Relationship between histological prognosis of chronic hepatitis C and amount of hepatitis C virus core protein in serum

BACKGROUND: Hepatitis C virus (HCV) viraemia is one of the factors for histological prognosis of chronic hepatitis C. METHODS: One hundred and thirty-five patients who received hepatic biopsies twice at intervals of 5 years or longer were followed up for a mean of 9.7 +/- 4.0 years were studied retrospectively. The amount of HCV viraemia present was measured as the concentration of HCV core protein by using the fluorescence enzyme immunoassay method. RESULTS: Multiple-regression analysis, using deterioration of the histological stage as a dependent variable, showed that greater age (P = 0.041), higher stage of hepatic histology at the start of follow up (P = 0.029), and higher serum concentration of core protein (P < 0.001) were independent factors affecting the deterioration of the liver's histological stage. At follow up, no significant difference in histological stage was seen between patients with serum HCV core protein > or = 100 pg/mL (n = 60) and those with serum core protein < 100 pg/mL (n = 75). The histological grade in patients with high serum core-protein levels tended to be significantly worse and the deterioration rate of the histological stage was significantly higher than in those with low HCV core protein levels (68 vs 35%, P < 0.001). The mutation rate of the HCV envelope-2/non-structural 1 (E2/NS1) nucleotide region was compared in two patients who had high serum concentrations of HCV core protein and whose histological stage had deteriorated with two patients who had low serum concentrations of the core protein and whose histological stages remained unchanged. No significant difference in E2/NS1 mutation was found. CONCLUSIONS: The amount of HCV viraemia was suggested to be a significant factor for determining histological outcome in patients with chronic hepatitis C. The mutation rate in the E2/NS1 region did not seem to be associated with the prognosis of chronic hepatitis C.     

Changes in serum levels of metalloproteinases and their inhibitors by treatment of chronic hepatitis C with interferon

We treated 18 patients with chronic hepatitis C by recombinant interferon-α (6 MIU for 24 weeks). In seven patients, serum aminotransferase levels declined to normal (responders). To evaluate the effect of interferon on matrix metalloproteinases (MMPs) and their inhibitors, namely tissue inhibitors of metalloproteinases (TIMPs), the serum levels of these enzymes were determined by enzyme immunoassay (EIA) using a specific monoclonal antibody. In responders, there was a tendency, but not a significant one, towards either an increase in serum MMP 1 levels or a decrease in serum TIMP 1 levels. In contrast, in nonresponders, both a significant decrease in MMP 1 and MMP 3 and a significant increase in TIMP 1 were observed. The number of cases of either increase in serum MMP levels or decrease in serum TIMP levels was significantly larger in responders than in nonresponders. Furthermore, the ratio of MMP 1 to TIMP 1 significantly increased in responders, suggesting that the balance between matrix formation and degradation in hepatic fibrosis tended to move toward degradation. These data indicate that interferon may exert a beneficial effect on hepatic fibrosis in parallel with improvement of aminotransferase activity.     

Morphology and biochemistry of the lung from guinea pig after repeated injections of freund’s complete adjuvant

Guinea pigs received 5 daily injections of Freund’s complete adjuvant and the changes in the lung were investigated by light microscope and electron microscope. In the 20th week of experiment, fibrotic changes were found around the granulomata close to the surface of the lung. In addition the fraction of glycosaminoglycans was isolated from the lung and analyzed quantitatively. As a result, a decrease in quantity of hyaluronic acid and an increase in quantity of dermatan sulfate were observed.     

Improvement of postprandial hyperglycemia has a positive impact on epicardial flow of entire coronary tree in acute coronary syndromes patients.

BACKGROUND: Recent studies have shown that a global flow abnormality affects the entire coronary tree in patients with acute coronary syndrome (ACS), and that it is associated with adverse outcomes. Postprandial hyperglycemia is also thought to promote coronary endothelial dysfunction, as well as the release of inflammatory and vasoconstrictive factors. This study used the corrected Thrombolysis In Myocardial Infarction frame count (CTFC) to investigate whether optimal control of postprandial hyperglycemia improves pan-coronary flow. METHODS AND RESULTS: Eighty ACS patients with postprandial hyperglycemia who had successful coronary intervention and who had undergone a 75-g oral glucose tolerance test (OGTT) were included. A second OGTT and angiogram were performed 8 months after procedures. The patients were divided according to postprandial glycemia after the second 75-g OGTT; optimal postprandial hyperglycemia was defined as a 2-h blood glucose concentration <7.8 mmol/L. Changes in the CTFC of culprit/non-culprit arteries, glucose response, and other clinical variables were compared. Forty patients improved to an optimal control at 8 months. In the culprit artery, the 8-month angiogram revealed a significantly improved CTFC among those with optimal control compared with the initial angiogram (30+/-9 vs 24+/-12, p<0.05). In contrast, the CTFC was not evidently improved among patients with suboptimal control. The CTFC at 8 months had thus obviously improved more in patients with optimal, than with suboptimal control (24+/-12 vs 30+/-11, p<0.05). CONCLUSION: Optimal control of postprandial hyperglycemia improves epicardial blood flow in both arteries and this beneficial effect might be from improved coronary endothelial function.     

Differential Regulation of DC Function by Siphonodiol

Siphonodiol is a polyacetylene diol isolated from marine sponges Callyspongia sp. We demonstrate that the effect of Siphonodiol on the phenotypic and functional maturation of human monocyte derived DC in vitro. Human monocytes were exposed to Siphonodiol alone, or in combination with LPS and thereafter co-cultured with naïve T cells. The expression levels of CD1a, CD80, CD83, CD86 and HLA-DR on LPS-primed DC were partially enhanced by Siphonodiol. Siphonodiol augmented the T cell stimulatory capacity in an allo MLR to LPS-primed DC. Siphonodiol dose-dependently enhanced the production of IL-12p70 by LPS-primed DC and this cytokine production was inhibited by anti-TLR4 mAb. IFN-γ secretion from naïve T cells co-cultured with DC differentiated with LPS was augmented by Siphonodiol. These results suggest that the enhancement of Th1 cells polarization to LPS-primed DC induced by Siphonodiol depends on TLR4 and via the activation of IL-12p70.     

Generation and characterization of a novel shoulder contracture mouse model

Frozen shoulder is a relatively common disorder that leads to severe pain and stiffness in the shoulder joint. Although this disorder is self‐limiting in nature, the symptoms often persist for years, resulting in severe disability. Recent studies using human specimens and animal models have shown distinct changes in the gene expression patterns in frozen shoulder tissue, indicating that novel therapeutic intervention could be achieved by controlling the genes that are potentially involved in the development of frozen shoulder. To achieve this goal, it is imperative to develop a reliable animal joint contracture model in which gene expression can be manipulated by gene targeting and transgenic technologies. Here, we describe a novel shoulder contracture mouse model. We found that this model mimics the clinical presentation of human frozen shoulder and recapitulates the changes in the gene expression pattern and the histology of frozen shoulder and joint contracture in humans and other larger animal models. The model is highly reproducible, without any major complications. Therefore, the present model may serve as a useful tool for investigating frozen shoulder etiology and for identifying its potential target genes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1732–1738, 2015.