Evaluation of the reasons for preferring root canal treatment in mature permanent teeth potentially indicated for pulp preservation: a clinical case/photo-based questionnaire study.

BACKGROUND: With advances in pulp preservation procedures (PPP), indications for PPP extend to exposed pulp with symptoms in teeth with carious lesions. Scenario/text-based questionnaire studies report a high preference for PPP for exposed pulp with no pulpal symptoms. However, negative perceptions towards PPP for exposed pulp in carious teeth are prevalent among dentists. Identifying the differences in PPP preference rates in questionnaire studies and actual clinical situations is necessary to determine the current status of PPP. In this study, a clinical case/photo-based design was devised to overcome the limitations of scenario/text-based questionnaires. This study aimed to evaluate the reasons dentists prefer root canal treatment (RCT) in cases where PPP is potentially indicated. METHODS: A questionnaire containing three cases of PPP with successful results was administered to dentists. The cases were selected to elicit comprehensive responses from the dentists. Clinical photos of the pulp exposure sites were presented to dentists without describing the tooth conditions, including the extent of pulp exposure and tooth decay, pulpal surface conditions, or restorability. The questions were focused on the reasons for selecting RCT in cases where was practiced. Questionnaire data were collected using Google e-forms. Chi-squared and Fisher's exact test (P < 0.05) were used for statistical analyses. RESULTS: Pulpal diagnosis was not a dominant factor in treatment decision-making for pulp exposure during caries removal. Reasons for selecting RCT where PPP was potentially indicated included the event of pulp exposure itself and the dentists' desire to prevent post-PPP symptoms. Apart from symptomatic pulp, the tooth conditions influenced the establishment of pulpal diagnosis and selection of treatment modality. Moreover, the tooth condition and dentists' desire for good patient prognosis influenced the negative perceptions towards PPP. CONCLUSIONS: Unfavourable tooth conditions, in association with a desire for preventing post-PPP symptoms, prevent dentists from attempting PPP for pulp exposed during caries removal with no/slight symptoms. Improving negative perceptions towards PPP through accumulation of data on the high success rates of PPP is a prerequisite for achieving widespread application of PPP.

Association of coffee drinking with all-cause and cause-specific mortality in over 190,000 individuals: data from two prospective studies.

We examined the association of coffee drinking with all-cause and cause-specific mortality in a pooled analysis of two Korean prospective cohort studies: The Korea National Health and Nutrition Examination Survey and the Korean Genome and Epidemiology Study. We included 192,222 participants, and a total of 6057 deaths were documented. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), and the HRs were combined using a random-effects model. Coffee drinking was associated with a lower risk of all-cause mortality [HR (95% CI) = 0.84 (0.77-0.92), for ≥3 cups/day of coffee drinking versus non-drinkers; p for trend = 0.004]. We observed the potential benefit of coffee drinking for mortality due to cardiovascular disease, respiratory disease, and diabetes, but not for cancer mortality. Overall, we found that moderate coffee drinking was associated with a lower risk of death in population-based cohort analysis of Korean adults.

Clinical outcomes of patients with advanced hepatocellular carcinoma treated with sorafenib: a retrospective study of routine clinical practice in multi-institutions.

