Ca2+-induced reactive oxygen species production promotes cytochrome c release from rat liver mitochondria via mitochondrial permeability transition (MPT)-dependent and MPT-independent mechanisms: role of cardiolipin.

Release of cytochrome c from mitochondria is considered a critical, early event in the induction of an apoptosis cascade that ultimately leads to programmed cell death. Mitochondrial Ca(2+) loading is a trigger for the release of cytochrome c, although the molecular mechanism underlying this effect is not fully clarified. This study tested the hypothesis that distinct Ca(2+) thresholds may induce cytochrome c release from rat liver mitochondria by membrane permeability transition (MPT)-dependent and independent mechanisms. The involvement of reactive oxygen species (ROS) and cardiolipin in the Ca(2+)-induced cytochrome c release was also investigated. Cytochrome c was quantitated by a new, very sensitive, and rapid reverse-phase high performance liquid chromatography method with a detection limit of 0.1 pmol/sample. We found that a low extramitochondrial Ca(2+) level (2 microM) promoted the release of approximately 13% of the total alamethicin releasable pool of cytochrome c from mitochondria. This release was not depending of MPT; it was mediated by Ca(2+)-induced ROS production and cardiolipin peroxidation and appears to involve the voltage-dependent anion channel. High extramitochondrial Ca(2+) level (20 microM) promoted approximately 45% of the total releasable pool of cytochrome c. This process was MPT-dependent and was also mediated by ROS and cardiolipin. It is suggested that distinct Ca(2+) levels may determine the mode and the amount of cytochrome c release from rat liver mitochondria. The data may help to clarify the molecular mechanism underlying the Ca(2+)-induced release of cytochrome c from rat liver mitochondria and the role played by ROS and cardiolipin in this process

Decrease in Mitochondrial Complex I Activity in Ischemic/Reperfused Rat Heart

Reactive oxygen species (ROS) are considered an important factor in ischemia/reperfusion injury to cardiac myocytes. Mitochondrial respiration is an important source of ROS production and hence a potential contributor to cardiac reperfusion injury. In this study, we have examined the effect of ischemia and ischemia followed by reperfusion of rat hearts on various parameters related to mitochondrial function, such as complex I activity, oxygen consumption, ROS production, and cardiolipin content. The activity of complex I was reduced by 25% and 48% in mitochondria isolated from ischemic and reperfused rat heart, respectively, compared with the controls. These changes in complex I activity were associated with parallel changes in state 3 respiration. The capacity of mitochondria to produce H 2 O 2 increased on reperfusion. The mitochondrial content of cardiolipin, which is required for optimal activity of complex I, decreased by 28% and 50% as function of ischemia and reperfusion, respectively. The lower complex I activity in mitochondria from reperfused rat heart could be completely restored to the level of normal heart by exogenous added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids nor by peroxidized cardiolipin. It is proposed that the defect in complex I activity in ischemic/reperfused rat heart could be ascribed to a ROS-induced cardiolipin damage. These findings may provide an explanation for some of the factors responsible for myocardial reperfusion injury

Postoperative regression of retroperitoneal fibrosis in patients with inflammatory abdominal aortic aneurysms: Evaluation with spiral computed tomography

Partial or total regression of aortic and retroperitonel fibrosis after surgery has been reported in combination with inflammatory abdominal aortic aneurysm (AAA). In this report, we consider the most recent 21 patients with inflammatory AAA consecutively operated on at our institution. The group was composed of 19 men and 2 women, with a mean age of 66 years. In addition to preoperative CT angiographic study, abdominal ultrasound and aortoiliac angiography were also performed. There were no perioperative deaths. The perioperative morbidity rate was 9.5%. In 20 cases (95.2%), the aortic wall was subjected to histological examination with calculation of an inflammatory index. Each patient was reexamined with spiral CT angiography after surgery; postoperative results were assessed in terms of changes in maximal fibrotic-mantle thickness observed on follow-up spiral CT angiograms, expressed both in millimeters and percentage of change. Regression was analyzed for possible correlation with preoperative severity of fibrotic reaction, time of the postoperative exam, inflammatory index, and changes in the fibrotic process involving the adjacent structures. The results show that postoperative improvement was significantly more marked in cases characterized by higher preoperative inflammatory indices in the aneurysmal wall; the time course of regression was highly variable; but on the whole, improvement was more substantial during the early months after surgery, with significant slowing after the second or third year

The endovascular management of open aortic surgery complications with emergency stent-graft repair in high-risk patients

