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•Control of radicals that cannot be controlled in plasma using a exhaust system.•Reduces the amount of radicals reacting to the pattern sidewall in the dry etching.•To analyze changes ...in ions and radicals in the process of radial control.
Radicals generated during reactive ion etching (RIE) cannot be electrically controlled, causing isotropic etching and chemical damage to the sidewall of the etched feature during the etching process. In this study, using a reactive ion beam etcher (RIBE) installed with a dual exhaust system, where an additional exhaust valve was introduced to pump out radicals from the inductively coupled plasma (ICP) source chamber in addition to the conventional main gate valve in the process chamber, the radical flux relative to ion flux during the RIE process has been controlled and the effect of additional exhausting through the ICP source chamber for the control of radical flux relative to ion flux on the properties of etching has been investigated using CF4 gas. The results showed that the additional exhausting of the radicals through the ICP source chamber not only decreased the ICP source chamber pressure but also decreased the ratio of radical flux to ion flux to the substrate. The lower ICP source chamber pressure could be also obtained without additional exhausting through the ICP source chamber by decreasing the CF4 gas flow rate to the ICP source chamber, however, the lower ratio of radical flux to ion flux was observed for the dual exhaust system. It is believed that, for the next generation RIBE, multiple exhausting is beneficial for anisotropic etching of nanoscale features by controlling the radical flux to the sidewall and ion flux to the bottom of a nanoscale feature during the etching.
Background and Aim: This study evaluated the long‐term outcome and prognostic factors of chronic hepatitis B, based on histological grade and stage.
Methods: A total of 188 patients with chronic ...hepatitis B were followed for a mean 119.8 months. Ultrasonography and clinical assessment were performed regularly. In addition, liver biopsy specimens were re‐evaluated based on histological grade and stage.
Results: During follow‐up, cirrhosis developed in 62 patients, decompensation in 20 patients, and hepatocellular carcinoma (HCC) in 21 patients. The serum alanine aminotransferase (ALT) level at the time of liver biopsy was significantly correlated with the grades of lobular and porto‐periportal activity. The development of cirrhosis correlated well with the grade of porto‐periportal activity and stage of fibrosis. The probabilities of developing cirrhosis, decompensation and HCC were significantly higher in patients whose ALT levels were persistently elevated without flares or flared‐up without normalization than in patients whose ALT levels flared‐up then normalized or were normally sustained. By multivariate analysis, age and biochemical profile during follow‐up were independent prognostic factors for chronic hepatitis B.
Conclusions: The results demonstrate that histological grade and stage, and biochemical profile during follow‐up in patients with chronic hepatitis B are important prognostic factors. Therefore, effective control of hepatitis activity might improve the long‐term outcome of chronic hepatitis B patients.
Gram-positive bacterial products such as peptidoglycan (PGN) and lipoteichoic acid (LTA) are potent stimulators of innate inflammatory responses. We previously reported that lipopolysaccharide (LPS), ...a major biologically active agent of gram-negative bacteria, induces a proinflammatory response via the Toll-like receptor (TLR) 4 in hepatic stellate cells (HSCs). Here we investigated the mechanism of proinflammatory action by PGN and LTA in activated human HSCs. Following treatment with either TNF-α or IL-1β, expression of TLR2 and CD14 was determined by real-time PCR and Western blotting. NF-κB activation was assessed by NF-κB-driven luciferase assay and electrophoretic mobility shift assay. Interleukin-8 (IL-8) from culture supernatant was measured by ELISA. Activated human HSCs express TLR2 and CD14, which are receptors for PGN and LTA signaling. TNF-α and IL-1β significantly upregulated the expression of TLR2 mRNA and protein in HSCs. PGN and LTA induced NF-κB activation and stimulated production of IL-8 in HSCs. Pretreatment with TNF-α or IL-1β augmented NF-κB activation and IL-8 production in response to PGN or LTA. Both PGN- and LTA-induced NF-κB activation and IL-8 secretion were completely inhibited by anti-TLR2 blocking antibody (T2.5). These findings suggest that TNF-α or IL-1β primed HSCs enhance the production of IL-8 in response to PGN and LTA through augmentation of the TLR2 system.