BACKGROUND: Sorafenib is an orally administered multikinase inhibitor with antiangiogenic and antiproliferative properties. The results of large clinical trials demonstrate that sorafenib prolongs survival and the time to progression of patients with advanced hepatocellular carcinoma (HCC). The aim of the present study was to determine the outcomes of such patients who were routinely treated with sorafenib at multi-institutions in Korea, in contrast to formal clinical trials. METHODS: Between August 2007 and March 2012, patients with advanced HCC in seven referral medical centers in Daejeon-Chungcheong Province of Korea were retrospectively enrolled to evaluate treatment response, survival, and tolerability following administration of sorafenib. The treatment response was assessed in accordance with the Response Evaluation Criteria in Solid Tumor 1.1 guidelines. RESULTS: Among 116 patients, 66 (57%) had undergone treatment for HCC, and 77 (66%) were accompanied with Child-Pugh A cirrhosis. The median duration of sorafenib treatment was 67 days (range 14-452 days). Median overall survival and median time to progression were 141 days and 90 days, respectively. Complete response, partial response, and stable disease were achieved for 0%, 2%, and 29% of patients, respectively. Overall median survival, but not the median time to progression, was significantly shorter for patients with Child-Pugh B cirrhosis compared with those with Child-Pugh A cirrhosis (64 days vs 168 days, P = 0.004). Child-Pugh B cirrhosis (P = 0.024) and a high level of serum alpha-fetoprotein (P = 0.039) were independent risk factors for poor overall survival. Thirty-nine (34%) patients experienced grade 3/4 adverse events such as hand-foot skin reactions and diarrhea that required dose adjustment. CONCLUSIONS: The clinical outcomes of sorafenib-treated patients with advanced HCC were comparable to those reported by formal clinical trial conducted in the Asia-Pacific region. Underlying hepatic dysfunction was the most important risk factor for shorter survival.

Analysis of balance ability dependent on the angle of the knee joint in females in their 20s.

The aim of this study was to investigate how balance ability according to angle of the knee joint changes in young female adults wearing a knee orthosis. [Methods] This study was conducted with 11 healthy female adults. The subjects used a knee brace that could be set to angles of 0°, 15°, and 30° of knee flexion. The ability to balance was evaluated by balance assessment. A total of four postures were used for measurements: a forward-facing posture with the eyes open on a stable surface (NO), a forward-facing posture with the eyes closed on a stable surface (NC), a forward-facing posture with the eyes open on an unstable surface (PO), and a forward-facing posture with the eyes closed on an unstable surface (PC). [Results] Regarding the weight distribution index and stability index on a stable surface, there was no interaction according to whether there was visual deprivation or not or according to knee flexion angle. Furthermore, the stability index on an unstable surface showed no interaction according to whether there was visual deprivation or not or according to knee flexion angle. But the WDI on a stable surface showed no interaction according to whether there was visual deprivation or not or according to knee flexion angle. [Conclusion] There were significant differences in the knee extension range of motion of normal elderly people and knee osteoarthritis, and the quadriceps femoris played an important role in knee function in individuals with knee osteoarthritis.

Effectiveness and Safety of Recombinant Human Follicle-Stimulating Hormone (Follitrope™) in Inducing Controlled Ovarian Stimulation in Infertile Women in Real-World Practice: a Prospective Cohort Study.

To evaluate the safety and effectiveness of recombinant human follicle-stimulating hormone (rhFSH [Follitrope™]) in infertile women undergoing in vitro fertilization (IVF). To identify predictors of ovarian response that induce optimal clinical outcomes. This multicenter prospective study enrolled infertile women who were scheduled to undergo IVF after ovarian stimulation with rhFSH (Follitrope™) following the gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist protocol. Predictive factors for ovarian response were identified in the GnRH antagonist group based on the number of oocytes retrieved. A total of 516 infertile women were enrolled, among whom 136 (except one who withdrew before administration) received rhFSH using the GnRH agonist protocol and 379 using the antagonist protocol. The mean number of oocytes retrieved was 13.4 in the GnRH agonist group and 13.6 in the GnRH antagonist group. The clinical pregnancy rates were 32.3% (30/93) and 39.9% (115/288) in the GnRH agonist and antagonist groups, respectively. The incidence of ovarian hyperstimulation syndrome was 1.8% and 3.4% in the GnRH agonist and antagonist groups, respectively. No other significant safety risks associated with rhFSH administration were identified. Body mass index, basal serum FSH and anti-Müllerian hormone levels, and antral follicle count were identified as predictors of ovarian response by multiple regression with backward elimination, and the final regression model accounted for 26.5% of the response variability. In real-world practice, rhFSH (Follitrope™) is safe and effective in inducing ovarian stimulation in infertile women. Patient characteristics identified as predictors can be considered to be highly related to optimal clinical outcomes.

