Urinary trypsin inhibitor and biliary atresia--providing protection for the liver?

Urinary Tyrosine Inhibitor (UTI) is produced in the liver and excreted in urine hepatic inflammation, infection or malignancy. We assess the possible implications of UTI in biliary atresia (BA). Liver function was used to divide 34 postoperative BA patients into 2 groups: Group 1 (n=25), anicteric (total bilirubin [T-Bil] <2.0 mg/dl); and Group 2 (n = 9), icteric (total bilirubin >2.0 mg/dl) with abnormal liver function test results, and repeated episodes of cholangitis. 26 age-matched subjects with no history of liver disease acted as controls     

A case of unilateral leg edema due to abdominal aortic aneurysm with aortocaval fistula.

Aortocaval fistula (ACF) is a rare complication of abdominal aortic aneurysm (AAA), and its preoperative diagnosis is often difficult. A 71-year-old woman was admitted to our hospital due to unilateral leg edema. Abdominal computed tomography (CT) showed an abdominal aortic aneurysm (AAA), a common iliac aortic aneurysm (CIAA) and ACF was suspected. Digital subtraction angiography (DSA) was performed, enabling us to identify the region of ACF with AAA preoperatively. ACF is associated with high mortality because it is difficult to control venous bleeding from ACF. Detailed preoperative diagnosis of ACF can provide many advantages to control bleeding from ACF during an operation.     

Gemcitabine and paclitaxel chemotherapy as a second-line treatment for advanced or metastatic urothelial carcinoma

OBJECTIVES: We report that a combination of gemcitabine and paclitaxel will effectively treat patients with advanced urothelial carcinoma (UC) who have been previously treated with methotrexate, vinblastine, adriamycin, and cisplatin (MVAC). The objective of this study was to assess the tumor responses, toxicity, and overall survival of these patients as second-line treatment. METHODS: Ten eligible patients were enrolled in this study. All patients had been previously treated with MVAC. Patients received paclitaxel 200 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1, 8, and 15. The treatment was repeated every 21 days. Tumors were assessed every two cycles by imaging study. RESULTS: The median number of treatment courses was 4 (range 2-7). Two patients had complete response and five patients had partial response after two courses of treatment. Median overall survival was 10.3 months. Median overall survival from the first MVAC was 19.1 months. Median progression-free survival was 4.1 months. Of the seven responders, median progression-free survival was 7.4 months. Myelosuppression was the most common toxicity. Nonhematologic toxicity consisted of hypersensitivity reactions to paclitaxel. There were no therapy-related deaths. CONCLUSIONS: Gemcitabine and paclitaxel chemotherapy is a favorable therapeutic alternative for patients with advanced or metastatic UC who have previously been treated with MVAC chemotherapy. Given the safety and benefit profile seen in this study, a large prospective research study is warranted to consider the potential role of gemcitabine and paclitaxel chemotherapy as a second-line treatment for urothelial cancer.     

A Rat Model of Dilated Cardiomyopathy to Investigate Partial Left Ventriculectomy

Background: This study is the first to assess a small animal model of dilated cardiomyopathy (DCM) for evaluation of partial left ventriculectomy. Method: Eighteen Dahl salt-sensitive (DS) rats were divided into three groups. Six rats were fed an 8% high-salt diet from the age of 7 weeks (Group 1), and similarly six rats from 8 weeks (Group 2) and six from 9 weeks (Group 3). Blood pressure (BP) was measured by the tail-cuff method and left ventricular (LV) dimensions by echocardiography. Results: In Groups 1 and 2, systolic BP rose and reached 200 mmHg by the 10th to 11th week, when all rats died within a week without signs of heart failure. However, in Group 3, systolic BP gradually rose to 196 ± 15 mmHg (mean ± SD) at the age of 14 weeks, when LV end-diastolic diameter (EDD) was 6.2 ± 0.4 mm (control 5.1 ± 0.7 mm) and LV fractional shortening (FS) was 77 ± 3% (control 68 ± 3%). At the age of 25 to 30 weeks, all rats in Group 3 showed signs of congestive heart failure, systolic BP remained high, EDD markedly increased (8.7 ± 0.6 mm), and LVFS decreased (38.9 ± 8.1%). From this stage, rats survived for 13.7 ± 5.9 days. We employed the Group 3 model for our pilot PLV study. Eight rats had PLV with a beating heart by plicating the LV area between the papillary muscle bases. Two rats died perioperatively but the rest survived (60% survival 3 weeks after PLV). Postoperatively, the rats' LVEDD decreased and FS improved significantly. Conclusions: Using DS rats, we developed a DCM model for investigating PLV. The model may contribute to scientific investigation of PLV.     

Effect of ursodeoxycholic acid on autoimmune-associated chronic hepatitis C

BACKGROUND: Hypergammaglobulinaemia and various auto-antibodies which are commonly seen in autoimmune hepatitis are also found in patients with chronic hepatitis C. We recently reported that ursodeoxycholic acid (UDCA) improved liver function tests and immunoserological markers in patients with type I autoimmune hepatitis. The aim of this study was to prospectively evaluate the efficacy of UDCA on autoimmune-associated chronic hepatitis C. METHODS: Immunoglobulin G (IgG), anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) were determined in 95 patients with chronic hepatitis C. All patients were positive for hepatitis C virus RNA. Autoimmune-associated chronic hepatitis C (C-AIH) was defined by elevated serum IgG level (> or = 2.0 g/dL) and high titres of ANA and/or ASMA (> or = 1 : 160). Nine (9%) of 95 patients were diagnosed as C-AIH. All the C-AIH patients and 30 of the remaining 86 chronic hepatitis C patients without autoimmune features (CHC) were treated with UDCA (600 mg/day) for 1 year. RESULTS: Autoimmune-associated chronic hepatitis C patients included one man and eight women and their AIH scores, as defined by the International Autoimmune Hepatitis Group, were significantly higher than the CHC patients. Before UDCA therapy, there were no significant differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and y-glutamyl transpeptidase (gamma-GTP) levels between C-AIH and CHC patients. However, after 1 year UDCA therapy, AST, ALT and gamma-GTP were significantly lower in C-AIH patients (P< 0.05) than in CHC patients. In C-AIH, ANA titres in seven of nine patients and ASMA titres in five of seven patients were reduced after 1 year UDCA treatment. CONCLUSIONS: These results suggest that UDCA is a useful therapeutic agent for autoimmune-associated chronic hepatitis C.     

Neuronal migration in the adult brain]

Production of new neurons in the subventricular zone (SVZ) continues into adulthood. Neuroblasts generated in the SVZ migrate in chains rostrally toward the olfactory bulb (OB), where they are differentiated into olfactory interneurons. In this paper, we will review our recent studies on production, migration and survival of newly-generated neurons in the adult mouse brain. Although the precise mechanisms controlling the migration of neuroblasts remain unclear, some molecules related to cell adhesion, cytoskeletal regulation or attractive/repulsive cues have been shown to be involved in this process. We have recently demonstrated that neuroblast migration parallels cerebrospinal fluid flow caused by integrated beating of ependymal cilia. While SVZ neuroblasts migrate only toward the OB under physiological conditions, we found that they could reach striatum in a mouse model of focal ischemia using blood vessels as their scaffold. The majority of the newly-generated neurons are known to die before they are integrated into neuronal circuits. However, we found that their survival could be promoted by the long-term administration of donepezil, an acetylcholinesterase inhibitor that is widely used for the treatment of Alzheimer's disease. Understanding more precise and comprehensive mechanisms of adult neurogenesis should lead to future development of regenerative therapies for neuropsychiatric diseases.