Influence of colour background on anti-viral activity against viral haemorrhagic septicaemia virus in zebrafish regulated by circadian rhythm signalling pathway.

The influence of colour background on the regulation of behavioural and physiological responses in zebrafish is widely recognized. However, its specific effect on virus infection in zebrafish remains unclear. This study aimed to explore the susceptibility of zebrafish to viral haemorrhagic septicaemia virus (VHSV) infection in relation to background colour, investigate the underlying mechanisms, and elucidate the involvement of key molecules, using proteomic and gene expression analyses. The results revealed that zebrafish housed in a blue tank exhibited higher survival rates and considerably reduced VHSV replication compared to those housed in a yellow tank. Further, up-regulation of apolipoprotein 1 (APOA1) was identified as a crucial shared mechanism associated with survival in zebrafish exposed to VHSV infection and reared in a blue background. The mRNA expression level of bmal1a, a core gene involved in the circadian rhythm, was consistently downregulated in fish from the blue tank compared to fish from the yellow tank, regardless of infection status. Subsequently, zebrafish in the blue tank were exposed to daylight conditions to stimulate per2 and pgc1a expression, aiming to investigate their potential impact on VHSV infection. The validity of these interconnected events, triggered by background colour, involving APOA1 up-regulation, circadian rhythm modulation, and antiviral responses, was confirmed by treatments with hesperetin and cyclosporine A, an activator and inhibitor of apoa1 respectively. Our findings revealed the influence of background colour on the apoa1 expression level, thus establishing the involvement of a novel network through circadian rhythm signalling.

Gammaherpesvirus latency accentuates EAE pathogenesis: relevance to Epstein-Barr virus and multiple sclerosis.

Epstein-Barr virus (EBV) has been identified as a putative environmental trigger of multiple sclerosis (MS), yet EBV's role in MS remains elusive. We utilized murine gamma herpesvirus 68 (γHV-68), the murine homolog to EBV, to examine how infection by a virus like EBV could enhance CNS autoimmunity. Mice latently infected with γHV-68 developed more severe EAE including heightened paralysis and mortality. Similar to MS, γHV-68EAE mice developed lesions composed of CD4 and CD8 T cells, macrophages and loss of myelin in the brain and spinal cord. Further, T cells from the CNS of γHV-68 EAE mice were primarily Th1, producing heightened levels of IFN-γ and T-bet accompanied by IL-17 suppression, whereas a Th17 response was observed in uninfected EAE mice. Clearly, γHV-68 latency polarizes the adaptive immune response, directs a heightened CNS pathology following EAE induction reminiscent of human MS and portrays a novel mechanism by which EBV likely influences MS and other autoimmune diseases.

Restoration of the center of rotation in revision total hip arthroplasty.

We measured the change of the center of hip rotation after the revision of acetabular loosening using an acetabular reconstruction ring and an impaction allogenic bone grafting. Thirty-five revision total hip arthroplasties were performed. The average follow-up was 3.8 years. Horizontal distance was changed from 34.01±10 mm preoperatively to 41.07±6 mm at the latest follow-up. Vertical distance was changed from 32.06±9 mm preoperatively to 20.21±7 mm at the latest follow-up. The Harris hip score was improved from an average of 47 in the preoperative period to 86 at the final follow-up. The restoration of the anatomical hip center has shown to be favorable in terms of functional and radiologic evaluation in total hip revision.

Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B.

AIM: To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naive chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone. METHODS: Eighty patients who had received lamivudine treatment for various periods and had a lamivudine-resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for > or = 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus (HBV) DNA at 0, 12 and 48 wk and serum alanine aminotransferase (ALT) levels after 0, 12, 24 and 48 wk of adefovir treatment in each group. RESULTS: We found serum ALT became normalized in 72 (87.5%) of the 80 patients, and HBV DNA decreased by > or = 2 log10 copies/mL in 60 (75%) of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups. CONCLUSION: These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.

[Is C3435T polymorphism of MDR1 related to inflammatory bowel disease or colorectal cancer in Korean?].