Fyn mediates transforming growth factor-beta1-induced down-regulation of E-cadherin in human A549 lung cancer cells.

Transforming growth factor-beta (TGF-ß) signaling positively contributes to the regulation of tumor metastasis. However, the underlying molecular mechanisms are less well defined. We here show that Fyn, a member of Src family tyrosine kinases, plays a critical role in mediating TGF-ß1-induced down-regulation of E-cadherin in human A549 lung cancer cells. Blockade of Fyn with siRNA knockdown or ligand-binding defective mutant significantly lowered the ability of TGF-ß1 to repress E-cadherin expression. Furthermore, our results demonstrated that Fyn facilitates TGF-ß1-mediated suppression of E-cadherin through p38 kinase-dependent induction of Snail. Collectively, our findings identify a Fyn-p38-Snail cascade as a new signaling pathway mediating oncogenic TGF-ß function.

Coffee Consumption, Genetic Polymorphisms, and the Risk of Type 2 Diabetes Mellitus: A Pooled Analysis of Four Prospective Cohort Studies.

The association between coffee consumption and the risk of type 2 diabetes may vary by genetic variants. Our study addresses the question of whether the incidence of type 2 diabetes is related to the consumption of coffee and whether this relationship is modified by polymorphisms related to type 2 diabetes. We performed a pooled analysis of four Korean prospective studies that included 71,527 participants; median follow-up periods ranged between 2 and 13 years. All participants had completed a validated food-frequency questionnaire (FFQ) at baseline. The odds ratios (ORs) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using logistic regression models. The ORs were combined using a fixed or random effects model depending on the heterogeneity across the studies. Compared with 0 to <0.5 cups/day of coffee consumption, the OR for type 2 diabetes was 0.89 (95% CI: 0.80-0.98, p for trend = 0.01) for ≥3 cups/day of coffee consumption. We did not observe significant interactions by five single nucleotide polymorphisms (SNPs) related to type 2 diabetes (CDKAL1 rs7756992, CDKN2A/B rs10811661, KCNJ11 rs5215, KCNQ1 rs163184, and PEPD rs3786897) in the association between coffee and the risk of type 2 diabetes. We found that coffee consumption was inversely associated with the risk of type 2 diabetes.

Interactions of Habitual Coffee Consumption by Genetic Polymorphisms with the Risk of Prediabetes and Type 2 Diabetes Combined.

Habitual coffee consumption and its association with health outcomes may be modified by genetic variation. Adults aged 40 to 69 years who participated in the Korea Association Resource (KARE) study were included in this study. We conducted a genome-wide association study (GWAS) on coffee consumption in 7868 Korean adults, and examined whether the association between coffee consumption and the risk of prediabetes and type 2 diabetes combined was modified by the genetic variations in 4054 adults. In the GWAS for coffee consumption, a total of five single nucleotide polymorphisms (SNPs) located in 12q24.11-13 (rs2074356, rs11066015, rs12229654, rs11065828, and rs79105258) were selected and used to calculate weighted genetic risk scores. Individuals who had a larger number of minor alleles for these five SNPs had higher genetic risk scores. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) to examine the association. During the 12 years of follow-up, a total of 2468 (60.9%) and 480 (11.8%) participants were diagnosed as prediabetes or type 2 diabetes, respectively. Compared with non-black-coffee consumers, the OR (95% CI) for ≥2 cups/day by black-coffee consumers was 0.61 (0.38-0.95; p for trend = 0.023). Similarly, sugared coffee showed an inverse association. We found a potential interaction by the genetic variations related to black-coffee consumption, suggesting a stronger association among individuals with higher genetic risk scores compared to those with lower scores; the ORs (95% CIs) were 0.36 (0.15-0.88) for individuals with 5 to 10 points and 0.87 (0.46-1.66) for those with 0 points. Our study suggests that habitual coffee consumption was related to genetic polymorphisms and modified the risk of prediabetes and type 2 diabetes combined in a sample of the Korean population. The mechanisms between coffee-related genetic variation and the risk of prediabetes and type 2 diabetes combined warrant further investigation.

