P73 regulates cisplatin-induced apoptosis in ovarian cancer cells via a calcium/calpain-dependent mechanism.

P73 is important in drug-induced apoptosis in some cancer cells, yet its role in the regulation of chemosensitivity in ovarian cancer (OVCA) is poorly understood. Furthermore, if and how the deregulation of p73-mediated apoptosis confers resistance to cisplatin (CDDP) treatment is unclear. Here we demonstrate that TAp73α over-expression enhanced CDDP-induced PARP cleavage and apoptosis in both chemosensitive (OV2008 and A2780s) and their resistant counterparts (C13* and A2780cp) and another chemoresistant OVCA cells (Hey); in contrast, the effect of ΔNp73α over-expression was variable. P73α downregulation attenuated CDDP-induced PUMA and NOXA upregulation and apoptosis in OV2008 cells. CDDP decreased p73α steady-state protein levels in OV2008, but not in C13*, although the mRNA expression was identical. CDDP-induced p73α downregulation was mediated by a calpain-dependent pathway. CDDP induced calpain activation and enhanced its cytoplasmic interaction and co-localization with p73α in OV2008, but not C13* cells. CDDP increased the intracellular calcium concentration ([Ca(2+)](i)) in OV2008 but not C13* whereas cyclopiazonic acid (CPA), a Ca(2+)-ATPase inhibitor, caused this response and calpain activation, p73α processing and apoptosis in both cell types. CDDP-induced [Ca(2+)](i) increase in OV2008 cells was not effected by the elimination of extracellular Ca(2+), but this was attenuated by the depletion of internal Ca(2+) store, indicating that mobilization of intracellular Ca(2+]) stores was potentially involved. These findings demonstrate that p73α and its regulation by the Ca(2+)-mediated calpain pathway are involved in CDDP-induced apoptosis in OVCA cells and that dysregulation of Ca(2+)/calpain/p73 signaling may in part be the pathophysiology of CDDP resistance. Understanding the cellular and molecular mechanisms of chemoresistance will direct the development of effective strategies for the treatment of chemoresistant OVCA.

A survey of anorexia nervosa using the Arabic version of the EAT-26 and "gold standard" interviews among Omani adolescents.

OBJECTIVE: The purpose of this study was to assess the validity of the Eating Attitude Test (EAT) in identifying the presence and severity of eating pathology in male and female Omani urban adolescents and to establish cut-off scores that matched those of anorexia identified by gold standard interviews without fear of fatness criteria. METHODS: Both females (n=126) and males (n=136) were screened using the Arabic version of the EAT-26 and interviewed using a semi-structured, Composite International Diagnostic Interview (CIDI) in order to investigate the relationship between false positives and false negatives at various EAT-26 cut-off points. A receiver operating characteristics (ROC) curve was calculated to discriminate the power of the EAT-26 for every possible threshold score. RESULTS: The EAT-26 identified 29% of the subjects as probable anorexic cases as against 9.5% identified during the structured interview based on the anorexia gold standard (32% males and 68% females). The sensitivity and specificity of the EAT-26 were respectively 24% and 69.6%. When using the ROC curve, a cut-off score of 10 gave the best compromise between sensitivity (64%) and specificity (38%). DISCUSSION: Although the EAT-26 is the most widely used screening instrument in cross-cultural studies, it does not appear to be reliable in identifying probable cases of anorexia among Omani adolescents. The use of a gold standard interview without fat phobia criteria indicated that the rate of anorexia nervosa may be more prevalent among males than previously estimated. This intriguingly high preponderance of males is discussed in terms of prevailing demographic trends in Oman.

Tooth extraction, bleeding and pain control.

Local anaesthesia is used routinely in dental surgery; it is effective in both pain control and--through the vasoconstrictors often contained within it--the reduction of bleeding. The extraction of deciduous teeth under general anaesthesia is often carried out without these local effects. There are no previous studies to investigate the combined effect of local anaesthesia with general anaesthesia on blood loss and pain control. A randomised, controlled clinical trial was carried out with one hundred children aged 3-5 years. Ethical approval and informed consent were obtained. Surface anaesthetic cream (EMLA) was placed on the hand into which the intravenous access was to be placed. One to two ml of blood was taken at the time of induction as a baseline of the patient's level of haematin pigment. Children in the experimental group were given one quarter of a cartridge (0.5 ml) of local anaesthetic containing epinephrine (1:80,000) in each quadrant before tooth extraction; all blood in swabs, suction equipment and disposables was collected and digested with NaOH. The children were observed for 11 minutes post-operatively for any signs of distress. Total blood loss was calculated by comparison of the baseline sample and the shed blood digests. This study showed that using local anaesthesia for dental extractions under general anaesthesia was associated with decreased blood loss (p = 0.001). The second finding--which has not been reported before--was that this use of local anaesthesia was shown to cause distress to this age group of children upon recovery from the general anaesthetic (p <0.0001). The use of local anaesthetic in this situation provided a useful reduction in post-operative bleeding. However, its use was associated with greater post-operative distress.