Duck hepatitis B virus and liver diseases

The presence of duck hepatitis B virus in serum was studied in 61 ducks (24 from Chi-tung county, China, 20 from Changchun, China, and 17 from Chiba, Japan) with relation to liver disease. None of the 37 ducks from Chiba and Changchun was positive for duck hepatitis B virus as assayed by electron microscopy, endogenous deoxyribonucleic acid-polymerase activity, and hybridization with duck hepatitis B virus deoxyribonucleic acid. No liver disease was seen in these ducks. In contrast, viruslike particles were present in the serum of 12 of 24 (50%) ducks from Chi-tung, China. The presence of duck hepatitis B virus in serum was indicated by the hybridization spot test and deoxyribonucleic acid-polymerase activities. A variety of liver diseases including chronic hepatitis and cirrhosis were seen in the livers of a majority of the ducks from Chi-tung. One duck hepatitis B virus-positive duck had multicentric hepatocellular carcinoma with underlying cirrhosis. Comparison of serum duck hepatitis B virus markers and liver disease in the affected flock revealed a tendency for seronegative ducks to have advanced liver diseases. Duck hepatitis B virus infection may be used as an experimental model to test various hypotheses concerning the pathogenesis of hepatitis B virus-associated liver disease in humans.     

Combination of short-term prednisolone and adenine arabinoside in the treatment of chronic hepatitis B. A controlled study

The efficacy of adenine arabinoside (Ara-A) alone or in combination with prednisolone utilizing its withdrawal effect was studied in 43 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis. Ten patients were treated with 10 mg/kg body wt of Ara-A alone for 4-8 wk. In 9 cases, prednisolone (40 mg/day) was given at a constant dosage for 4 wk before Ara-A treatment. Fourteen patients received oral prednisolone alone for 4 wk, and 10 patients served as untreated controls. Six of 9 patients (67%) undergoing the combination therapy became seronegative for hepatitis B e antigen, whereas only 4 of 24 patients (17%) treated either with Ara-A alone or prednisolone alone lost the antigen. Two of the 10 untreated patients became seronegative for hepatitis B e antigen during the same follow-up period of 9 mo. This prospective controlled study suggests that the combination of immunomodulation by steroid withdrawal and subsequent Ara-A is more effective in the treatment of patients with chronic liver disease and active hepatitis B virus replication than treatment with Ara-A alone.     

Silymarin enhanced cytotoxic effect of anti-Fas agonistic antibody CH11 on A375-S2 cells

Silymarin is a polyphenolic flavonoid from milk thistle (Silybum marianum), which has anti-inflammatory, cytoprotective as well as antioxidant effects. Our previous study demonstrated that silymarin has anti-apoptotic effect against UV irradiation. In this study, we assessed the effect of silymarin on anti-Fas agonistic antibody CH11-treated human malignant melanoma, A375-S2 cells. Pretreatment with silymarin (3 x 10(- 4) mol/L) significantly induced cell apoptosis in CH11-treated A375-S2 cells. Mitochondrial transmembrane potential (DeltaPsi(m)) was also down-regulated by silymarin pretreatment. Caspase-8, -9, -3 and pan-caspase inhibitors partially reversed silymarin-induced apoptosis of CH11-treated cells. The expression of Fas-associated proteins with death domain (FADD), a downstream molecule of the death receptor pathway, was increased by silymarin pretreatment, followed by cleavage of procaspase-8, whose activation induced cell apoptosis. Moreover, cleavage of procaspase-3 and digestion of its substrate, the inhibitor of caspase-activated DNase (ICAD), were also increased by silymarin pretreatment. These results suggested that silymarin could also exaggerate the apoptotic effect of anti-Fas agonistic antibody CH11 on A375-S2 cells.     