The purpose of this study was to evaluate the long-term tumor response after phase IIb clinical study and the safety of percutaneous holmium-166 ((166)Ho)/chitosan complex injection (PHI) therapy for ...small hepatocellular carcinoma as a local ablative treatment. (166)Ho is a radioactive isotope derived from natural holmium-165. We developed a (166)Ho/chitosan complex (Milican, Dong Wha Pharmaceutical Co., Seoul, Korea) using chitosan as a vehicle to retain the radioactive material within the tumor.
Forty patients with single hepatocellular carcinoma < 3 cm in maximal diameter were enrolled in this study. The patients either had refused surgery or were poor surgical candidates and were treated with only single session of PHI.
Two months after PHI, complete tumor necrosis was achieved in 31 of 40 patients (77.5%) with hepatocellular carcinoma lesions < 3 cm and in 11 of 12 patients (91.7%) with hepatocellular carcinoma < 2 cm. Tumors recurred in 28 patients during the long-term follow-up period, of which 24 recurred at another intrahepatic site. The 1-year and 2-year cumulative local recurrence rates were 18.5% and 34.9%, respectively. The survival rates at 1, 2, and 3 years were 87.2%, 71.8%, and 65.3%, respectively. Transient bone marrow depression was serious adverse event requiring hospitalization in two patients.
PHI was found to be a safe and novel local ablative procedure for the treatment of small hepatocellular carcinoma and could be used as a bridge to transplantation. A phase III randomized active control trial is clearly warranted among a larger study population.
Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, ...therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p = 0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the post- treatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0 --> 4.2, p = 0.000); lactulose group (11.3 --> 5.0, p = 0.000)). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.
The early emergence of lamivudine (3TC)-resistant tyrosine-methionine-aspartate-aspartate (YMDD) mutants has been reported during 3TC therapy in patients with chronic hepatitis B (CHB) in hepatitis B ...virus (HBV)-endemic areas; however, its clinical impact during long-term 3TC therapy is unknown. This study was performed to investigate the impact of the early emergence of YMDD mutants 3 months after the initiation of treatment on the outcomes of long-term 3TC therapy in HBV e antigen (HBeAg)-positive CHB. We analysed YMDD genotypes in consecutive samples from 30 patients with HBeAg positive CHB throughout 3TC treatment using both restriction fragment length polymorphism and mass spectrometric assays. Long-term outcome was compared between patients who had YMDD mutations detected at 3 months and those who had no mutations. YMDD mutation was detected in 16 (53.3%) out of 30 patients at 3 months and only the rtM2041 mutation was found. Cumulative HBeAg loss rates at 3 years was 12.5% and 57.4% in patients who had the rtM2041 mutant and wild-type virus at 3 months, respectively (P=0.010). Cumulative viral breakthrough rates at 3 years was 75.0% and 14.3% in patients who had the rtM204I mutant and wild-type virus at 3 months, respectively (P=0.002). Logistic regression revealed that YMDD mutation at 3 months was significantly related to viral breakthrough within 24 months (P=0.003). In conclusion, early detection for HBV YMDD mutation at 3 months may be useful to predict the long-term outcomes of 3TC therapy in patients with HBeAg-positive CHB in HBV-endemic areas.
Background/Aims
: Analysis of isolated hepatic stellate cells (HSCs) from the injured liver may provide direct information on HSC apoptosis. However, it has not been established whether apoptotic ...HSCs would be isolated using the usual density gradient centrifugation method. The aim of this study was to observe the serial pattern of proliferation and apoptosis in isolated HSCs in comparison with that of liver tissue sections in CCl
4 induced acute liver injury.
Methods
: Male Sprague–Dawley rats were treated with a single intraperitoneal injection of carbon tetrachloride (CCl
4) and were killed at various time points after the treatment.
Results
: HSC proliferation showed a maximal increase at 32 h after CCl
4 injection. Apoptosis of HSC, examined by quantitative analysis of annexin-V-fluorescein isothiocyanate (FITC
)staining, showed the maximal increase at 64 h. Apoptosis of HSC in liver tissue sections examined by counting desmin and Tdt-mediated-dUTP biotin nick end labeling (TUNEL) double staining cells, peaked at 64 h. The number of TUNEL positive HSCs in liver tissue sections correlated significantly with annexin-V-FITC binding of isolated HSC.
Conclusions
: Studying apoptosis using apoptotic HSCs isolated by a usual density gradient centrifugation method from injured tissue sections would be feasible since it correlated with in vivo apoptosis of HSC.
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