Anti-hepatitis C virus activity of geranylgeranylacetone treatment in hepatitis C-infected patients

Background. Geranylgeranylacetone (GGA), which is an isoprenoid compound, has been used orally as an antiulcer drug inJapan. GGA induces antiviral gene expression by stimulating the formation of interferon-stimulated gene factor 3 in humanhepatoma cells. This study verified the anti-hepatitis C virus (HCV) activity of GGA in chronic hepatitis C-infected patients.Methods. The present prospective study included 20 consecutive anti-HCV antibody-positive, HCV-genotype 1b, and chronicgastritis patients who visited Nagasaki University Hospital between January 1999 and December 1999. GGA (150 mg per day,which is the dose generally used for chronic gastritis) was taken orally for four weeks. We evaluated HCV-RNA titers and otherclinical parameters at pretreatment, posttreatment, and at the endpoint of the study. Pretreatment was the beginning point ofGGA treatment. Posttreatment was the termination point of GGA treatment. The endpoint was the point four weeks after theposttreatment point.Results. All patients completed four weeks of GGA treatment and four weeks of observation. HCV-RNA titers at postpointwere not significantly diminished compared to those at pretreatment. However, HCV-RNA titers were significantly diminishedat endtreatment compared to pretreatment. Unfortunately, we did not observe a case with no titer of HCV-RNA. Alanineaminotransferase values and other parameters were not affected by GGA treatment.Conclusion. GGA has anti-HCV activities in chronic hepatitis C-infected patients. In the future, it will be necessary to examinethe clinical effectiveness of the combination of treatment with both GGA and interferon in HCV patients

Interferon-alpha-induced mTOR activation is an anti-hepatitis C virus signal via the phosphatidylinositol 3-kinase-Akt-independent pathway.

OBJECT: The interferon-induced Jak-STAT signal alone is not sufficient to explain all the biological effects of IFN. The PI3-K pathways have emerged as a critical additional component of IFN-induced signaling. This study attempted to clarify that relationship between IFN-induced PI3-K-Akt-mTOR activity and anti-viral action. RESULT: When the human normal hepatocyte derived cell line was treated with rapamycin (rapa) before accretion of IFN-alpha, tyrosine phosphorylation of STAT-1 was diminished. Pretreatment of rapa had an inhibitory effect on the IFN-alpha-induced expression of PKR and p48 in a dose dependent manner. Rapa inhibited the IFN-alpha inducible IFN-stimulated regulatory element luciferase activity in a dose-dependent manner. However, wortmannin, LY294002 and Akt inhibitor did not influence IFN-alpha inducible luciferase activity. To examine the effect of PI3-K-Akt-mTOR on the anti-HCV action of IFN-alpha, the full-length HCV replication system, OR6 cells were used. The pretreatment of rapa attenuated its anti-HCV replication effect in comparison to IFN-alpha alone, whereas the pretreatment with PI3-K inhibitors, wortmannin and LY294002 and Akt inhibitor did not influence IFN-induced anti-HCV replication. CONCLUSION: IFN-induced mTOR activity, independent of PI3K and Akt, is the critical factor for its anti-HCV activity. Jak independent mTOR activity involved STAT-1 phosphorylation and nuclear location, and then PKR is expressed in hepatocytes

Dynamic Gesture Recognition System with Gesture Spotting Based on Self-Organizing Maps

In this paper, a real-time dynamic hand gesture recognition system with gesture spotting function is proposed. In the proposed system, input video frames are converted to feature vectors, and they are used to form a posture sequence vector that represents the input gesture. Then, gesture identification and gesture spotting are carried out in the self-organizing map (SOM)-Hebb classifier. The gesture spotting function detects the end of the gesture by using the vector distance between the posture sequence vector and the winner neuron’s weight vector. The proposed gesture recognition method was tested by simulation and real-time gesture recognition experiment. Results revealed that the system could recognize nine types of gesture with an accuracy of 96.6%, and it successfully outputted the recognition result at the end of gesture using the spotting result

Predictive Value of the Fibrosis Scores in Patients with Chronic Hepatitis C Associated with Liver Fibrosis and Metabolic Syndrome

Objective We evaluated patients with chronic hepatitis C (CHC) and compared the clinical and pathological features of steatosis and metabolic syndrome to identify the risk factors for CHC with severe fibrosis. Methods One hundred seventy-one patients with biopsy-confirmed CHC were included in the study: 90 males and 81 females, age 56.2±12.8 years; 46 with obesity (BMI>25 kg/m2); 51 with hypertension; 36 with type 2 diabetes mellitus; and 20 with hypertriglyceridemia. Results Steatosis was detected in 79 patients (46%); 92 patients (54%) showed no steatosis. Seventy-four patients (43%) showed mild fibrosis and 97 patients (56%) showed severe fibrosis. The variables that were significantly associated with steatosis were obesity [odds ratio 2.160 (1.010-4.727), p=0.046] and type 2 diabetes [odds ratio 3.667 (1.559-8.430), p=0.027]. The variables that were significantly associated with severe fibrosis were older age [odds ratio 2.675 (1.309-5.464), p=0.007], obesity [odds ratio 2.156 (1.006-4.619), p= 0.048] and type 2 diabetes [odds ratio 8.739 (2.845-26.846), p=0.0002]. Nagasaki (N) score (the total number of specific risk factors, namely an older age, obesity, and type 2 diabetes) was higher in the severe fibrosis group than in the mild fibrosis group (mild fibrosis: severe fibrosis=1.48±1.14 vs.2.66±94, p<0.001). Conclusion Metabolic syndrome factors, including obesity and diabetes, play a critical role in the pathogenesis of fibrosis in CHC. The N score was therefore found to be a significant predictor of severe fibrosis in CHC