BACKGROUND/AIMS: Multidrug resistance 1 (MDR1) gene encodes P-glycoprotein in intestinal epithelium, which serves as a transmembrane efflux pump of various toxins. mdr1 knockout mice develop spontaneous colitis under specific pathogen free conditions. However, it is unclear that C3435T polymorphism of MDR1 is related to ulcerative colitis. Other studies suggest MDR1 may have an important role in colorectal carcinogenesis. Thus, we evaluated whether MDR1 C3435T polymorphism is present in Korean and it is associated with inflammatory bowel disease or colorectal cancer. METHODS: The genotype distributions of the C3435T polymorphism were investigated by PCR-RFLP method in 94 patients with ulcerative colitis, 24 patients with Crohn's disease, 64 patients with colorectal cancer and each of gender-matched controls with equal numbers. RESULTS: There was no significant difference in frequencies of 3435T allele and 3435TT genotype between patients with ulcerative colitis and controls (p=0.443, p=0.194). No significant difference was present in frequencies of 3435T allele and 3435TT genotype between patients with Crohn's disease and controls (p=0.378, p=1.000). There was neither significant difference in frequencies nor 3435T allele or 3435TT genotype between patients with colorectal cancer and controls (p=0.250, p=0.211). C3435T genotype was not associated with the age of onset or other clinical characteristics in patients with ulcerative colitis, Crohn's disease or colorectal cancer. CONCLUSIONS: MDR1 C3435T polymorphism is also present in Korean and the dominant allele is C. However, there is no evidence that C3435T polymorphism of MDRI is associated to inflammatory bowel disease or colorectal cancer in Korean.

Expression of trefoil peptides in the subtypes of intestinal metaplasia.

We studied the expression of trefoil peptides in the different types of intestinal metaplasia of the stomach. Endoscopic biopsy was performed in 132 patients with dyspepsia. Intestinal metaplasia subtype was classified according to the pattern of alcian blue/PAS staining and high iron diamine staining. Expression of trefoil peptides was measured by immunohistochemistry. TFF1 and TFF3 were mainly expressed in goblet cells and TFF2 in columnar cells in all the types of intestinal metaplasia. There was a gradual decrease of TFF1 and TFF3, and increase of TFF2, during the progression of intestinal metaplasia from type I to type III via the type II intermediate.

Oltipraz therapy in patients with liver fibrosis or cirrhosis: a randomized, double-blind, placebo-controlled phase II trial.

OBJECTIVES: Oltipraz, a cancer chemopreventive agent, has an anticirrhotic effect in animals. A phase II trial was designed to investigate the preliminary efficacy of oltipraz therapy in liver fibrosis or cirrhosis. METHOD: Of 83 patients who were randomized to receive placebo, oltipraz 60 mg bid or oltipraz 90 mg qd for 24 weeks, 68 completed the study without any major protocol violation. Pre- and post-treatment liver biopsies, and blood fibrosis markers were assessed. KEY FINDINGS: Twenty-four weeks of oltipraz treatment showed no significant differences in the proportions of patients showing an improvement in histological outcomes, including Ishak fibrosis score. In the oltipraz 60 mg bid group, there was a trend of decreases in hepatic collagen area and plasma transforming growth factor-ß1 (TGF-ß1, a blood fibrosis marker) levels from baseline to week 24. In the per-protocol population (n = 68), decreases in plasma TGF-ß1 correlated with those in the Ishak fibrosis score, suggesting that circulating TGF-ß1 serves a possible indicator for fibrosis treatment. CONCLUSIONS: No significant differences in liver histological outcomes were seen among the three treatment groups in this 24-week pilot study. Our finding indicates an association between TGF-ß1 repression and improvement in the histological index of fibrosis.

Clevudine-induced viral response, associated with continued reduction of HBsAg titer, was durable after the withdrawal of therapy.

BACKGROUND: This study was conducted to evaluate the durability of clevudine-induced viral response after the withdrawal of treatment. METHODS: Patients who showed a complete response [alanine aminotransferase (ALT) normalization and hepatitis B virus (HBV) DNA <4,700 copies/mL for hepatitis B envelope antigen (HBeAg)-negative patients; ALT normalization, HBV DNA <4,700 copies/mL, and HBeAg seroconversion for HBeAg-positive patients] in the previous clevudine phase III trials were followed for an additional 96 weeks without any treatment for hepatitis B. RESULTS: Of the 63 patients in the study cohort, 73% and 35% of the patients had HBV DNA <141,500 and <4,700 copies/mL, respectively, and 75% of the patients had normal ALT at the end of follow-up. HBeAg seroconversion was maintained in 81% of the patients and hepatitis B surface antigen (HBsAg) loss occurred in 3 patients. Continued HBsAg titer decrease (-0.5 log IU/mL) was observed in the sustained viral responders, suggesting the reduction of covalently closed circular DNA in hepatocytes. CONCLUSIONS: The clevudine-induced viral response was durable in the majority of patients for 2 years after the withdrawal of treatment.

Vascular injury associated with blunt trauma without dislocation of the knee.

