Induction of the mitochondrial permeability transition by selenium compounds mediated by oxidation of the protein thiol groups and generation of the superoxide

The cancer chemopreventive effect of selenium compounds cannot be fully explained by the role of selenium as a component of antioxidant enzymes, suggesting that other mechanisms, such as thiol oxidation or free radical generation, also underlie this effect. The toxicities of six different selenium compounds (selenite, selenate, selenocystine, selenocystamine, selenodioxide, and selenomethionine) have now been compared in HepG2 human hepatoma cells and isolated rat liver mitochondria. Selenite, selenocystine, and selenodioxide induced apoptosis in HepG2 cells and mediated oxidation of protein thiol groups in both HepG2 cells and isolated mitochondria. Selenocystamine oxidized protein thiol groups in isolated mitochondria and crude extracts of HepG2 cells but not in intact HepG2 cells, suggesting that this compound is not able to cross the cell membrane. The selenium compounds capable of oxidizing thiol groups also induced the mitochondrial permeability transition (MPT) in isolated mitochondria. Furthermore, they generated the superoxide (O(2) .-) on reaction with glutathione in the presence of mitochondria, and an O(2) .-) scavenger inhibited their induction of the MPT. These results suggest that the pro-apoptotic action of selenium compounds is mediated by both thiol oxidation and the generation of O(2) .-), both of which contribute to opening of the MPT pore.     

Growth factor releasing porous poly (ɛ-caprolactone)-chitosan matrices for enhanced bone regenerative rherapy

Drug releasing porous poly(epsilon-caprolactone) (PCL)-chitosan matrices were fabricated for bone regenerative therapy. Porous matrices made of biodegradable polymers have been playing a crucial role as bone substitutes and as tissue-engineered scaffolds in bone regenerative therapy. The matrices provided mechanical support for the developing tissue and enhanced tissue formation by releasing active agent in controlled manner. Chitosan was employed to enhance hydrophilicity and biocompatibility of the PCL matrices. PDGF-BB was incorporated into PCL-chitosan matrices to induce enhanced bone regeneration efficacy. PCL-chitosan matrices retained a porous structure with a 100-200 microm pore diameter that was suitable for cellular migration and osteoid ingrowth. NaHCO3 as a porogen was incorporated 5% ratio to polymer weight to form highly porous scaffolds. PDGF-BB was released from PCL-chitosan matrices maintaining therapeutic concentration for 4 week. High osteoblasts attachment level and proliferation was observed from PCL-chitosan matrices. Scanning electron microscopic examination indicated that cultured osteoblasts showed round form and spread pseudopods after 1 day and showed broad cytoplasmic extension after 14 days. PCL-chitosan matrices promoted bone regeneration and PDGF-BB loaded matrices obtained enhanced bone formation in rat calvarial defect. These results suggested that the PDGF-BB releasing PCL-chitosan porous matrices may be potentially used as tissue engineering scaffolds or bone substitutes with high bone regenerative efficacy.     

Linezolid, levofloxacin, and vancomycin against vancomycin-tolerant and fluoroquinolone-resistant Streptococcus pneumoniae in an in vitro pharmacodynamic model

STUDY OBJECTIVE: To compare the pharmacodynamic profiles of linezolid, levofloxacin, and vancomycin against clinical strains of Streptococcus pneumoniae, including vancomycin-tolerant and fluoroquinolone-resistant isolates. DESIGN: In vitro pharmacodynamic model. SETTING: Biosafety level 2, university research laboratory. BACTERIAL STRAINS: Ciprofloxacin-susceptible (79), ciprofloxacin-resistant (R921), and vancomycin-tolerant (P9802-020) clinical strains of S. pneumoniae. INTERVENTION: An in vitro pharmacodynamic model was used to simulate standard dosing regimens of linezolid, levofloxacin, and vancomycin against the isolates 79, R921, and P9802-020. MEASUREMENTS AND MAIN RESULTS: Bacterial density was profiled over 48 hours. Minimum inhibitory concentrations (MICs) for linezolid, levofloxacin, and vancomycin, respectively were 1, 1, 0.5 microg/ml for isolate 79; 1, 4, 0.5 microg/ml for R921; and 0.5, 0.5, 0.5 microg/ml for P9802-020. Vancomycin minimum bactericidal concentration (MBC) values varied across large ranges for the tested strains. Linezolid achieved 99.9% kill against 79 and R921 by 24 and 28 hours, respectively. Levofloxacin achieved 99.9% kill against 79 and P9802-020 by 28 and 4 hours, respectively. Vancomycin achieved 99.9% kill against 79 and R921 by 8 and 24 hours, respectively. Levofloxacin did not demonstrate activity against R921 at the 48-hour end point. Minimal kill (< 2 log) at 48 hours was noted for vancomycin and linezolid against P9802-020. Conclusion. Vancomycin tolerance appeared to be more reliably characterized by persistent viability in time-kill analyses than by MBC:MIC ratios. Vancomycin exhibited bactericidal activity against the non-vancomycin-tolerant strains of S. pneumoniae. Linezolid exhibited both bactericidal and bacteriostatic activity against all three strains tested, whereas levofloxacin demonstrated bactericidal activity against the fluoroquinolone-susceptible isolates. Further investigation of treatment alternatives for infections due to vancomycin-tolerant S. pneumoniae are needed.     