The aim of the study was to demonstrate the utility of endovascular stent-graft repair for emergency management of aorto-iliac surgery complications. Between 1997 and 2004, in our institute, 201 patients underwent transluminal endovascular graft placement. In 3 patients (1.4%), previously submitted to conventional aortic surgery, endovascular treatment was carried out due to the occurrence of late complications: 1 secondary aortocaval fistula, 1 impending rupture of aortic pseudoaneurysm and 1 secondary aorto-enteric fistula. All candidates were high surgical risk patients (ASA III-IV) suitable for endoprosthesis positioning by endovascular stent-graft implantation presenting with severe worsening conditions in an emergency situation. The patients were treated under local anesthesia and mild sedation. After treatment there was complete resolution of the clinical presentation and an improvement of general conditions in all 3 patients. In the 1(st) patient legs edema disappeared and in the 2(nd) patient mesogastric pain is absent, respectively at 30 and 8 months. The 3(rd) patient, with secondary aorto-enteric fistula, was submitted 2 months later to aortic graft removal and axillo-bifemoral bypass because of infection development. For the treatment of abdominal aortic surgery complications in high risk patients, particularly in emergency situations, endovascular approach is a feasible and safe alternative to conventional open repair. Further evaluation of this technique and longer follow-up will determine its exact role in the management of these life-threatening complications

Comparative study of oncoplastic versus non-oncoplastic breast conserving surgery in a group of 211 breast cancer patients

Breast conserving surgery (BCS) followed by radiotherapy is the standard of care for most patients with early breast cancers; however, the aesthetic outcomes of this procedure is not always desirable. Oncoplastic breast surgery is an innovative approach that aims at the safe and effective treatment of the cancerous lesion while achieving the best possible aesthetic outcome. The aim of this study was to evaluate and compare oncoplastic and non-oncoplastic procedures

Extracranial tthromotically active carotid plaque as a risk factor for ischemic stroke

Abstract CONTEXT: Recent studies suggest that factors other than the degree of carotid stenosis are involved in ischemic stroke pathogenesis, especially modifications of plaque composition and related complications. OBJECTIVE: To examine the role of carotid plaque rupture and thrombosis in ischemic stroke pathogenesis in patients undergoing carotid endarterectomy, excluding those with possible cardiac embolization or with severe stenosis of the circle of Willis. DESIGN, SETTING, AND PATIENTS: A total of 269 carotid plaques selected from an Interinstitutional Carotid Tissue Bank were studied by histology after surgical endarterectomy between January 1995 and December 2002. A total of 96 plaques were from patients with ipsilateral major stroke, 91 plaques from patients with transient ischemic attack (TIA), and 82 plaques from patients without symptoms. MAIN OUTCOME MEASURES: Differences in the frequency of thrombosis, cap rupture, cap erosion, inflammatory infiltrate, and major cardiovascular risk factors between study groups. RESULTS: A thrombotically active carotid plaque associated with high inflammatory infiltrate was observed in 71 (74.0%) of 96 patients with ipsilateral major stroke (and in all 32 plaques from patients operated within 2 months of symptom onset) compared with 32 (35.2%) of 91 patients with TIA (P < .001) or 12 (14.6%) of 82 patients who were without symptoms (P < .001). In addition, a fresh thrombus was observed in 53.8% of patients with stroke operated 13 to 24 months after the cerebrovascular event. An acute thrombus was associated with cap rupture in 64 (90.1%) of 71 thrombosed plaques from patients with stroke and with cap erosion in the remaining 7 cases (9.9%). Ruptured plaques of patients affected by stroke were characterized by the presence of a more severe inflammatory infiltrate, constituted by monocytes, macrophages, and T lymphocyte cells compared with that observed in the TIA and asymptomatic groups (P = .001). There was no significant difference between groups in major cardiovascular risk factors. CONCLUSION: These results demonstrate a major role of carotid thrombosis and inflammation in ischemic stroke in patients affected by carotid atherosclerotic disease

Pathological classification of DCIS and planning of therapeutic management

Background: Ductal intraepitelial neoplasia (DIN) represents a spectrum of disease that may progress from usual hyperplasia to ductal carcinoma in situ (DCIS) grade 3. The aim of the study was to asses the correlation between the DIN classification and the surgical treatment including sentinel lymph node biopsy (SLNB). Patients and Methods: In this retrospective study, 229 patients with DIN had undergone conservative or radical surgical treatment and SLNB in cases of DIN1C-DIN3. Results: Breast conservative surgery was the definitive treatment in 80% of the cases. The H&E evaluation of excised sentinel nodes was negative for metastatic disease; neverthless the immunohistochemical (IHC) evaluation revealed the presence of metastatic cells in 6 patients (3.7%). Conclusion: In cases of DIN lesions SLNB is not indicated. The only reason SLNB should be considered is when there is an evidence of invasive foci at definitive histology or when radical mastectomy is proposed