Sucralfate protects intestinal epithelial cells from radiation-induced apoptosis in rats

Radiotherapy for malignant pelvic disease is often followed by acute radiation colitis (ARC). It has been reported that sucralfate treatment has a protective effect against ARC, though the mechanisms of action are unknown. The effects of sucralfate on X-ray radiation-induced apoptosis was studied at 4 Gy in the colonic crypt cells of rats. Sucralfate enemas given prior to radiation resulted in the following: (1) reduction in number of apoptotic colonic crypt cells; (2) reduction in number of caspase-3 positive cells; (3) decreases in p53 accumulation and p21 expression; (4) decreases of Bax/Bcl-2 ratio. The protective effects of sucralfate against ARC may be partially due to the suppression of radiation-induced apoptosis by way of p53 in the colon and the protection of the colonic epithelial stem cell region.     

Etodolac induces apoptosis and inhibits cell adhesion to bone marrow stromal cells in human myeloma cells

OBJECTIVES: Cyclooxygenase-2 (COX-2) is reported to regulate apoptosis and to be an important cellular target for therapy. METHODS: We examined whether etodolac, meloxicam, and thalidomide inhibited proliferation and induced apoptosis in myeloma cell lines (RPMI 8226 and MC/CAR cells). RESULTS: Etodolac induced apoptosis more strongly compared with thalidomide or meloxicam. Etodolac induced down-regulation of Bcl-2 protein and mRNA, activation of Caspase-9, -7 and -3, cIAP-1 and Survivin, and loss of mitochondrial membrane potential in a dose-dependent manner. In addition, when myeloma cells were coincubated with 50 microM etodolac on bone marrow stromal cells (BMSCs), myeloma cell adhesion to BMSCs was significantly inhibited compared with thalidomide or meloxicam coincubation, and the adhesion molecules VLA-4, LFA-1 (CD11a), CXCX4, and CD44 were suppressed on myeloma cells treated with etodolac. Moreover, 50-100 microM racemate of etodolac significantly inhibited the proliferation of myeloma cells compared to 100 microM R-etodolac or S-etodolac. CONCLUSIONS: Etodolac induced loss of mitochondrial membrane potential and apoptosis via a COX-2-independent pathway, suppressed the expression of adhesion molecules, and inhibited myeloma cell adhesion to BMSCs compared with thalidomide or meloxicam. The activities of etodolac potentially extend to the treatment of patients with myeloma resistant to standard chemotherapy, including thalidomide.     

The combination of isoflurane and caspase 8 inhibition results in sustained neuroprotection in rats subject to focal cerebral ischemia

Although isoflurane can reduce ischemic neuronal injury after short postischemic recovery intervals, data from our laboratory have demonstrated that this neuroprotection is not sustained and that delayed apoptotic neuronal death, mediated in part by activation of caspases, contributes to the gradual increase in the size of the infarction. We tested the hypothesis that the neuroprotective efficacy of isoflurane can be prolonged with the administration of z-IETD-fmk, a specific inhibitor of caspase 8. Fasted Wister rats were anesthetized with isoflurane and randomly allocated to awake-vehicle, isoflurane-vehicle, awake-IETD, or isoflurane-IETD groups (n = 25 per group). Animals were subjected to 60 min focal ischemia by filament occlusion of the middle cerebral artery (MCAO). Daily intracerebroventricular injections of z-IETD-fmk or vehicle were administered via an implanted cannula starting before ischemia and continuing until 14 days post-MCAO. Neurological assessment was performed 14 days after ischemia after which the volume of cerebral infarction and number of intact neurons in the peri-infarct cortex were determined. Total infarction volume was less in the isoflurane-IETD group than in awake-vehicle, isoflurane-vehicle, and awake-IETD groups. Infarction volume was also less in the awake-IETD group versus the awake-vehicle group. The number of intact neurons within the peri-infarct cortex was significantly less in the awake-vehicle group in comparison with the other three experimental groups. The isoflurane-IETD group had better neurologic outcomes than both vehicle-treated groups at 14 days post-MCAO. These results suggest that a combination of isoflurane and a caspase 8 inhibitor can produce neuroprotection that is evident even after a recovery period of 14 days. This combination demonstrated greater efficacy than the administration of either isoflurane or z-IETD-fmk alone. These results are consistent with the premise that continuing apoptosis contributes to the enlargement of cerebral infarction during the recovery period and that its inhibition can provide sustained neuroprotection.     

Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behçet's disease with refractory uveoretinitis

OBJECTIVE: Beh?et's disease (BD) with uveoretinitis is a chronic refractory disease accompanied by ocular attacks. As the decrease in visual acuity due to ocular attack is seriously life-threatening, development of a new drug is anticipated. Since tumor necrosis factor-a (TNF-a) is involved in the symptoms of BD, particularly the activity of ocular symptoms, suppression of TNF-a might be effective in treating BD with uveoretinitis. We conducted a clinical trial of infliximab, an anti-TNF-a chimeric monoclonal antibody, in patients with BD. METHODS: In this open label trial, the efficacy, safety, and pharmacokinetics of repeated administration of infliximab were evaluated in 13 patients with BD accompanied by refractory uveoretinitis. Infliximab was administered 4 times at Weeks 0, 2, 6, and 10 at doses of either 5 or 10 mg/kg by intravenous drip infusion. Frequency of ocular attacks was used as the primary index for evaluation of efficacy, with visual acuity and extraocular symptoms as secondary indices. RESULTS: The mean numbers of ocular attacks, converted to frequency per 14 weeks, were 3.96 times for the 5 mg/kg group and 3.79 times for the 10 mg/kg group during the observation period. Following treatment with infliximab, they decreased to 0.98 times and 0.16 times, respectively. A serious adverse event, tuberculosis, was observed in one case in the 10 mg/kg group. Serum infliximab concentration increased with dosage. CONCLUSION: Administration of infliximab in patients with BD with refractory uveoretinitis suppressed the frequency of ocular attacks, and multiple administration was well tolerated, suggesting that infliximab is effective for this condition.     

Three-dimensional computed tomography for lung cancer in a patient with three right vein ostia

Some variations in pulmonary vein anatomy can have serious consequences in patients undergoing lung surgery, but clinicians rarely encounter patients with these variations. We report here a thoracoscopic lobectomy for right lung cancer in a patient with three right vein ostia. Preoperative review of three-dimensional 64-row multidetector computed tomography (3D-MDCT) of the patient showed a variation that was not confirmed in transverse plane computed tomography films. However, the variant anomaly was confirmed during thoracoscopic right lower lobectomy. The postoperative course was uneventful, and the patient was discharged on postoperative day 10. Preoperative 3D-MDCT of the pulmonary vein produced a precise preoperative simulation for the surgeon and clearly showed the orientation of the patient’s vascular variant during surgery. This imaging technology contributes to safer thoracic surgery, especially thoracoscopic surgery.     

Use of a laryngeal mask airway to stop a supraglottic air leak which prevented adequate ventilation via a tracheostomy in a patient with cerebral palsy and pneumonia

We report an adolescent developing ventilation failure due to supraglottic air leakage with the use of an uncuffed hand-made tracheal tube fit to her tracheobronchial deformity. To eliminate the supraglottic air leakage, a size 2.5 laryngeal mask airway (LMA) was inserted into the oral pharynx. Most of air leakage arose from the LMA. Supraglottic air leakage was not detected under mandatory mechanical ventilation following sealing of the 15-mm connector of the LMA with a piece of tape, and the respiratory condition of the patient gradually improved. The combination of a hand-made Y-shaped tube and the LMA was useful in restoring adequate ventilation. In conditions where air leaks through the glottis during mechanical ventilation interfere with adequate ventilation or the maintenance of airway pressure, the use of an LMA may be adequate to stop or significantly decrease the leak.     

Assessment of intraoperative motor evoked potentials for predicting postoperative paraplegia in thoracic and thoracoabdominal aortic aneurysm repair

Purpose  

Monitoring motor evoked potentials (MEPs) has been recognized as a highly reliable method to detect intraoperative spinal cord ischemia (SCI) in aortic repair. However, the data regarding the sensitivity and specificity of MEPs for predicting postoperative paraplegia are limited. We retrospectively assessed the value of intraoperative MEP amplitudes for predicting postoperative paraplegia.     

Vascularized rib support for chest wall reconstruction using Gore-Tex dual mesh after wide sternochondral resection

Only a few reports describe chest wall reconstruction after sternal resection using Gore-Tex dual mesh, and very few reports describe the use of a vascularized rib to support the thoracic cage. We present a case of a breast cancer patient who underwent anterior chest wall resection for recurrent sternal cancer. Her sternoclavicular joints bilaterally and lower sternum were divided using an electric saw. The bony chest wall was reconstructed using Gore-Tex dual mesh, and a vascularized rib was used to bridge the space between the clavicular heads to support the thoracic cage. The patient's postoperative course was uneventful, without complications, such as paradoxical respiration or pneumonia.