Carnitine reduces the lipoperoxidative damage of the membrane and apoptosis after induction of cell stress in experimental glaucoma.

The pathological damage caused by glaucoma is associated to a high intraocular pressure. The ocular hypertone is most likely due to a defective efflux of aqueous humor from the anterior chamber of the eye. Ocular hypertension causes apoptotic death of retinal ganglion cells and overexpression of molecular markers typical of cell stress response and apoptosis. In this work, we report on the neuroprotective, antiapoptotic and antioxidant action of a natural substance, -carnitine. This compound is known for its ability to improve the mitochondrial performance. We analyze a number of cellular and molecular markers, typical of ocular hypertension and, in general, of the cell stress response. In particular, L-carnitine reduces the expression of glial fibrillary acidic protein, inducible nitric oxide synthase, ubiquitin and caspase 3 typical markers of cell stress. In addition, the morphological analysis of the optic nerve evidenced a reduction of the pathological excavation of the optic disk. This experimental hypertone protocol induces a severe lipoperoxidation, which is significantly reduced by L-carnitine. The overall interpretation is that mortality of the retinal cells is due to membrane damage.

[Treatment of major iatrogenic lesions of the bile ducts]. / Trattamento delle lesioni iatrogene maggiori della via biliare.

BACKGROUND: The appropriate treatment of major bile duct injuries is mandatory in order to avoid serious complications, such as bile peritonitis or secondary biliary liver cirrhosis. In the last fourty years, surgical, endoscopic or radiologic techniques of cure have been proposed, but in our opinions, the preferred option is given by Roux-en-Y choledochojejunostomy or hepaticojejunostomy. Creating an anastomosis on narrow bile duct could be difficult; in these really rare cases, the jejunal loop could be secured by a second suture to the hilar plate with satisfactory long-term results. PATIENTS AND METHODS: In the last four years, in our Institution, six patients underwent surgery for major bile duct injuries. A Roux-en-Y hepaticochojejunostomy was performed for all of them. Two patients had the jejunal loop secured to the hilar plate. RESULTS: Operative morality was nil, and long-term results at a mean follow-up of 20 months are encouraging. CONCLUSIONS: The prevention of major bile duct injuries remains the main target during cholecystectomy or surgery in the area of the hepatoduodenal ligament. In our experience, in general agreement with data from literature, bile reconstruction is best achieved by Roux-en-Y hepaticojejanostomy. In patients unsuitable for surgery, endoscopic balloon dilatation and stent positioning represent a satisfactory alternative.

To do or not to do: desirability and consistency mediate judgements of regret.

In 4 studies, the authors demonstrated that when errors associated with action were inconsistent with decision nakers' orientation, they were undesirable and produced more regret than did errors associated with inaction. Conversely, when errors associated with action were consistent with decision makers' orientation. they were desirable and produced less regret than did errors associated with inaction. Desirability and consistency mediated this relationship, independent of mutability. These results were obtained when judgments and decisions to act or not act were made in close temporal proximity to one another as well as when participants reflected on their past decisions. The authors provide an analysis of when counterfactuals would and would not be expected to mediate judgments of normality and regret.

Fas antigen expression and outcome of oral squamous cell carcinoma.

Paraffin sections of biopsy specimens obtained from 46 patients with oral squamous cell carcinomas were stained with both anti-peptide antibody against human Fas antigen and monoclonal mouse antibody against human proliferating cell nuclear antigen (PCNA). The patients received chemotherapy with a combination of carboplatin and peplomycin sulfate or mitomycin C and peplomycin sulfate before surgery. The relation between the expression of Fas antigen and the clinical features of each case was examined. The correlation between PCNA and Fas antigen expression was also studied. The mean PCNA labeling index of the 22 Fas-negative cases was 46.9%, which was significantly higher than that of the 24 Fas-positive cases (39.5%). Strong correlations were found between the expression of Fas antigen and the response to chemotherapy, tumor recurrence, and survival. The Fas-negative group had only a minor response to chemotherapy and a poor outcome, whereas the Fas-positive group had a better response to chemotherapy and a good outcome. Although lymph node metastasis was significantly related to survival, there was no correlation between Fas antigen expression and lymph node metastasis. The Kaplan-Meier survival curve of patients positive for Fas antigen was significantly better than that of patients negative for Fas antigen. Our results suggest that Fas antigen expression is an independent predictor of outcome whose usefulness should be evaluated in prospective studies.

Fas expression and Fas monoclonal antibody-induced apoptosis in a human squamous cell carcinoma cell line, SCC-25.