Failure to recognize popliteal artery injury and restore vessel continuity of flow after blunt trauma is a major cause of lower extremity amputation and morbidity. A high index of suspicion and early recognition of the injury are paramount for limb salvage. We experienced a rare case of poplitial artery occlusion with the presence of arterial pulses due to collateral circulation after blunt trauma. Expeditious revascularization was achieved by using posterior approach, allowing two surgical teams to work simultaneously. This case illustrates that, even in the absence of knee dislocation, surgeons must always consider the possibility of a popliteal artery damage whenever a blunt trauma near the knee.

Antiapoptotic effects of anthocyanins on rotator cuff tenofibroblasts.

Degeneration of the rotator cuff tendon, which involves apoptosis of the tenofibroblasts, is one of the most common shoulder problems that can lead eventually to a full-thickness rotator cuff tendon tear. The current authors evaluated both the ability of anthocyanins, which are powerful antioxidants, to reduce apoptosis in oxidation-stressed rotator cuff tenofibroblasts, and the molecular mechanism for this antiapoptotic action. Anthocyanins demonstrated a dose-dependent ability to inhibit H(2)O(2)-induced apoptosis in cultured tenofibroblasts, as assessed by MTT assay and FACS analysis. H(2)O(2) increased the phosphorylation of extracellular regulated kinase1/2 (ERK1/2) and of c-Jun N-terminal kinase (JNK) and the production of reactive oxygen species (ROS). In contrast, treatment with anthocyanins decreased this activation of ERK1/2 and JNK, as confirmed by Western blot analysis, and reduced the production of ROS, as verified by fluorescent microscopic and FACS analyses. These findings suggest that anthocyanins, by suppressing JNK, ERK1/2, and intracellular ROS production, have a concentration-dependent antiapoptotic effect on rotator cuff tenofibroblasts exposed to an oxidative stressor, and may have therapeutic potential.

Revision total knee arthroplasty with a cemented posterior stabilized, condylar constrained or fully constrained prosthesis: a minimum 2-year follow-up analysis.

BACKGROUND: The clinical and radiological outcomes of revision total knee arthroplasty with a cemented posterior stabilized (PS), condylar constrained knee (CCK) or a fully constrained rotating hinge knee (RHK) prosthesis were evaluated. METHODS: This study reviewed the clinical and radiological results of 36 revision total knee arthroplasties with a cemented PS, CCK, and RHK prosthesis in 8, 25, and 13 cases, respectively, performed between 1998 and 2006. The mean follow-up period was 30 months (range, 24 to 100 months). The reason for the revision was aseptic loosening of one or both components in 15, an infected total knee in 18 and a periprosthetic fracture in 3 knees. The average age of the patients at the time of the revision was 65 years (range, 58 to 83 years). The original diagnosis for all primary total knee arthroplasties was osteoarthritis except for one case of a Charcot joint. All revision prostheses were fixed with cement. The bone deficiencies were grafted with a cancellous allograft in the contained defect and cortical allograft fixed with a plate and screws in the noncontained defect. A medial gastrocnemius flap was needed to cover the wound dehiscence in 6 of the 18 infected cases. RESULTS: The mean Knee Society knee score improved from 28 (range, 5 to 43) to 83 (range, 55 to 94), (p < 0.001) and the mean Knee Society function score improved from 42 (range, 10 to 66) to 82 (range, 60 to 95), (p < 0.001) at the final follow-up. Good or excellent outcomes were obtained in 82% of knees. There were 5 complications (an extensor mechanism rupture in 3 and recurrence of infection in 2 cases). Three cases of an extensor mechanism defect (two ruptures of ligamentum patellae and one patellectomy) were managed by the RHK prosthesis to provide locking stability in the heel strike and push off phases, and two cases of recurrent infection used an antibiotic impregnated cement spacer. The radiological tibiofemoral alignment improved from 1.7 degrees varus to 3.0 degrees valgus in average. Radiolucent lines were observed in 18% of the knees without progressive osteolysis. CONCLUSIONS: Revision total knee requires a more constrained prosthesis than primary total knee arthroplasty because of the ligamentous instability and bony defect. This short to midterm follow-up analysis demonstrated that a well planned and precisely executed revision can reduce pain and improve the knee function significantly. Infected cases showed as good a result as those with aseptic loosening through the use of antibiotics-impregnated cement beads and proper soft tissue coverage with a medial gastrocnemius flap.

Polyps in the gastrointestinal tract: discrepancy between endoscopic forceps biopsies and resected specimens.

