Recombinant human soluble thrombomodulin decreases the plasma high-mobility group box-1 protein levels, whereas improving the acute liver injury and survival rates in experimental endotoxemia.

OBJECTIVE: In addition to the hyperactivation of the inflammatory cytokines, high-mobility group box-1 protein (HMGB1), recently identified as a lethal late-phase mediator is suspected to be closely correlated with the development of sepsis. Therefore, the therapeutic efficacy of recombinant human soluble thrombomodulin (ART-123) administration on the production of inflammatory cytokines and the plasma level of HMGB1 was investigated in experimental endotoxemia. DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory animal research center at a university. SUBJECTS: Male Sprague-Dawley rats (250-300 g). INTERVENTIONS: Endotoxemia was induced in rats by a bolus intravenous injection of lipopolysaccharide (LPS) at a dosage of 4 mg/kg (LPS group). ART-123 (1 mg/kg) was administered as a bolus injection 30 minutes before or 4 hours after injection of LPS (ART-123 pretreated/treated group). As a control, an equal volume of physiologic saline was administered instead of LPS and ART-123 (control group). MEASUREMENTS AND MAIN RESULTS: Rats were randomly divided into ART-123 pretreated group, ART-123 treated group, and LPS group, respectively. After the injection of LPS, the levels of inflammatory cytokines and thrombin-antithrombin III complex, plasma HMGB1 concentrations, liver immunohistochemical and histopathologic characteristics, liver dysfunction, and survival rate were examined. The increased levels of inflammatory cytokines and plasma HMGB1 induced by LPS in this rat model were improved by the administration of ART-123; additionally, reduced liver dysfunction and increased survival rate were observed. CONCLUSIONS: This study demonstrated that ART-123 inhibits the expression of inflammatory cytokines and decreases the plasma HMGB1 levels in experimental endotoxemia. In addition, ART-123 administration markedly reduced liver dysfunction and mortality even with delayed treatment of ART-123. The use of ART-123 may therefore be a beneficial treatment for septic patients.

[A case of acalcuous cholecystitis developed after cardiopulmonary resuscitation].

A 47-year-old man was found at his home in a state of cardiopulmonary arrest. His family performed cardiopulmonary resuscitation on him. He was brought to our hospital by ambulance. On arrival, his pupils were dilated and his heart was in a state of ventricular fibrillation. After returning to spontaneous circulation by the cardiopulmonary resuscitation, the electrocardiogram revealed ST elevation at V2-V5. Cardiac catheterizatin revealed a left anterior descending coronary obstruction. Percutaneous coronary angioplasty was performed. On the 26th day after admission, acalculous cholecystitis was found. It was difficult to perform emergent surgery, because the patient was taking an anticoagulant drug. We performed PTGBA (percutaneous transhepatic gallbladder aspiration) on the same day, and the gallbladder inflammation was improved. We consider that PTGBA is an effective treatment for difficult cases of acalcuous cholecystitis.

Significance of lymphangiogenesis as assessed by immunohistochemistry for podoplanin in patients with esophageal carcinoma.

BACKGROUND: Although lymph node involvement is an important prognostic factor for survival in patients with esophageal carcinoma, little is known about lymphangiogenesis in esophageal carcinoma. Podoplanin, a mutin-type transmembrane glycoprotein, specifically recognizes the lymphatic endothelium and is used as a lymphatic-specific marker. Anti-human podoplanin antibody was therefore used to quantify and evaluate the lymphangiogenesis in esophageal carcinoma. PATIENTS AND METHODS: Lymphatic endothelial cells were detected by immunohistochemistry using mouse monoclonal anti-human podoplanin antibody. The relationship between lymphatic microvessel density (LMVD) and lymphatic vessel invasion (LVI), clinicopathological factors and the prognosis in 29 patients with esophageal carcinoma was investigated. RESULTS: LMVD was significantly higher in esophageal carcinoma patients who had any of the following characteristics: T3-T4 (p=0.0370), tumors more advanced than stage III (TNM staging) (p=0.0351), lymphatic invasion (p=0.0095) and LVI (+) (p=0.0016). LVI significantly correlated with lymph node metastasis (p=0.0003), TNM staging (p=0.0182) and LMVD (p=0.0388). The survival rate of patients with a low LMVD tended to be higher than that of patients with a high LMVD (5-year survival rate, 62.5% vs. 29.4%, p=0.0832). CONCLUSION: The evaluation of lymphangiogenesis using podoplanin immunohistochemistry may be useful in predicting lymph node metastasis and the prognosis in patients with esophageal carcinoma.

4- [3,5-bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) induced fas expression and activated caspase-3 and -8 in a DLD-1 colon cancer cell line.

BACKGROUND: 4-[3,5-Bis (trimethylsilyl) benzamido] benzoic acid (TAC-101) is a novel retinobenzoic acid derivative which has a specific binding affinity to the retinoic acid receptors (RAR)alpha and RARbeta. Using time-dependent FACScan analysis, it was observed that TAC-101 induced apoptosis in a DLD-1 human colon cancer cell line. In this study, the induction of apoptosis-related proteins and the activities of caspases in a DLD-1 cell line under medication with TAC-101 were investigated. MATERIALS AND METHODS: DLD-1 cells were cultured with different concentrations of TAC-101 for 12, 24 and 48 h. The expressions of Fas, TNF-R1, DR3, bcl-2, Bax and Bid were measured using a Western blot analysis. The activities of caspase-3, -8 and -9 were measured using a colorimetric protease assay kit. RESULTS: The Western blot analysis showed that TAC-IO1 had almost no effect on the level of Bcl-2, Bax or Bid protein. Although TAC-101 did not change the expression of TNF-R1 and DR3, TAC-101 increased the expression of Fas in both a time- and a dose-dependent manner. A 3-fold increase in caspase-3 activity and a 1.5-fold increase in caspase-8 activity were observed in cells treated with TAC-101 in comparison to the control cells (p<0.01). CONCLUSION: Our data indicate that the death receptor root of the apoptotic signal transduction in DLD-1 cells mainly participates in the apoptotic induction of TAC-101. Because the compounds inducing apoptotic activity are frequent targets of cancer therapy, TAC-101 may be a good candidate for use in the treatment of colon cancer.

[A case of multiple trauma with sinking skull, whose life was saved by consistent team medical treatment].

A 54 year old man was brought to our hospital by ambulance. He had been injured by falling heavy steel. An examination was performed, and he was diag nosed as having sinking skull, acute extradural hematoma, trauma of the righ eye, right eye laceration, injury of the optic canal (right blind), and multipl fractures. Open fractures were observed in the right ring finger and little finger Simple fractures were observed in the zygomatic bone nasal bone and maxillary bone. An emergency operation (external skeletal fixation, taxis of the skull and maxillary bone, extradural hematoma depletion, suture of right eyelid) was performed. His life was saved by consistent team treatment from preoperation t postoperation. He was discharged from our hospital on foot at 45 days after th operation.