Dietary copper triggers onset of fulminant hepatitis in the Long-Evans cinnamon rat model

AIM:To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS:The Long-Evans cinnamon (LEC) rat model of Wilson's disease (WD) was used to study the impact of high dietary copper (hCu) on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults (month 5) for three months. Animals that received reduced dietary copper (rCu) throughout their lifetime served as a control. Hepatitis-associated serum markers (alanine aminotransferase, aspartate transaminase, bilirubin) were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis (Vegfa), fat metabolism (Srebf1), ex-tracellular matrix (Timp1), oxidative stress (Hmox1), and the cell cycle (Cdkn1a) were analyzed by real-time polymerase chain reaction. RESULTS:Regardless of the time point when hCu was started, LEC rats (35/36) developed fulminant hepatitis and died. Animals receiving rCu (36/36) remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals (477 ± 75 μg/g). With regard to start of hCu, onset of fulminant hepatitis was significantly (P < 0.001) earlier in adults (35 ± 9 d) that showed pre-accumulation of liver copper as compared to the pup group (77 ± 15 d). Hepatitis-associated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats receiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION:Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper suggests that there is a critical threshold of liver copper which is important to trigger the course of WD.

Managementofearlyasymptomaticgastrointestinalstromaltumorsofthe stomach

Gastrointestinal stromal tumors(GIST) are the most common mesenchymal tumors of the digestive tract. Approximately two thirds of clinically manifest tumors occur in the stomach, nearly one third in the small bowel, and the rest in the colorectal region with a few cas-es in the esophagus. GIST originate within the smooth muscle layer in the wall of the tubular gastrointestinal tract and grow mostly toward the serosa, far less often toward the mucosa. In the latter case, ulceration may develop and can cause gastrointestinal bleeding as the cardinal symptom. However, most GIST of the stomach are asymptomatic. They are increasingly detected incidentally as small intramural or submucosal tumors during endoscopy and particularly during endoscopic ultra-sound. Epidemiological and molecular genetic findings suggest that early asymptomatic GIST of the stomach(< 1 cm) show self-limiting tumorigenesis. Thus, early(< 1 cm) asymptomatic gastric GIST(synonym: micro-GIST) are found in 20%-30% of the elderly. The mostlyelderly people with early gastric GIST have an excellent GIST-specific prognosis. Patients with early GIST of the stomach can therefore be managed by endoscopic sur-veillance.

比较性基因组杂交在病理学中的应用——一项新的细胞遗传学方法

新的分子病理学方法如多聚酶链反应(PCR)及荧光原位杂交(FISH)等的迅速发展,为分子病理学这一新学科带来了新进展。从近年来的一些方法中,最近又发展出比较性基因组杂交(CGH)这一在病理学中具有发展前景的崭新方法。 在病理学特别是儿童和肿瘤病理学中,此新的筛选方法具有广阔的应用领域,诸如应用于诊断、亚分类、分级以及预后估计和制订合理的治疗方案等。