BACKGROUND AND AIM: An endoscopic forceps biopsy (EFB) carries the risk of missing the neoplastic foci within a polyp as only a small portion of the lesion is sampled using this technique. Accordingly, the histological examination of specimens obtained by an EFB is of limited accuracy and patient management based on the histological findings is controversial. The aim of this prospective study was to determine the diagnostic concordance between an EFB and resected tissues of gastric and colon polyps. METHODS: Between January 2006 and October 2007, 1312 gastrointestinal polyps from 896 patients were resected in our hospital. Patients with polyps of epithelial origin of at least 8 mm in diameter and not associated with polyposis syndromes were included in the study. Polyps of nonepithelial origin were excluded. One thousand two hundred and sixty-four polyps of epithelial origin [gastric polyps (n=268) and colon polyps (n=996)] obtained from 813 patients met the inclusion criteria. All patients underwent an EFB and resection of the polyp by endoscopic mucosal resection and endoscopic submucosal dissection. RESULTS: Multiple polyps existed in 31.6% of the patients. The pathological diagnoses of resected gastric polyps were as follows: adenomas with low-grade dysplasia, 46 (17.2%); adenomas with high-grade dysplasia, 42 (15.7%); hyperplastic polyps, 126 (47.0%); chronic inflammatory polyps, 29 (10.8%); and adenocarcinomas, 25 (9.3%). The discrepancy rate between an EFB and the pathology of the resected gastric polyps was 39.2% (the Kendall's tau-b and the kappa coefficient for agreement between the EFB and resected specimens of gastric polyps were 0.577 and 0.472, respectively; P value <0.001). No relationship between the size of the gastric polyp and the concordance rate was observed. The pathological diagnoses of the resected colon polyps were as follows: adenomas with low-grade dysplasia, 559 (56.1%); adenomas with high-grade dysplasia, 229 (23.0%); hyperplastic polyps, 44 (4.4%); adenocarcinomas, 53 (5.3%); and inflammatory polyps, 111 (11.1%). The discrepancy rate between the EFB and the pathology of the resected colon polyps was 39.8%. (the Kendall's tau-b and the kappa coefficient for agreement between the EFB and the resected specimens of the colon polyps were 0.479 and 0.293, respectively; P value <0.001). No relationship between the size of the colon polyp and the concordance rate was observed. CONCLUSION: Considerable discrepancies were observed in histological findings between the EFB and the resected specimens. Therefore, complete removal of the entire polyp is recommended to confirm the diagnosis, to remove precancerous lesions, and to develop an optimal management plan.

Endoscopic evaluation in gastrointestinal graft-versus-host disease: comparisons with histological findings.

The gastrointestinal (GI) tract is the major target site of the graft-versus-host disease (GVHD). Whether endoscopic findings can predict the histological diagnosis and degree of severity in GVHD remains controversial. We investigated the degree of correlation between endoscopic and histological findings, and evaluated the impact of endoscopic examination on clinical decision in GVHD management. This study was conducted as a retrospective single-center study. One hundred and one patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and at the risk of GI GVHD were referred for endoscopic evaluation. Endoscopic images and histology were reviewed to diagnose and grade in a blind fashion, and the histological findings were used as the "gold standard" for diagnosis. Endoscopic findings revealed a significantly positive association with histological abnormalities of GVHD (odds ratio [OR] = 33.6, 95% CI 4.3-261.1), and the sensitivity and specificity were 98 and 44%, respectively. The kappa coefficient for agreement between the endoscopic and histological grading was 0.423 (p-value < 0.001). Ten (18%) patients out of 57 histology-negative cases were managed successfully as GVHD on the endoscopic finding. Though the overall reliability of endoscopic diagnosis in GVHD is still insufficient in terms of sensitivity and specificity, high-grade cases such as grades 3 or 4 showed specific endoscopic findings to draw a significant agreement with histological findings. Endoscopic examination can give critical information and impose a pivotal impact on clinical decision when the histology is discordant with clinical presentation.

A large inflammatory fibroid polyp in the sigmoid colon treated by endoscopic resection.

Inflammatory fibroid polyp (IFP) is a rare, localized, nonneoplastic lesion originating from the submucosa of the gastrointestinal tract. Microscopically, these lesions are made up of a complex network of variable-size blood vessels and diffuse inflammatory cells contained in the edematous stroma. They are most often found in the stomach, followed by the small intestine, and rarely in the esophagus or the large intestine. We report a case of sigmoid colonic IFP presenting bloody stool treated with endoscopic resection.

Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression.

