Arterial CO and monocyte HO-1 protein expression were increased in critically ill patients, particularly those with severe sepsis or septic shock, suggesting that oxidative stress is closely related to HO-1 expression. The HO-1/CO system may play an important role in sepsis.
Abstract. Cyclooxygenase-2 (COX-2) activity is reported to increase apoptosis, inhibit angiogenesis and reduce metastasis. We analyzed COX-2 expression in patients with invasive bladder cancer to evaluate the feasibility of selective COX-2 inhibitor treatment targeting COX-2. Forty patients with pathologically diagnosed invasive transitional cell carcinoma of the urinary bladder (pT2-pT4) were evaluated. Immunohistochemical staining was used to evaluate COX-2 expression, and cases with staining of ≥10% of tumor cells were defined as positive. In 2 patients, 0% of the primary tumors stained for COX-2, while 1-5% was stained in 16 patients, 5-10% in 3 patients and ≥10% in 19 patients (19/40, 47.5%). In terms of grade, 2 patients with grade 2 (2/3, 66.6%) and 17 patients with grade 3 (17/37, 45.4%) were COX-2 positive. When categorized by stage, 11 patients with pT2 (11/22, 50.0%), 6 with pT3 (6/13, 46.1%) and 2 with pT4 (2/5, 40.0%) were positive. Lymph node metastasis was observed in 10 patients; 2 of them, with pN2, were COX-2 positive. Those with COX-2-positive metastatic lymph nodes had grade 3 primary tumors, which were also COX-2 positive. In addition, COX-2-negative metastatic lymph node patients also had negative primary tumors. The results of this study suggest that 47.5% of patients with invasive bladder cancer may benefit from treatment with selective COX-2 inhibitors targeting COX-2, and that treatment efficacy can be expected in patients with lymph node metastasis when their primary tumors are COX-2 positive.
The standard operative procedure for ureteral transitional cell carcinoma is nephrouterectomy with partial cystectomy at the affected ureteral orifice. However, nephronsparing surgery and endoscopic surgery and management have become common practice for low-grade and low-stage cases. We investigated the follow-up results of patients who underwent endoscopic surgery using the holmium:YAG laser, and evaluated its treatment effect. The patients were 4 men and 3 women aged from 68 to 87 years (mean: 74.7 years). Two were imperative cases and 5 were elective cases. The tumor size ranged from 8 to 25 mm (mean: 15.4 mm). Hydronephrosis was not found in any case, and urinary cytology was negative in all cases. Biopsy revealed 5 cases of grade 1, and 2 of grade 2. A Versa Pulse Select 80 laser generator, a 365-μm slim line laser fiber, and a rigid ureteroscope with 8F-point diameter were used. A 6F double J catheter was placed postoperatively for 3 weeks. Pulse energy was set at 0.5-1.0 J (mean: 0.8 J) with a frequency of 10 Hz. The total amount of energy was 0.9-11.22 KJ (mean: 2.89 KJ) and the operation time including ureteral stent placement was 20-97 min (mean: 66 min). Neither urinary tract perforation nor ureteral stricture associated with laser irradiation was observed. The postoperative follow-up period ranged from 23-88 months (mean: 67.8 months). Patients underwent urinary cytological examination once a month, and cystoscopy, retrograde pyelography and urethroscopy once every 3 months for 2 years, then once every 6 months thereafter. One patient developed tumor recurrence 23 months after surgery and received another laser treatment, but no recurrence has been observed in the other 6 patients (85.7%). Transurethral endoscopic surgery and management using the holmium:YAG laser is safe and effective nephron-sparing surgery for ureteral transitional cell carcinoma, and good long-term treatment results can be expected even in elective cases if the indications are carefully selected.
IntroductionWe previously showed that erythropoietin (EPO) attenuates the morphological signs of spinal cord ischemia/reperfusion (I/R) injury in swine [1] without, however, improving neurological function. The clinical use of EPO has been cautioned most recently due to serious safety concerns arising from an increased mortality in acute stroke patients treated with EPO and simultaneously receiving systemic thrombolysis [2]. Carbamylated EPO (cEPO) is an EPO derivative without erythropoietic activity and devoid of the EPO side eff ects, but with apparently well maintained cytoprotective qualities [3]. We therefore tested the hypothesis whether cEPO may be equally effi cient as EPO in reducing morphological as well as functional aortic occlusion-induced spinal cord I/R injury. Methods In a randomized and blinded trial pigs received either vehicle (control, n = 9), EPO or cEPO, respectively (n = 9 each; 5,000 IU/kg over 30 minutes before and during the fi rst 4 hours of reperfusion). Animals underwent 30 minutes of thoracic aortic balloon occlusion with catheters placed immediately downstream of the A. subclavia and upstream of the aortic trifurcation. Spinal cord function was assessed by motor evoked potentials (MEP as percentage of the amplitude before aortic occlusion) and lower limb refl exes (assessed as the subjective strength of response) for a period of 10 hours after reperfusion. Tissue damage was evaluated using Nissl staining. Results Both EPO-treated and cEPO-treated animals presented with attenuated spinal cord injury in the Nissl staining (median (quartile) percentage of damaged neurons in the thoracic segments: control 27 (25,44), cEPO 8 (4,10), and EPO 5 (5,7), P <0.001 vs control group; in the lumbar segments: control 26 (19,32), cEPO 7 (5,13), EPO 8 (5,10), P <0.001 vs control group). However, while only cEPO treatment was associated with recovery of the MEP amplitude to pre-occlusion values when compared with the control group (P <0.05), lower limb refl ex response was comparably restored stronger in both treatment groups (P <0.05 vs control). Conclusions In a clinically relevant porcine model mimicking aortic crossclamping during vascular surgery repair of thoracic aortic aneurysm, cEPO protected spinal cord function and integrity as eff ective as EPO when applied at equipotent doses. Acknowledgements Supported by the Deutsche Forschungs gemeinschaft (SCHE 899/2-2). References Introduction Unfolded protein response (UPR)-mediated apoptosis plays a pivotal role in ischemia-reperfusion injury. Sodium 4-phenylbutyrate (PBA) has been reported to act as a chemical chaperone inhibiting UPR-mediated apoptosis triggered by ischemia in various organs other than the heart. Therefore we investigated whether PBA reduces UPR-mediated apoptosis and protects against myocardial ischemia-reperfusion injury in mice. Methods C57BL/6 mice were subjected to 30 minutes LAD ischemia followed by reperfusion. PBA (100 mg/kg) or PBS (control) was administrated intraperitoneally just before ischemia. Apoptosis, infarct ...
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