BACKGROUND: It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular carcinoma (HCC). AIM: To reveal the clinical relevance of compact lipiodolisation after TACE. METHODS: We studied 490 patients with unresectable HCC who had first been treated with TACE. Compact lipiodolisation was defined as the absence of an arterial enhancing lesion, reflecting complete lipiodol uptake, as assessed by dynamic computed tomography (CT) 1 month after treatment. The rate of initial compact lipiodolisation was analysed according to multiplicity and size of tumour, and survival of patients who achieved compact lipiodolisation was compared to that of patients who did not. RESULTS: Of the 490 patients, 409 (83.5%) were in Child-Pugh class A and 81 (16.5%) in class B. The rate of initial compact lipiodolisation in single HCCs was higher than that in multinodular HCCs (33.7% vs. 14.6%, P < 0.001). Among single HCCs, the rate of compact lipiodolisation in tumours ≤5, 5-10 and >10 cm was 46.6%, 13.6%, and 0% respectively. The 1-, 3- and 5-year survival rates of patients with compact uptake were 92.7%, 70.7% and 52.4% compared to 60.8%, 28.0% and 16.9% in patients with noncompact lipiodolisation. Multivariate analysis revealed that Child-Pugh class, alpha-fetoprotein level, tumour node metastasis stage, portal vein thrombosis and initial compact lipiodolisation were independent predictors of survival. CONCLUSIONS: Initial compact lipiodol uptake after transarterial chemoembolisation is associated with improved survival in patients with unresectable hepatocellular carcinoma. Accordingly, initial complete lipiodolisation should be considered a relevant therapeutic target.

BACKGROUND AND AIMS: Few studies have adequately examined the efficacy of lamivudine plus adefovir (LAM+ADV) combination therapy vs. entecavir (ETV) monotherapy in HBeAg-positive hepatitis B patients who fail to respond to sequential treatment with LAM and ADV. We compared directly the efficacy of LAM+ADV vs. ETV in such patients and assessed prognostic factors associated with a virologic response at month 12. METHODS: In total, 72 HBeAg-positive patients who showed resistance (n = 33) or a suboptimal virologic response (n = 39) to ADV monotherapy with resistance to LAM therapy underwent rescue therapy (31 LAM+ADV and 41 ETV). All patients were followed for at least 12 months. RESULTS: Following 12 months of treatment, in the LAM+ADV and ETV groups, a virologic response was observed in 7/31 (22.6%) and 8/41 (19.5%; P = 0.777) patients; ALT normalization occurred in 11/13 (84.6%) and 16/18 (88.9%; P = 0.566); HBeAg seroconversion in 1/31 (2.3%) and 4/41 (9.8%; P = 0.341) and a virologic breakthrough in 3/31 (9.0%) and 5/41 (12.1%; P = 0.452) respectively. Independent prognostic factors associated with a virologic response were the baseline HBV-DNA level (OR = 0.37; 95% CI 0.17-0.80; P = 0.011) and the duration of prior ADV monotherapy (OR = 0.89; 95% CI 0.83-0.95; P = 0.044). CONCLUSIONS: Neither LAM+ADV nor ETV was adequately effective in patients with sequential LAM and ADV treatment failure. Thus, when chronic hepatitis B patients show resistance or suboptimal response to ADV monotherapy, early modification of treatment should be considered.

Allopurinol, one of the most commonly used uric acid-lowering agents, can cause serious adverse events. To investigate the risk factors for allopurinol-induced adverse events, the authors enrolled 94 patients who developed allopurinol-induced adverse events and 378 controls who were randomly chosen from 1934 patients who used allopurinol but did not develop any adverse events in this retrospective case control study. Univariate analysis showed that patients who developed allopurinol-induced adverse events had more chronic kidney disease (46% vs 30%, P =.005), more hypertension (42% vs 30%, P =.036), less tumor lysis syndrome (P =.030), higher cholesterol (P =.013), and lower aspartate aminotransferase (P =.002) and alanine aminotransferase levels (P =.033) and more commonly used angiotensin receptor blockers (27% vs 15%, P =.007), colchicines (16% vs 5%, P =.010), or statins (19% vs 8%, P =.002) than those who did not. In multiple logistic regression analysis, the use of colchicines (odds ratio, 3.11; 95% confidence interval, 1.28-7.58; P =.012) and statins (2.10; 1.03-4.25; P =.041) was an independent risk factor predicting adverse events in allopurinol users. In conclusion, patients who use colchicine or statins are at significant risk for developing allopurinol-induced adverse events.