[Efficacy of initial treatment with peginterferon alpha-2a versus peginterferon alpha-2b in combination with ribavirin in naive chronic hepatitis C patients living in Daejeon and Chungcheong Province in Korea: a comparative study].

BACKGROUNDS/AIMS: Peginterferon alpha-2a or -2b is the standard treatment regimen in chronic hepatitis C. However, there have been few comparative studies of the efficacies of these two types of peginterferon. We evaluated their efficacies in combination with ribavirin as a initial treatment for chronic hepatitis C. METHODS: Ninety-seven patients were treated with peginterferon alpha-2a (180 microg/week, n=48) or peginterferon alpha-2b (1.5 microg/kg/week, n=49) plus ribavirin (800 mg/day for 24 weeks in genotype non-1 or 1,000-1,200 mg/day for 48 weeks in genotype 1). Virologic responses including the early virologic response (EVR), end-of-treatment response (ETR), sustained virologic response (SVR), and adverse effects were analyzed retrospectively. RESULTS: The virologic response rates did not differ significantly between peginterferon alpha-2a and -2b: 89.6% and 89.7% for EVR, 79.2% and 79.5% for ETR, 72.9% and 73.5% for SVR, respectively. Analysis of the virologic responses according to genotype also revealed no significant differences in SVR between peginterferon alpha-2a and -2b (59.3% vs. 59.7% for genotype 1 and 90.5% vs. 83.3% for genotype non-1, respectively), or in adverse effects including flu-like symptom, rash, itching, neutropenia, and thrombocytopenia. CONCLUSIONS: We found no significant differences in therapeutic efficacies and adverse effects between the alpha-2a and -2b types of peginterferon as the initial treatment regimen in naive chronic hepatitis C patients.

Transformation of Cortex-wide Emergent Properties during Motor Learning.

Learning involves a transformation of brain-wide operation dynamics. However, our understanding of learning-related changes in macroscopic dynamics is limited. Here, we monitored cortex-wide activity of the mouse brain using wide-field calcium imaging while the mouse learned a motor task over weeks. Over learning, the sequential activity across cortical modules became temporally more compressed, and its trial-by-trial variability decreased. Moreover, a new flow of activity emerged during learning, originating from premotor cortex (M2), and M2 became predictive of the activity of many other modules. Inactivation experiments showed that M2 is critical for the post-learning dynamics in the cortex-wide activity. Furthermore, two-photon calcium imaging revealed that M2 ensemble activity also showed earlier activity onset and reduced variability with learning, which was accompanied by changes in the activity-movement relationship. These results reveal newly emergent properties of macroscopic cortical dynamics during motor learning and highlight the importance of M2 in controlling learned movements.

[A randomized, prospective, comparative, multicenter study of rabeprazole and ranitidine in the treatment of reflux esophagitis].

BACKGROUND/AIMS: This study was done to evaluate the efficacy of rabeprazole (proton-pump-inhibitor) and ranitidine (H(2)-receptor antagonist) in the symptom relief and treatment of erosive esophagitis diagnosed by endoscopy. METHODS: A total of 110 patients with typical gastroesophageal reflux disease (GERD) symptoms were enrolled in this multicenter study. They were randomized into rabeprazole group (53 patients) and ranitidine group (57 patients) respectively. The patients in rabeprazole group were given 10 mg of rabeprazole and ranitidine group received 300 mg of ranitidine before breakfast and dinner for 8 weeks. After the end of treatment, we evaluated the endoscopic healing rate of reflux esophagitis and symptomatic improvement. RESULTS: After 8 weeks of treatment, rabeprazole group showed significantly higher complete endoscopic cure rate than ranitidine group (86.8% [46/53] vs. 57.9% [33/57], p=0.001) and higher symptomatic improvement of heartburn (91.2% [31/34] vs. 76.2% [32/42], p=0.085), especially in the first 7 days (76.7% vs. 45.3%, p=0.008). Also, rabeprazole group showed significantly higher improvement of regurgitation symptom than ranitidine group (100% [35/35] vs. 83% [39/47], p=0.009). Both group showed no differences in the improvement of chest pain and globus sensation. All the adverse events (rabeprazole group 4 events vs. ranitidine group 3 events) were mild and there was no abnormality in laboratory test. CONCLUSIONS: In patients with GERD, rabeprazole 10 mg b.i.d. is superior to ranitidine 300 mg b.i.d. in healing of reflux esophagitis and resolving typical GERD symptoms. Rabeprazole is an effective and well-tolerated drug for GERD treatment.

