The Possibility of Acute Drug-Induced Liver Injury Associated With Prednisolone.

A female patient was referred to our hospital with complaints of liver injury. She had been treated for immunoglobulin (Ig)A nephropathy using prednisolone and other medications. Drug-induced liver injury (DILI) was suspected, as no evidence of viral infection or autoimmune liver disease was apparent. All medications except for prednisolone were discontinued, but liver enzyme levels remained elevated. Percutaneous liver biopsy showed the characteristics of DILI and drug lymphocyte stimulation testing yielded positive results for prednisolone. After stopping administration of prednisolone, liver enzyme levels recovered to near-normal. Prednisolone has immunosuppressive effects and is sometimes used to treat DILI. Some reports have revealed that high-dose corticosteroids can induce liver injury, but liver injuries associated with low-dose corticosteroid therapy have not been described. Prednisolone-induced liver injury is a rare phenomenon. When low-dose corticosteroids are used for treatment, care should be taken regarding the possibility of liver injury.

Accumulation of the myosin-II-spectrin complex plays a positive role in apical extrusion of Src-transformed epithelial cells.

At the initial stage of carcinogenesis, transformation occurs in single cells within the epithelium. Recent studies have revealed that the newly emerging transformed cells are often apically eliminated from epithelial tissues. However, the underlying molecular mechanisms of this cancer preventive phenomenon still remain elusive. In this study, we first demonstrate that myosin-II accumulates in Src-transformed cells when they are surrounded by normal epithelial cells. Knock-down of the heavy chains of myosin-II substantially diminishes apical extrusion of Src cells, suggesting that accumulated myosin-II positively regulates the apical elimination of transformed cells. Furthermore, we have identified ß-spectrin as a myosin-II-binding protein under the coculture of normal and Src-transformed epithelial cells. ß-spectrin is also accumulated in Src cells that are surrounded by normal cells, and the ß-spectrin accumulation is regulated by myosin-II. Moreover, knock-down of ß-spectrin significantly suppresses apical extrusion of Src cells. Collectively, these results indicate that accumulation of the myosin-II-spectrin complex plays a positive role in apical extrusion of Src-transformed epithelial cells. Further elucidation of the molecular mechanisms of apical extrusion would lead to the establishment of a novel type of cancer preventive medicine.

Prognostic impact of aortic calcification index and ankle-arm blood pressure index in patients under hemodialysis.

The mortality rate is high in patients receiving hemodialysis (HD), atherosclerotic diseases being the major cause of death. As marker of clinical outcome, a prospective examination of atherosclerotic tests and atherosclerotic risk factors in patients receiving HD was performed. On April 2000, 84 patients receiving HD were followed up until April 2002. At entry to the study, several atherosclerotic tests, including ankle-arm blood pressure index (API), aortic calcification index (ACI), and atherosclerotic risk factors, were performed. In 36 patients with old thrombotic events, 26 had new thrombotic events. Of 48 patients without previous thrombotic events, 15 had new thrombotic events. During 2 years, 41 patients had new thrombotic events and 15 patients died due to thrombotic disorders. The HD durations were significantly longer in non-survivors than survivors and the body mass index was lower in non-survivors than survivors. There was a significant difference in the values of ACI and API between survivors and non-survivors, and between patients with and without thrombotic events. These findings suggest that the ACI and API have a prognostic value because they might predict the occurrence of thrombosis.

Effects of lipid abnormalities on arteriosclerosis and hemostatic markers in patients under hemodialysis.

Vascular events caused by arteriosclerosis are the major cause of death in patients under hemodialysis (HD). Arteriosclerosis is associated with lipoprotein abnormalities such as increased serum levels of low-density lipoprotein (LDL), especially of modified LDL (M-LDL) and oxidized LDL (Ox-LDL). We examined the relationship between markers of arteriosclerosis, hemostasis, and lipid metabolism in patients with chronic renal failure, hyperlipidemia, and healthy volunteers. In patients under HD, the serum levels of total cholesterol, LDL, and triglyceride (TG) were decreased, but the serum levels of M-LDL were increased compared to HL and healthy volunteers. In patients with CRF, the serum levels of Ox-LDL in patients under HD were lower than in those under continuous ambulatory peritoneal dialysis or conservative therapy. The plasma levels of antithrombin and protein C were significantly lower and the plasma levels of thrombomodulin were significantly higher in patients under HD compared to those under conservative therapy. These data show that patients under HD were more in hypercoagulable state than those under conservative therapy. Among patients under HD, only the plasma levels of von Willebrand factor were significantly increased in patients with more than 30 U/L of Ox-LDL compared to those with less than 30 U/L of Ox-LDL. There was no significant difference in the tests of arteriosclerosis among M-LDL values and Ox-LDL values. These findings suggest that abnormalities of lipid are not the main risk factor for arteriosclerosis disease in patients under HD.