Chimpanzees and bonobos are the closest living relatives of humans and diverged relatively recently in their phylogenetic history. However, a number of reports have suggested behavioral discrepancies between the two Pan species, such as more cooperative and tolerant social interaction and poorer tool-using repertoires in bonobos. Concerning hunting behavior and meat consumption, recent studies from the field have confirmed both behaviors not only in chimpanzees but also in bonobos. The present study reports an encounter by wild bonobos at Wamba with a duiker trapped in a snare. Bonobos interacted with the live duiker for about 10 min but did not eventually kill the animal. They showed fear responses when the duiker moved and exhibited behaviors related to anxiety and stress such as branch-drag displays and self-scratching. Although bonobos manipulated nearby saplings and parts of the snare, they did not use detached objects to make indirect contact with the duiker. Juveniles and adults of both sexes engaged in active interactions with the trapped duiker. Overall, bonobos' behavioral responses indicated species-specific cognitive characteristics largely different from those of chimpanzees.

Status epilepticus increases brain-blood barrier (BBB) permeability leading to vasogenic edema. This BBB disruption is usually confined within relatively limited cerebral regions including the piriform cortex (PC), and leads to epileptogenesis and contributes to progression of epilepsy. Although cytokines are at least partly responsible for changes in BBB permeability, the role of interleukin-18 (IL-18) in vasogenic edema is not yet explored in detail. In the present study, we investigated the role of IL-18 in SE-induced vasogenic edema formation. Following SE, IL-18/interferon-γ (IFN-γ) system was up-regulated in astrocytes and microglia/macrophages. Recombinant rat (rr) IL-18 infusion decreased vasogenic edema formation, while anti-rat IL-18 infusion increased it. In contrast, rrIFN-γ, and anti-rat IFN-γ infusion showed reverse effects on vasogenic edema formation. rrIL-18 or anti-rat IFN-γ IgG infusion elevated dystrophin expression accompanied by the reduction in vasogenic edema. However, rr-IFN-γ or anti-rat IL-18 IgG infusion significantly decreased dystrophin immunoreactivity within the PC following SE. These findings indicate that IL-18-mediated up-regulation of dystrophin expression may play either a direct or indirect role in maintenance of BBB function following SE. Therefore, our findings suggest that IL-18 may have protective effect on SE-induced BBB disruption in IFN-γ independent mechanism.

ABSTRACT: BACKGROUND: Status epilepticus (SE) induces severe vasogenic edema in the piriform cortex (PC) accompanied by neuronal and astroglial damages. To elucidate the mechanism of SE-induced vasogenic edema, we investigated the roles of tumor necrosis factor (TNF)-alpha in blood-brain barrier (BBB) disruption during vasogenic edema and its related events in rat epilepsy models provoked by pilocarpine-induced SE. METHODS: SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, and soluble TNF p55 receptor (sTNFp55R) prior to SE induction. Thereafter, we performed Fluoro-Jade B staining and immunohistochemical studies for TNF-alpha and NF-kappaB subunits. RESULTS: Following SE, most activated microglia showed strong TNF-alpha immunoreactivity. In addition, TNF p75 receptor expression was detected in endothelial cells as well as astrocytes. In addition, only p65-Thr435 phosphorylation was increased in endothelial cells accompanied by SMI-71 expression (an endothelial barrier antigen). Neutralization of TNF-alpha by soluble TNF p55 receptor (sTNFp55R) infusion attenuated SE-induced vasogenic edema and neuronal damages via inhibition of p65-Thr435 phosphorylation in endothelial cells. Furthermore, sTNFp55R infusion reduced SE-induced neutrophil infiltration in the PC. CONCLUSION: These findings suggest that impairments of endothelial cell functions via TNF-alpha-mediated p65-Thr 485 NF-kappaB phosphorylation may be involved in SE-induced vasogenic edema. Subsequently, vasogenic edema results in extensive neutrophil infiltration and neuronal-astroglial loss.

