Membrane depolarization of isolated rat liver mitochondria attenuates permeability transition pore opening and oxidant production

It has been suggested that one key feature of mitochondrial permeability transition (PT) regulation is its control by the proton electrochemical gradient and that depolarization favors pore opening, swelling, and reactive oxygen species (ROS) production. Moreover, ROS have been suggested to facilitate the process of mitochondrial PT pore opening. The aim of this study was to show that collapsing the mitochondrial membrane potential with the mitochondrial uncoupler, carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), at concentrations of up to 10 microM, does not induce mitochondrial swelling and, in fact, stabilizes mitochondria exposed to oxidant, protecting them from tert-butyl hydroperoxide (TBH)-induced high-amplitude swelling. FCCP decreased polyethylene glycol-induced mitochondrial contraction following exposure to TBH, indicating closing of the PT mega-channel. In the presence of the calcium uniporter inhibitor ruthenium red, FCCP induced PT due to suppression of calcium efflux. Under PT-favorable conditions, ROS production was evaluated in mitochondria following treatments with TBH, inorganic phosphate, or FCCP (with or without ruthenium red). FCCP alone and in combination with ruthenium red attenuated mitochondria-derived ROS production. FCCP also decreased the augmented ROS production induced by inorganic phosphate. It is concluded that mitochondrial depolarization protects and prevents high-amplitude swelling and PT-derived ROS production.     

Sweet's syndrome and subacute thyroiditis

A 63 year old woman developed biopsy documented lesions of acute febrile neutrophilic dermatosis (Sweet's syndrome) one week after the onset of subacute thyroiditis. This is only the second reported case of such an association. The role of cytokines in the development of both subacute thyroiditis and Sweet's syndrome may be the link between these two conditions.     

Genitourinary malignancy presenting as an ocular metastasis: A case report and review of the literature

Metastases to the eye or orbit as the initial presentation of genitourinary malignancy are unusual and can be a diagnostic challenge. We report an 81-year-old man who presented with pain and proptosis in an eye that had been blind for 50 years. Radiologic investigations identified a mass involving the left globe and orbit. Histology of the enucleation specimen was consistent with a metastatic poorly differentiated carcinoma suggestive of a prostate primary. With the constellation of obstructive urinary symptoms, an abnormal digital rectal examination, elevated prostate-specific antigen and a positive bone scan, androgen deprivation therapy was initiated for metastatic prostate cancer. After an initial response to treatment, the patient’s disease progressed in a manner atypical for prostate cancer. After describing our case, we review the literature on ocular and orbital metastases and their relation to genitourinary malignancies.     

The predominance of benign histology in small testicular masses

ObjectivesTo evaluate the concordance between testicular tumor size and benign histology in order to identify a cut-off size, below which the rate of benign lesions would be highest.Methods and materialsDuring the years 1995–2008, we performed 131 consecutive testicular operations for testicular tumors. Ten of these were testicular preserving surgery, whereas the other 121 patients had radical orchiectomy. We searched for the rate of benign lesions in the following 3 groups of tumor diameter: 10 mm or less, 11–20 mm, and greater than 20 mm. ROC analysis was used to find the optimal size cut-off below which the rate of benign lesions would be highest.ResultsBenign lesions were found in 11 patients (8%), including epidermoid cyst (n = 4), Leydig cell tumor (n = 3), fibrosis (n = 1), adenomatoid tumor (n = 2), and 1 patient with a simple cyst. Small tumor size strongly correlated with benign histology. The mean diameter of benign vs. malignant lesions was 15 mm and 41 mm, respectively (P < 0.05). The rate of benign lesions in tumors with a diameter of 10 mm or less, 11–20 mm and greater than 20 mm was 50%, 17%, and 2%, respectively. Receiver Operating characteristic (ROC) analysis with 87% sensitivity and 83% specificity revealed a cut-off value of 18.5 mm tumor diameter below which the proportion of benign lesions was 38.5% compared with 2% above it (P < 0.05).ConclusionsWhile benign lesions comprise only 8% of all testicular tumors, their proportion among small lesions is much higher. With a size cut-off of 18.5 mm, 38.5% of smaller lesions are benign. These findings support consideration of testicular exploration for small testicular lesions aiming at preservation rather than predetermined radical orchiectomy.