Cytology of morcellated renal specimens: significance in diagnosis and dissemination

PURPOSE: Controversy surrounds the process of morcellation for retrieving laparoscopically removed specimens. The inability to assess tumor stage, increased difficulty in pathological examination and the potential for tumor spillage are cited as significant disadvantages of the technique. We examined cytological findings in bag washings after laparoscopic nephrectomy for benign and malignant diseases. MATERIALS AND METHODS: We prospectively obtained cytology washings from the retrieval bag after laparoscopic nephrectomy and manual morcellation. In 22 consecutive cases after specimen fragmentation in a LapSac (Cook Urological, Spencer, Indiana) the bag was thoroughly irrigated with 30 cc normal saline. This wash was then processed by ThinPrep (Cytyc Corp., Marlborough, Massachusetts) and stained with Papanicolaou stain. Standard pathological examination of the morcellated specimen was performed to determine renal histology. RESULTS: The histological diagnosis was clear cell renal carcinoma in 10 cases, multicystic renal carcinoma in 2, papillary renal cell carcinoma in 1, angiomyolipoma in 1, and oncocytoma in 1. Bag cytological results were accurate in 9 of 13 patients with carcinoma (69%), while in 3 cytological study provided additional information. In all 9 cases of benign histology, cytological findings were consistent with benign cellular features. Neoplastic cells were easily detected and classified into type and grade. CONCLUSIONS: Cytological examination of LapSac washings after specimen morcellation provided a pathological diagnosis in the majority of patients. This method may complement existing techniques and be useful for increasing the accuracy of pathological analysis of morcellated specimens. In addition, these data suggest that malignant cells are liberated during the morcellation process, which has significant implications for potential tumor dissemination.     

Hepatic arteries in potential donors for living related liver transplantation: evaluation with multi-detector row CT angiography

PURPOSE: To assess the accuracy of multi-detector row computed tomographic (CT) angiography in the evaluation of hepatic arterial anatomy in living related liver transplantation (LRLT) donors. MATERIALS AND METHODS: During a 10-month period, 62 potential LRLT donors were evaluated with CT and conventional angiography. Multi-detector row CT was performed after intravenous injection of 150 mL of contrast material at 3 mL/sec. CT angiograms of the hepatic arteries were generated by a radiologist who used volume rendering and maximum intensity projection techniques without knowledge of results of conventional angiography. Two reviewers reviewed CT and conventional angiograms retrospectively in consensus. The results of the two examinations were then compared. RESULTS: CT examinations were technically adequate in 56 (90%) donors. Respiratory motion artifact compromised detailed hepatic artery analysis in six donors (10%). Second-order branches of right hepatic arteries were visualized in 58 donors (94%), and second-order branches of left hepatic arteries were visualized in 51 (82%). A total of 27 hepatic arterial anatomic variations were detected in 22 donors at conventional angiography. CT angiography accurately depicted 25 (93%) anatomic variations in 20 donors (91%). CT angiography did not depict an accessory right hepatic artery in two donors. The number and origins of dominant arteries supplying segment IV were accurately identified at CT angiography in 51 donors (82%). Hepatic arterial anatomy depicted at CT angiography was identical to that at conventional angiography in 50 donors (81%). CONCLUSION: Multi-detector row CT angiography is useful but limited in its ability to depict the dominant artery supplying segment IV and small accessory hepatic arteries.     

Case report: magnetic resonance imaging of vaginal malignant melanoma

We report two cases of vaginal melanoma with magnetic resonance imaging findings. The first melanoma was a bilobular polypoid mass with melanotic and amelanotic components, which arose from the lateral wall of the vaginal canal. The melanotic melanoma showed high signal intensity (SI) on T1-weighted images and low SI on T2-weighted images, which was not suppressed by a fat-saturated sequence. Another melanoma showed a pale brown polypoid mass in the vagina, which revealed intermediate SI on T1-weighted images and high SI on T2-weighted images. On fat-suppressed images, both tumors were more clearly demonstrated with high SI.     

Lithiasis in a heterotopic pancreas of the stomach

A heterotopic pancreas is a relatively uncommon abnormality and usually of no clinical importance. A heterotopic pancreas is subject to various pathologic changes occurring in the pancreas, however, such as acute pancreatitis, cyst or abscess formation, pancreatic cancer, and islet cell tumor. We describe a rare case of a heterotopic pancreas presenting as a gastric submucosal mass with punctate calcifications occurring in a 43-year-old man.     

Adhesive capsulitis of the shoulder: diagnosis using magnetic resonance arthrography, with arthroscopic findings as the standard

OBJECTIVE: The purpose of this study was to assess the usefulness of magnetic resonance (MR) arthrography of the glenohumeral joint in the diagnosis of adhesive capsulitis. METHODS: MR arthrography of the glenohumeral joint was performed in 16 patients with arthroscopically proven adhesive capsulitis and 11 controls. Thickness of the joint capsule and synovium, filling ratio of the fluid-distended axillary recess to the posterior joint cavity, and a width of the rotator cuff interval were measured by 2 musculoskeletal radiologists. The measurements of those parameters for the patients with adhesive capsulitis and the controls were compared. Interobserver variability for the measurements of each parameter was calculated. RESULTS: The mean thickness of the joint capsule and synovium was 2.97 mm in patients with adhesive capsulitis and 1.86 mm in controls (P < 0.001). The mean filling ratio of the fluid-distended axillary to the posterior joint cavity was 0.51 in patients with adhesive capsulitis and 0.82 in controls (P = 0.004). The mean width of the rotator cuff interval was 7.45 mm in patients with adhesive capsulitis and 8.48 mm in controls (P > 0.05). Intraclass correlation coefficient for interobserver variability showed good agreement (95% CI; 0.72-0.95). CONCLUSIONS: On MR arthrography, thickening of the joint capsule and synovium and diminished filling ratio of the axillary recess to posterior joint cavity appeared to be useful diagnostic criteria for the diagnosis of adhesive capsulitis of the shoulder.