UNLABELLED: Clevudine is a pyrimidine analog with potent and sustained antiviral activity against HBV. In the present study, we evaluated the safety and efficacy of clevudine 30 mg daily for 24 weeks and assessed the durability of antiviral response for 24 weeks after cessation of dosing in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB). We randomized a total of 86 patients (3:1) to receive clevudine 30 mg (n = 63) or placebo (n = 23) daily for 24 weeks. We followed patients for an additional 24 weeks after withdrawal of treatment. The median changes in HBV DNA from baseline were -4.25 and -0.48 log(10) copies/mL at week 24 in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained after withdrawal of therapy, with 3.11 log(10) reduction at week 48. At week 24 and week 48, 92.1% and 16.4% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (<300 copies/mL). The proportion of patients who achieved ALT normalization was 74.6% and 33.3% in the clevudine and placebo groups at week 24, respectively (P = 0.0006). ALT normalization in the clevudine group was well-maintained during the post-treatment follow-up period. The incidence of adverse events was similar in the 2 groups. No resistance to clevudine was detected during treatment. CONCLUSION: A 24-week clevudine therapy was well-tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e-CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission.

Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B.

UNLABELLED: Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n=182) or placebo (n=61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log10 copies/mL in the clevudine and placebo groups, respectively (P<0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log10 reduction at week 34 and 2.02 log10 reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P<0.0001). ALT normalization in the clevudine group was well maintained during post-treatment follow-up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug. CONCLUSION: A 24-week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg-positive chronic hepatitis B.

Laceration of femoral vessels by an avulsion fracture fragment of the lesser trochanter after bipolar hemiarthroplasty.

Femoral vessel injuries after bipolar hemiarthroplasty have not been reported. The current report describes a case of a dual major vessel (superficial femoral artery and vein) injury associated with an avulsion fracture fragment of the lesser trochanter in a 76-year-old woman who had been treated with bipolar hemiarthroplasty because of a femoral neck fracture. The superficial femoral artery was repaired and the defect of the superficial femoral vein was reconstructed with a Gore-Tex graft (WL Gore and Associates Inc, Flagstaff, Ariz). The clinical result was satisfactory and there was no vascular problem at 1-year follow-up. Early diagnosis of this vascular injury prevents serious complications including gangrene of the injured limb.

Role of thrombotic and fibrinolytic disorders in osteonecrosis of the femoral head.

Some studies have suggested that thrombotic and fibrinolytic disorders may be etiologic causes of osteonecrosis of the femoral head. A case-control study was done to determine whether these disorders are associated with osteonecrosis of the femoral head in East Asian patients with nontraumatic osteonecrosis of the femoral head. Twenty-four consecutive patients who had been diagnosed as having nontraumatic osteonecrosis of the femoral head were matched with 24 control subjects for gender, age (1-year range), and the time of presentation (1-year range). Thrombotic factors including protein C activity, protein S activity, antithrombin III, anticardiolipin antibody immunoglobulins G and M, and lupus antibody were investigated. Fibrinolytic factors including tissue-plasminogen activator, plasminogen activator inhibitor-1, tissue-plasminogen activator and plasminogen activator inhibitor-1 ratio, lipoprotein (a), and plasminogen also were investigated. There were no significant differences in the levels of thrombotic and fibrinolytic factors. In eight patients with idiopathic osteonecrosis, anticardiolipin antibody immunoglobulin G, an antiphospholipid antibody which is associated with thrombotic phenomena, was lower than that in respective control subjects. These data do not confirm an etiologic role for thrombotic and fibrinolytic disorders in East Asian patients with nontraumatic osteonecrosis of the femoral head.

Role of thrombotic and fibrinolytic disorders in the etiology of Perthes' disease.

The etiologic role of thrombotic and fibrinolytic disorders in Perthes' disease has not been determined. A case control study was conducted to determine whether thrombotic and fibrinolytic disorders are associated with Perthes' disease. Twenty-six patients with Perthes' disease were matched with 26 control patients for gender, age (2-year range), and time of presentation (1-year range). Thrombotic disorders were investigated for protein C activity, protein S activity, antithrombin III, anticardiolipin antibody immunoglobulins G and M, and lupus anticoagulant. Fibrinolytic disorders were investigated for tissue-plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-1 to tissue plasminogen activator ratio, lipoprotein (a), and plasminogen. The activity of protein C, which suppresses factor Va and leads to an increase of coagulant activity when decreased, was increased in patients. There were no significant differences in the levels of other factors between the patients and controls. No evidence was found to prove a relationship between Perthes' disease and thrombotic or fibrinolytic disorders in the patients in the current study.