Subtype-specific plasticity of inhibitory circuits in motor cortex during motor learning.

Motor skill learning induces long-lasting reorganization of dendritic spines, principal sites of excitatory synapses, in the motor cortex. However, mechanisms that regulate these excitatory synaptic changes remain poorly understood. Here, using in vivo two-photon imaging in awake mice, we found that learning-induced spine reorganization of layer (L) 2/3 excitatory neurons occurs in the distal branches of their apical dendrites in L1 but not in the perisomatic dendrites. This compartment-specific spine reorganization coincided with subtype-specific plasticity of local inhibitory circuits. Somatostatin-expressing inhibitory neurons (SOM-INs), which mainly inhibit distal dendrites of excitatory neurons, showed a decrease in axonal boutons immediately after the training began, whereas parvalbumin-expressing inhibitory neurons (PV-INs), which mainly inhibit perisomatic regions of excitatory neurons, exhibited a gradual increase in axonal boutons during training. Optogenetic enhancement and suppression of SOM-IN activity during training destabilized and hyperstabilized spines, respectively, and both manipulations impaired the learning of stereotyped movements. Our results identify SOM inhibition of distal dendrites as a key regulator of learning-related changes in excitatory synapses and the acquisition of motor skills.

Ultraviolet-C efficacy against a norovirus surrogate and hepatitis A virus on a stainless steel surface.

In this study, the effects of 10-300 mWs/cm(2) of ultraviolet radiation (UV-C) at 260 nm were investigated for the inactivation of two foodborne viruses: murine norovirus-1 (MNV-1; a human norovirus [NoV] surrogate) and hepatitis A virus (HAV). We used an experimentally contaminated stainless steel surface, a common food-contact surface, to examine the effects of low doses of UV-C radiation on MNV-1 and HAV titers. The modified Gompertz equation was used to generate non-linear survival curves and calculate dR-values as the UV-C dose of 90% reduction for MNV-1 (R(2)=0.95, RMSE=0.038) and HAV (R(2)=0.97, RMSE=0.016). Total MNV-1 and HAV titers significantly decreased (p<0.05) with higher doses of UV-C. MNV-1 and HAV were reduced to 0.0-4.4 and 0.0-2.6 log10PFU/ml, respectively, on the stainless steel surfaces by low-dose UV-C treatment. The dR-value, 33.3 mWs/cm(2) for MNV-1 was significantly (p<0.05) lower than 55.4 mWs/cm(2) of HAV. Therefore, the present study shows that HAV is more resistant to UV-C radiation than MNV-1. These data suggest that low doses of UV-C light on food contact surfaces could be effective to inactivate human NoV and HAV in restaurant, institutional, and industrial kitchens and facilities.

Survival of hepatitis A virus on various food-contact surfaces during 28days of storage at room temperature.

