[A case of tuberculous peritonitis accompanied by lymphadenitis in a patient with liver cirrhosis in which lymph node biopsy was useful for establishing the diagnosis].

A 62-year-old woman with liver cirrhosis developed ascites. She had been previously treated with a combination of interferon and ribavirin therapy. The ascites was bloody and of exudative nature. Radiological examinations showed supraclavicular, axillar, and mediastinal lymphadenopathy. Biopsy of the axillar lymph node was performed because of suspected malignancy, and the results showed that the lymph node had granulomatous inflammation with caseous necrosis and Langhans giant cells, suggestive of mycobacterial infection. Furthermore, a DNA sequence specific to Mycobacterium tuberculosis was recovered from the same lesion, leading to a diagnosis of tuberculous lymphadenitis. The ascites and the lymphadenopathy subsided with anti-tuberculosis chemotherapy. Although bacilli were not detected in the ascites, a high level of adenosine deaminase in the ascites, the coexistence of tuberculous lymphadenitis, and the response to anti-tuberculosis agents supported the diagnosis of tuberculous peritonitis. Although tuberculous peritonitis is often difficult to diagnose, lymph node biopsy was useful to establish the diagnosis in the present case.

ASP4,000, a novel, selective, dipeptidyl peptidase 4 inhibitor with antihyperglycemic activity.

ASP4,000, (2S)-1-{[(1R,3S,4S,6R)-6-hydroxy-2-azabicyclo[2.2.1]hept-3-yl]carbonyl}-2-pyrrolidinecar bonitrile hydrochloride, is a novel dipeptidyl peptidase (DPP) 4 inhibitor. In the present study, we characterized the compound as an oral antidiabetic agent both in vitro and in vivo. ASP4,000 inhibited human recombinant DPP4 with an IC(50) value of 2.25 nM, and the enzyme-kinetic curve indicated that the inhibition type was competitive. In addition, ASP4,000 also potently inhibited DPP4 activity in human, rat, dog, and monkey plasma at concentrations of the order of 10(-9) M, and showed high selectivity against other related enzymes, including DPP8 and DPP9. The antihyperglycemic activity of ASP4,000 in vivo was examined using Zucker fa/fa rats, a type 2 diabetes animal model. A single oral administration of ASP4,000 at doses of 0.03-1 mg/kg suppressed plasma DPP4 activity, and then reduced the glucose level with increasing the active GLP-1 and insulin levels in oral glucose tolerance test. These results indicate that ASP4,000 is a potent, competitive, selective DPP4 inhibitor with antihyperglycemic activity, and could be a promising candidate agent for the treatment of patients with type 2 diabetes.

Clinical characteristics of lower bowel perforation with chronic renal failure.

BACKGROUND/AIMS: This study was conducted to evaluate the clinical characteristics of lower bowel perforation (LBP) with chronic renal failure (CRF). METHODOLOGY: In 58 patients with LBP, clinical variables, such as findings of clinical examinations, operative findings, and results of laboratory blood tests were examined as possible prognostic factors for in-hospital death, and compared between CRF and non-CRF groups. RESULTS: Of the 58 patients, 21 died during hospitalization (mortality rate, 36.2%). The mortality rate of patients with CRF was 54.2%. In the patients with LBP, the following variables were significantly correlated with in-hospital death (p<0.05): hypotension, CRF, fecal peritonitis, and low white blood cell (WBC) count, and low albumin and base excess (BE) levels. The odds ratios of in-hospital death were highest for a WBC count of 9000/mm3 and a BE of -3mEqL. Between the CRF and non-CRF groups, significant differences in the rates of age < 70 years, fecal peritonitis, in-hospital death, and low WBC count and BE were found (p<0.05). CONCLUSIONS: We identified prognostic factors of LBP and demonstrated the clinical characteristics of LBP with CRF. These results indicate that patients who have LBP with CRF tend to have immediate sepsis and a poor prognosis.

Intussusception of the appendix that reduced spontaneously during follow-up in a patient on hemodialysis therapy.

A 63-year-old man on long-term hemodialysis therapy was hospitalized due to right lower abdominal pain. CT scan demonstrated a multiple concentric structure in the ileocecal region. Colonoscopy showed a polyp-like tumor arising from the expected location of the appendix, with a dimple at the top. Barium enema study revealed a submucosal tumor-like filling defect in the cecum with non-filling of the appendix. A diagnosis of intussusception of the appendix (IA) was made. During the follow-up, IA reduced spontaneously. The present case report is the first description of IA in a patient on hemodialysis therapy. Furthermore, spontaneous reduction of IA is indeed rare.

[Gastrointestinal stromal tumor of the omentum: report of a case].

A 69-year old man was found a mass becoming larger in abdominal computed tomography. The mass consisted of intermingling solid and cystic component was located below the liver. Abdominal angiography showed tumor staining supplied from right gastroepiploic artery. We considered the mass cystadenoma, lymphangioma, cystic mesothelioma, or gastrointestinal stromal tumor (GIST) preoperatively, and then surgical resection was performed. The tumor was found localized in the greater omentum. Pathological examination showed the tumor composed of proliferation of atypical sort spindle cells and tumor cells were immunohistochemically positive for C-KIT and CD34, identifying the tumor as a primary GIST of the greater omentum.

A novel potent radical scavenger, 8-(4-fluorophenyl)-2-((2E)-3-phenyl-2-propenoyl)-1,2,3,4-tetrahydropyrazolo[5,1-c] [1,2,4]triazine (FR210575), prevents neuronal cell death in cultured primary neurons and attenuates brain injury after focal ischemia in rats.

Reactive oxygen species (ROS) play a vital role in brain damage after cerebral ischemia-reperfusion injury, and ROS scavengers have been shown to exert neuroprotective effects against ischemic brain injury. We have recently identified 8-(4-fluorophenyl)-2-((2E)-3-phenyl-2-propenoyl)-1,2,3,4-tetrahydropyrazolo[5,1-c][1,2,4]triazine (FR210575) as a novel, powerful free-radical scavenger. In the present study, the neuroprotective efficacy of FR210575 was evaluated in two neuronal death models in vitro as well as rat focal cerebral ischemia models in vivo. In the first model, primary cortical cultures were exposed to a high oxygen atmosphere (50% O2) for 48 h to induce cell death with apoptotic features. Treatment with FR210575 (10-7-10-5 M) significantly inhibited neuronal death. The second model used a growth-factor withdrawal paradigm. Withdrawal of TIP (transferrin, insulin, putrescine and progesterone)-supplemented medium induced apoptotic cell death after 2 days, but treatment with FR210575 exhibited dramatic protection against neuronal death. In two models of cerebral ischemia [photothrombotic occlusion of middle cerebral artery (MCA) for transient model and by permanent MCA occlusion for permanent model], rats received 3-h intravenous infusion (1-10 mg/kg/3 h) of FR210575, with brain damage determined 24 h later. FR210575 (3.2 mg/kg/3 h) significantly reduced the volume of focal damage in the cortex by 36% in the transient model and also reduced the size of ischemic brain damage in the permanent model. These findings indicate that the powerful radical scavenger FR210575 has potent neuroprotective activity and that FR210575 could be an attractive candidate for the treatment of stroke or other neurodegenerative disorders.