Fe-36Ni alloy nanopowder was prepared via electrical explosion of wire in DI water. The nanopowder was reduced in hydrogen at 500 degrees C for 30 min. Spark plasma sintering at 800 and 1000 degrees C for 10 min was used to obtain bulk samples from the hydrogen-reduced nanopowder. The sintered samples were annealed at 500 degrees C for 2 h. X-ray diffraction was used to analyze the phases of the nanopowder and sintered samples. The results showed that the sintered samples were formed in gamma-(Fe-Ni) solid solution. The particles sizes and morphologies of the as-synthesized and hydrogen-reduced nanoparticles were observed via transmission electron microscopy. The morphologies of the as-synthesized nanoparticles had spherical core-shell structures. Core was gamma-(Fe-Ni) and the shell was FeO. The nanoparticles of the as-synthesized and hydrogen reduced samples were found to be nearly spherical in shape, with average diameters of 32 and 70 nm, respectively. The hysteresis loops of the as-synthesized nanopowder, hydrogen reduced nanopowder, and sintered samples revealed ferromagnetic characteristics.

Few studies have reported on the clinical characteristics of hepatocellular carcinoma (HCC) at the time of diagnosis with regard to pre-S and basal core promoter (BCP) mutations. In this study, the clinical features and prognosis of 126 Korean HCC patients were examined with respect to pre-S deletion and BCP mutations of hepatitis B virus. The proportion of HCC patients according to tumor-node-metastasis stage are as follows: 8.7% in stage I, 31% in stage II, 30.2% in stage III, 21.4% in stage IV-A, and 8.7% in stage IV-B. Overall, 40.5% of HCC patients were treated by surgery or ablation, 59.5% by other methods. Patients were divided according to pre-S deletion and BCP mutations (103 without pre-S deletion, 23 with pre-S deletion; 44 without BCP mutation, 82 with BCP mutation). The tumor characteristics and prognosis were evaluated between the groups, including size, number, type, vessel invasion, portal vein thrombosis, and metastasis. No significant difference in tumor characteristics between the HCC patients with pre-S deletion was observed, compared with the HCC patients without pre-S deletion. In contrast, the survival rate was lower in those with pre-S deletion than in those without it (P = 0.024). No difference in tumor characteristics was found in non-BCP and BCP mutation patients. Unlike the pre-S deletion group, no difference was observed in survival rate between the non-BCP and BCP patients. In conclusion, pre-S deletion and BCP mutations did not affect the initial tumor features. However, pre-S deletion was an independent risk factor affecting HCC survival.

Background: The interactions among hepatitis B virus (HBV) mutations in developing hepatocellular carcinoma (HCC) remain unclear and thus we investigated the risk of HCC related with single or multiple HBV mutations in Korean patients infected with HBV subgenotype C2. Methods: From January 2003 to December 2008, HBV isolates from 135 patients with HCC were compared with those from 135 patients without HCC, matching for age, gender, and HBeAg status. The prevalence of preS deletions and G1896A and A1762T/G1764A mutations was evaluated. Results: The frequency of preS deletions significantly differed between the non-HCC and HCC groups, with 6 (4.4%) versus 25 (18.5%) patients, respectively (p < 0.001). Additionally, the frequency of A1762T/G1764A mutations was higher in the HCC than the non-HCC group [82 (60.7%) versus 30 (22.2%), p < 0.001]. For combined mutations, the odds ratio (OR) was highest in patients with both preS deletions and the A1762T/G1764A mutation, with 1 (0.7%) versus 11 (8.1%) patients (p = 0.005; OR 11.887). Conclusions: HCC was associated with preS deletions and A1762T/G1764A mutations, and the combination of both mutations had a stronger association with HCC in Korean patients infected with HBV subgenotype C2.

Recently, we have reported that astroglial activations in response to status epilepticus (SE) show regional-specific manners in the rat hippocampus. However, it is unknown that microglial responses to SE would show regional-specific patterns. Therefore, the present study was designed to elucidate the regional-specific microglial activation and relationship between P2X7 receptor functions and SE-induced microglial responses in the rat brain. Following SE, microglia appeared amoeboid or phagocytic in the dentate gyrus and the piriform cortex. In contrast, elongated microglia were observed in the CA1 hippocampal regions and the frontoparietal cortex. In the dentate gyrus, the CA1 hippocampal regions, and the frontoparietal cortex, these microglial activation accelerated by BzATP (a P2X7 receptor agonist)-infusion, but inhibited by OxATP (a P2X7 receptor antagonist). However, SE-induced microglial activation in the piriform cortex was not affected by BzATP or OxATP-infusion. Therefore, our findings indicate that SE-induced microglial activation may show regional-specific manners, and suggest that P2X7 receptor function differently modulates SE-induced microglial responses in distinct brain regions.