controlled trial demonstrated the biochemical efficacy and safety of iron reduction therapy for patients with CHC.