Acquired hemophilia A developed at relapse of minimal change nephrotic syndrome

We present a case of a 74-year-old male, who had a relapse of minimal change nephrotic syndrome (MCNS) as the initial presentation of acquired hemophilia A. MCNS had been maintained in remission with prednisolone 10 mg for 15 years. In early December 2005, the patient developed edema of the right leg, was admitted to a local general hospital, and was diagnosed as having a relapse of MCNS based on massive proteinuria (urine protein 6.1 g/day). One week later, severe anemia (hemoglobin 4.4 g/dl) and acute renal failure (creatinine 2.0 mg/dl) developed, and a CT scan of the abdomen revealed a hematoma in the left iliopsoas muscle. He was referred to our hospital with bleeding tendency. Laboratory examination revealed prolonged APTT 80.5 seconds), reduced factor VIII activity (<1%) and thepresence of factor VIII inhibitor at a titer of 19 Bethesda units/ml, based on which he was diagnosed as having acquired hemophilia A. With recombinant activated FVII, hemostasis was obtained and prednisolone administration 60 mg/day (1 mg/kg) was started. Both the acquired hemophilia A and MCNS responded well to the treatment with prednisolone. Six weeks after initiation of the treatment, factor VIII inhibitor and urine protein disappeared. This patient is considered to be a rare case; to the best of our knowledge, this is the third report of acquired hemophilia A with nephrotic syndrome.     

Animal models of bipolar disorder

Animal models of human diseases should meet three sets of criteria: construct validity, face validity, and predictive validity. To date, several putative animal models of bipolar disorder have been reported. They are classified into various categories: pharmacological models, nutritional models, environmental models, and genetic models. None of them, however, totally fulfills the three validity criteria, and thus may not be useful for drug development. Mounting evidence suggests that mitochondrial dysfunction has a role in bipolar disorder. To test whether accumulation of mtDNA deletions in the brain can cause bipolar disorder, we generated transgenic mice with neuron-specific expression of mutant Polg (D181A). These mice showed altered diurnal activity rhythm and periodic activity change associated with the estrous cycle. These phenotypes were worsened by administration of a tricyclic antidepressant, but improved after lithium treatment. This mouse model of bipolar disorder potentially fulfills the three validity criteria, and therefore might be used for future drug development studies.     

Prevalence and Clinical Characteristics of Acute Myeloid Leukemia Associated with Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC) is one of the important complications to develop in patients with acute myeloid leukemia (AML). While acute promyelocytic leukemia (APL) is a strong risk factor for DIC, other clinical features have not been fully defined. We retrospectively analyzed 161 consecutive adult patients with de novo non-APL AML. DIC was diagnosed in 52 patients (32%); 28 patients at diagnosis and 24 soon after the initiation of induction chemotherapy. Leukocyte counts, C-reactive protein, and lactate dehydrogenase were significantly higher in the DIC+ group. Negative expressions of CD13, CD19, CD34, and HLA-DR were more prevalent in the DIC+ group. On multivariate logistic-regression analysis, variables that were independently associated with the development of DIC were high C-reactive protein, high leukocyte count, negative expressions of CD13 and HLA-DR, and cytogenetics with a normal karyotype or 11q23 abnormality. Although DIC is considered to be associated with serious morbidity and occasional mortality, we did not find any significant differences in the complete remission rate, overall or disease-free survival between DIC+ and DIC- groups. This study is the first to define the clinical characteristics associated with DIC in patients with non-APL AML, but exactly how and when DIC should be treated remains to be determined.     

Low burden of a JAK2-V617F mutated clone in monoclonal haematopoiesis in a Japanese woman with Budd-Chiari syndrome

Approximately one-half of the cases of Budd-Chiari syndrome (BCS) are caused by bcr/abl negative chronic myeloproliferative disorders (CMPDs). Furthermore, a mutation in the Janus kinase protein (JAK2-V617F) is detected in half of the patients with BCS. However, whether the JAK2 mutation is the primary event leading to CMPDs and BCS is controversial. We present a report concerning a young woman who suffered from BCS prior to the onset of CMPDs. Analysis of X-chromosome inactivation patterns in this patient, using the human androgen receptor gene demonstrated monoclonal haematopoiesis in her granulocytes. In contrast, she had a low burden of a JAK2-V617F mutation positive clone among granulocyte populations. These results suggest that the JAK2-V617F mutation occurs after the onset of monoclonal haematopoiesis; thus the V617F mutation of JAK2 may not be the primary event in the induction of BCS.     

The effects of zolpidem and zopiclone on daytime sleepiness and psychomotor performance.