Hepatitis A virus (HAV) infections constitute one of the leading causes of food-borne disease outbreaks. HAV spreads readily from one infected person to another through contaminated water or food, via the fecal-oral route. The prevention of HAV infection is therefore important in the preparation of food. The objective of this study was to investigate the survival of HAV on six different food-contact surfaces: ceramic, wood, rubber, glass, stainless steel and plastic. The survival of HAV was measured during storage at room temperature for 28days. On the food-contact surfaces, the greatest reduction in HAV was 2.3log10plaque-forming units (PFU)/coupon, observed on stainless steel, while the lowest HAV reduction was 1.4log10PFU/coupon, observed on wood. The values of dR (time required to reduce the virus by 99%) on survival plots of HAV determined by a modified Weibull model were 1396.9h (R2=0.97) on ceramic, 1676.4h (R2=0.98) on wood, 852.7h on rubber (R2=0.95), 1386.4h (R2=0.97) on glass, 428.6h (R2=0.96) on stainless steel and 833.0h (R2=0.97) on plastic. The infectivity of the virus on all six food-contact surfaces was maintained after 28days. Studies show that HAV from food preparation or processing will survive persistently on cookware. This study provides information useful for the control of HAV on different food-contact surfaces and the prevention of food-borne disease.

Survival of norovirus surrogate on various food-contact surfaces.

Norovirus (NoV) is an environmental threat to humans, which spreads easily from one infected person to another, causing foodborne and waterborne diseases. Therefore, precautions against NoV infection are important in the preparation of food. The aim of this study was to investigate the survival of murine norovirus (MNV), as a NoV surrogate, on six different food-contact surfaces: ceramic, wood, rubber, glass, stainless steel, and plastic. We inoculated 10(5) PFU of MNV onto the six different surface coupons that were then kept at room temperature for 28 days. On the food-contact surfaces, the greatest reduction in MNV was 2.28 log10 PFU/coupon, observed on stainless steel, while the lowest MNV reduction was 1.29 log10 PFU/coupon, observed on wood. The rank order of MNV reduction, from highest to lowest, was stainless steel, plastic, rubber, glass, ceramic, and wood. The values of d R (time required to reduce the virus by 90%) on survival plots of MNV determined by a modified Weibull model were 277.60 h (R(2) = 0.99) on ceramic, 492.59 h (R(2) = 0.98) on wood, 173.56 h on rubber (R(2) = 0.98), 97.18 h (R(2) = 0.94) on glass, 91.76 h (R(2) = 0.97) on stainless steel, and 137.74 h (R(2) = 0.97) on plastic. The infectivity of MNV on all food-contact surfaces remained after 28 days. These results show that MNV persists in an infective state on various food-contact surfaces for long periods. This study may provide valuable information for the control of NoV on various food-contact surfaces, in order to prevent foodborne disease.

Long-term treatment outcomes of clevudine in antiviral-naive patients with chronic hepatitis B.

AIM: To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B (CHB). METHODS: We retrospectively analyzed the clinical data of CHB patients treated with clevudine 30 mg/d and compared their clinical outcomes with patients treated with entecavir 0.5 mg/d. The biochemical response, as assessed by serum alanine aminotransferase (ALT) activity, virologic response, as assessed by serum hepatitis B virus DNA (HBV DNA) titer, serologic response, as assessed by hepatitis B e antigen (HBeAg) status, and virologic breakthrough with genotypic mutations were assessed. RESULTS: Two-hundred and fifty-four patients [clevudine (n = 118) vs entecavir (n = 136)] were enrolled. In clevudine-treated patients, the cumulative rates of serum ALT normalization were 83.9% at week 48 and 91.5% at week 96 (80.9% and 91.2% in the entecavir group, respectively), the mean titer changes in serum HBV DNA were -6.03 and -6.55 log(10) copies/mL (-6.35 and -6.86 log(10) copies/mL, respectively, in the entecavir group), and the cumulative non-detection rates of serum HBV DNA were 72.6% and 83.1% (74.4% and 83.8%, respectively, in the entecavir group). These results were similar to those of entecavir-treated patients. The cumulative rates of HBeAg seroconversion were 21.8% at week 48 and 25.0% at week 96 in patients treated with clevudine, which was similar to patients treated with entecavir (22.8% and 27.7%, respectively). The virologic breakthrough in the clevudine group occurred in 9 (7.6%) patients at weeks 48 and 15 (12.7%) patients at week 96, which primarily corresponded to genotypic mutations of rtM204I and/or rtL180M. There was no virologic breakthrough in the entecavir group. CONCLUSION: In antiviral-naive CHB patients, long-term treatment outcomes of clevudine were not inferior to those of entecavir, except for virologic breakthrough.