Fas antigen is a cell surface protein that mediates apoptosis via signal transduction from the plasma membrane. Using reverse transcriptase-polymerase chain reaction (RT-PCR), messenger RNA for Fas antigen was detected in the human oral squamous cell carcinoma cell line, SCC-25. In serum-free medium, a monoclonal anti-Fas antibody (CH-11) induced Fas antigen expression in SCC-25 cells, as determined by immunocytochemistry and Western blotting, using an anti-Fas polyclonal antibody (Fas D) as primary antibody. Fas antigen was localized to the cytoplasm and the cell membrane. The molecular weight of the protein recognized by Western blot analysis was 35,000, consistent with the value reported for the Fas antigen. The CH-11 antibody did not induce Fas antigen expression in serum-containing medium. To determine whether CH-11 could induce apoptosis in oral squamous cell carcinoma, we examined its effects on the survival of cultured SCC-25 cells. Anti-Fas monoclonal antibody in serum-free medium induced cytotoxicity in SCC-25 cells in a time-dependent manner up to 8 h, as determined by phase-contrast microscopy and WST-1 assay. Marked nuclear condensation and fragmentation of chromatin were observed in the CH-11-treated cells using Hoechst 33342 staining. This anti-Fas monoclonal antibody also induced DNA ladder formation in SCC-25 cells in a time-dependent manner. The present results indicate that the anti-Fas monoclonal antibody (CH-11) may mediate apoptosis by binding to the Fas antigen expressed in SCC-25 cells.

Induction of apoptosis in human oral squamous carcinoma cell lines by protein phosphatase inhibitors.

To determine whether protein phosphorylation and dephosphorylation can affect apoptosis in oral epithelial cells we examined the effects of protein phosphatase inhibitors, okadaic acid (OA) and calyculin A (CA), on cultured human oral squamous carcinoma (SCC) cell line, SCC-25 cells. After reaching subconfluence these cells were exposed to varying concentrations of the protein phosphatase inhibitors, OA and CA. Both OA and CA induced cell death in SCC-25 cells in a dose-dependent fashion as determined by phase-contrast microscopy and WST-1 cell viability assay. By using the Hoechst 33342 staining, marked nuclear condensation and fragmentation of chromatin was observed. DNA ladder formation also was detected in SCC-25 cells by treatment with OA and CA. The induced nuclear fragmentation and DNA ladder formation were dose-dependent with maximal effect at concentrations of 20 nM OA and 2 nM CA, respectively. OA also induced DNA ladder formation in other human oral SCC cell lines, SCCKN and SCCTF. To further determine if new gene transcription and protein synthesis are required for OA-induced apoptosis in SCC-25 cells, the cells were treated for 48 h with varying concentrations of cycloheximide in the presence of 20 nM OA. Cycloheximide did not protect the cells against OA-induced cytotoxicity and DNA ladder formation. Based on the known selectivity of OA and CA, the present results indicate that the pathway of the apoptosis in the cultured oral SCC cells is in part regulated by protein phosphatase type 1 and type 2A. Our results also indicate that new protein synthesis is not involved in OA-induced apoptosis in SCC-25 cells.

Big fish in small ponds: a social hierarchy analysis of intergroup bias.

High- and low-self-esteem group members received feedback about their individual performance as well as that of their own group and an out-group. They then evaluated both groups. Yoked-control observer individuals also provided group evaluations. In the in-group success/out-group failure condition, in-group enhancement tendencies were attenuated by individual failure feedback and augmented by individual success feedback. Low-self-esteem group members who received individual failure feedback showed favoritism toward the unsuccessful out-group over their own successful in-group. In the in-group failure/out-group success condition, in-group enhancement tendencies were attenuated by individual success feedback and augmented by individual failure feedback. Thus individuals' position in a social hierarchy mediates upward and downward social mobility strategies.

Task performance and perceptions of anxiety: averaging and summation in an evaluative setting.

Suggests that individuals' "stage fright," or perceptions of anxiety and performance, is a function of tendencies to both average and summate the impact of audience members. We found that under certain conditions adding an evaluative member to an audience decreased anxiety, whereas in other conditions the addition of evaluative members increased anxiety. These results are not expected from social impact theory or social facilitation research and suggest that individuals do not react to groups of individuals in a manner analogous to the way in which trait information is typically averaged in forming impressions of individuals (Anderson, 1981). An averaging-summation model that does account for these findings is presented. This research has implications for research on crowding, stress, social influence, and affective responses.