[Successful treatment of duodenal Crohn disease with infliximab: report of 3 cases].

We present 3 patients with Crohn disease (CD) of the duodenum with progressive symptoms. A 31-year-old man with Crohn ileocolitis presented epigastralgia. A 32-year-old man with Crohn ileocolitis presented upper GI bleeding. In both patients, endoscopy revealed duodenal stenosis. A 33-year-old man was given a diagnosis of CD by gastroduodenal endoscopy. They received an infliximab infusion and had symptomatic relief and macroscopic healings without any adverse effects. Several treatments for upper GI lesions of the CD patients have been tried, but there is no high-quality level evidence-based data to guide the medical management of gastroduodenal CD. Our experience with 3 patients suggests that infliximab is a safe and effective treatment for duodenal CD and it may be appropriate for early use to avoid surgery or balloon dilatation.

[A case of ruptured ileal varices associated with alcoholic liver cirrhosis].

The case was a 33-year-old woman with alcoholic liver cirrhosis. Her chief complaint was melena. She had undergone the abdominal operation in the past. Upper and lower gastrointestinal endoscopy did not reveal the bleeding point in the gastrointestinal tract. We diagnosed the bleeding from the ileocecum by the hemorrhage scintigraphy, the superior mesenteric artery angiography, and CT angiography. She had varices at the terminal ileum and adhesion between the ovary and the ileum end. The subtotal resection of the ileum was performed.

Lack of mitochondrial DNA enhances growth of hepatocellular carcinoma in vitro and in vivo.

To elucidate the role of mitochondrial DNA (mtDNA) in determination of growth of hepatocellular carcinoma, we examined wild-type Hepa1-6 cells and their rho(0) cells with depleted mtDNA in vitro and in vivo. Cultured rho(0) cells grew more rapidly than did wild-type cells. Production of reactive oxygen species (ROS) was higher in wild-type cells than in rho(0) cells. Hypoxia inhibited the growth of wild-type cells more markedly than that of rho(0) cells. Resistance to mitochondrial respiratory inhibitor-induced cell death was stronger in rho(0) cells than in wild-type cells. rho(0) cells subcutaneously inoculated in the hind thigh of mice grew more rapidly and formed larger solid tumors. These findings indicate that lack of mtDNA increases growth of hepatocellular carcinoma by decreasing ROS production and increasing resistance to mitochondrial respiratory inhibition.

Production of reactive oxygen species in peripheral blood is increased in individuals with Helicobacter pylori infection and decreased after its eradication.

BACKGROUND: Helicobacter pylori infection has been reported to cause gastroduodenal ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Recent studies have suggested that H. pylori infection may also associate with other diseases, including hematologic and dermatologic disorders, and cardiovascular injury, by unknown mechanisms. METHODS: Production of reactive oxygen species (ROS) was determined in peripheral blood samples from 86 patients (34 H. pylori-negative and 52 H. pylori-positive subjects) using a highly sensitive chemiluminescence probe, L-012 (8-amino-5-chloro-7-phenylpyrido(3,4-d) pyridazine-1 and 4 (2H, 3H) dione). Eleven H. pylori-positive individuals were also analyzed their ROS production in peripheral blood after H. pylori eradication. RESULTS: ROS production was significantly higher in individuals with H. pylori infection than in those without infection. Enhanced production of ROS was decreased significantly after eradication of H. pylori. No correlation was found between the extent of ROS production and sex, age, smoking status, alcohol ingestion, use of medications, or serum level of C-reactive protein. CONCLUSION: These findings suggest that ROS production was enhanced in peripheral blood by H. pylori infection. Chemiluminescence analysis of blood samples using L-012 permits evaluation of systemic oxidative stress in patients with H. pylori infection.

Mannose-conjugated alendronate selectively depletes Kupffer cells and inhibits endotoxemic shock in the mice.

To elucidate the roles of Kupffer cells in the host-defense mechanisms and liver injury, we synthesized a mannose-conjugated alendronate (MANA) and examined its effects on Kupffer cells and lipopolysaccharide (LPS)-induced liver injury in the mice. Intravenous administration of a small amount of MANA (50mumol/kg) rapidly and selectively depleted Kupffer cells in the mice. The depletion of Kupffer cells by MANA resulted in a marked decrease of the production of both TNF-alpha and IL-1beta in the plasma during the liver injury induced by low (1mg/kg) and lethal (75mg/kg) doses of LPS. The effect was so remarkable that all animals treated with a lethal dose of LPS survived without any sign of endotoxemia. These findings indicate that Kupffer cells play critical roles in the development of endotoxemia, and that MANA will be useful in studies to elucidate pathophysiological roles of Kupffer cells in various liver diseases.

Mitochondrial density determines the cellular sensitivity to cisplatin-induced cell death.

We studied the relationship between the mitochondrial density in the cells and the cellular sensitivity to the toxicity of cis-diaminedichloroplatinum II (cisplatin), a potent anticancer agent. Biochemical analyses revealed that the density of mitochondria in the intestinal epithelium changed markedly along its entire length. The density was the highest at the duodenum, medium at the jejunum, and the lowest at the ileum. The sensitivity of epithelial cells to cisplatin toxicity was the highest at the duodenum, medium at the jejunum, and the lowest at the ileum as judged from the occurrence of apoptosis. Similar correlation between the cisplatin sensitivity and mitochondrial density was also observed with in vitro experiments, in which intestinal epithelial cells (IEC-6) and their rho0 cells with reduced number of mitochondria were used. The rho0 cells had a strong resistance to cisplatin compared with the control cells. Cisplatin markedly increased mitochondrial generation of reactive oxygen species in IEC-6 but not in rho0 cells. We analyzed the sensitivity of eight cell lines with different density of mitochondria to cisplatin and found the same positive correlation. These observations clearly show that cellular density of mitochondria is the key factor for the determination of the anticancer activity and side effects of cisplatin.