Up-regulation of heme oxygenase-1 expression through CaMKII-ERK1/2-Nrf2 signaling mediates the anti-inflammatory effect of bisdemethoxycurcumin in LPS-stimulated macrophages.

We have identified a novel anti-inflammatory signaling pathway that leads to the expression of heme oxygenase-1 (HO-1) in response to bisdemethoxycurcumin (BDMC), an analog of curcumin. Treatment with BDMC suppressed inducible nitric oxide synthase expression and nitric oxide (NO) production by down-regulating NF-kappaB activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. These effects were reversed by blocking HO-1 activity or expression. The signaling pathway involved in BDMC-mediated HO-1 induction included Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase 1/2 (ERK1/2). BDMC induced phosphorylation of ERK1/2 in a CaMKII-dependent manner. Pretreatment with the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor, U0126, inhibited CaMKII-induced stimulation of HO-1 promoter activity, suggesting that ERK1/2 is a downstream mediator of CaMKII in BDMC signaling to HO-1 expression. Furthermore, the CaMKII-ERK1/2 cascade targets the transcription factor, NF-E2-related factor-2 (Nrf2). Finally, inhibition of the Ca(2+)-CaMKII-ERK1/2-linked cascade attenuated significantly suppression by BDMC of LPS-induced iNOS expression and subsequent NO production. Collectively, our findings identify a Ca(2+)/calmodulin-CaMKII-ERK1/2-Nrf2 cascade as a novel anti-inflammatory pathway mediating BDMC signaling to HO-1 expression in macrophages.

Efficacy of initial treatment with clevudine in naive patients with chronic hepatitis B.

BACKGROUND/AIMS: Clevudine, a pyrimidine nucleoside analogue, has potent antiviral effects in patients with chronic viral hepatitis B (CHB). We report the efficacy of initial treatment with clevudine in naïve patients with CHB living in Daejeon and Chungcheong Province, South Korea. METHODS: One hundred five adults with CHB were administered 30 mg of clevudine per day for an average of 51 weeks. We evaluated viral markers and liver biochemistry retrospectively every 3 months. RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatitis B virus (HBV) DNA before the treatment were 184 ± 188 IU/L, 150 ± 138 IU/L, and 7.1 ± 1.2 log copies/mL, respectively. Undetectable rates (< 60 IU/mL) of DNA were 36.2%, 68.9%, 83.6%, 76.2%, and 75.8% at 12, 24, 36, 48, and 60 weeks, respectively. Seroconversion rates were 9.1%, 13.6%, 24.6%, 26.5%, and 26.1% and ALT normalization rates were 64.5%, 78.1%, 87.9%, 90.0% at 12, 24, 36, and 48 weeks, respectively. Six patients (5.7%) had a viral breakthrough. CONCLUSIONS: Clevudine is a useful drug in the initial treatment of patients with CHB, with a potent antiviral effect and low incidence of viral breakthrough.

Acute drug-induced hepatitis caused by albendazole.

Albendazole binds to parasite's tubulin inhibiting its glucose absorption. Its common adverse effects are nausea, vomiting, constipation, thirst, dizziness, headache, hair loss and pruritus. Although mainly metabolized in the liver, abnormal liver function tests were a rare adverse effect during clinical trials and we found no literature about albendazole-induced hepatitis requiring admission. This patient had a previous history of albendazole ingestion in 2002 resulting in increase of liver function tests. And in 2005, the episode repeated. We evaluated the patient for viral hepatitis, alcoholic liver disease, and autoimmune hepatitis, but no other cause of hepatic injury could be found. Liver biopsy showed periportal steatosis and periportal necrosis. The initial abnormal liver function test improved only with supportive care. These findings and the Roussel Uclaf Causality Assessment Method of the Council for International Organizations of Medical Sciences (RUCAM/CIOMS) score of 9 are compatible with drug-induced hepatitis so we report the case of this patient with a review of the literature.