Zolpidem (ZLP), which has selective affinity to the BZ1 (omega 1) receptor and a short half-life, is a novel hypnotic. The objective of this study is to compare the residual effects of standard clinical doses of ZLP and zopiclone (ZPC), a short-acting hypnotic marginally selective for the BZ1 (omega 1) receptor, given in a single dose on daytime sleepiness and psychomotor function. This study was carried out as a double-blind cross-over study with 10 mg ZLP, 7.5 mg ZPC and a placebo in 12 healthy male adults. In the multiple sleep latency test, sleep latency was not reduced but increased by ZLP and ZPC as well as the placebo when drug plasma levels had nearly reached the peak. Subjects administered ZLP were significantly more feeble, lethargic and antagonistic in mood rating scales than those administered ZPC. The incidence of severe behavioral side effects was higher in the case of ZLP than in the case of ZPC over the same period. Sleep latency the next morning was significantly shorter in the case of ZPC than in the case of ZLP or the placebo. The tapping test performed at the same time demonstrated that the number of taps was significantly less in the case of ZPC than in the case of ZLP or the placebo. The results of the present study suggest that ZLP acts more rapidly than ZPC. On the other hand, ZLP has less residual effect on sleepiness and psychomotor function the next morning.     

Management of Major Portosystemic Shunting in Small-for-Size Adult Living-Related Donor Liver Transplantation with a Left-Sided Graft Liver

PURPOSE: We investigated the mechanisms of small-for-size graft syndrome by time-lag ligation, a novel approach to treating major portosystemic shunts in small-for-size adult living-related donor liver transplantation (LRDLT) using left-sided graft liver. METHODS: Five patients with end-stage liver failure and major splenorenal shunting underwent LRDLT using left lobe grafts. The average graft volume to recipient body weight (GV/RBW) ratio was 0.68 +/- 0.14. Two patients underwent time-lag ligation of their splenorenal (SR) shunts on postoperative days (PODs) 8 and 14, respectively. The shunts of the other three patients were untreated. RESULTS: The portal pressures in the first patient who underwent time-lag ligation rose above 300 mmH(2)O and remained there for 2 weeks. Thus, we ligated the SR shunt in the second patient on POD 14, resulting in an increase from 177 mmH(2)O to 258 mmH(2)O, but it decreased again thereafter. In the other three patients, the SR shunt was not ligated because portal blood flow volumes remained sufficient. Total bilirubin levels in the first time-lag ligation patient rose to 16 mg/dl, paralleling the rise in portal pressures. Although they increased after ligation in the second patient, they did not exceed 10 mg/dl. CONCLUSIONS: We recommend time-lag ligation if portal venous blood flow decreases in the early post-transplant period, but not until at least 2 weeks after transplantation. If the portal venous blood flow does not decrease, early postoperative ligation is unnecessary. If there are no major portosystemic shunts, making a portosystemic shunt might decompress excessive portal hypertension. With donor safety priority in LRDLT, novel approaches must be developed to enable the use of smaller donor grafts. We describe a potential means of using left lobe grafts in adult LRDLT.     

Steroid-refractory chronic idiopathic thrombocytopenic purpura associated with hepatitis C virus infection

OBJECTIVES: Hepatitis C virus infection has often been suggested as a possible cause of various kinds of autoimmune diseases. The aim of this study was to determine the relationship between chronic idiopathic thrombocytopenic purpura (ITP) and hepatitis C virus infection and to characterize the clinical features of anti-HCV antibody (HCVab) positive chronic ITP patients. SUBJECTS AND METHODS: We studied HCVab in 79 patients with chronic ITP (25 males, 54 females, mean age 42.3 yr, range 11-86 yr) using the third-generation ELISA method. RESULTS: HCVab was detected in 11 of the 79 patients (13.9%). Quantitative HCV-RNA studies showed a high serum concentration of HCV-RNA in these patients. The platelet counts in these 11 HCVab-positive patients (Group 1) were lower than in the 68 HCVab-negative patients (Group 2) [(2.6 +/- 0.9) versus (4.9 +/- 3.0) x 10(10)/L, respectively; p<0.02]. Significantly more patients in Group 1 required prednisolone therapy (10/11, 90.9%) than in Group 2 (31/68, 45.6%) (P < 0.005). The response rate to prednisolone treatment was significantly higher in Group 2 (19/31, 61.3%) than in Group 1(0/10, 0%) (P < 0.001). There was no difference in the response to splenectomy between Groups 1 (4/7, 57.1%) and 2 (3/5, 60%). CONCLUSION: Given these findings, we recommend that HCVab is measured upon diagnosis of chronic ITP, and that splenectomy is planned in patients with HCVab in the event that prednisolone treatment is ineffective.